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ilustraciones, gráficas, tablas En el aprendizaje del inglés los estudiantes generan estados emocionales que facilitan o bloquean el desarrollo de la habilidad oral. Por tal razón, la presente investigación de corte mixto tuvo como propósito analizar los posibles cambios o transformaciones en la fluidez en presentaciones orales de estudiantes del nivel A1 de inglés que hicieron parte de un programa diseñado para el fortalecimiento de competencias emocionales de consciencia y regulación. Se llevó a cabo durante ocho semanas, durante las cuales se propuso una estrategia para desarrollar las competencias de consciencia y regulación emocional en 24 estudiantes de un centro binacional de inglés ubicado en el centro de la ciudad de Bogotá, Colombia. Inicialmente, se eligieron aleatoriamente dos grupos participantes, uno experimental y uno de control; ambos tomaron una prueba de entrada para comparar su nivel de fluidez antes del inicio del proceso. Luego, se diseñó una serie de talleres en los cuales los estudiantes del grupo experimental fueron instruidos sobre cómo trabajar las competencias de consciencia y regulación emocional, mientras el grupo control tomó sus clases de forma regular. Tras implementar los talleres, se realizó una prueba de salida en los dos grupos con el fin de comparar sus resultados. Adicionalmente, se recopilaron diarios de campo, videograbaciones y entrevistas que validaron cualitativamente los resultados del proceso. En los hallazgos, tanto cuantitativos como cualitativos, se evidenció que el grupo experimental tuvo un incremento en su fluidez oral y que el desarrollo de los talleres impactó positivamente en el desarrollo emocional de los participantes dentro y fuera del salón de clase. (Texto tomado de la fuente) In the language learning process, students have affective factors that can either facilitate or block the development of oral skills. Therefore, the purpose of this mixed research study was to analyze the possible changes or transformations in oral fluency in oral presentations of A1 level English students who were part of a program designed to strengthen emotional awareness and regulation competencies. The project was conducted for eight weeks, to 24 students from a binational English center located in the center of the city of Bogotá, Colombia. Initially, two participating groups were randomly chosen, one experimental and one control; both groups took a fluency pretest to compare their level of fluency before the beginning of the research process. After the test, several workshops were designed and participants of the experimental group were instructed on how to work on awareness and emotional regulation competencies, while the control group took their regular language classes. After implementing the workshops, a fluency pos test was carried out in the two groups in order to compare their results. Additionally, students’ journals, class video recordings and interviews were compiled to validate the results of the process qualitatively. As for the findings, in both quantitative and qualitative results, it was evidenced that not only did the experimental group increase their oral fluency, but also the development of the workshops had a positive impact on the emotional development of the participants inside and outside the classroom. (Text taken from source) Maestría Magíster en Educación La metodología utilizada para el estudio actual fue de perspectiva mixta porque, como propuso Creswell (2014), está constituido por dos realidades, una objetiva y una subjetiva. Objetiva, dado que con datos cuantificados se analiza el perfil de entrada y salida de los participantes del estudio. Subjetiva, debido a la intervención de la propuesta metodológica durante la ejecución inspirada en la investigación acción. Además, su diseño es paralelo convergente, puesto que se analizaron de forma separada los datos cuantitativos y cualitativos para comparar los resultados. Sumado a esto, al implementar el método mixto se incrementa la confianza en los resultados, que son una representación fiel y genuina de lo que ocurre en el fenómeno. Educación en lenguas extranjeras

Study question How was the Logbook for the Nurses and Midwives Certification programme of the European Society of Human Reproduction and Embryology (ESHRE) developed? Summary answer The Logbook for the ESHRE Nurses and Midwives Certification programme, which questions 56 roles, was developed based on an extensive literature review and expert opinion. What is known already The ESHRE Executive Committee established the Nurses and Midwives Certification Committee (NMCC) in 2012. Since inception (2015), the certification programme has been delivered annually, with the exception of 2020 because of SARS-CoV-2. One-hundred-fourteen nurses/midwives have obtained ESHRE certification (passing rate=72%) and the programme is now accessible to nurses/midwives globally. The Certification program aims (i) to recognise the extended role of nurses/midwives delivering fertility care and (ii) to expand their theoretical background. The pre-requisites for certification are (i) being educated to a bachelor level of education and (ii) completing a practice based Logbook to demonstrate supervision of professional experience. Study design, size, duration Between 2012 and 2014, the NMCC completed a systematic literature search for papers relating to clinical, non-clinical and extended roles of nurses and midwives in fertility settings. In addition, the NMCC invited a larger expert panel of European senior nurses and midwives to a meeting to discuss their needs and preferences regarding the certification programme and to survey the diverse roles performed by nurses and midwives in their country. Participants/materials, setting, methods The NMCC comprised four nurses/midwives, one clinical embryologist, and one medical doctor (both in advisory capacity). The Medline database was searched by entering a search string in PubMed combining (MeSH) terms related to reproductive medicine and nursing or midwifery. Opinion and empirical papers relating to roles of nurses/midwives in fertility settings were included. The surveyed expert panel included twelve nurses/midwives, representing Belgium, Denmark, Finland, France, Norway, Slovenia, Sweden, Turkey, Ukraine, and the United Kingdom. Main results and the role of chance A total of 49 papers, of which 24 empirical papers, were identified with the search string (n = 47) and snowball strategy (n = 2). The papers originated from 13 countries spread across Asia, Oceania, Europe, and North America. All twelve European senior nurses and midwives responded to the survey. Finally, 56 different roles were included in the Logbook. Forty-four roles were performed by nurses/midwives working in fertility settings according to the surveyed expert panel (n = 18), the literature (n = 8), or both the surveyed expert panel and literature (n = 18). An additional twelve observations of laboratory procedures were added by the NMCC. Substantial variation in roles and responsibilities existed across the countries from which the evidence originated. Whereas a considerate proportion of roles were performed in at least five countries (n = 16/56), a minority of roles were only performed by nurses/midwives in some countries (n = 7/56). Eight specialist roles (e.g. embryo transfer) were performed independently by nurses/midwives in some countries, whilst in other countries, nurses/midwives merely had an assisting role. In addition to completing the Logbook, participants were expected to write two ethical cases according to a guideline, testifying to their ability to reflect as a senior nurse/midwife. From 2015, the content of the Logbook was further developed. Limitations, reasons for caution This abstract relates to the development and content of the Logbook and not the curriculum/educational material required for the theoretical exam of the Nurses and Midwives Certification programme. The NMCC continuously improves the Logbook and elements have been added and removed since its creation. Wider implications of the findings The review and survey illustrated the variation in roles and responsibilities of nurses/midwives across the studied countries, further highlighting the opportunity for professional development within fertility care. Further research is required to elicit the experience of certified nurses/midwives with the programme and its impact on their professional and personal development. Trial registration number Not applicable

Study question How do infertility patients, endometriosis patients and health care providers rate the virtual care that was provided during the first lockdown of the COVID-19 pandemic? Summary answer Patients and health care providers rate telephone- and video consultations as good alternatives during the pandemic but it cannot replace future physical consultations. What is known already Virtual alternatives to regular care such as telephone and video consultations are gaining more attention as replacement for physical consultations and are ideal for use in a social distancing situation as the COVID-19 pandemic. However, infertility and endometriosis patients often rely on physical consultations for reassurance as well as for treatments such as artificial reproductive technology and surgery. Not being able to receive these reassurances and treatments may cause stress especially as infertility patients are known to experience a high sense of urgency to obtain treatment. For patients with endometriosis, regular follow-up visits are important for continuity of care. Study design, size, duration: A cross-sectional cohort study was performed, including 555 patients and 101 health care providers in the field of infertility and endometriosis in the Netherlands. Online questionnaires were sent between May and October 2020. Participants/materials, setting, methods Patients with infertility and endometriosis patients from a university hospital and members of the respective national patients organizations, as well as health care providers in the fields of infertility and endometriosis were asked to participate. The questionnaires consisted of demographics, appraisal of telephonic and video consultations (TCs and VCs) and assessment of fertility related quality of life (FertiQoL) and patient-centeredness of endometriosis care (ENDOCARE). Main results and the role of chance The questionnaires were completed by 374 infertility patients, 181 endometriosis patients and 101 health care providers. 75.9% of the infertility patients, 64.8% of the endometriosis patients and 82.7% of the health care providers rated TCs as a good alternative for physical consultations during the COVID-19-pandemic. Only 21.3%, 14.8% and 21.3% rated TCs as a good replacement of physical consultations in general. 76.6% and 35.9% of the infertility and endometriosis patients reported to experience an increase in stress due to the altered care during the COVID-19 pandemic. 38.7% and 58.0% reported to have received sufficient information from their care givers. Infertility patients scored lower on the FertiQoL than the reference population, while the ENDOCARE results of endometriosis patients were comparable to the reference. Limitations, reasons for caution This study was limited to the Dutch population. As the organization of infertility care varies internationally, the results will not be directly applicable to other countries or health care systems. Wider implications of the findings: Virtual care options are a good alternative for infertility and endometriosis patients in situations where physical consultations are not possible. Self-reported stress is especially high in infertility patients during the COVID-19-pandemic. Health care providers should provide more information to patients in order to increase their ability to cope with stress. Trial registration number N/A

text In clinical practice, infertility treatment delays can occur due to medical, logistical, or financial reasons. Concerns over treatment delays were brought to the forefront in March 2020 when the SARS-CoV-2 pandemic prompted both the ESHRE and ASRM to recommend the suspension of new infertility treatment cycles. At the time, little was known about the risk of viral transmission on reproductive health and necessary medical resources urgently needed to be reallocated to the front lines of the pandemic. These society recommendations were met with resistance from some clinicians and patients that raised valid concerns about whether delaying IVF treatment for a few months could negatively affect pregnancy outcomes. To help answer this question, we designed a retrospective cohort study to assess whether a delay up to 180 days in initiating IVF treatment affects pregnancy outcomes in infertile women with diminished ovarian reserve. This population was selected because their treatment outcomes were the most likely to affected by treatment delays due to the continuous decline in ovarian reserve over time. Infertile women treated at our IVF center were included if they had diminished ovarian reserve and started an ovarian stimulation cycle within 180 days of their initial consultation that resulted in an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. Diminished ovarian reserve was defined as an anti-Mŭllerian hormone (AMH) < 1.1 ng/mL. In total, 1,790 patients met inclusion criteria (1,115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1-90 days after presentation (immediate) or 91-180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH < 0.5 and for patients >40 years old with an AMH < 1.1 ng/mL (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred. The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85-1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH < 0.5 ng/mL (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65-1.51) and in patients >40 years old with an AMH < 1.1 ng/mL (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77-1.91). Overall, we observed that a delay in initiating IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. This observation persisted for patients who in the highest-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistical, or financial reasons, treatment outcomes will not be negatively affected.

Study question Is there a variation in ovarian reserve in women who have passed the disease? Summary answer The fact of having passed SARS-CoV-2 does not affect the ovarian reserve status What is known already Despite the overwhelming magnitude of this pandemic and its worldwide prevalence, information regarding the effects of the novel coronavirus on human reproduction are currently limited. As the assisted reproductive technology programs resumed operations, it was important to gather information regarding the status of individuals infected with the novel coronavirus, and to assess gametes and reproductive outcomes for those who had SARS-CoV-2 virus. Since it was described the presence of receptors of the virus in the ovary, studies on the reproductive involvement of coronavirus infection are warranted, particularly within recovered patients Study design, size, duration During the period May-June 2020, women performing an Assisted Reproductive treatment in any of the 11 clinics belonging to the IVIRMA group in Spain and who had a positive IgG for SARS-CoV-2 were invited to participate in the study; this group of women had a previous AMH determination of no more than 6 months. The study was approved by an Institutional Review Board (2007-MADR-052-AR) and all women provided written informed consent. Participants/materials, setting, methods A new AMH determination was made (Elecsys® AMH, Roche Diagnostics) to detect possible variations in the hormone levels. Women were stratified in two groups, according their previous AMH levels: low responders (AMH < 1 ng/ml) or normo-high responders (AMH ≥ 1 ng/ml) Statistical analyses were performed using the Statistical Package for Social Sciences 19.0 (IBM Corporation, Armonk, NY, USA). Main results and the role of chance After filtering by the inclusion criteria described above, we included 46 patients in this phase of the study; 16 women were diagnosed as having low ovarian reserve (AMH < 1 ng/ml), with an average age of 38.6 years, whereas 30 were classified as having normal ovarian reserve (AMH ≥ 1 ng/ml), with an average age of 34.7 years. Generally, the data show no variation in AMH levels before and after SARS-CoV-2 infection (1.73 ng/ml vs. 1.61 ng/ml, respectively). However, when we analyzed these differences according to the study groups, we observed that, in women with normal ovarian reserve, average AMH level before infection was 4.6 ng/ml, whereas after infection AMH decreased to 3.1 ng/ml. For women with low ovarian reserve, AMH was 0.8 ng/ml before infection and remained at a similar value after infection (AMH = 0.7 ng/ml). Limitations, reasons for caution This is an observational study and thus possible confounders cannot be completely excluded. More data are needed to draw firm conclusions it will be critical to increase the sample size to check if the results observed in this work remains in the general population Wider implications of the findings The fact of having passed the disease does not affect the ovarian reserve status but the degree of the variation of AMH levels depending on the patient were low or high responder. Nevertheless, we could assume that the chances of success of the Assisted Reproductive treatment remain intact. Trial registration number Not apply

Study question Covid-19 pandemic has significantly affected the assisted reproductive technology (ART) practice. Understanding whether SARS-CoV-2 could infect endometrial tissues during ART is crucial for risk mitigation Summary answer Analyses of gene expression profiles of SARS-CoV-2 host entry candidates from microarray data suggest that endometrium should be considered as potential target for SARS-CoV-2 infection. What is known already Very few studies analyzed the gene expression profiles of SARS-CoV-2-associated receptors and proteases, mainly focusing on ACE2 and TMPRSS2 expression, resulting incomplete knowledge in different specimens from female genital tract. However, no studies have analyzed the potential impact of controlled ovarian stimulation (COS) protocols during ART procedure on the endometrial gene expression profiles of SARS-CoV-2-associated receptors and proteases Study design, size, duration To address this question, we retrospectively examined the gene expression profile of SARS-CoV-2-associated receptors and proteases in endometrial biopsies of a cohort of ART candidates using Affymetrix microarray data Participants/materials, setting, methods Human endometrial tissue under natural (n = 62) and COS cycles (n = 42) were analyzed. A focus was particularly made on the renin-angiotensin system relates genes with a prominent role in the virus infection, and gene expression levels of receptors and proteases closely related to SARS-CoV-2 infectionwas also studied. Main results and the role of chance Using our large cohort of endometrial samples, we reported a high prevalence of genes related to the ACE2 pathway, including AGT, AGTR1, ANPEP, CTSA, ENPEP, LNPEP, MME, NLN, THOP1, BSG and CTSL during both phases(early- and mid-secretory phase), and mainly during the mid-secretory phase for ACE2. The highest signal intensities were found for CTSA, LNPEP, MME, NLN, BSG and CTSL. The most representative of dual coexpression of SARS-CoV-2-associated receptor and protease in endometrium was BSG-CSTL and BSG-CTSA. It s also important to note high variation of SARS-CoV-2 receptors inter-patients under natural cycle.Globally, the impact of COS on endometrial gene expression profile of SARS-CoV-2-associated receptors and proteases of non Covid-19 patients is low, suggesting no additional potential risks of SARS-CoV-2 infection during stimulated ART procedure compared with natural cycles. Limitations, reasons for caution Analyses of Affymetrix microarray gene expression data were performed in non-COVID-19 patients. Whether the SARS-CoV-2 infection changes the endometrial gene expression profile of SARS-CoV-2-associated receptors and proteases is under investigation Wider implications of the findings Specimens from female genital tract may be considered as potential targets for SARS-CoV-2. Trial registration number not applicable

Study question Is the emotional experience of patients during IVF different since the start of the global Covid-19 pandemic? Summary answer Tracking data since re-opening demonstrated patients lower positive challenge emotions but no significant change in harm, threat, or stress. What is known already Covid-19 caused widespread shutdown of fertility centres, including in the UK, when the HFEA mandated closure from March until May 2020. Research shows clinic closure and an uncertain future were a significant psychological burden for patients anticipating treatment. However, emotional experiences before, during and after closure have not yet been compared, which is the aim of the study. Study design, size, duration Retrospective single-centre analysis of anonymised emotional tracking data entered by 707 patients using the MediEmo smartphone app alongside their IVF cycle, from May 2017-September 2020. MediEmo includes medication timeline/ notifications, coping tools and emotional tracking. Patients rate 2 questions daily in each emotion domain (challenge, threat, harm, e.g. ‘I am feeling tense’) on a 0-3 scale and indicate coping ability (‘I am unable to cope with the stress I am experiencing’) on a binary scale. Participants/materials, setting, methods Egg donor, recipient and fertility preservation cycles were excluded. First, mood scores were analysed by 2020 month of entry to capture the emotional impact of closure. Second, “Pre-Covid” (May 2017-Feb 2020) and “After Re-opening” (May 2020–Sept 2020) emotional experiences were compared, using student t-tests. Mean and standard deviation of scores in each mood domain entered on each cycle day were calculated, centred on luteal day 0/ egg collection, from cycle day -14 to + 14. Main results and the role of chance Graphical presentation of emotional data by month clearly demonstrates the significant increase in threat, harm and stress emotions and reduced positive emotions experienced immediately prior to and during mandatory clinic closure. Of patients entering emotional data during closure in March/April 2020, 40% (14/35) stated they felt unable to cope with the stress they were currently experiencing. From May 2020 after the clinic reopened, analysis of in-cycle emotional tracking data showed there are no significant differences in harm or threat emotion levels or numbers reporting intolerable stress during IVF, compared to cycles pre-pandemic (May17-Feb 2020). Patients undertaking IVF cycles since closure are logging lower challenge scores (confident, encouraged, positive, hopeful), demonstrating less optimism, particularly in the ‘two-week wait’ phase of the cycle. The mean (s.d) of challenge scores pre-Covid was 1.50 (1.07), compared to 1.38 (1.04) after re-opening, p = 0.00085. The women who had treatment cycles post re-opening from May 2020 onwards were older (33.4(5.2) vs 32.6(4.4)), which may reflect clinical treatment prioritisation decisions. There was no significant differences in number of eggs collected (mean(s.d) Pre-Covid 12.08 (8.0) vs After re-opening 11.83 (9.4), p = 0.84) or live birth/ ongoing pregnancy rates for undelivered pregnancies (p = 0.69) between the groups. Limitations, reasons for caution Emotional data was only available for those who chose to use MediEmo, entered emotional tracking data and who gave consent for use of their clinical data in research. As such, this analysis may not fully reflect all patients’ experiences. Most of the available data were entered prior to the pandemic. Wider implications of the findings For Covid-19 safety reasons, patients currently have less in-person staff contact when undertaking IVF. The findings reassuringly suggest emotional wellbeing was not markedly different in most domains. However, daily ratings did show the emotional fall-out of clinic closures which for most threatened attainability of parenthood goals (e.g., less hope). Trial registration number Not applicable

text Aberdeen Fertility Centre provides fertility investigation and treatment across the north east, highlands and islands (Orkney & Shetland) of Scotland, which includes rural and remote communities. Whilst the SARS-Cov-2 pandemic has accelerated the delivery of Tele-fertility Nursing, the National Health Service (NHS) in Grampian, Scotland launched both ‘No Delays’ and ‘Near Me’ platforms in 2019 to keep pace with the digital age and with the intention of improving the quality of patient care. No Delays (series of video packages and virtual consultations) has revolutionised clinical pathways, providing individualised patient information from investigation to treatment, permitting email ‘prescription’ of digital postcards (personalised package of short videos introducing members of the team and explaining their role) that explain the fertility journey and management plan in detail, from investigation (ie., tubal evaluation), to treatment (ie., ovulation induction or IVF), and self-administration of medicines. Thereafter, patients receive invitation to virtual ‘Near Me’ consultation which can take place in the comfort of their own home whilst acknowledging flexibility in lifestyle (partner can remotely access consultation from workplace, including overseas). Electronic patient records (EPR’s) provide immediate access to complete, accurate and up to date clinical patient data, which, together with Electronic Consents compliment the tele-nursing experience through a complete library of consent forms, automatically allocated to patient and partner according to treatment type and personal circumstances: information being provided in video format to meet the requirements for informed consent. Forms are completed online, at home or in the ‘virtual’ clinic via computers, tablets or smartphones, with workflow automation tools allowing for digital signature/s. The complete digital package ensures patients have an early understanding of the process, therefore better prepared for face-to-face appointments and ensuring quality care delivered at point of contact. The aims and objectives of ‘Tele-fertility Nursing’ were to: (1) reinforce key information routinely provided at consultation which may not always be understood, (2) meet patient need and lifestyle, (3) increase patient choice, (4) save time and money by reducing unnecessary travel (often complicated by adverse weather conditions from rural communities), (5) avoid unnecessary time off work, and (6) reduce environmental impact of attended appointments (health miles and miles not travelled). Whilst concern remains around the digital interface and nurse/patient relationship, preliminary evaluation of ‘Near Me’ consultations and patient feedback - relative to electronic consent - suggests overall patient satisfaction; the above aims and objectives being met. However, full evaluation of the patient and fertility nurse experience of the ‘digital fertility journey’ is required.

