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Introduction: Endometriosis has a negative effect on health-related quality of life (HRQoL), wellbeing and daily functioning. Endometriosis is an under-researched condition within non-western populations. Cultural representations are needed to understand the relative roles of societal norms, traditional factors, and religious sensitivities on the impact of endometriosis on HRQoL in various populations. In particular, there is a lack of emphasis placed in understanding the association of HRQoL on endometriosis in Arab women.Method: In this prospective case-control study, 2,610 Arab ancestry women in the United Arab Emirates were recruited to investigate the impact of endometriosis on HRQoL, diagnostic delay, psychological co-morbidities, work productivity, and physical activity. Participants completed the following standardized, validated questionnaires: Short Form-36 version 2 questionnaire, the World Endometriosis Research Foundation EPHect minimum clinical questionnaire version, and Work Productivity and Activity Impairment questionnaire. Translations to the Arabic language, validated using the forward-backward translation method, of the questionnaires were utilized.Results: HRQoL scores were significantly impaired in women with endometriosis, as demonstrated in the Physical Composite Scores and Mental Composite Scores in the symptomatic control group (p = 0.001; p = 0.003, respectively) and the asymptomatic control group (p < 0.001; p < 0.001, respectively). Susceptibility and severity of multiple pain syndromes and infertility in women with endometriosis was the main indicator of lower HRQoL. Anxiety (p = 0.007) and depression (p = 0.005) were significantly associated with endometriosis, in comparison to symptomatic controls. The average diagnostic delay was 11.61 years, however single women experience 15.81 years of diagnosis delay, with approximately 18% (n = 15) of the single women experiencing more than a 20-year delay in diagnosis. The intensity of physical activity was not associated with endometriosis, when compared to symptomatic (p = 0.405) or asymptomatic controls (p = 0.144).Conclusion: For the first time, we provide evidence from a combined hospital, clinic, and population-based study that Arab women with endometriosis experience significant impacts on HRQoL, substantial diagnostic delay after the onset of symptoms, significant association to psychological disorders (anxiety and depression), and a negative impact on work productivity. Future research must focus on understanding the personal and culturally centered beliefs of Arab women to ensure a positive HRQoL trajectory by improving diagnosis and management strategies.

Endometriosis is a chronic condition affecting ~10% of women globally. Little is known about the impact of the coronavirus disease 2019 (COVID-19) pandemic on their care. This brief report is aimed to explore the impact of COVID-19 on the care of people with endometriosis around the world, their priorities in relation to their clinical care during and coming out of the pandemic, and whether they believed that endometriosis makes them more vulnerable to COVID-19. An internet-based survey collected data in five languages between May 11, 2020, and June 8, 2020. Only participants with a surgical or radiological diagnosis of endometriosis aged 18 years or over were included. A total of 6,729 eligible respondents completed the survey with 80.7% [95% CI (79.7, 81.6)] reporting a negative impact on their care. This included difficulties obtaining medication (20.3%), cancelled/postponed gynaecology appointments (50.0%), and cancelled/postponed