Study question Is there evidence that infertile patients have been more likely to experience distress during the COVID-19 outbreak with the consequent interruption of treatment plans? Summary answer High levels of psychological distress among infertile patients have been found during the COVID-19 pandemic, greater than that reported in the general population. What is known already Preliminary research on the negative consequences of the COVID-19 outbreak on mental health evidenced heightened levels of anxiety, depression and post-traumatic stress in some clinical populations as well as in community samples. However, little is known about the impact of COVID-19 on psychological distress of infertile patients who have been forced to suspend infertility treatment and postpone parenthood goals during the pandemic. The aim of this meta-analytic review is to summarize extant literature on the prevalence of psychological distress symptoms in infertile patients during the COVID-19 pandemic. Study design, size, duration A systematic review and meta-analysis were conducted following the PRISMA guidelines on PsycInfo, PubMed, Embase, Web of Science, MedRxiv from March 2020 to mid-December 2020. Study inclusion criteria were specified according to the PICOS guideline. All naturalistic or RCT studies published in 2020 that examined infertility as the primary diagnosis and had a quantitative measurement of distress, were eligible. The primary outcomes were symptoms of psychological distress and secondary outcomes were indicators of psychological health. Participants/materials, setting, methods The database search identified 144 papers. Two reviewers independently screened potential studies by title and abstracts based on the inclusion criteria. The full texts were then screened for eligibility. The Newcastle-Ottawa Scale was used to judge the methodological quality of the studies. In order to estimate the pooled prevalence of distress, Odds Ratios with 95% Confidence Interval were calculated as the effect size by using a random-effects model. Heterogeneity was tested using I2 statistics. Main results and the role of chance Fourteen studies met the inclusion criteria and were summarized for the systematic review (N = 6473). Only six studies did not include males although, in the surveys, females made up 92% of the total sample. Ten studies adopted a cross-sectional study design. 100% gathered data through an online survey. Nine studies showed a high risk of bias, and five had a moderate risk. Review results showed that 56,4% of patients wished to resume treatment; participants were mostly worried about the delay in treatment because of their age (>35 years) or diminished ovarian reserve, or money constraints and low education level. Only five studies examined the role of protective factors such as social support, coping, optimism trait and intolerance of uncertainty. Nine studies were included for meta-analysis. The prevalence of psychological distress was 0.58 (95% CI 0.32÷0.84). The pooled point estimates of prevalence for anxiety (N = 6) were 0.56 (95% CI 0.24÷0.88), whereas the prevalence for depression (N = 5) was 0.46 (95% CI 0.15÷0.77). There was significant heterogeneity among studies to estimate the prevalence (I² ranging from 99% to 100%). Limitations, reasons for caution Results are preliminary, given the small number of studies and their cross-sectional data. The risk of bias was high or moderate across studies. Wider implications of the findings Infertile couples reported high levels of distress due to cancellation of their diagnostic procedures or treatment; they would benefit from information, appropriate support and advice from healthcare professionals, with an important role in maintaining the wishes of infertile couples to continue their parenthood goals. Trial registration number not applicable

Study question What is the current obstetric-perinatal and neonatal outcome of infected pregnant women and their newborns during the COVID-19 pandemic? Summary answer Miscarriage rates were What is known already A considerable number of systematic reviews, with substantial heterogeneity regarding their methods and included populations, on the impact of COVID-19 on infected pregnant women and their neonates, has emerged. Study design, size, duration Three bibliographical databases were searched (last search: September 10, 2020). Quality assessment was performed using the AMSTAR-2 tool. Primary outcomes included mode of delivery, preterm delivery/labor, premature rupture of membranes (PROM/pPROM) and abortions/miscarriages. Outcomes were mainly presented as ranges. A separate analysis, including only moderate and high-quality systematic reviews, was also conducted. The protocol was registered with PROSPERO (CRD42020214447); Participants/materials, setting, methods The search strategy followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. Keywords employed were (COVID-19 OR SARS-CoV-2 OR “Coronavirus disease 2019”) AND (“Neonatal outcom*” OR “Neonatal characteristic*” OR “Maternal outcom*” OR “maternal characteristic*” OR “pregnancy outcom*” OR “vertical transmission”). All retrieved studies were imported into the Rayyan QCRI and duplicated articles were removed. A snow-ball procedure was also implemented by hand-searching the reference lists of included systematic reviews for additional sources. Main results and the role of chance Thirty-nine reviews were analyzed. Twelve reviews (30.8%) were found to be of “very low quality”, 11 of “low quality”, 13 (33.3%) of “moderate”, and three (7.7%) of “high quality”. Ten articles dealt with miscarriages. One review integrated them into pregnancy terminations (1.4% (4/295)), one into intrauterine fetal deaths (1(3%)), while another one described them as “spontaneous abortions” (0.8% (3/385)). Taking into account reviews, which calculated these rates for their entire included population, miscarriage rates were Limitations, reasons for caution Results are presented in a narrative way using ranges as the primary mean of quantification. We also included studies with both RT-PCR positive women and women with suspected infection based on their clinical and imaging manifestations, whereas, if excluding them, we might have missed a considerable source of information. Wider implications of the findings In conclusion, a rapid increase of CS was observed, especially at the beginning of the pandemic, most likely due to lack of knowledge and robust recommendations. Preterm birth rates were elevated, with iatrogenic reasons potentially involved. Even though neonatal infections were rare, the probability of vertical transmission cannot be eliminated. Trial registration number not applicable’

Study question What is the SARS-CoV-2 positivity rate following the Spanish Fertility Society (SEF)/Association for the Study of Reproductive Biology (ASEBIR) screening recommendations? Summary answer The SARS-CoV-2 positivity rate in the centers following the SEF/ASEBIR screening recommendations was 0.316% after the first survey and 0.364% after the second one What is known already Due to the Sars-Cov-2 pandemic, all the Medical Assisted Reproduction (MAR) centers in Spain had to interrupt their activity most of the time during the first pandemic wave. On April 27th activity was restarted, and SEF and ASEBIR jointly elaborated a guide describing their SARS-CoV-2 screening recommendations for MAR centers. This document aims to achieve a safe environment for patients and staff. It includes the possibility of screening patients through a targeted clinical interview and the use of reverse-transcriptase polymerase chain reaction (RT-PCR). The aim of this study is to quantify the SARS-CoV-2 positivity rate based on these recommendations. Study design, size, duration National multicenter cross-sectional study. Information was gathered from centers using an anonymous survey asking for aggregated data about the number of positive cases among screened patients, sent twice. The first survey covered the period April 27th - June 30th. Second survey covered July 1st - August 31st. Response rates among centres were 9% (29/319) and 6% (20/319), respectively. This study includes 2,695 and 4,068 screenings performed in the first and the second survey, respectively. Participants/materials, setting, methods The SEF/ASEBIR recommendations describe two screening strategies. Strategy (a) consists in a targeted clinical interview (TCI) evaluating clinical symptoms and exposure risk, first before starting the cycle, and before egg-retrieval, intrauterine insemination (IUI), and/or embryo transfer (ET). Suspicious cases could be confirmed by further RT-PCR testing. Strategy (b) consists in conducting the same first TCI, and a systematic RT-PCR testing before the medical procedure in all patients. All patients in both strategies have a TCI. Main results and the role of chance In the 1st survey, 1,177 screenings and 919 RT-PCR (78.07%) were performed before the egg-retrieval. One patient with a negative TCI and positive RT-PCR was detected, and the cycle was cancelled. 1,518 screenings and 1,161 RT-PCRs (76.48%) were performed before the ET/IUI. Two patients with a positive TCI were detected, one did not perform a RT-PCR, while the other resulted in a positive RT-PCR. Both cycles were cancelled. Besides, 5 patients with negative TCI performed a RT-PCR with a positive result; all 5 were cancelled. Overall, the SARS-CoV-2 positivity rate was 8/2533 (0.316%), of which 7/2533 (0.276%) were identified by RT-PCR testing. The 2nd survey included 1,376 screenings and 1,009 RT-PCR (73.32%) performed before the egg-retrieval. Four patients with negative TCI and further positive RT-PCR were detected, and their cycle was cancelled. 2,692 screenings and 2,134 RT-PCR (79.27%) were performed before ET/IUI. Two patients had a positive TCI, one with a negative, the other with a positive RT-PCR testing; both cycles were cancelled. Besides, 8 patients with negative TCI, but positive RT-PCR testing, were detected and their cycles cancelled. Overall, the SARS-CoV-2 positivity rate was 14/3846 (0.364%), of which 13/3846 (0.338%) after positive RT-PCR testing. Limitations, reasons for caution The criteria for performing the RT-PCR testing were not the same in all MAR Centres or even in the same centre at different times. Due to the low response rate of the study, we should not extend these results to all the MAR Centres in Spain. Wider implications of the findings The results of the surveys suggest that the SEF/ASEBIR recommendations could be a good screening strategy for SARS-Cov-2 at MAR Centres. Further survey collected at different times of the pandemic are warranted, including new strategies for screening as antigen tests or vaccination status. Trial registration number Not applicable

text A highly infectious novel coronavirus (now referred to as SARS-CoV-2) was first noted in December 2019 in Wuhan, Hubei Province, China, and by March 11, 2020, was declared a global pandemic by the WHO. The widespread community transmission of a virus, new to our species, continues to raise urgent questions about implications for pregnant women and those considering conception. Almost immediately, international committees, including ASRM and ESHRE, drew up guidelines to protect the public and our patients. Across the globe, clinics were closed, patients turned away and questions regarding spread of the virus, safety during early pregnancy and potential impact on fertility and pregnancy began to arise. Where are we now? What have we learned? And what more do we need to know to improve our ability to care for and counsel our patients? Clinic Practice – While there was considerable controversy in the U.S., closing clinics was the correct course of action when an unknown virus had entered our countries and so little was known and resources (think NY, think Italy) were inadequate. The majority of clinics pivoted to more virtual visits and stopped transfers and retrievals. The duration of these changes varied across states and countries, with most clinics now functioning at full capacity for procedures but still utilizing virtual visits for many patients. We will discuss what we learned from this process, including impact on clinics and patients, as well as the greater community in which we all live. Pregnancy – The physiology of pregnancy, including increased heart rate and oxygen consumption, decreased lung capacity and a shift away from cell-mediated immunity, all increased the risk for severe illness. Studies have now shown this increased risk for severe disease, mechanical ventilation and even death in pregnant women compared with their non-pregnant counterparts. Additionally, there is increased risk for pre-term labor and fetal death. Studies suggest infection earlier in pregnancy increases risk for complications. What about our patients? The first trimester is a highly critical period for fetal development. As a result, infectious and non-infectious exposures, occurring during the first trimester, are most likely to lead to severe effects on fetal development. Preliminary results no increased risk for pregnancy loss and no effect on nuchal translucency. However, some studies have shown the possibility of vertical transmission and increase in fetal inflammation. We will review the literature and update on current understanding of first trimester exposure and consequences for both mother and child. Infertility – SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for viral entry. The ACE2 receptor is present in both the male and female reproductive systems. Early case studies of severe cases of COVID-19 identified orchitis, while the presence in non-fatal disease remains controversial. Lowered sperm counts have been identified and some studies have found SARS-CoV-2 viral particles in the semen. ACE2 receptor is present in both the ovary and the endometrium, while infection is possible, there have been few studies specifically looking at these endpoints and no clear risk identified for women. Vaccination – The rapid development and deployment of effective vaccination has brought hope to end the pandemic, even as new variants are arising. While vaccine hesitancy is common in many places, the mis-information regarding association between vaccines and infertility has hit our field particularly hard. Updating information to share with our patients, colleagues and friends will be critical to move forward and combat the pandemic. Trial registration number Study funding Funding source

Background Irritable bowel syndrome (IBS) patients are subtyped by predominant bowel habit rather than pathophysiological mechanisms and this may underlie challenges in identifying more effective targets for designing new treatments. Metabolomics and microbial analysis can distinguish IBS patients from healthy controls but it is unknown if they can identify pathophysiological IBS subgroups. Aims To phenotype subgroups of IBS patients using metabolomics and microbial analysis and determine if these subgroups have different underlying pain signalling mechanisms. Methods Symptom history, stool and urine were collected from 30 diarrhea predominant (IBS-D) and 30 constipation predominant (IBS-C) IBS patients (Rome IV). Liquid Chromatography-Mass Spectrometry quantified 130 metabolites in stool and urine. The GA-map™ Dysbiosis Test targeting ≥300 bacteria on different taxonomic levels was used to identify stool microbial composition. Multivariate OPLS discriminatory analysis assessed metabolomics and microbial profiles. To assess potential effects on pain signalling, the effect of stool supernatant on dissociated dorsal root ganglia (DRG) neuron responses to capsaicin (10nM) was assessed using Ca2+ imaging. Results Within both IBS-D and IBS-C, combined stool/urine metabolomic profiles of patients with a dysbiosis-like (DL) IBS (onset following antibiotics, enteric infection, or travel) were distinct from patients with a non-DL IBS onset (IBS-D R2=0.7, Q2=0.5; IBS-C R2=0.5, Q2=0.4); fecal glutamic acid and urinary pyruvic acid were the main metabolites driving separation. However, microbial profiles of DL vs non-DL onset could only be discriminated in IBS-D (R2=0.8, Q2=0.4). In the patients with a DL IBS onset, stool metabolomic profiles of the 7 IBS-C discriminated from the 8 IBS-D patients (R2=0.9, Q2=0.8). Profile differences were not seen between IBS-C and IBS-D with a non-DL onset of IBS. In preliminary studies, incubation of DRG neurons with stool supernatant from 1 DL IBS-D and 1 non-DL IBS-D increased peak [Ca2+]i responses to capsaicin compared to incubation with media (DL: 5.5±0.9 vs 2.3±0.7; non-DL: 6.9±0.7 vs 3.9±0.4% ΔF/F). Similarly, the number of responsive neurons to capsaicin was increased after incubation with IBS stool supernatant vs media (DL: 27% vs 8%; non-DL 19% vs 12%). Conclusions Different metabolomic and bacterial profiles between DL and non-DL onset of IBS-D suggests a novel means to better phenotype clinically defined IBS subgroups. While initial results with stool supernatants from both a DL and non-DL IBS-D patient suggest increased pain signalling in DRG neurons, more studies are needed to determine if there are differences between these two subgroups as well as healthy controls. Funding Agencies CIHRSoutheastern Ontario Academic Medical Organization (SEAMO)

Lipocalin 2 (Lcn2) is an essential component of the innate immune system and exerts significant immunomodulatory effects in vitro. The aim of current study was to investigate the expression profile of Lcn2 during inflammatory process and explore the role of Lcn2 in the anti-inflammatory responses. Western blot, real-time quantitative PCR, immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA) were employed. Firstly, we evaluated the temporospatial expression of Lcn2 of mice after inflammatory stimuli by lipopolysaccharides (LPS). In vivo, LPS induced both mRNA and protein levels of Lcn2 significantly (P < 0.01) in liver, jejunum and ileum. Lcn2 exhibited a continuous increase by 8 h and peaked by 24 h post challenges. Secondly, we challenged Lcn2-deficient (Lcn2-/-) mice and wild-type (WT) mice with peripheral LPS and determined effects on inflammation. In contrast to WT mice, Lcn2-/- mice showed distinct inflammatory injury in liver, jejunum, ileum and spleen with significantly elevated pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1b (IL-1b) and decreased anti-inflammatory cytokine interleukin-10 (IL-10). Thirdly, we isolated bone marrow-derived macrophages (BMDM) from Lcn2-/- mice and WT mice to evaluate their functions. After LPS challenge, Lcn2-/- BMDM showed aggravated inflammatory reaction as pro-inflammatory factors tumour necrosis factor-α (TNF-α), IL-6, IL-1b and inducible nitric oxide synthase (iNOS) increased (P < 0.05) while anti-inflammatory cytokines IL-10, transforming growth factor β1 (TGF-β1) and arginase-1(Arg-1) decreased significantly (P < 0.05) compared with WT BMDM. This phenomenon could be relieved when adding recombinant Lcn2 (P < 0.05). The exogenous addition of Lcn2 on mice RAW264.7 macrophages stimulated by LPS also conformed this point. These findings demonstrated that Lcn2 served as a potent protective factor in response to systemic inflammation, and elevated Lcn2 expression during inflammatory conditions was presumed to play an effective role in alleviating inflammatory responses.

Myocyte enhancer factor 2 C (MEF2C) is a transcription factor that plays a central role regulating cell differentiation, proliferation, survival and apoptosis. MEF2C has been implicated in each of the most recent GWAS of cognitive ability (CA) and educational attainment (EA). Animal studies have indicated that knockout of Mef2c interferes with healthy development of brain regions associated with cognitive function, e.g. hippocampal dentate gyrus, neocortex. Furthermore, mutation/deletion of MEF2C can cause severe intellectual and developmental disability. We therefore hypothesised that genes regulated by MEF2C would be associated with cognitive function. We created a set of differentially expressed genes (DEGs) based on an RNA-seq study that captured the transcriptional changes in mouse adult brain that result from early embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons. This mouse DEG list was converted to human orthologues (n=1052) and tested for enrichment of genes associated with 1) CA, and 2) EA, using MAGMA and recent GWAS summary statistics for each phenotype. We also performed hypergeometric tests to investigate if the DEGs were enriched for current primary intellectual disability (ID), autism, and loss-of-function (LoF) intolerant (i.e. highly constrained) genes. We then used Ingenuity Pathway Analysis (IPA) to explore functional pathways implicated by the MEF2C DEGs. The DEGs were significantly enriched for CA (p=1.08e-07) and EA (p=9.88e-09) genes; along with ID (p=0.008), autism (p=0.001) and LoF intolerant (p=5.55e-21) genes. The top functions IPA predicted to be decreased from these DEGs are ‘development of neurons’ (p=5.41e-38, z-score=-2.0) and ‘formation of cellular protrusions’ (p=1.02e-28, z-score=-2.1). These findings indicate that genes influenced by MEF2C are highly constrained and contribute to cognitive function and neurodevelopmental disorders with severe cognitive deficits., Nearly 50% of all colorectal cancer patients progress to develop metastatic lesions (mCRC) and despite ongoing efforts the survival rates for these patients remains significantly low (90% CRC-specific enhancer regions, which was subsequently integrated with RNAseq derived gene expression in order to identify gene-enhancer pairs. Applying motif and transcription factor identification algorithms to the methylation signature, showed intricate networks of disease-associated transcription factors whose binding sites are significantly impacted as a result of the altered methylation within these enhancer regions. Utilization of deep machine learning approaches to the methylation data, demonstrates specific methylation patterns that allow stratification of patients independent of their clinical features. Finally, we show that two methylation derived patient clusters overlap significantly with expression derived consensus molecular subtype (CMS) -2 (WNT-p53 cluster) and CMS-4 (EMT-like). This study for the first time presents a critical insight into an enhancer driven epigenomic landscapes, which potentially regulates disease-associated phenotype within mCRC., Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory aetiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n=100) and individuals without a history of depression (n=100) using the Illumina 450K microarray. Our analysis identified 6 significant (Sidak corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Sidak corrected P = 1.27 x 10-14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype., Mutations in RP2 are responsible for approximately 15% of X-linked Retinitis Pigmentosa cases. RP2 is ubiquitously expressed and involved in ciliary trafficking of lipid-modified proteins. A patient harbouring the most common nonsense RP2 mutation, R120X, was identified through the Target 5000 programme. This enabled the generation of a patient-derived primary fibroblast disease model. The aims of this study were (i) to identify a vector capable of effectively transducing primary fibroblasts, (ii) to rescue RP2 expression in the R120X cell model and (iii) to explore potential assays for evaluating rescue of RP2 function in these cells. Transduction efficiencies were determined by treating normal fibroblasts with a CAG.EGFP construct packaged in AAV2/2, 2/5 and 2/8 capsids. The results were 55.5% ± 2.5, 17.5% ± 15.4 and 2.2% ± 1.0, respectively. The expression level of RP2 mRNA in untreated R120X fibroblasts was 7.5 fold ± 3.2 lower than that of wild type fibroblasts, while RP2 protein was absent in R120X cells. Transduction of mutant cells with AAV2/2.CAG.RP2 resulted in overexpression of RP2 protein by 1.19 fold ± 0.67. The R120X cell line was evaluated for phenotypes associated with absence of RP2, including Golgi fragmentation and mislocalisation of an intraflagellar trafficking protein, IFT20.The areas of both GM130 and IFT20 were significantly larger in mutant fibroblasts compared to control cells. Treatment with AAV2/2.CAG.RP2 was beneficial in reversing Golgi fragmentation, as the Golgi area in transduced R120X fibroblasts was reduced by 1.5 fold ± 0.5 when compared to untreated cells (p < 0.0001)., Background: Genome-wide association studies (GWAS) identify associations of individual SNPs with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods: we conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product (sARTP) method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9,040 cases and 12,496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. Results: We identified 14 pathways and gene sets associated with PDAC at FDR < 0.05. After Bonferroni correction (P-value ≤ 1.3x10-5), the strongest associations were detected in five pathways and gene sets, including maturity onset diabetes of the young (MODY), regulation of beta cell development, role of epidermal growth factor (EGF) receptor transactivation by G-protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation, eQTL analysis and experimental validation provides insight into genes and pathways that maybe biologically relevant for risk of PDAC, including those not previously identified., We carried out a detailed genetic study of the population structure, local migration rates and population changes across in the Netherlands using cutting edge methods. Our dataset couples genome wide SNP data and geographic information (N=1422), which together allow us to investigate the interplay between genetics and local geography. To interrogate fine scale population structure we applied the haplotype-based method Chromo Painter/fineSTRUCTURE, which partitions data based on patterns of haplotype sharing. FineSTRUCTURE identified 16 genetic clusters which correlate closely with regional geography. At the finest level, this clustering has the resolution to distinguish subtly different eastern and western genetic groups within the North-Brabant province. At the coarsest level, clustering delineates a clear north/ south split in the Netherlands, reflecting deeper differences. We investigated whether our clustering reflects barriers to gene flow using the “Estimating Effective Migration Surfaces” (EEMS) method, and observed a strong migrational cold spot splitting the country, broadly overlapping the course of the Rhine. We also estimated recent changes in the effective population size (Ne) using the IBDNe method, observing super-exponential population growth across the past 50 generations. This expansion rapidly increases in rate from ~1650 CE onwards, potentially driven by the Dutch Golden age of the 17th Century. Notably our Ne estimates are systematically lower in northern populations than southern suggesting lower diversity in the north, which is consistent with reported ROH and IBD analysis. Combined our results paint a picture of the dynamic population genetics of the Netherlands that are strongly linked to geography., We present here a demographic scaffold for Irish prehistory based on the palaeogenomic analysis of 93 ancient individuals from all major periods of the island’s human occupation, sequenced to a median of 1X coverage. ADMIXTURE and principal component analysis identify three ancestrally distinct Irish populations, whose inhabitation of the island corresponds closely to the Mesolithic, Neolithic and Chalcolithic/Early Bronze Age eras. Large scale migrations into the island are implied during the transitionary periods carrying with them ancestry ultimately derived from Anatolia and later the Russian steppe. Patterns of haplotypic-sharing and Y chromosome analysis demonstrate strong continuity between the Early Bronze Age and modern Irish populations, suggesting no major population replacement has occurred on the island since this point in time. We further dissect the genetic affinities of each Irish population with reference to wider palaeogenomic datasets, using both allele and haplotype-sharing methods, the latter made possible through genotype imputation., Background: Rare diseases (RDs) affect at a minimum 5 per 10,000 people. Although individually rare and under-recognised in healthcare systems, collectively RDs are common with up to 8,000 diseases now described. The National Plan for RDs (2014), recommended the need for epidemiological studies, highlighting the requirement for RD coding to identify RD patients and thereby improve both cost efficiencies and care of patients with RDs. Objectives: To derive an estimate of the number of childhood onset RDs through analysis of records held at TSCUH & OLCHC. Methods: Reports of patients born in the year 2000 were extracted from: the National Paediatric Mortality Registry office; clinical, cytogenetics and molecular genetics databases, and the Hospital In-Patient Enquiry system (HIPE) TSCUH/OLCHC. RD cases were identified using electronic/manual results and assigned orpha-codes. Results: 54, 7893 livebirths, census 2000. National Paediatric Mortality Register, 73 deaths of children born in year 2000 of these 60 had a RD (82%). Clinical, cytogenetic and molecular genetics from TSCUH/OLCHC identified 603, 121 and 77 cases of RD respectively. HIPE TSCUH/OLCHC searches to-date have identified 202 and 242 cases of RD respectively. Conclusions: RD epidemiological data is difficult to acquire in the current structure of the Irish health service, requiring multiple sources and an inordinate amount of time accessing manual records. This study to-date has identified over 1,000 RD patients presenting by age 17 to OLCHC/TSCUH giving a minimum incidence of 2% for paediatric RDs. In the coming year records from TSCUH specialties will be accessed for inclusion in the study., Background & Aims: Newborn screening for Cystic Fibrosis (CF) commenced in the Republic of Ireland in July 2011. The aim of this study was to do a comprehensive review of the first five years, focusing on those who had CFTR genetic testing following an elevated IRT. Methods: This study included all neonates screened from July 2011 to June 2016. Data was expanded by cross-referencing patient charts, clinical and lab databases with the Non-NBS database to track down cascade tested relatives. Results: In this period a total of 342,424 infants were screened. 141 CF and 19 CF-SPID cases were identified in addition to 238 healthy carriers. 2 babies died from unrelated illnesses, before their Sweat Test. A total of 300/400 (75%) couples with a CF/CF-SPID/Carrier child were seen by a Genetic Counsellor. Phe508del was the most common mutation (79.9%) followed by Gly551Asp (8.7%). Consequently, 185/238 Carrier parents (78%) underwent genetic testing, identifying 1 carrier couple. 101/160 (63%) CF/CF-SPID parents were tested. 255 additional relatives came forward for cascade testing - 184 from 68/162 CF affected/CF-SPID/RIP families (42%), resulting in 3 new CF cases, 3 new CF-SPID cases and 64 additional carriers. Two cases were siblings born prior to NBS. One case was missed though NBS. 71 relatives from 33/238 Carrier families (14%) came forward for cascade testing, identifying a further 18 carriers. Conclusion: Through early detection of CFTR mutations, NBS provides the opportunity of early intervention and complication prevention as well as improvements in prenatal diagnoses and availability of cascade testing., Background: Multi-gene testing is useful in genetically heterogeneous conditions, including inherited cardiac pathologies. Extended panels increased diagnostic yield of variants where pathogenicity is certain (class 5), likely (class 4) and uncertain (class 3). Concerns exist regarding management of class 3 and 4 variants in conditions of oligogenic inheritance or variable expressivity. Aim: 1. To review diagnostic yield of genetic tests performed in families with inherited cardiac pathologies 2. To assess management of different classes of variants by clinicians internationally. Methods: A retrospective cohort analysis was undertaken. Patients in whom “cardiac” genetic tests were requested between 2015 and 2017 were identified from a prospectively maintained departmental patient database. Data regarding indication for testing, diagnostic yield, and classification of variants were retrieved by manual chart review. An electronic survey regarding clinical management of variants (http://www.surveymonkey.com/r/cardiacvariants) was distributed to colleagues internationally via professional bodies and direct email. Results: 636 tests (630 patients) were performed between 2015 and 2017 in our centre (183 diagnostic; 453 predictive). At least one variant was identified in 71(39%) patients (28(15%) class 5; 9(5%) class 4; 38(21%) class 3. 135 respondents (23 countries) completed the survey. Considering class 4 variants, 110(81%) counselled patients about the possibility of variant reclassification. In the case of a negative predictive test, 17(13%) were fully reassuring that the patient would not develop the familial phenotype. Conclusion: Considerable variability in management of class 3 and 4 variants exists. Decision-making relies on interpretation of the phenotype, family history and genotype. Close multi-disciplinary working between cardiology and clinical/molecular genetics teams is critical., Familial hypercholesterolaemia (FH) is an autosomal dominant disorder due primarily to mutations in LDLR, APOB and PCSK9, which causes marked increases in LDL cholesterol levels and predisposes to premature CVD. Given a prevalence of 1:250, there are approximately 23,000 FH sufferers in the Republic of Ireland, most of whom are as yet undiagnosed. The most cost-effective strategy for identifying FH is genetic cascade screening in kindreds with an identified proband. We report interim outcomes of a FH genetic diagnostic service configured around an initial screen of 40 known FH variants followed by either a confirmatory analysis or a full variant scan using PCR and direct nucleotide sequencing, in positive and negative screens respectively. To date our service has genetically diagnosed 69 patients with FH, including 50 index cases and 19 positive cascade screens. In total, 30 disease-associated variants in LDLR and APOB have been identified including four due to copy number variation using MLPA. Based on phenotypic classification by Dutch Lipid Clinic Network scoring 75% of those designated “Definite/Probable FH” were genetically confirmed compared with, Hereditary Breast & Ovarian Cancer syndrome (HBOC) is caused by mutations in BRCA1/2 genes and is associated with a high life time risk of breast cancer and ovarian cancer. Ovarian tumours with inherited (germline) or acquired (somatic) BRCA1/2 mutations respond to drugs that inhibit poly ADP-ribose polymerase (PARPi). Currently, mutation screening for HBOC patients are ‘sent away’ to the UK, with a predictive (pre-symptomatic) service for known familial mutations offered at DCG. At this time, there is no service for tumour BRCA testing for potential PARPi treatment. Supported by the National Cancer Control Programme, DCG & CMD have collaborated to assess next generation sequencing BRCA gene panels & platforms to establish a pathway for germline & tumour mutation analysis and validate an optimal clinical testing method for diagnostic and therapeutic use. The ThermoFisher Oncomine panel with the Ion Torrent PGM/S5 was used to target and sequence 64 unique germline samples with a wide range of known BRCA mutations. These were analysed using JSI SeqNext software and others. After optimisation, 99.84% (624/625) variants were detected at some level. However, there were 117 false positive calls, all in homopolymer regions. Distinguishing false positives from some true positives with a low variant fraction was challenging. Subsequently, the Nimagen EasySeq kit (employing single molecule Molecular Inversion Probes, smMIPs) with the Illumina MiSeq was used for 32 samples. There was a 100% variant call rate (376/376) with no false positive calls. Initial tumour results are also very convincing. Now proceeding to a full clinical validation., Establishing the pathogenicity of missense variants detected in Lynch syndrome / Hereditary Non Polyposis Colorectal Cancer (HNPCC) families is a challenge for diagnostic laboratories. Here we consider two families from Northern Ireland who meet Amsterdam II Criteria for HNPCC, in whom the presence of a PMS2 gene missense variant c.137G>T p.(Ser46Ile) rs121434629 has been shown. This variant occurs within a conserved ADP/ATP binding region of the PMS2 protein. Disruption of this domain is predicted to result in reduced mismatch repair efficiency and has previously been reported in the literature as a recurrent and founder variant in the PMS2 gene. However, no co-segregation data has been published for this variant. Adoption of the ACMG Standards and guidelines (Richards et al Genetics in Medicine 2015) along with the release of ACGS best practice guidelines for the interpretation of sequence variants has initiated a review of the classification of variants detected within the region against these standards. Bioinformatic analysis and evidence available in the published press, had led to a classification of likely pathogenic for this variant. However, addition of the co-segregation evidence provided by local families, at the strong level, enables the variant to be re-classified as pathogenic. In conclusion, we have shown co-segregation of the PMS2 c.137G>T p.(Ser46Ile) variant with Lynch syndrome associated phenotype to a Path P1 strong level of significance through family studies., The C677T polymorphism in the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with hypertension. Riboflavin is a cofactor for MTHFR in one-carbon metabolism, for generating methyl groups important in DNA methylation. Supplementation with riboflavin has been shown to lower blood pressure in MTHFR 677TT genotype individuals. The mechanism regulating this gene-nutrient interaction is currently unknown but may involve aberrant DNA methylation also implicated in hypertension. This study examined DNA methylation of hypertension-related genes in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on methylation of these genes in the MTHFR 677TT genotype group. We measured DNA methylation using pyrosequencing in a set of candidate genes associated with hypertension including angiotensin II receptor type 1 (AGTR1), G nucleotide binding-protein subunit alpha 12 (GNA12), insulin-like growth factor 2 (IGF2) and nitric oxide synthase 3 (NOS3). Stored leukocyte samples from participants with the MTHFR C677T genotype who had participated in targeted RCTs (1.6mg/d for 16wks) at Ulster University were accessed for this analysis (n=120). Baseline methylation differed between MTHFR C677T genotype groups at NOS3 (p=0.026) and AGTR1 (p=0.045). Riboflavin supplementation in the MTHFR 677TT genotype group resulted in altered average methylation at IGF2 (p=0.025) and CpG site specific alterations at the AGTR1 and GNA12 loci. This study demonstrates an interaction between DNA methylation of hypertension-related genes and riboflavin supplementation in adults with the MTHFR 677TT genotype. Further work using a genome-wide approach is required to better understand the role of riboflavin in altering DNA methylation in these genetically at-risk individuals., Chronic kidney disease (CKD) is considered a major public health problem, affecting approximately 10% of the global population. While a comprehensive review of known CKD biomarkers yielded many results, it also highlighted a lack of research in chromosome Y. Single nucleotide polymorphisms (SNPs) on chromosome Y have previously been associated with a 50% increase in risk of developing coronary artery disease, a condition with close links to CKD. Therefore, Y chromosome SNPs may also impart increased risk of developing CKD. Individuals from the Genetics of Nephropathy: an International Effort (GENIE) consortium (n=791) and the Northern Ireland Cohort for the Longitudinal Study of Aging (NICOLA; n=1241) were genotyped using the Illumina HumanOmni1-Quad array and the Illumina CoreExome-24 array, respectively, to determine if any association exists between Y chromosome SNPs and CKD, or estimated glomerular filtration rate (eGFR), a measure of kidney function. However, poor coverage of chromosome Y resulted in only 3 SNPs in the GENIE cohort and 421 SNPs in the NICOLA cohort passing quality control. Association analysis of both datasets did not reveal any significant associations. Due to limitations of this study, further analysis is required to determine whether SNPs on chromosome Y are associated with CKD and/or eGFR. An array with greater Y chromosome coverage will be selected and be used to re-genotype these individuals, and individuals from additional cohorts, allowing greater SNP coverage and direct comparison of SNPs between these cohorts. Increased SNP coverage and increased participant numbers will allow meta-analysis to be performed with sufficient power., Background: Tumour hypoxia is a major driver of prostate cancer progression and metastasis. miR-21 is a microRNA which has been previously linked to hypoxia, but this relationship remains poorly characterised in a prostate cancer setting. Therefore, in this study, we investigate the link between hypoxia and miR-21 in prostate cancer cells. Methods: We have used 2D and 3D cell prostate cell models of hypoxia to investigate the functionality of miR-21. Expression levels of miR-21 have been measured by qPCR and functional bioassays used to examine its effect on prostate cell behaviour. Target genes have been identified and bioinformatic analysis has been employed to investigate a clinical significance for miR-21 in prostate cancer. Results: miR-21 is induced by hypoxia in prostate cancer cell-lines. Over-expression of miR-21 impacts upon target genes which in turn affects cell behaviour. Data-mining of online repositories of clinical data and bioinformatic analysis of miR-21 cellular networks reveal that miR-21 exerts a wide influence on several important cell processes, the dysregulation of which can lead to development of prostate cancer. Conclusions: We propose that miR-21 could be an important microRNA in the pathogenesis of prostate cancer and has potential as a biomarker in this disease., The Neolithic period begins in Europe around 8500 years before present (BP) and is characterized by the adoption of farming and domestication of various types of animal. In our project we focus on the structure of the Maltese population during the latter part of the Neolithic period. Nine individuals, from 4900 to 4350 years BP, collected from the Xaghra Circle site in the island of Gozo, were sampled. DNA was extracted from both teeth and the inner part of petrous bones giving an average endogenous DNA respectively of: 1.7% for 4 teeth and of 21% for 5 petrous bones. We then used a median of 363,579 SNPs from the Human Origin dataset to compare our samples with 37 ancient individuals from Neolithic and Bronze Age period and 604 present-day European individuals already published. PCA analysis shows, for the 5 high coverage samples, places the Maltese individuals with the early European farmers (EEF) from Germany and Hungary. Further analysis with D-statistics depict that the Maltese population do not resemble any hunter-gatherer population from Caucasus or Eastern Europe, while they show a higher affinity with Western European hunter gather individuals (WHG)., According to the WHO, glaucoma is the second leading cause of blindness in the world and is the leading cause of irreversible blindness. The total number of suspected cases of glaucoma is estimated to be over 60 million worldwide, increasing to 79.6 million by 2020. Commonly, glaucoma is treated using eye drops containing prostaglandin analogs, including latanoprost and bimatoprost. However, these treatments come with ocular adverse reactions including ocular surface irritation, acute iritis, conjunctival hyperemia, thickening and elongation of eyelashes, induced iris darkening as well as periocular skin pigmentation. Patient compliance has been shown to be affected by these side-affects including non-compliance for cosmetic reasons with thickening and lengthened eyelashes and the occurrence of pigmentation. This study aimed to identify whether there are differences in gene expression between those prostaglandin treatments containing preservatives and those without preservatives. Primary human trabecular meshwork cells were stained with phalloidin to determine morphology. The cells were treated with prostaglandins either with or without preservatives, gene expression analysis was performed by PCR to determine differences between preservative containing and preservative free treatments. Differences in gene expression were shown at different time-points after treatment. Differences were also shown between treatments which were preservative free and those treatments which contained preservative. With the significant differences in gene expression levels between prostaglandins containing preservatives and those without preservatives, it indicates that prostaglandins without preservatives are likely to produce less side effects in glaucoma patients., For the majority of its history the field of ancient population genetics was restricted to non-human samples due to the difficulties with modern contamination and the nature of ancient DNA (aDNA) sequences: short, highly degraded, chemically modified and present in low concentrations with high concentrations of microbial contamination. The development of efficient extraction techniques, the discovery that the petrous part of the temporal bone is a rich reservoir for aDNA and the development of high-throughput next-generation sequencing (NGS), have resulted in the rapid expansion of the field, with sequences from over 1000 ancient individuals published to date. Portugal occupies a unique position in Europe; facing both the Atlantic and the Mediterranean it was connected to two major maritime trade and migration routes, as well as experiencing influx from central mainland Europe throughout its prehistory. Many open questions remain about population changes in the Iberian Peninsula at major transition periods in European prehistory, such as the transition to the Bronze Age involving migrations from the Pontic Steppe, the source for the R1b Y-chromosome haplotype now dominant in European populations. In this study we present high quality whole genome sequences (0.052.9X, 13 samples at ~1X) from 25 ancient Portuguese individuals, covering a period of over 3000 years, to examine the demographic and selection processes acting on prehistoric Portuguese populations. We use principal component analysis (PCA), outgroup f3 statistics, Patterson’s D-statistic and ADMIXTURE analysis to investigate questions such as hunter-gatherer admixture in the Neolithic and Steppe introgression in the Bronze Age., Background: Epilepsy is a neurological condition affecting an estimated 50 million people worldwide and roughly 40,000 people in Ireland. Levetiracetam (LEV) is an effective anti-epileptic drug, but 10-20% of patients exposed to LEV report behavioural side-effects and up to 1% of those treated experience acute psychosis. We set out to determine contribution of common genetic variation to these adverse drug responses (ADRs). Methods: Individuals from the EpiPGX study cohort were screened for European ancestry and matched to predefined phenotypic criteria. Controls were exposed to LEV, but without any adverse reactions. GWAS were carried out on patients who experienced behavioural disorders (n=149), acute psychosis (n=19), or any affective symptoms in response to LEV treatment (n=90). After identification of a genome-wide significant hit in the affective disorder analysis, a further GWAS was performed in a replication cohort (n=68). Following this, polygenic risk scores (PRS) for all cases and controls were calculated using the results from the Psychiatric Genomics Consortium’s GWASes of Schizophrenia (SCZ) and Bipolar Disorder (BIP). Results: A genome-wide significant result was found in SNP rs7500119 in the CALB2 gene. Upon replication the SNP lost genome-wide significance but maintained nominal significance. PRS analysis for both SCZ and BIP were predictive of LEV-induced psychosis. Discussion: The univariate analysis did not identify a genome-wide significant signal for neurological ADRs to LEV that survived replication in an independent cohort. Further work with larger sample sizes may identify such variants. Increased PRS for SCZ and BIP are associated with LEV-induced psychosis, this analysis will also benefit from a larger sample, The impact of natural selection on beneficial alleles can be observed in modern human genetic variation; however deciphering the origins of these alleles is complicated by the vast complexity of human history, in which many population splits and admixture events have occurred. Here we describe a new statistical framework of Approximate Bayesian Computation (ABC) that can detect which ancestral group an allele undergoing selection first appeared. We assume a specific model in which a source population splits into two groups that later undergo admixture to form the lineage leading to the contemporary population and simulate the origin of beneficial alleles at different stages of the population’s history. Using genetic variation observed at the allele at the present time, as well as the knowledge we have of the timing of demographic changes and admixture events, we test if our approach can accurately predict the time the allele arose, and in which ancestral population it first emerged in. In this presentation, we will show preliminary results from our simulation study and discuss a potential application of the method for whole-genome data from an admixed human population., There are over 12000 people in Northern Ireland living with rheumatoid arthritis (RA); a painful, systemic autoimmune disease, causing swelling, stiffness, loss-of-function in joints, disability and significantly lowering ones quality of life. Various medication options are available; low-dose (10 to 25 mg/wk.) methotrexate (MTX), a small-molecule disease-modifying anti-rheumatic drug (DMARD), is a first-line therapy, due to its affordability, cost-effectiveness and efficacy. Other DMARDs used in RA are sulfasalazine, chloroquine, hydroxychloroquine, azathioprine, and leflunomide. However, there is significant person-to-person variability in treatment responses with nearly 50% of patients indicating poor or no-response to any of these medications. Serum drug metabolite concentration of 100 RA patients treated with DMARDs were determined using tandem mass-spectrometry. Allelic discrimination analysis using Taqman probes was performed on the following SNPs; rs246240 (ABCC1), rs1476413 (MTHFR), rs2231142 (ABCG2), rs3740065 (ABCC2), rs4149081 (SLCO1B1), rs4846051 (MTHFR), rs10280623 (ABCB1), rs16853826 (ATIC), rs17421511 (MTHFR) and rs717620 (ABCC2). Demographic analysis, clinical parameters and disease scores (e.g. DAS28) were also recorded. These SNPs are located within the genes involved in the metabolism of DMARDS and anecdotal evidence has been reported in the literature of their participation in modulating normal metabolism and function of DMARDs. Correlation statistics was used to determine if the genetic profiles associate with the emergence of drug metabolites responsible for poor or non-response to DMARDs. Our findings suggest that genetic-profiling studies may help predict future treatment responses of patients to certain DMARDs. A stratified medicine strategy can help prioritise treatments to those patients most likely to respond while avoiding ineffective treatments. Abbreviations: single nucleotide polymorphisms (SNP); rheumatoid arthritis (RA), disease-modifying anti-rheumatic drug (DMARD), methotrexate (MTX), Rare mutations in genes that encode centrosomal or ciliary proteins cause disorders that present with severe cognitive deficits and variable neuropsychiatric phenotypes. We set out to explore the involvement of centrosomal/ciliary genes in schizophrenia, a neuropsychiatric disorder that affects 1% of adults and is a major global health issue. Our analysis of publicly-available genome-wide association study (GWAS) data revealed that seven schizophrenia risk genes encode proteins with centrosomal functions. Of these, SDCCAG8 is also associated with educational attainment. To analyse the molecular function of SDCCAG8, we used genome editing to ablate it in SHSY5Y neuronal and hTERT-RPE1 retinal epithelial cells. Loss of SDCCAG8 impairs cells’ ability to make primary cilia and the signalling capacity of residual cilia, although centrosome structure appears normal by immunofluorescence microscopy. Recent RNA-Seq analysis on RPE1 SDCCAG8 deficient cells compared to wildtype cells revealed a large number of differentially expressed genes (DEGs; n=2,045) in the absence of SDCCAG8. Pathway analysis of DEGs revealed that there is enrichment in axonal guidance signalling (p=2.51-15). There were also significant enrichments for several pathways that are involved in the production and turnover of extracellular matrix (ECM). Previously, many components of the ECM have been shown to be perturbed in patients with schizophrenia. Using MAGMA gene-set analysis, we found that set of DEGs were enriched for genes associated with schizophrenia (p=0.03) and cognitive ability (p=0.03). This study shows that a combination of gene editing and genomic analyses can help uncover the processes that implicate centrosome/ciliary genes in neurodevelopmental phenotypes., Scotland and Ireland are separated in places by less than 20 kilometres of sea. They share the Gaelic language and similar frequencies of particular alleles and phenotypes, hinting at shared ancestry. The population structure within England and Ireland have recently been described. However, the extent of structure within the majority of Scotland, its surrounding islands, and their links to Ireland are currently unknown. We present an analysis of the British Isles and Ireland using a combined and comprehensive sample (n=2,556) of all major regions – expanding coverage in mainland Scotland (n=567), the Hebrides (n=57), the Isle of Man (n=40), Orkney (n=111) and Shetland (n=172). By analysing individuals with extended ancestry from specific regions, we demonstrate extensive structure in all regions of the British Isles and Ireland, as well as some of the finest scale structure observed worldwide within Orkney. We resolve the shared genetic history between Ireland and Mainland Scotland, confirm the strongest differentiation of Orkney and Shetland from other populations, show the major differentiation in Mainland Scotland is between the south-west and the north-east, and reveal the distinctiveness of the Hebrides and the Isle of Man. We additionally show decreasing cline of Norwegian ancestries across northern Britain, following the spread of the Norse Vikings. Our work represents a comprehensive description of genetic structure in the British Isles and Ireland and greatly expands the knowledge of genetic stratification within the north of the British Isles, informing on the study of rare genetic variants and genetic trait associations in these populations., The Savage et al. (in press) GWAS meta-analysis of intelligence of healthy controls supports increasing findings on variability in intelligence and evidence of overlap with schizophrenia. Utilising convenience sample of pre-existing Irish dataset of broad psychosis cases (916 cases and 330 controls), wherein the controls participated in the Savage et al. (in press) meta-analysis, the present study functioned as secondary analysis of said meta-analysis findings regarding the broad psychosis cases. With the five most significant single nucleotide polymorphisms (SNPs) as identified by Savage et al. (in press) and patient diagnosis as independent variables, this statistical regression analysis focused on the extent to which these genetic variances were of importance in a clinical population by examining the effects in schizophrenia of previously identified genetic variation associated with intelligence (IQ) in healthy controls. Further objective was to extend the Savage et al. (in press) findings to investigate the effects in schizophrenia of genetic variation on memory (working memory and episodic memory). As hypothesized the present study observed nominal trend association for SNP rs2726491 with decreased errors in performance IQ, and a nominally significant association with decreased errors in working memory for rs2726491 across both healthy and clinical population samples. These nominal associations would be suggestive of stronger effects in psychosis, however, the present study was underpowered to observe an association at the corrected level. Nevertheless, future research building on these suggestive findings could further our understanding of the biological psychopathology of schizophrenia, and crucially bring about improved cognitive function in schizophrenia patients., We present a model, algorithm, and results for multiway admixture events. This is where two or more genetically differentiated groups come together. Data from such events can inform us of the demographic history of a species, carry signatures of natural selection, and may increase the power of genome wide association studies. Our model is based on Li and Stephens style haplotype copying and delivers accurate local ancestry estimation along the genome for each admixed individual. Unlike existing methods that return local ancestry, we do not assume knowledge of the relationship between sub-groups of donor reference haplotypes and the unseen mixing ancestral populations. Instead, our approach infers these in terms of conditional copying probabilities. We also infer admixing proportions, timings, and recombination rates. Furthermore, we can estimate drift between modern reference populations and the unseen mixing groups using a version of Fst that is computed on putative partial genomes derived by assignment of chromosome segments to ancestral backgrounds. We demonstrate compelling results using the Human Genome Diversity Panel, including replication of some known admixture events, and we detail novel findings such as a recent 4-way admixture in San-Khomani individuals. Keywords: Population Genetics, admixture, demography, local ancestry estimation., Sibling transplant pairs have better transplant outcomes than unrelated donor-recipient (DR) pairs suggesting shared genetic ancestry between donors and recipients has potential for predicting transplant outcome. We set out to evaluate methods to detect and quantify shared ancestry using GWAS data, to see which could best predict renal-transplant outcome. We tested three different methods for estimating shared genetic ancestry on deceased donor DR pairs of European ancestry. Method 1 calculated identity by descent (IBD) which was then used to estimate the degree of relationship. Method 2 calculated genetic distance using identity by state which examines the number of shared alleles across the genome. Method 3 created a mosaic of an individual’s genome from the haplotypes of the other individuals in the dataset. The similarity of mosaic genomes in a given DR pair was used as a measure of shared ancestry. These measures were then tested against estimated glomerular filtration rate (eGFR) at 1 year (DR pairs, n=1,450) and 5 years (DR pairs, n=1,309) post-kidney transplant, change in eGFR between 1 and 5 years (Δ eGFR; DR pairs, n=982) and time to graft failure (DR pairs, n = 1,806). We did not find significant correlations between any of the measures of shared ancestry in the European ancestry deceased-donor DR pairs and graft function. The genetic relationship between the vast majority of our donor-recipient pairs was distant, and not detectable via IBD. The effect size of shared ancestry at the genomic level on eGFR is limited, and not detectable in our analysis., Background: The treatment of comorbidities remains costly and represents a major priority in Evidence Based Medicine (EBM). Determining genetically the molecular-subclasses of pro-inflammatory comorbid conditions is important to stratify patients that may more effectively respond to specific treatment interventions. The objective of this study is to develop a Machine Learning (ML) based classifier to stratify patients with Type-2-Diabetes and different comorbidities. Methods: A preliminary dataset of samples from 254 people with Type-2-Diabetes recruited at NICSM were genotyped with an Affymetrix UKBioBank Axiom Array. SNP results for 80 patient samples of class DCM1 (i.e. Type-2 Diabetes associated with comorbidities of circulatory system) and 90 patient samples of class DCM2 (i.e. Type-2-Diabetes associated with comorbidities of digestive system) were filtered through feature selection using ANOVA, Chi-square and Fast Correlation Based Filter. The top-10 SNPs along with information from Electronic Care Records (ECR), were selected for building 5 ML binary classifiers, using Support Vector Machine, Random Forest, Artificial Neural Network, Decision Tree and Naive Bayes algorithms, and their performances were tested with a 10-fold cross validation. Results: Of the 5 classifiers, the Naive Bayes algorithm outperformed all others with an Area under the Curve score of 0.681, overall Classification Accuracy of 65.68% and Mathews Correlation Coefficient of 0.316. Conclusion: Further improvement in the performance of our ML classifier is currently in-progress. With the inclusion of further data from ECR, as well as data from public repositories, we hope to build a better classifier., This project aims to investigate the relationship between folate status and the accumulation of mutations within the human mitochondrial genome. Folate is an essential B vitamin that is required for DNA synthesis, methylation reactions and is a major contributor to NADPH production through the folate one-carbon metabolism (FOCM) pathway. As a diet with a suboptimal level of folate can impact on DNA precursor availability, there is a strong biological plausibility that this will cause an increased occurrence of mutations within a cell’s genome due to errors in DNA replication. Mitochondrial dysfunction has been linked to many age-related conditions such as cardiac myopathies, neurological disorders and muscular wastage. The accumulation of mutations within the mitochondria over one’s lifetime may increase the level of mitochondrial dysfunction thus increasing the likelihood of developing such diseases. This project will look at the potential relationship between folate-status and the frequency of mutations occurring within the mitochondrial genome using a combination of both cell line and animal models plus a human cohort with known folate status and age ranges., Common variants associated with schizophrenia are enriched among highly constrained (HC) genes. As schizophrenia and cognition are genetically correlated, we hypothesized that genes associated with cognitive function are enriched for HC genes. Using MAGMA to perform gene set analysis of the largest available GWAS datasets, we found that HC genes (n=3,230 (loss-of-function intolerant)) are strongly enriched for genes associated with educational attainment(EA; p=1.27E-09) and cognitive ability(CA; p=5.64E-09) in comparison to genes under lesser or weak constraint (p>0.05 for both EA and CA). This signal remained significant following conditional analysis to co-vary for ‘brain-expressed’ (n=14,243) and ‘brain-specific’ (n=1,424) gene-sets. In schizophrenia, evidence shows that common variants are likely to persist in the population due to background selection (BGS) mechanisms. BGS refers to the phenomenon by which selection against deleterious variants reduces genetic diversity, impairing the overall efficiency of selection and allowing alleles with small effects to rise in frequency by drift. We ran a stratified linkage disequilibrium score regression (LDSR) analysis to test for heritability enrichment in EA and CA for SNPs within genomic regions that are under various types of selection. The heritability of EA and CA is enriched for SNPs in regions under background selection(p=0.028 for EA and p=0.002 for CA) and depleted for SNPs in regions under positive selection. Recent studies suggest that natural selection is acting against phenotypes such as EA or CA. This study suggests a mechanism by which variants contributing to these phenotypes are not removed by negative selection and are maintained in the population., Mutations in the photoreceptor-specific tubby-like protein 1 (TULP1) are associated with recessive retinitis pigmentosa 14 and Leber congenital amaurosis 15; severe, early-onset forms of retinal degeneration. We have explored an adeno-associated virus (AAV)-mediated gene replacement therapy in a murine model carrying a targeted disruption of the Tulp1 gene (Tulp1 -/- mice). The human TULP1 cDNA driven by the chicken beta-actin promoter (CBA) promoter was generated in an AAV serotype 5 (AAV-CBAP-TULP1). 1x10e11 vg of AAV-CBAP-TULP1 (+1:600 of an AAV-EGFP vector for tracing) was delivered to TULP1-/- mice at postnatal day 2 via sub retinal injection. Immunoblotting and qPCR demonstrated that the replacement TULP1 protein had the correct molecular weight and that the level of expression of protein achieved was ~55 % (n=8; p, Background: Diabetic kidney disease (DKD) is the most frequent cause of end stage renal disease. There is a need for improved biomarkers for the early detection of DKD. MicroRNAs (miRNAs) are short, non-coding regulatory RNA molecules commonly found in urinary exosomes that may be differentially expressed during renal dysfunction. Therefore, we profiled urinary exosomal miRNA expression in type 2 DKD (T2DKD). Methods: Qiagen Human Urine Exosome Focus miRNA Panel was used to profile 87 miRNAs in a discovery cohort of 14 T2DKD and 15 age and gender matched type 2 diabetic patients with normal renal function (T2NC). Differentially expressed miRNAs were validated in a second cohort of 22 T2DKD, 18 non-diabetic patients with poor renal function (CKD), and 22 T2NC. Results: Three urinary miRNAs (miR-21-5p, let-7e-5p and miR-23b-3p) were significantly upregulated (P, Werner syndrome (WS) is a rare genetic disorder due to mutations in the WRN or LMNA genes, with an estimated global incidence of 1 in 1,000,000 - 10,000,000. It is a segmental progeroid disorder characterised by an array of clinical features consistent with accelerated aging. We report the case of a 28 year old female patient, the offspring of a consanguineous union, who was referred to our metabolic clinic for review. She reported a history of vocal cord paralysis aged 19 years and subcapsular cataracts aged 24 years. Moreover, she had been diagnosed with primary hypothyroidism, primary hyperparathyroidism and subfertility despite normal menstruation. Further diagnoses included NAFLD with mild fibrosis. On examination, she had skin atrophy, hyperkeratosis, a loud S2, scalp alopecia, axillary acanthosis nigricans, and marked visceral adiposity with lipodsytrophic upper and lower limbs. Echocardiography confirmed trace regurgitation in aortic, mitral and tricuspid valves and DEXA confirmed osteoporosis. HOMA score was > 11 confirming severe insulin resistance and AMH levels were low. Phenotypically the patient had a diagnosis of definite WS but genetic confirmation was sought. Analysis of LMNA did not identify pathogenic variants. An RT-PCR method with direct sequencing was developed in-house to examine the extensive coding region of WRN. This revealed a homozygous genotype for the nonsense variant g.129, 248C>T, c.3961C>T, p.Arg132Ter. To our knowledge this is the first reported case of WS in the Republic of Ireland. In cases with multiple early-onset morbidities a genetic basis should be considered, particularly if there is a risk of consanguinity., Hyperlucent zones within areas of pulmonary consolidations may represent cavitatory lung lesions on CT imaging, from multi-factorial causes such as TB, pulmonary infarction, pyogenic lung abscess, pneumocystis pneumonia, Klebsiella pneumonia and less frequently due to necrotic processes from fungi. We were presented with this clinical conundrum in a patient against a background of refractory asthma, chronic cough, worsening dyspnoea, poor spirometry results and becoming progressively unwell. Due to a strong history of cancer in the family, EBUS-TBNA was carried out to obtain lung-biopsy samples. Laboratory histological analysis and ROSE revealed hyphae and fungal spores within the tissue samples biopsied, no malignant cells were recovered from the lymph node biopsy samples in all stations. We initiated anti-fungal treatment; itraconazole, 200mg once daily for 2 days after which the patient began to show signs of improvement. Seven family members with prior history of fungal-lung disease had developed lung-cancer later in life, and anecdotal prior research had shown that a premature stop-codon mutation at the tyrosine-238 residue of the dectin-1 gene in a Dutch family had predisposed patients to risks of contracting fungal-lung disease and subsequently developing lung-cancers in the long-term. We carried out Sanger-sequencing of all the exons of the dectin-1 gene as well as whole-exome sequencing on the HiSeq (Illumina) platform to identify candidate markers that may explain the heritability in this Kent family of Irish descent. We highlight the results of this study in this presentation. Abbreviations: endo-bronchial ultra-sound transbroncial-needle-aspiration; EBUS-TBNA, Rapid-OnSite-Examination; ROSE, tuberculosis; TB, Lynch syndrome (LS) (previously Hereditary Non-Polyposis Colorectal Cancer syndrome) is a cancer predisposition syndrome conferring variable risks of endometrial, colorectal, upper gastrointestinal, urinary and biliary tract cancers. Lynch syndrome is a dominantly inherited trait, caused by pathogenic germline variants in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2; and more rarely by deletions in EPCAM causing hypermethylation of the MSH2promoter. A recent report suggested that germline variants in MSH6 or PMS2 are associated with an increased incidence of breast cancer. Other data with respect to this association is conflicting, and prospective studies have not shown evidence for this association. Here, we report a case of a 37-year old female patient with multifocal breast cancer demonstrating defective MMR, associated with a germline variant in MSH2. This prompted us to undertake a respective cohort study to assess the prevalence of breast cancer in patients with Lynch syndrome managed in our centre. We report on 60 consecutive patients (including the case described here above) tested and found to carry germline pathogenic/likely pathogenic variants in MMR genes were identified from a prospectively maintained departmental database. Pedigrees from these patients were analysed, and number of breast cancers in probands and first and second degree relatives were recorded. Age at diagnosis, phenotypic data and genotype were noted., Amyotrophic lateral sclerosis (ALS), usually23 known as a motor neuron disease, is a fatal neurodegenerative disorder which causes death of neurons controlling voluntary muscles. ALS has no cure, and its underlying cause is mostly unknown, although a strong genetic component is known to play a role. The gene ATXN2 normally has a repeat structure of around 22-23 triplets encoding for glutamine (CAG) within the reading frame of the gene encoding the ataxin two protein. Studies have shown that harbouring more than 40 repeats causes spinocerebellar ataxia type 2 (SCA2). Recently, it was discovered that intermediate-length repeat expansions (27-33 repeats) in ATXN2 are significantly associated with the risk of ALS. The aim of this study is to genotype the ATXN2 gene in a cohort of controls and patients from the Irish ALS bank in order to assess the association between this genotype and ALS. The most common alleles in this cohort were 22, 23, and 27 repeats, at frequencies (cases and control combined) of 87.0%, 8.3% and 1.9%. Trinucleotide repeat counts ≥27, ≥29 and ≥30 for the larger allele were significantly associated with ALS (p < 3.6×10-3, corresponding to α = 0.05) and the odds ratio for ALS in the established ALS risk range was 1.90 (95% CI 1.03-3.51). This study further exemplifies the correlation between this gene and ALS in the Irish population, contributing to the research of causative genes for this devastating disease. Currently, our research is assessing the length of repeat expansions in other ataxia-associated genes, including ATXN1., Introduction: Huntington’s disease (HD) is a progressive, incurable, autosomal dominant, neurodegenerative disease. Genetic testing for HD has been available in the Department of Clinical Genetics since 1995. This clinic employs the gold-standard multistep approach to genetic testing, involving pre-test counselling, two blood draws and psychiatric review, allowing patients time to consider the consequences of testing and to withdraw at any time. Aims: To establish the uptake of predictive testing among first-degree relatives of patients diagnosed with HD. Methods: Families with at least one relative referred for genetic counselling between 2014 and 2016 were identified from a prospectively maintained departmental database. Familial pedigrees were analysed to identify at-risk relatives. Data was collected by retrospective chart review regarding number of first-degree relatives of the family proband attending clinical genetics for predictive testing, number who completed testing, diagnostic yield and patient demographics. Results: 241 asymptomatic adult first-degree relatives of the proband in 35 families were identified. 125 of these were children of the proband and 106 were siblings. 41 (17.4%) self-referred for predictive testing and 26 (10.8%) completed testing (9 positive; 17 negative). The median age for those seeking genetic testing was 36y (23-69). Patients completing testing were younger than those withdrawing from process (median 35 (23-55)-vs-40 (33-69y)). Conclusion: Uptake of genetic testing among relatives of patients affected by HD is currently low, in-keeping with rates reported in international literature. However, this may change in time with increasing advent of therapy. Decision-making in an incurable disorder is complex and may explain this low figure., Introduction: Over recent decades the life expectancy of those with Down Syndrome (DS) has increased dramatically. Much of this improvement can been attributed to early intervention, and the research which supports these interventions. Despite medical advancements, individuals with DS still have a greater mortality and morbidity compared with individuals from the general population and those with other forms of intellectual disability. Demonstrably there is a need for ongoing research to improve the quality and duration of life for those with DS. In modern academia there have been significant developments in the prenatal diagnosis of DS (e.g. Non-Invasive Prenatal Testing). Some of these developments have been met with controversy from members the DS community. Methods: A structured PubMed search was performed utilising comprehensive terms to identify publications focusing on DS, childhood and the prenatal period. This was compared to the total number of publications available on PubMed per year (1990-2017). Results: Since 1990, there are has been a general increase in the number of publications focusing on DS. However, the proportion of publications focusing on DS, compared to total PubMed publications, has decreased. Among those publications focusing on DS there has been a decline in the proportion of studies focusing on childhood and a proportionate increase in those focusing on the prenatal period. Conclusion: The results of this preliminary review of the literature suggest a general decline in the proportion of academic publications focusing on DS and a shift in focus away from childhood and towards prenatal studies, Introduction: Interstitial deletions of 12q are rare with around 6 cases including 12q21 deletions described in the literature. We identified a male infant with 12q21.1-q21.33 deletion with phenotypic features including wide sandal gap and longitudinal plantar creases, short upturned nose, low set ears, feeding difficulties and delayed development. Methods: Array-CGH using the Agilent (ISCA*v2) 8x60K oligo array (genome assembly Build GRCh37) was undertaken on a chorionic villus sample at 13 weeks gestation due to raised nuchal translucency, and confirmed on venous blood after birth. A comparison of a-CGH microarray profiles was undertaken on the existing described cases. Results: Array-CGH confirmed a ~16Mb deletion containing nine OMIMMorbid genes ALX1 (OMIM *601527), BBS10 (OMIM *610148), CEP290 (OMIM *610142), DUSP6 (OMIM *602748), KITLG (OMIM *184745), MYF6 (OMIM *159991), OTOGL (OMIM *614925), PTPRQ (OMIM *603317) and TMTC3 (OMIM *617218). Using overlapping features of different 12q21 cases allowed microarray profiles to confirm a common deletion region including a non-morbid gene LIN7A. Its role encodes a scaffold protein within the CASK pathway which is important in synaptic function and is a possible responsible gene for the intellectual disability and cortical development present in all described cases. Parental a-CGH was normal confirming our case is de-novo. Conclusion: We delineate a 12q21 deletion syndrome with characteristic phenotypic features. LIN7A is a consistent deleted gene in this region and may be responsible for the intellectual disability due to cortical maldevelopment in this syndrome., Trisomy 18 (T18) is a relatively common chromosomal disorder with a prenatal prevalence of ~1/2,500. Features associated with T18 include congenital heart defects (CHD), microcephaly, overriding fingers and rocker bottom feet. Radial ray anomalies (RRA) occur in ~ 1/10,000 pregnancies. RRA are associated with prenatal teratogen exposure, abnormal glycaemic control in pregnant women and syndromic disorders. To date there are few reported cases of T18 and bilateral RRA in the literature. We describe two cases of T18 with bilateral RRA: Case A: Male infant who passed shortly after delivery at 31 weeks gestation to 37 year old mother with a history of Crohn’s disease. PM identified CHD, significant growth restriction, overlapping fingers, bilateral talipes equinovarus and bi-lateral absent radii and thumbs. Case B: Male infant born at 16+4 weeks gestation to a 44 year old mother. PM examination identified significant growth restriction, an omphalocele, absent left radius, dysplastic right radius and absent thumbs, among other anomalies. For Case A and B karyotype and FISH analysis performed at post mortem confirmed T18. In both cases the diagnosis of T18 was not made antenatally. Here we discuss the importance of antenatal assessment which combines the use of ultrasound, clinical, genetic, cytogenetic and molecular testing in order to obtain the correct diagnosis from a wide spectrum of differentials. Foetal karyotype analysis should be considered in cases of RRA, especially if other malformations are detected. Cases with bilateral lesions have a significantly higher association with aneuploidy, in particular T18., Background: Clinical Genetics services provide a diagnostic, counselling and genetic testing service for children and adults affected by, or at risk of, a genetic condition, most of which are rare, or genetically heterogeneous. Appropriate triage of referrals is crucial to ensure the most urgent referrals are seen as quickly as possible, without negatively impacting the waiting times of less urgent cases. Aim: To examine triage practice in 6 Clinical Genetic centres across the UK and Ireland. Method: Thirteen simulated referrals were drafted based on common referrals to Clinical Genetics. Copies of each referral were forwarded to each centre, where 10 nominated clinicians were asked to triage each referral. Triaged referrals were returned to the coordinating author for analysis. An electronic questionnaire was contemporaneously completed by clinical leads in each unit to gather local demographic details and local operating procedures relevant to triage. Results: Widespread inconsistencies were noted both within and between units, with respect to acceptance of referrals to services, prioritisation, and designated clinic type. Referral rates, staffing levels, and waiting lists varied widely between units. Conclusion: Inconsistencies observed between units are likely influenced by a number of factors including; staffing levels, referral rates, and average family size. Inconsistency within units likely reflects the complex nature of many Clinical Genetic referrals and triage guidelines should help improve decision making in this setting., Ireland’s breast cancer(BC) incidence is 122.6/100,000. 3% of BCs are attributed to variants in BRCA1/BRCA2. Knowledge of pathogenic variants drastically changes the risk management of patients. Variants in other genes(CHEK2, ATM) confer moderate-risk; up to 50% of inherited BC risk is unexplained. Analysing multiple genes in a cost-effective manner is possible through next-generation sequencing(NGS). We aimed to identify variants contributing to Irish BC susceptibility using NGS. A custom gene-panel was designed; genes were primarily selected from clinical panels (BC, BC and ovarian cancer, broad cancer) and candidate genes identified through GWAS. Captured libraries from 90 BCs and 77 controls were sequenced using Illumina’s NextSeq. Variant calling was performed following GATK best practices. Following variant annotation (VEP, ANNOVAR, SnpEff), loss-of-function(LOF) and missense variants were analysed. Missense deleteriousness prediction scores were obtained from five sources. Clinvar reports were considered. Frequencies were obtained from ExAC/gnomAD. LOF variants were identified in BCs/controls in known BC risk genes BRCA1, ATM, CHEK2, and MSH6(candidate risk gene). A splice-region LOF variant in PBRM1 was identified (4 BCs:1 control). 22 novel LOF variants were identified. Deleteriousness prediction tools unanimously scored 40 missense variants “damaging”; three in BRCA1, BRCA2, ATM had opposing Clinvar reports. Rare missense variants were identified in FANCD2, SFN, ARID1B. Novel missense variants were identified in genes appearing on clinical panels(XPC, FANCA) and reported in GWAS(PTGS2, NOTH2, CYP1B1). These results demonstrate the challenges of accurately predicting variant pathogenicity, and highlights the need for caution when considering the use of broad panel testing on an unselected population., Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a population frequency of ~1 in 88, frequently co-occurring with other psychiatric disorders. While it is accepted that ASD is a highly heritable disorder (h2 >0.8), much of the effect of genetic variation on autism remains unclear. A major search is currently underway to seek out the variation underpinning this disorder. Methods and Results: A family was enrolled comprised of unaffected parents and 4 ASD-affected offspring. DNA was extracted from saliva samples using Perkin Elmer Prepito D cyto kit. All six samples were sequenced using SOPHiA GENETICS Whole Exome Panel covering 26,000 genes, run on HiSeq 4000 (2x250). QC was performed as standard. Data analysis was carried out using SOPHiA DDM. The identification and annotation of variants implicated in ASD will be reported. Discussion: This study will contribute to the autism genomics field with the most up to date technology in a clinically relevant family based study. The genes identified will add to those already associated with ASD, giving a deeper understanding of the genomics of the disorder. In turn, this genomic understanding will bring a clearer picture of the mechanism of disease, both on an individual level and on a global level. This gives the opportunity to develop personalised therapies and management strategies, improving patient outcomes. Genomics is certain to play a crucial role in the diagnosis and intervention of ASD in the future., Background: Little is known of the true epidemiological burden or character of mitochondrial disease in Ireland. Yet such information is important for provision/planning of evidence-based health policies/future services. Aim of study: 1) to characterise the cohort of patients with mitochondrial disease attending the National Centre for Inherited Metabolic Disease(NCIMD)/Adult Metabolic Service in reference to phenotype (clinical and biochemical), genotype, treatments/management and outcomes. Methods: A retrospective study was conducted on all patients attending the NCIMD/Adult Metabolic Service with a diagnosis of mitochondrial disease. Results: Fifty five patients (33/55 (60%) male and 22/55 (40%) female) have a mitochondrial disease diagnosis. Pathogenic variants were identified in 39/55 (71%), testing pending in 5/55 (9%) and no pathogenic variants were identified in 11/55 (20%). 31/55 (57%) patients have MELAS; 2/55 (4%) have Kearns-Sayre syndrome and 1/55 (2%) have leber hereditary optic neuropathy or pyruvate dehydrogenase deficiency (PDD) deficiency or neuropathy, ataxia and retinitis pigmentosa. 19/55 patients (34%) have another mitochondrial disorder with only 9/19 (47%) having a confirmed genetic diagnosis. Conclusions: MELAS, due to m.3243A>G, is the most common mitochondrial disorder which is in keeping with international studies. 30% of patients have a mitochondrial diagnosis due an abnormal biochemistry. Mitochondrial disease criteria (Wolf NI et al., 2002) will be applied to identify those for further genetic testing. Low numbers of patients suggest there is a large cohort of mitochondrial patients not yet captured by this clinic. The study will be expanded to calculate the prevalence of adult mitochondrial disease in the Irish population., Abnormal methylation affecting allele-specific expression of the H19, IGF2, KCNQ1 and CDKN1C genes at the 11p15.5 locus are variably associated with congenital disorders of growth including Beckwith Weidemann syndrome (BWS), Silver Russell syndrome (SRS), and isolated lateralizing overgrowth. Methylation defects causing isolated hemi-hypertrophy commonly overlap with those causing BWS. At the 11p15.5 locus, hypomethylation of the H19 DMR (differentially methylated region) (IC1) on the paternal allele, or hypermethylation of the KCNQ1OT1: TSS – DMR (IC2) on the maternal allele are mechanisms underlying SRS. We present atypical cases related to SRS methylation abnormalities at the 11p15.5 locus. Patient 1 is a 2y-old girl with leg-length discrepancy, and asymmetric facies. Relatively small at birth (5lb 4oz), post-natal growth velocity was normal. Patient 2 is a 16y-old boy measuring over 6ft with isolated hemi-hypertrophy. In both cases, hypomethylation at H19 was reported. Patient 3 is a 2y-old boy with history of IUGR, speech delay and short stature. Investigations identified a maternally inherited duplication of KCNQ1OT1: TSS – DMR. His mother inherited the same duplication from her mother, and was mildly affected, with final adult height of 4’ 11”, without growth hormone treatment, and no issues with development or feeding. The Netchine-Harbison Clinical Scoring system outlines diagnostic criteria for SRS, including pre- and post-natal growth restriction, feeding issues, and characteristic facies. None of these cases would fulfil these criteria and yet have molecular defects consistent with SRS. A low threshold for investigation of methylation abnormalities should be adopted in cases of short stature or isolated hemi-hypertrophy., SHOX deficiency is characterised by a clinical spectrum from idiopathic short stature to Leri Weill dyschondroestosis with triad of disproportionate short stature, Madelung deformity and mesomelia. Heterozygous mutations or deletions of the SHOX gene located in terminal Pseudo-Autosomal pairing region (PAR1) of either Yp11.2 or Xp22.33, cause this condition in both sexes. This disorder behaves as an autosomal dominant disorder, (rather than X linked) due to its location within the pseudo-autosomal region. Case: The proband was seen by clinical geneticist due to a co-incidental paternally inherited chromosome deletion in her son. The proband was noted to be short (143cm, 7cm below 3rd centile) and has shortened and bowed forearms. Analysis by aCGH showed an atypical Xp chromosome deletion of 881kb that included the SHOX gene. (Typical deletion involving SHOX is about 1.5Mb). In addition, she had gain of Yq11.221-q12 chromosomal material, which was inserted onto the distal region of Xp. She and her elder sister attended paediatric endocrinologist 25 years ago for their short stature. Her sister responded to growth hormone therapy, pre-treatment height (10cm below the 3rd centile) improved to above 3rd centile, height 10cm > than the proband who was not treated. Their parents heights were both, Malan syndrome, also known as Sotos 2 syndrome as it clinically resembles Sotos syndrome, is a recently described overgrowth syndrome. It is associated with deletions or mutations affecting the N terminal DNA binding site and dimerization domain (exons 2 and 3) in the Nuclear Factor I type X encoding gene (NFIX) on chromosome 19p13. Other mutations within the donor splice site of exon 6 of NFIX are known to cause the distinct clinical entity Marshall Smith syndrome. Typical clinical features are tall stature, macrocephaly, craniofacial features such as narrow and long face with high forehead, developmental delay, intellectual disability and behavioural abnormalities such as autistic traits and anxiety. Musculoskeletal abnormalities such as advanced bone age and scoliosis are also well described. Here we report a case of Malan syndrome with typical and atypical features, thus expanding the known phenotype, who was originally treated and referred as clinically suspected Marfan’s syndrome. She presented to the Department of Clinical Genetics at 13 years of age having been referred by her General Paediatrician. She was tall and slim, macrocephaly, with mild intellectual disability who showed a mildly dilated aortic root for which she was prescribed a beta-blocker. Subsequent to genetic and biochemical investigation, a pathogenic mutation was identified in the NFIX gene. This case emphasises the need to consider NFIX gene analysis in FBN1 negative Marfanoid appearing patients presenting with an atypical history and features such as intellectual disability, joints contractures, and dilated aortic root. Moreover, screening Malan syndrome patients for aortic root dilatation may help further understanding of the possible involvement in vasculature development of the NFIX gene function., Guidelines published by the Institute of cancer research (2013) and NICE (2017) recommend testing all women diagnosed with high grade serous ovarian carcinoma (HGSOC) for germline pathogenic variants in the BRCA1 and BRCA2 genes. It is predicted that using these guidelines that 10% of cases in this cohort harbour a pathogenic variant. We have carried out a retrospective study on 2years of data (April 2016-March 2018) from genetic screening of BRCA1 and BRCA2 genes on HGSOC patients. The aim of this audit was to establish the number and incidence of germline BRCA1 and BRCA2 pathogenic variants identified within this cohort in Northern Ireland and to explore the contributing factors to these results. During this period, 155 women with ovarian cancer were screened for germline mutations in the BRCA1 and BRCA2 genes by fluorescent sequence analysis of the coding sequence and associated splice sites and screening for whole exon deletion/duplication variants. The clinical details and family history of these patients were reviewed in light of existing screening guidelines and amendments to local testing protocols considered., The rapidly emerging field of Genomics promises improved diagnosis and personalised medicine at the front line of patient care. Genetic counsellors (GCs) bring essential skills and knowledge for delivering genomic information to patients and in education of healthcare professionals. In the Republic of Ireland there are 13 Genetic Counsellors (GC) working across different hospital sites with a variety of clinical roles. The majority have attained professional registration through the UK Genetic Counselling Registration Board (GCRB) or the European Board of Medical Genetics (EBMG) and/or an MSc in Genetic Counselling. The number of GCs falls significantly below recommendations for the Irish population as compared to other European countries. We are in the process of setting up a professional body called the Irish Association of Genetic Counsellors (IAGC) to represent the profession in Ireland. To achieve this two working groups have been established: Professional body: this working group has developed a constitution detailing membership, council roles and setting out the aims for the organisation - advocating for the profession, development of CPD opportunities and education of allied health professionals. Regulation: Given the significant implications associated with mishandling of genomic information this working group will aim to achieve consideration for the statutory regulation of the Genetic Counselling profession. Initial steps include direct approach to CORU - Ireland’s health and social care professional regulator. Our goal is to promote high standards of professional conduct, education, training and competency in the Genetic Counselling profession., Immunohistochemistry (IHC) performed on tumour tissue to detect loss of mis-match repair (MMR) protein expression is used to screen individuals at risk of Lynch Syndrome (HNPCC). Germline mutation analysis for HNPCC is guided by loss of expression of MMR proteins on IHC and it has been local practice to arrange MLH1 mutation analysis for isolated loss of MLH1/PMS2 protein expression for all cases without testing the tumour tissue for BRAF or promoter hypermethylation as recommended by NICE guidelines due to lack of access to BRAF/promoter hypermethylation testing locally. Presence of BRAF and/or presence of methylation of MLH1 promoter region suggest sporadic cancer and therefore molecular testing for HNPCC is not indicated in these cases. It is likely that sporadic bowel cancer is being tested for HNPCC based on IHC results alone as per existing practice. This audit would help us to quantify the issue and will help us in creating a testing pathway incorporating BRAF/ promoter hypermethylation testing for better diagnostic yield. This would avoid unnecessary genetic testing and would be a cost saving measure for the service helping us to utilize our resources efficiently, Mutations in the LMX1B gene cause nail-patella syndrome, a rare autosomal dominant disorder which is characterized by abnormalities of the nails, knees, elbows, and pelvis. The features of nail-patella syndrome vary in severity between affected individuals, even among members of the same family. Other areas of the body that can be affected in this condition are eyes (glaucoma) and kidneys where progressive disease can cause renal failure. The LMX1B gene provides instructions for producing a protein that binds to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the LMX1B protein is called a transcription factor. The LMX1B protein appears to be particularly important during early embryonic development of the limbs, kidneys, and eyes. Mutations in the LMX1B gene lead to the production of an abnormally short, nonfunctional protein or affect the protein’s ability to bind to DNA. It is unclear how mutations in the LMX1B gene lead to the signs and symptoms of nail-patella syndrome. We describe a family with significant history of kidney failure and no systemic manifestations of nail-patella syndrome Molecular studies identified a pathogenic variant in one allele of LMX1B c.737G>A missense p.Arg246Gln predicted to result in an arginine to glutamine substitution at amino acid position 246. This variant has been described previously in multiple unrelated families who presented with autosomal dominant nephropathy without nail and patellar abnormalities, which suggest this variant mutation is phenotype specific. This case reports adds to a growing evidence of LMX1B-associated nephropathy without nail and skeletal manifestations seen in classical nail-patella syndrome., ICR guidelines recommended testing all women diagnosed with triple negative breast cancer (i.e. negative for the oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)) under 50 years old should be offered genetic testing for BRCA 1 and 2 pathogenic mutations. It was predicted that testing in this population should identify pathogenic mutations in around 10% of this cohort. This retrospective study will analyse 2 years (April 2016 – March 2018) of BRCA 1 and 2 testing in women diagnosed with triple negative breast cancer under 50 years of age. The main aim would be to find out if BRCA 1 and 2 mutations are accurately represented for our population and to explore the contributing factors to these results. For example, establish true pathology of the triple negative referrals tested and the strength of the family history of cancer in these cases. The hope is to identify whether tighter departmental guidelines for testing and developing a testing criteria proforma for mainstreaming could be beneficial for better mutation pick up rate., Background: Polycystic kidney disease, the most common inherited renal disease, is characterized by renal cysts and progressive reduction in kidney function. Although it is well established that autosomal dominant (ADPKD) is primarily caused by mutations in PKD1 and PKD2, sequencing of PKD1 is difficult due to multiple pseudogenes. Further, there is considerable unexplained variance in the age-of-onset of PKD even within families. Aims: Firstly, to apply NGS technologies for the molecular diagnosis of ADPKD. Secondly, to identify, using genomic and clinical data, large PKD ‘super-families’ to facilitate investigation of genetic modifiers of age-of-onset. Methods: NGS sequencing was performed using a custom Roche NimbleGen SeqCap targeted panel on the Illumina platform. Bioinformatics was performed using a custom, in-house pipeline based on GATK best practices. Copy number variants were identified from NGS data. Whole exome sequencing was performed on selected families using Roche NimbleGen library preparation. Pathogenicity was assigned to variants using ACMG pathogenicity guidelines. Results: 73 ADPKD patients were sequenced and a molecular diagnosis was obtained in 63% (41/73) indicating that NGS technologies were successful for variant identification in difficult to sequence PKD1 regions. We identified five pairs of individuals recorded as unrelated who shared rare PKD1 variants and have inflated genomic relatedness (IBD) scores. Conclusions: NGS with specific capture methods is suitable for the sequencing of renal disease genes including PKD1. We identified one large ADPKD pedigree chart using genomic data for the generation of Irish ADPKD ‘super-families’. Sequencing of additional ADPKD patients (underway) will facilitate expansion of ‘super-families’ concept., Approximately 80% of breast cancers overexpress the estrogen receptor α (ERα) and depend on this key transcriptional regulator for growth. The discovery of novel mechanisms controlling ERα function represents major advances in our understanding of breast cancer progression and potentially offers new therapeutic opportunities. Here, we investigated the role of deubiquitinating enzymes (DUBs), which remove ubiquitin moieties from proteins, in regulating ERα in breast cancer. We performed an RNAi loss-of-function screen using a library of shRNA vectors targeting all 108 known or putative human DUB genes. Suppression of a number of DUBs repressed or enhanced the activity of an estrogen-response-element (ERE) luciferase reporter. Interestingly, suppression of the BRCA2-associated DUB, USP11, was found to downregulate ERα transcriptional activity. Subsequent validation using two individual siRNAs targeted to USP11 revealed a reduction in expression of endogenous ERα target genes in ZR-75-1 cells, as quantified using qRT-PCR. Estradiol (E2) stimulation enhanced USP11 expression in the cell nucleus, while proteomic analysis by mass spectrometry revealed a significant change to the proteome in USP11 knockdown cells in the presence of E2 only. Furthermore, USP11 expression was found to be upregulated in LCC1 breast cancer cells when compared to other cell lines. RNA-seq in LCC1 USP11 knockdown revealed a downregulation of several putative ERα target genes and many cell cycle-associated genes. To support the prognostic relevance of USP11, immunohistochemical staining of a breast cancer tissue microarray (103 ERα+ patients) was performed. Kaplan-Meier analysis of this cohort revealed a significant association between high USP11 expression and poor overall (p=0.030) and breast cancer-specific survival (p=0.041). These results suggest a role for USP11 in ERα transcriptional activity and identify USP11 as a potential therapeutic target in ERα+ breast cancer.

Euthanasia of mature swine and cattle can be challenging. On-farm euthanasia should be used as a tool to eliminate pain and suffering. However, clear guidelines regarding making euthanasia decisions and alternative euthanasia techniques available for use is limited in the United States (US). In order to prevent prolonged suffering and pain in compromised animals, science-based recommendations are needed to ensure timely and humane euthanasia can be performed when needed on-farm. This presentation will focus on two euthanasia challenges currently faced in swine and dairy cattle systems in the US today: 1) Swine: Validating alternative euthanasia techniques for use in mature breeding stock and 2) Dairy Cattle: Identifying producer barriers preventing timely euthanasia decision-making using surveys and focus groups. The swine study evaluated the effectiveness of two penetrating captive bolt gun styles (cylinder or pistol) using a frontal, temporal and behind-the-ear placement. Four treatments were 100% effective in achieving cardiac arrest and death. The cylinder style captive bolt gun resulted in greater brain trauma and death compared to a pistol style gun and behind-the-ear and temporal placement showed promise as an alternative placement site for euthanizing mature pigs. In the dairy cattle study, dairy producers were recruited to participate in a survey and focus group. Survey results indicated that farm owners were most commonly responsible for on-farm euthanasia and most respondents would treat and monitor compromised cattle for a majority of health conditions, regardless of condition severity. Participants in focus groups focused primarily on animal welfare as the most important factor influencing the decision to euthanize and the desire to eliminate animal suffering by using euthanasia as a tool. This work highlights the complicated challenges that arise when euthanizing livestock and the importance of not only identifying appropriate techniques to humanely euthanize livestock but address the emotional and animal welfare factors that influence these decisions.

DON has been shown to induce anorexia, oxidative stress, and more recently, alterations in calcium (Ca) and phosphorus (P) metabolism. It was thus hypothesized that vitamin D3 or 25-OH-D3 can counteract the effects of DON in piglets. The objectives were to confirm the DON effect and to evaluate the impact of a vitamin D supplementation on growth performance and Ca and P metabolism on piglets receiving a DON contaminated feed. A total of 66 piglets received one of the 6 treatments in 2 x 3 factorial design: control treatments (CON) or DON unsupplemented or supplemented with VitD3 or 25-OH-D3. After 21 days, piglets were weighted and feed intake was measured. Bone mineral content of each piglet was measured with dual-intensity X-ray absorptiometry at 21 days. Blood samples were taken to assess concentrations for VitD, P and Ca. Results showed that, DON reduced average daily feed intake and average daily gain (P < 0.001). DON increased BMC per kg live body weight (P < 0.001). Piglets fed DON diet had lower plasma concentrations of 25-OH-D3, 1,25-(OH)2-D3 and phosphate (P < 0.001). The sodium-dependent phosphate transporter 1 (SLC20A2; P < 0.050), sodium/calcium exchanger 1 (SLC8A1; P < 0.032) and Klotho (P < 0.014) gene expression was downregulated by DON contamination in intestinal mucosae. The calbindin d28K (CALB-1) (P < 0.042), SLC8A1 (P < 0.026), TRPV5 (P < 0.041), calbindin d9K (S100G) (P < 0.029) and Klotho (P < 0.013) gene expression was downregulated by DON contamination in the kidney. The 1α-hydroxylase gene expression tended to be downregulated by DON contamination in the kidney as well. The VitD3 and 25-OH-D3 supplementation upregulated vitamin D receptor (VDR, DON x VitD, P < 0.014), SLC8A1 (DON x VitD, P < 0.036) and Klotho (DON x VitD, P < 0.025) in intestinal mucosae, although those gene expressions were downregulated by DON contamination. Thus, DON induced an alteration of vitamin D-calcium-phosphorus metabolism by modifying Ca utilization from mechanisms still under investigation.

Colostrum intake by neonatal piglets can be measured using the immunoglobulin immunocrit assay (iCrit). Lactocrine effects occur when maternally derived, milk-borne bioactive factors are transferred to the neonatal circulation with consumption of colostrum during nursing and affect development of somatic tissues, which can have long-term consequences in adulthood. Lactocrine deficiency, indicated by low neonatal iCrit, altered uterine gene expression and reduced fecundity in adult, neonatally lactocrine-deficient gilts. Litter size in pigs is dependent on both ovarian and uterine function. It was hypothesized that lactocrine deficiency affects development of ovarian follicles in gilts. The objective was to determine the number of primordial, primary, and secondary follicles in ovaries of gilts with high (12% ± 0.5; n = 10) or low (1.9% ± 0.4; n = 10) iCrit, determined on postnatal day (PND) 1 after birth. Paired high- and low-iCrit gilts were chosen from the same litters (birth weight; 3.1 ± 0.2 lbs). On PND 14, ovaries were collected and histological sections prepared (3 sections per animal; 30–150 µm apart). Ovarian follicles in each section were staged and the number of follicles in each category were quantified and subjected to ANOVA. Total number of ovarian follicles did not differ with iCrit (P = 0.55; 1,370.6 ± 147.8 follicles per section). The proportion of primordial, primary, and secondary follicles was 89.6 ± 1.15%, 7.7 ± 0.87%, 2.7 ± 0.51%, respectively. The number of primordial (P = 0.55), primary (P = 0.64), and secondary (P = 0.93) follicles did not differ with iCrit. Results indicate that ovarian follicular development of neonatal gilts is not sensitive to immunocrit status. Although lactocrine deficiency did not influence the ovarian follicular profile at PND 14, it remains unknown whether lactocrine programming alters ovarian follicular dynamics in neonatally lactocrine-deficient adults. USDA is an equal opportunity provider and employer.

Statistical training is a major component in the education of animal science graduate students (ASGS). Although most graduate courses in animal science require ASGS to take credits in statistics courses, ASGS differ on their educational and professional interest in statistics. Thus, the aim of this study was to identify associations between the overall graduate and statistical training of ASGS with the statistical interest related to their professional career path. Data from a nationwide statistical training survey was used and included information on 381 ASGS from 42 universities. Analyses focused on identifying overall graduate and statistical training factors associated with ASGS’s answers to the following questions: “Gives statistical advices to lab peers” (No/Yes), “Gives statistical advices to others outside the lab” (No/Yes), “Desired career path after graduation” (Academia/Industry/Other), and “Desire to be involved in statistical analysis in desired career path” (No/Somewhat/Yes). Data were analyzed using logistic regression model including 11 fixed effects, such as degree being pursued (MS/PhD), years of graduate education (covariate), previous professional experience (No/Yes), preferred stats software (SAS/R/SAS and R/Other), etc. There were significant associations (P < 0.05) for all four analyses. ASGS were more likely to give statistical advice to lab peers as they had more years of graduate education [odds-ratio (OR)=1.33], had additional training in statistics (OR=1.92), and had analyzed their own dataset (OR=4.46). ASGS with and without previous professional experience had greater desire to go to industry (OR=1.3) and academia (OR=1.23), respectively. ASGS interested in being involved in statistics in their future career had greater years of graduate education (OR=1.31) and credits in stats courses (OR=1.31), had previously completed a graduate degree (OR=1.49), had previous research experience (OR=1.5), and had additional training in statistics (OR=1.54). These results indicate that a variety of experiences prior to and during graduate ASGS education are associated with their interest in statistics.

This study evaluated the effect of housing newly-weaned pigs in uniform versus mixed weight groups on nursery growth performance (5.9 ± 1.1 to 26.2 ± 2.9 kg BW). Pigs were assigned to a weaning weight (WW) quartile: Q1 (light; 4.2 ± 0.1 kg), Q2 (medium-light; 5.5 ± 0.1 kg), Q3 (medium-heavy; 6.3 ± 0.2 kg), and Q4 (heavy; 7.5 ± 0.1 kg). A RCBD was used (blocking factor = start date) with 5 treatments: Control (equal number of pigs from each quartile); Uniform Q1 (all pigs from Q1); Uniform Q2 (all pigs from Q2); Uniform Q3 (all pigs from Q3); Uniform Q4 (all pigs from Q4). There were 16 replicates and 3,503 pigs, with mixed-gender pens of 44. Pen was the experimental unit; data were analyzed using PROC MIXED of SAS (fixed effect = treatment; random effect = replicate). Overall ADG and ADFI increased (P < 0.05) according to WW quartile for the Uniform treatments, with the Control being intermediate. There were no differences (P > 0.05) between treatments for Overall G:F. A contrast statement was used to compare Control to the mean of all 4 Uniform treatments. Compared to Control, the mean of the 4 Uniform treatments had similar (P > 0.05) overall ADG (0.44 vs. 0.44 kg, respectively) and ADFI (0.72 vs. 0.68 kg, respectively), but greater (P < 0.05) overall G:F (0.637 vs. 0.611, respectively). Comparison of pigs from each quartile within Control pens with the respective quartile in Uniform pens suggested no effect (P > 0.05) of weight quartile on ADG (respective means for Control vs Uniform: Q1 0.34 vs. 0.36 kg; Q2 0.39 vs. 0.40 kg; Q3 0.42 vs. 0.42 kg; Q4 0.47 vs. 0.45 kg). These results suggest that penning nursery pigs in uniform versus mixed weight groups had limited effect on growth performance.

The objectives were to: 1) determine the relationship of fecal characteristics with ruminal pH, dry matter intake (DMI) and dry matter digestion and 2) determine the ability of fecal characteristics to predict ruminal pH, DMI, and dry matter digestion. Data were collected in two metabolism studies using eighteen ruminally cannulated steers (n = 36). Each study was a completely randomized design evaluating the effect of a direct-fed microbial during an acidosis challenge. Ruminal pH, DMI, total tract DM digestion and fecal characteristics (fecal pH, washed fecal particle size and mucin casts) were measured for 4 d after the acidosis challenge. Rumen pH was not correlated (P ≥ 0.15) with mucin cast score or mean fecal particle size but was negatively associated with fecal pH (r = -0.42; P < 0.01). Total tract DM digestion was correlated (r ≥ 0.53; P ≤ 0.02) to fecal pH and fecal particle sizes between 1180 and 2360 µm. Dry matter intake was correlated (r ≥ 0.41; P < 0.01) to mean fecal particle size and fecal particle sizes between 2360 and 4750 µm. Multiple regressions were performed with the GLMSELECT procedure of SAS 9.4 using stepwise selection. Ruminal pH was best predicted (r2 = 0.20) by fecal pH and fecal particle size between 1400 and 1700 µm. Total tract DM digestion was best predicted (r2 = 0.92) by fecal pH, mucin cast score, and fecal particle size between 3350 and 1700 µm. Dry matter intake was best predicted (r2 = 0.51) by mean fecal particle size, fecal pH and fecal particle size between 1400 and 850 µm. Overall, results indicated fecal pH was correlated to ruminal pH and total tract DM digestion. Fecal characteristics including washed particle size can also predict total tract DM digestion in feedlot cattle.

Two studies were conducted to evaluate narasin inclusion level on the growth performance and carcass characteristics of growing-finishing pigs. The studies were carried out using a randomized complete block design with three narasin levels: 0 vs. 15 vs. 20 mg/kg. Study 1 (2,232 pigs) was carried out over a fixed time of 85 days from 33.4 ± 1.7 kg to 117.0 ± 2.6 kg. Study 2 (1,125 pigs) was carried out over a fixed time of 113 days from 28.0 ± 2.2 kg to 124.4 ± 6.0 kg. All pigs were fed diets that met or exceeded nutrient recommendations of growing-finishing pigs (NRC, 2012). Pigs were offered ad libitum access to feed and water throughout the study and weighed on day 0, 28, 56, and 84. Feed additions and feed remaining in the feeder at the time of pig weighing was recorded. Due to disruptions at the slaughter facility, carcass data were not collected on Study 1. For Study 2, pigs were sent for slaughter over five weeks, with the heaviest 20% of each pen being sent for slaughter each week. At slaughter, hot carcass weight was collected. Compared to controls, feeding 15 mg/kg narasin increased (P < 0.05) final body weight (1.2 kg and 1.4 kg for Study 1 and 2, respectively), increased (P < 0.05) hot carcass weight (1.3 kg), and tended (P = 0.07) to improve carcass yield (0.3 percentage units). Feeding 20 mg/kg narasin increased (P < 0.05) overall G:F compared to controls (1.5% and 1.9% for Study 1 and 2, respectively). There were limited differences between the 15 and 20 mg/kg narasin levels. The results of this study confirm improvements in growth performance and carcass characteristics from feeding narasin to growing-finishing pigs. The outcomes of feeding 20 mg/kg narasin were unexpected and warrant further research.

Nursery pigs are frequently faced with disease challenges and producers are seeking nutritional strategies to help pig performance and health. Therefore, our objective was to evaluate five dietary formulation strategies that may improve performance in poor health nursery flow pigs (confirmed Rotavirus A and hemolytic E. coli positive at d 14). A total of 431 weaned pigs (5.5 ± 1.25 kg BW) were assigned to pens (10–11 pigs/pen) and one of five diets (n = 8 pens/treatment) over a 63-day test period consisting of 4 diet phases using a complete randomized design. In phase 1 and 2, treatments were: 1) 15–25% low soybean meal (LSBM), 2) 35–45% high soybean meal (HSBM), 3) 130% increase in valine and isoleucine branched-chain amino acids (BCAA) to Lys, 4) 2.1% combination of C8, C10 and C12 medium chain fatty acids (MCFA), and 5) 20% modified oats (MO). All pigs were fed a common diet for phases 3 and 4. Within phase, all diets were isocaloric with similar SID Lys:ME. Pen was considered the experimental unit and data were analyzed with contrast statements comparing each diet against the LSBM control. Across all phases, compared to LSBM, HSBM, BCAA and MO did not alter ADG, ADFI and G:F (P > 0.10). However, MCFA reduced (P < 0.05) ADG in phase 1 (0.20 vs 0.16 kg) and 2 (0.45 vs 0.39 kg) and phase 2 ADFI (0.66 kg vs 0.58 kg) compared to the LSBM treatment. Overall (0–63 days), compared to the LSMB, the MCFA treatment reduced ADG (0.46 vs 0.42 kg, P = 0.004) and ADFI (0.75 vs 0.68 kg, P = 0.009). Diet did not affect mortality. These data report that MCFA attenuated nursery pig performance, while HSBM, MO and BCAA diets fed in phases 1 and 2 had no longitudinal impact on pig performance or health.

This study evaluated the effects of a liquid prototype (LIQP) and dry (XPC®; Diamond V) Saccharomyces cerevisiae feed additives on blood and uterine cytokine profiles in sows (n = 40). On d 112 of pregnancy sows were allotted to dietary treatments: 1) Control diet (CON), 2) CON +15 mL of LIQP (LIQ), 3) CON +0.20% of XPC (DRY), and 4) DRY +15 mL of LIQP until d 7 post-farrowing (D+L). Interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were quantified from serum samples collected on d 112 of gestation, d 2 and 6 post-farrowing, and from uterine fluid collected on d 2, 4, and 6 post-farrowing. Serum C-Reactive protein (CRP) and haptoglobin concentrations were evaluated. No interactions between treatments and day of collection were observed (P > 0.13). LIQ and D+L sows had the greatest serum IL-10 concentration (P < 0.001) and sows fed CON tended to have lower concentration of IL-8 (P < 0.06) vs. other treatments. Serum CRP concentrations were greatest on d 2 (P < 0.001), serum IL-10 (P < 0.04) and IL-4 (P < 0.07) linearly decreased while serum haptoglobin (P < 0.02) and INF-γ (P < 0.001) linearly increased post-farrowing. In the uterine fluid, LIQ and D+L sows had greater INF-γ (P = 0.04) concentrations and CON tended to have the least concentration of TNF-α (P = 0.08). Uterine fluid IL-1 tended to linearly increase (P < 0.07) and IL-6 linearly decrease (P < 0.01) post-farrowing. No strong correlations were detected between cytokines in the serum and uterine fluid within day. LIQ sows had the greatest daily feed intake and CON the least during the first week of lactation (P = 0.04). Providing LIQP post-farrowing to sows modified immune response increasing both pro- and anti-inflammatory cytokines in serum and uterine fluid in an independent manner, allowing animals a quicker recovery and increased feed intake.

Within the last decade, pelvic organ prolapse (POP) resulting in sow mortality has become an increasing concern for the U.S. swine industry, contributing approximately 21% of all sow deaths. While little is known regarding the etiology preceding POP in sows, many have proposed an association with vitamin and trace minerals abundance to POP incidence. We tested the hypothesis that sows differing in POP risk would have differences in serum trace minerals and vitamins. A perineal scoring (PS) system (PS1 - presumed low risk; PS2 - presumed moderate risk; and PS3 - presumed high risk) to assess risk for POP during late gestation was used to score 213 individual sows. Blood was collected from sows of two different farms during late gestation (days 105–115) that scored a PS3 (n = 20) and a parity matched sow scored as PS 1 (n = 16). Subsequently, 1.5, 0.8, and 23.1% of sows scored as PS1, PS2, or PS3, respectively, experienced POP. Serum was analyzed at the Iowa State University Veterinary Diagnostic Lab for trace mineral content (Calcium, Copper, Iron, Potassium, Magnesium, Manganese, Molybdenum, Phosphorus, Selenium, and Zinc). Additionally, vitamin E was evaluated in serum via GC-MS. Differences (P < 0.05) in copper, potassium, molybdenum, phosphorus, and selenium was observed between farms. Further a PS x Farm interaction (P = 0.06) was observed for serum copper abundance which across all farms was 12% less (P < 0.04) in PS3 compared to PS1 sows. No impact on serum vitamin E was observed between PS sows. These data demonstrate sows with greater POP risk may have potential differences in serum factors although these data also underscore the importance of measuring vitamin and mineral quantities in a tissue specific manner. This project was supported by the National Pork Board and the Foundation for Food and Agriculture Research.

To find an in vitro predictor of in vivoM/em> semen motility prompted this study. Our objective was to evaluate semen motility for an 8-hour period immediately following a breeding soundness exam. Ejaculates from 52 Angus and 56 Charolais bulls were evaluated. Motility, morphology, scrotal circumference and pH of ejaculate were evaluated at the time of collection. Ejaculates were then extended using a one to one ratio and incubated in a water bath held at 37 degrees Celsius and evaluated hourly. Motility was evaluated hourly for 8 hours, or until motility of the sample reached zero. Data were analyzed for breed and hourly effects using the GLIMMIX procedure of SAS. There was statistical evidence for difference (P < 0.0001) between breeds for motility over time. Angus ejaculates had higher pH values than Charolais ejaculates showing an association between breed and pH (6.82 vs 6.76, respectively). Primary spermatozoa abnormalities were greater (P < 0.0001) for Angus bulls compared to Charolais bulls (13.33% vs. 10.91%, respectively). Scrotal circumference between breeds tended to be different (P < 0.07), with Charolais bulls having a larger scrotal circumference compared to Angus bulls (38.29 vs. 38.03 centimeters, respectively). There was no difference (P > 0.05) between breeds for secondary abnormalities. There was a significant interaction (P < 0.01) between breed and time of motility measurement. Angus bull’s motility decreased drastically until hour 4, it then had a more gradual decrease until hour 8. Charolais bulls had a more gradual decrease in the percentage of motile sperm over time. In conclusion, there was evidence for difference between breeds for pH, primary spermatozoa abnormalities, and long-term motility, and a scrotal tendency. Understanding the effects of breed and individual biological factors may help producers adjust BSE expectations and lead to future research in long term semen motility.

Sow litter sizes have increased over recent decades, increasing the need for cross-fostering. The objective of this study was to determine the effect of the number of source litters used to create cross-fostered litters on piglet pre-weaning mortality (PWM) and weaning weight. A RCBD was used with 26 blocks of 5 litters (total 130 litters/1820 piglets), all litters consisted of 14 piglets. Blocking factors were farrowing day, sow parity, body condition score, and functional teat number, and the average and CV of piglet birth weight. Five cross-fostering treatments were compared: 0%, 1 source (all piglets remaining on the birth sow); 100%, 1 source (all piglets moved from birth to a different sow); 100%, 6+ sources (piglets from ≥ 6 birth sows used to form a litter on a different sow); 50%, 2 sources (7 piglets remaining with birth sow, 7 from one other sow); 50%, 4+ sources (7 piglets remaining with the birth sow, 7 from ≥ 3 other sows). The single-source litters were selected from those with > 14 piglets at birth, with excess piglets removed. For other treatments, piglets were selected to meet blocking factors. Piglets were weighed 24 h after birth and at weaning (19.5 ± 0.50 d); all PWM was recorded. Weight data were analyzed using PROC MIXED of SAS; PWM data were analyzed using PROC GLIMMIX of SAS. Models included Treatment and sow within block. There was no effect (P > 0.05) of treatment on weaning weights. Pre-weaning mortality was greater (P < 0.05) for the 0%, 1 source compared to the 50%, 2 source treatment, with the others being intermediate and generally not statistically different (Table 1). In conclusion, cross-fostering and/or mixing litters had no effect on weaning weights, but pre-weaning mortality was highest for the non-fostered treatment.

Post-weaning Escherichia coli diarrhea (PWD) remains a major cause of economic losses for the pig industry. PWD, caused by enterotoxigenic E. coli (ETEC), typically provokes mild to severe watery diarrhea between 5–10 days after weaning, which may result in mortality. Most common adhesins in ETEC are F4 and F18 fimbriae. Therapy to combat PWD typically consists of antibiotic treatment in combination with ZnO (3,000 ppm). Recently, an oral live bivalent E. coli F4/F18 vaccine (Coliprotec® F4/F18; Elanco) was approved on the European market, which reduces the impact of PWD provoked by F4-ETEC and F18-ETEC. The objective was to evaluate mortality and antibiotic use following E. coli F4/F18 vaccination under field conditions. A 160-sow farm (weaning at 26 days) with diagnosed problems of PWD due to F4-ETEC was selected. Piglets were vaccinated at 21 days with the oral live bivalent E. coli F4/F18 vaccine. At weaning, no standard group medication (ZnO and antibiotics) was applied for prevention of PWD. Several performance parameters were collected: treatment incidence (TI100), mortality and days in nursery. Vaccination (n = 3 groups) was compared to a historical control (n = 3 groups) Oral E. coli F4/F18 vaccination significantly reduced TI100 (18.6 ± 6.3 days to 2.4 ± 1.9 days; P < 0.05) due to the reduction in days of antimicrobial group treatment. Mortality rate significantly reduced (11.2 ± 2.6% in control to 4.5 ± 1.5% in vaccinated group; P < 0.05) following vaccination. Days in nursery (48.5 ± 0.3 days) remained constant throughout the trial. The results show that live E. coli F4/F18 vaccination against PWD has significantly impacted mortality, in combination with a reduction in medication use. In conclusion, control of PWD through oral vaccination is a successful option in order to prevent piglets from the negative clinical outcomes of F18-ETEC infection during the post-weaning period.

Three hundred twenty newly weaned pigs (6.7±0.3 kg BW) were used to determine the effect of low complexity diets contaminated with deoxynivalenol (DON) and supplemented with NutraMixTM or fish oil on nursery pig growth performance. Pigs were randomly divided into 40 pens and assigned to 1 of 5 dietary treatments (n = 8): [1] high-complexity diet containing animal proteins (HC) or one of four low complexity diets with protein supplied only by corn and soybean meal with [2] no DON contamination (LC), or [3] DON contamination of 3 ppm without supplements (DON-), [4] with NutraMixTM supplementation (2 g/kg; DONNM), or [5] with fish oil supplementation (2.5%, as-fed; DONω3). Diets were fed over two phases (7 and 15 days, respectively) and a common phase III diet was fed to all pigs for 20 days. In phase I, ADG, ADFI, and G:F were not different between pigs fed the HC and LC diets, but were lower for pigs fed DONNM and DONω3(P < 0.05). In phase II, pigs fed the DON- and DONω3 diets had lower ADG than LC (375 vs. 410 g/d; P < 0.05) and lower ADFI than HC (452 vs. 519 g/d; P < 0.05), while pigs fed DON- and DONω3 had greater G:F than those fed HC (0.83 vs. 0.78; P < 0.05). The BW at the end of phase II were not different between HC and LC (13.0 kg), but tended to be less for DONω3 (12.6 kg; P = 0.084 and 0.079, respectively). In phase III and over the entire nursery period, there were no treatment effects on ADG, ADFI, G:F, or final BW (26.0±0.7 kg). Feeding low complexity diets contaminated with 3 ppm DON initially reduced growth performance, but pigs were still able to achieve BW not different from HC pigs at the end of the nursery period, regardless of supplementation.

California’s Proposition 12, also known as the Farm Animal Confinement Initiative, will go into full effect starting in January 2022. This measure changes the minimum space requirement for egg-laying hens, calves raised for veal, and breeding sows within the state of California. These changes include housing that provides 1 to 1.5 square feet of floor space per hen within a cage-free system, 43 square feet of floor space per veal calf, and 24 square feet of floor space per sow. In addition, Proposition 12 would require producers to move the sows from gestation pens into farrowing crates for a maximum of 5 days before they are due to farrow. This measure also prohibits producers outside of California from importing their eggs, veal, or pork into the state unless they meet these minimum housing requirements. The goal of these requirements is to ensure that they animal can lie down, stand up, turn around, and fully extend their limbs without touching the sides of their stalls or another animal. While the intent of this new housing requirement may allow for a greater freedom of movement, animal welfare concerns are still prominent for group housing. For breeding sow, such concerns include injuries caused by social aggression, and, abnormal or harmful behaviors related to feed restriction. These welfare concerns can be addressed when considerations are given to the group composition (e.g., age and size of sows), pen mixing practices (e.g., pre or post breeding), feeding schedule [e.g., collective (trough, floor fed) or individual (electronic sow feeding, free access stalls)], and, pen structural quality (e.g., flooring, enrichment). Given that California represents approximately 15 percent of the American pork market, this measure will have considerable economic and ethical implications related to barn renovations, animal care staff training, and husbandry practices for the entire U.S. pork industry.

The sustainability of the beef industry has become a point of national interest, particularly the investment of land and water resources. Our objective was to estimate how much land and irrigation water are required to maintain a simulated Angus cow-calf operation in the North Central Great Plains (NCGP) for an average year. A stochastic model was used, which enabled consideration of biological variation. The model computed 100 iterations of a 24-year timeframe (1995–2018). The simulated herd had 100 breeding females with replacement heifers being retained annually. The nutrients required to maintain a body condition score 5 for each individual animal, adjusting for temperature and physiological state, were calculated. A stocking rate of 3.3 hectares (ha) per cow-calf pair and mature cow weight of 600 kg was set, which is representative of the NCGP. Replacement heifers were assumed to be 65% of mature cow weight and allotted 1.22 ha. Bred heifers were assumed to be 85% of mature cow weight and allotted 1.81 ha. The herd was assumed to be grazing from May 1 to October 31. A supplemented ration of 60% alfalfa and 40% corn was provided if an individual’s nutritional needs were not met. Animals were assumed to be delivered a base ration from November 1 to April 30, which consisted of 73% alfalfa, 19% wheat straw, and 8% corn. The amount of irrigation necessary to grow feed was determined by estimating evapotranspiration of each crop then subtracting the amount of precipitation during the growing season. Average crop yield was determined using county level data from the UDSA NASS to estimate how much land would be needed for feed production. Sustaining a 100 head cow-calf herd in the NCGP for an average year requires 103.5 million liters for irrigation, 1288.5 ha for crop production, 357 ha grazing land.

The reliability of spot urinary Ca to P ratio (uCa:P) to assess P intake adequacy in sows was evaluated. Thirty-six multiparous sows were fed one of six concentrations of dietary total P (0.40, 0.48, 0.56, 0.64, 0.72, and 0.80%), with a constant Ca to total P ratio (1.25:1), from day 7.5+1 after breeding until the end of lactation (day 26.6+1). Total 24-hour urine samples were collected in mid (day 77.1+2) and late gestation (day 112.4+1), and early (day 4.5+1 and late (day 18.2+1) lactation. In parallel to 24-hour collections, spot urine samples were collected at three times (early morning, late morning, and late afternoon) in late gestation and late lactation. Urine Ca and P concentrations were measured and uCa:P was calculated. Sows were classified as P-adequate or P-deficient according to dietary P intake. Sows fed P-deficient diets had greater uCa:P than sows fed P-adequate diets (P < 0.001). Receiver operator characteristic (ROC) curves were used to determine cut-off values for uCa:P to predict P intake adequacy. The area under the ROC for uCa:P was 0.88 (95% CI 0.81–0.95). Best cut-off value of uCa:P was 1.5 (sensitivity 94% and specificity 68%) to identify sows fed P-deficient diets, and 0.5 for P-excessive diets (sensitivity 82% and specificity 82%). A strong relationship between uCa:P in 24-hour and spot urine samples was determined (r = 0.93, P < 0.01), independent of physiological state and collection time of spot samples (adjusted-R2 = 0.86, P < 0.01). The degree of agreement between spot and 24-hour urine for P intake adequacy, assessed by Cohen’s weighted kappa analysis, was substantial (0.78, 95% CI 0.69–0.88). Measurements of uCa:P in spot urine samples provide a reliable prediction of the adequacy of P intake in reproducing sows. Values of uCa:P > 1.5 were associated with P-deficient diets, whereas uCa:P < 0.5 reflected excessive P intake.

Our objective was to determine the effects of different pre-farrow feeding levels on sow and litter performance. On d 112 of gestation, a total of 309 sows (Camborough; PIC, Hendersonville, TN) were blocked by parity (P1, P2, P3+) and body weight and allotted to one of three treatments in a randomized complete block design. Treatments consisted of different feeding levels, which included: 1) 1.81 kg/d; 2) 2.72 kg/d; and 3) ad libitum access to feed. Sows were fed a corn-soybean meal-dried distillers grains with solubles-based lactation diet containing 3.36 Mcal of ME/kg and 1.17% SID Lys. Sows were weighed and visual BCS and caliper units were recorded at entry into the farrowing room at d 112 of gestation and at weaning. Daily feed intake was recorded from the beginning of the study until weaning. Litters were cross-fostered within treatment within 24-h after farrowing, and litter weights were collected at 12-h post-farrow and at weaning. Data were analyzed using the GLIMMIX procedure of SAS with sow as the experimental unit and block as a random effect. Covariates were used if they significantly improved the model fit. Ad libitum sows had the greatest (P < 0.05) feed intake from d 112 to farrow, followed by 2.72 kg/d and 1.81 kg/d treatments; however, no evidence (P > 0.10) for differences in lactation feed intake were observed. Wean-to-estrus interval was greater (P < 0.05) for ad libitum sows compared to sows fed 1.81 kg/d. Removal plus mortality rate was marginally lower (P < 0.10) for sows fed 2.72 kg/d compared to sows fed 1.81 kg/d. No evidence (P > 0.10) for treatment differences were observed in total born, stillbirth rate, and litter or piglet weight gain during lactation. In conclusion, results from this study do not support increasing feeding levels for sows prior to farrowing starting on d 112 of gestation.

Pre-weaning mortalities have become a pressing issue in modern swine production. Litter size at birth has greatly increased through direct genetic selection. Unfortunately, little emphasis was placed on improving functional teat number, resulting in a nutrient access shortage. Therefore, a total of 750 sows consisting of three genetic lines in a commercial barn in Nebraska, USA, were used to evaluate the impact of functional teat number on piglet survival. Teat traits recorded at farrowing included total teat number (TT), functional teat number (FT), and non-functional teat number (NFT); with population means of 14.84 (1.21), 14.55 (1.30), and 0.28 (0.56), respectively. Production traits recorded included total number born (TNB), wean number (WN), total pre-weaning mortality (PWM), and post-cross foster mortality (CFPWM). The lm function within RStudio was used to estimate regressions, with parity and piglets placed (PP) used as covariates for WN and CFPWM, and parity, PP, and TNB for PWM. One additional FT increased WN (P < 0.01; 0.33), and reduced PWM (P < 0.01; -3.04%) and reduced CFPWM (P < 0.01; -3.71%). A subset of 274 sows were used to determine the effects of increasing functional teats on sow and piglet efficiency. Additional traits recorded included sow average daily feed intake (ADFI), backfat loss (BF) and average piglet weaning weight (WW). Parity, ADFI, backfat-entry, and WN were used as covariates for BF; parity, backfat-entry, and WN for ADFI; and parity, PP, ADFI, and WN were used for estimating WW. Regression estimates showed that an additional functional teat had no significant impact (P > 0.05) on ADFI, BF, or WW. Taken together, these results suggest that improving functional teat number does not impact ADFI or BF for sows and does not influence average piglet weaning weight, but it does decrease PWM resulting in more pigs weaned per litter.

Heat stress reduces livestock performance while supplementation of beta-adrenergic agonists (βAA) such as zilpaterol hydrochloride (ZH) improve production efficiency; both stimulate lipolysis. The objective of this study was to understand the effects (independent, interacting) of heat stress and ZH on the subcutaneous adipose transcriptome in fed steers. 24 Red Angus steers were assigned to thermoneutral (TN; THI=68) or heat stress (HS; THI=83) conditions and fed no supplement (NS) or ZH (8.33 mg/kg/day) for 21d in a 2x2 factorial. TN steers were pair-fed the HS daily average. Subcutaneous adipose samples were collected at day -3, 3, 10, and 21. RNA was isolated and sequenced using 3’ Tag-Seq reads to a depth of 3.6 million reads/sample. Transcripts were mapped to ARS-UCD1.2 and quantified. After quality control, differential expression (DE) analyses were performed in DESeq2 with a significance threshold (FRD) of 0.05. Pathway analysis was used to explore pathways affected by HS, ZH, and their interaction using DE loci (P < 0.05). The acute phase response signaling pathway was predicted to be activated at 3d, but inhibited at 10d and 21d by the combination of HS and ZH. At multiple time points, inflammatory pathways including those for interferon and IL-8 were predicted to be activated by HS. Mitochondrial function pathways including oxidative phosphorylation, mitochondrial dysfunction, and TCA cycle II were altered by ZH. Adipose centric pathways for phospholipase-C and protein kinase-A signaling were altered by HS/ZH interaction while glycolysis was altered solely by HS. These data support the hypothesis that exposing cattle to HS conditions and ZH supplementation alters the subcutaneous adipose transcriptome, but not necessarily in an additive fashion. These data provide information regarding the supplementation of βAA in heat stress environments, especially if it mediates the effects of HS.

A survey of South Dakota pork producers in 2019 demonstrated that water flow rate for nipple drinkers was highly variable among barns. Sixty-eight percent had water flow rates above the recommended rate of 500–1,000 mL/min (NSNG, 2010). The objective of this study was to determine the impact of water flow rate on finishing pig performance during the summer months. A total of 396 mixed-sex pigs, in two groups, were utilized in a 77-day trial (34.55 to103.8 kg BW) with 6 pigs/pen. Pens were assigned to one of three water flow rates (high, medium, low) based on the 3-hole diameters of the commercial water nipples used in the facility (2.0, 1.0, 0.80 mm; n = 22 pens/treatment). Daily water usage was recorded for each treatment along with room temperature, outside temperature, and relative humidity. Individual pen water flow rate was recorded every two weeks. At every diet phase change (26± 2.6 days), feed disappearance and individual pig body weight were recorded. Water flow rates averaged 1846±188, 906±214, 508±100 mL/min for high, medium, and low flow rates, respectively. Daily water disappearance for high, medium, and low treatments were 6.8, 2.3, 1.7±3.2 liters/pig, respectively. Final body weight (BW; 103.8±7.4 kg) did not differ. Daily gain (ADG) from 34.5±4.5 to 55.5±4.6 kg BW was greatest (P < 0.05) for high treatment. Daily intake (ADFI) and gain:feed (G:F) from 55.5±4.6 to 79.1±5.3 kg BW were greatest (P < 0.05) for high treatment. Cumulative ADFI was 2.27, 2.18, 2.16±0.16 kg (P < 0.05) in high, medium, and low flow ranges, respectively. There was no differences in cumulative ADG or G:F. Water flow rate had a significant impact on ADFI although there was minimal impact on gain and G:F. Water nipples should be regularly checked as part of normal barn maintenance to ensure adequate, but not excessive, water is available.

The impact of feeding growing pigs with high wheat millrun diets on the global warming potential (GWP) of pork production was investigated. In study 1, a 2 × 2 factorial arrangement of wheat millrun (0 or 30%) and multi-carbohydrase enzyme (0 or 1 mg kg-1) as main effects was utilized. For each of 16 reps, 6 pigs (60.2±2.2 kg BW) were housed in environmental chambers for 14d. Air samples were collected and analyzed for carbon dioxide (CO2); nitrous oxide (N2O); and methane (CH4). In study 2, data from study 1 and performance data obtained from a previous feeding trial were utilized in a life cycle assessment (LCA) framework that included feed production. The Holos farm model (Agriculture and Agri-Food Canada, Lethbridge. AB) was used to estimate emissions from feed production. In study 1, total manure output from pigs fed 30% wheat millrun diets was 30% greater than pigs on the 0% wheat millrun diets (P < 0.05), however, Feeding diets with 30% millrun did not affect greenhouse gas (GHG) output (CH4, 4.7, 4.9; N2O, 0.45, 0.42; CO2, 1610, 1711; mg s-1 without or with millrun inclusion, respectively; P > 0.78). Enzyme supplementation had no effect on GHG production (CH4, 4.5, 5.1; N2O, 0.46, 0.42; CO2, 1808, 1513; mg s-1 without or with enzymes, respectively; P > 0.51). In study 2, the LCA indicated that the inclusion of 30% wheat millrun in diets for growing pigs resulted in approximately a 25% reduction in GWP when compared to the no wheat millrun diets. Our results demonstrate that 30% wheat millrun did not increase GHG output from the pigs, and thus the inclusion of wheat millrun in diets of growing pigs can reduce the GWP of pork production.

Lactobacillus and Bacillus probiotics may serve as an alternative to antibiotics in milk replacer for pre-ruminant calves by altering gastrointestinal microflora to prevent the proliferation of harmful bacteria. However, there are limited studies evaluating their impact on calf growth and efficiency. The objective of this trial was to discover the impact of probiotic-containing milk replacer on pre-ruminating calf growth performance. A total of 44 pre-ruminant calves (50% Angus/50% Holstein, average weight 39.3 kg + 7.5 kg) were fed milk replacer with either no probiotic or 1.25x10^9 colony forming units/head/day of a probiotic blending containing Lactobacillus and two different Bacillus species (Church & Dwight Animal Nutrition (Princeton, NJ). Calves were blocked by age and randomly assigned within block to one of two treatments in a randomized complete block design. Calf was the experimental unit, with 22 calves per treatment. Calf weight and hip height was measured on d 0 and 30 to calculate average daily gain (ADG) and average growth per day. Calves were offered 1.36 kg milk replacer [15% dry matter (DM)] twice daily and up to 0.5 kg starter feed (88% DM) once daily. Refusals were recorded to calculate average daily intake and gain to feed ratio (G:F). Initial weight differed (P = 0.020) between treatments, and was therefore used as a covariate in all response criteria. Calves fed milk replacer with probiotic had greater (P < 0.05) ADG (0.53 vs. 0.42 kg/d, respectively) and G:F (0.50 vs. 0.41, respectively) than those fed the control. There was no evidence (P >0.05) that probiotic inclusion impacted hip height on d 30 or daily intake. In summary, Lactobacillus and Bacillus probiotic inclusion in milk replacer improved calf growth performance without impacting intake. Subsequent research is warranted to elucidate mode of action and evaluate impact relative to an antibiotic-containing positive control.

One of the leading challenges facing the swine industry in recent years that will likely continue has been assembling a talented work force that can consistently execute farm protocols. Talented labor is difficult to find and animal husbandry is becoming a lost art. One production task that particularly requires skill is timely detection of estrus in gilts and sows. While recruiting and training talented people must remain a priority, it is important to pursue solving these problems such as estrus detection by other means, and technology utilization offers a viable path forward. Camera technologies have the potential to not only reduce the need for skilled labor to assess signs of estrus, but improve the ability to inseminate in a timely manner prior to ovulation, which could lead to improved fertility and a reduction in total sperm per mating. Several studies have been conducted to evaluate the use of infrared thermal cameras for detecting body surface temperature changes in sows. Variations in anatomical location, external ambient temperature, skin moisture, and camera technology used all have the potential to impact the applicability of those measurements. There is some evidence in the literature that vulva surface temperature or, perhaps more interesting, its relationship with other anatomical body surface locations may offer predictability of the onset of estrus and warrants additional research. It is also generally accepted that sow behavior and activity level changes, especially in the presence of boars, during the onset of estrus. Camera technologies have the ability to continuously monitor changes in temperature and behavior and offer exciting opportunities for future development.

Cereal rye, winter wheat, and winter triticale are commonly planted cover crops in corn and soybean systems and have the potential to provide early spring grazing. The three cover crops differ in growth pattern. Therefore, a study was conducted to investigate the grazing potential of the three species, including the timing of the start of grazing and nutritive value of forage as measured by growing calf gain. A 7.3 hectare field was divided into 9, 0.81-hectare paddocks. Three paddocks (n = 3 replicates per treatment) were randomly assigned to each treatment: variety not stated cereal rye, Pronghorn winter wheat, or NT11406 triticale. Pastures were seeded in Mid-September following early maturity soybean harvest and received no fertilizer. Fifty-four steers (305 kg SD ± 5 kg) were stratified by weight and assigned to one of nine groups which were then assigned to a paddock. The paddocks were split in half. Steers were turned out when forage reached a 12.7 cm height and rotated to the other half once the occupied half reached 5 cm. Grazing began April 3 for rye pastures and April 9 for triticale and wheat pastures. Two groups of cattle grazing rye were pulled April 29 due to limited forage. All remaining cattle were pulled May 8 to allow for soybean planting. Throughout the grazing period pre and post-graze biomass did not differ (P ≥ 0.36) among treatments. Average daily gain did not differ among treatments (P = 0.88) averaging 1.79, 1.86, 1.84 kg/day for rye, wheat and triticale, respectively. Likewise, gain per hectare did not differ (P = 0.80) among treatments with 378, 399, 394 kg/ha for rye, wheat, and triticale, respectively. Rye offered grazing a full week before triticale and wheat, but all three small grain cereal species resulted in desirable animal performance.

The objective was to determine effects of interlocking rubber floor matting in slatted indoor cattle feeding facilities on cattle locomotion. In experiment 1, Fall-born Angus × Simmental steers (N = 206; BW = 228 ± 34 kg) were blocked by weight and assigned to 32 pens. Pens were randomly assigned to 1 of 4 treatments: new Max Grip Animat matting (MG), new Animat Pebble matting (PEB), old Animat Pebble matting (OLD), and no matting/concrete slating (CONC). Steers were fed a common diet for 209 d with an average stocking density of 3.70 m2 per steer. Locomotion scores were assigned by two trained staff using a 0–3 scale of the Step-Up® Locomotion Scoring System (Zinpro, Eden Prairie, MN) throughout both experiments. There was no treatment by day interaction (P = 0.88) observed. Treatment affected (P < 0.01) locomotion scores with CONC being the greatest and MG, PEB, and OLD being lesser and not different from each other. Locomotion scores also increased (P < 0.01) over time. In experiment 2, Fall-born Angus × Simmental steers (n = 189; BW = 352 ± 43 kg) were blocked by weight and assigned to 21 pens. Pens were randomly assigned to 1 of 3 treatments: new Animat Pebble matting (PEB2), old Animat Pebble matting (OLD2), or no matting/concrete slating (CONC2). Steers were fed a common diet for 152 d with an average stocking density of 2.64 m2 per steer. There was no treatment by day interaction (P = 0.42) observed. However, both treatment and day affected (P ≤ 0.02) locomotion scores. Steers on CONC2 had the greatest locomotion score, while PEB2 and OLD2 were not different from each other. Locomotion scores were the greatest on d 152. Overall, results suggest new and old rubber floor matting improved locomotion scores of feedlot steers in slatted indoor cattle feeding facilities.

A consistent theme in swine production is to increase efficiency and reduce input costs. In this study, sow activity traits and lesions were analyzed to identify associations with lameness and gilt retention. Gilts (n = 73) were culled based on structural unsoundness as determined by an experienced herdsman. Females (n = 132) that had been retained for breeding, but either did not show estrus at an appropriate age or were excessed due to limited farrowing space were used as controls. Gilts were recorded with the NUtrack System for 1 week prior to selection. The NUtrack System records distance travelled (m), time standing (s), eating (s), and laying (s), angle rotated (degrees) and average speed (m/s). Animals were humanely harvested in a USDA inspected abattoir. Both ends of the humerus and the femur head were evaluated for osteochondrosis or osteoarthritis lesions. Joint lesions were categorized as Major or Minor lesions. Major lesions were severe osteochondrosis lesions where cartilage was severely fractured or cartilage exhibited a region of necrosis larger than 2 millimeters in diameter. Minor lesions were defined creases or indentations in the cartilage or where abnormal blood flow existed in bone tissue underneath cartilage. Ninety-eight animals were identified with minor or major lesions (28 cull and 70 control). Unexpectedly, chi-square analysis did identify control animals as having higher incidences of minor or major lesions than cull animals (p < 0.05). Data were analyzed using logistic regression (RStudio V1.2.5033) with farrowing group included in the model. No NUtrack trait was predictive of joint lesions (P > 0.1). However, time standing (P < 0.001) and average speed (P < 0.05) were significantly associated with being retained for breeding. These data suggest that animal behavior and movement, as analyzed by NUtrack, can enhance herdsman efforts in making culling decisions of breeding animals.

An experiment was conducted to determine the effects of the initial nursery diet budget on growth performance. A total of 3,264 pigs (initial BW = 5.5 kg), placed in pens with 51 pigs each, were used in a 45-d trial. There were 4 treatments consisting of different feed budgets of the initial nursery diet: 4.1 kg, 5.4 kg, 6.8 kg, or 8.2 kg. The experimental diet was corn, soybean meal, and whey permeate-based and contained 1.38% SID Lys. After the allocated budget was consumed, pigs were provided a common corn and soybean meal-based diet. There were 16 replicates per treatment. Pigs were weighed weekly to calculate ADG, ADFI, and G:F. Data were analyzed with SAS MIXED procedure. In the first 14 d of the trial there was no evidence for differences (P > 0.10) in growth performance as all pigs were receiving their allocated budget of the initial diet. From d 14 to 21 as well as d 0 to 21, pigs that received a budget of 6.8 or 8.2 kg had improved ADG (quadratic, P < 0.05) and G:F (linear, P < 0.05) compared to those fed budgets of 4.1 or 5.4 kg. From d 21 to 45, when all pigs received a common diet, there was no evidence for differences (P > 0.10) in ADG. However, there was a linear response (P < 0.05) in G:F, with pigs previously fed the lowest feed budget presenting improved G:F. Overall (d 0 to 45), there was an improvement (linear, P < 0.05) in ADG and ADFI as feed budgets increased, with the best performance observed when pigs were fed 6.8 or 8.2 kg of the initial nursery diet. In conclusion, providing a 6.8 or 8.2 kg budget of the initial nursery diet resulted in improved overall nursery performance.

Yearling beef steers (n = 238; initial BW=402 ± 31.2 kg) were used to evaluate a Bacillus subtilis probiotic on growth performance, dietary net energy (NE) utilization, carcass characteristics, and fecal and subiliac lymph node Salmonella prevalence during a 140-d finishing period. Steers were allotted to 24 pens (n = 9 to 10 steers/pen) and assigned to one of two treatments (12 pens/treatment): no probiotic (CON) or 0.50 g·steer-1·d-1 of a Bacillus subtilis PB6 probiotic (CLOSTAT® 500, Kemin Industries, Des Moines, IA; CLO). Steers were transitioned to a 90% concentrate diet (DM basis) over 14-d. Steers were fed once daily at 0700 h; bunks were managed according to a slick bunk management. Fecal samples were collected on d 1, 28, 56, 112, and 140 from each pen (n = 5 steers/pen) via rectal palpation and composited by pen for determination of Salmonella prevalence. Upon harvest, subiliac lymph nodes were obtained from 60 steers in CON and 57 steers in CLO. Data were analyzed as a randomized complete block design; pen was the experimental unit; α of 0.05 determined significance. No differences were detected (P ≥ 0.25) between treatments for live or carcass-adjusted average daily gain, dry matter intake, gain efficiency, dietary NE utilization, nor calculated dietary NE content based upon performance. No differences were detected between treatments for any carcass traits (P ≥ 0.15). Salmonella was not recovered in any fecal samples except on d 112, where steers from CLO had a numerically lower (P = 0.17; 8.3 vs. 25.0%) incidence of fecal Salmonella compared to CON and on d 140 fecal, where Salmonella incidence did not differ (P = 0.34; 0.0 vs. 8.3%) for CON and CLO, respectively. Salmonella was not recovered in any subiliac lymph nodes. These data indicate that CLO did not influence growth performance or Salmonella prevalence.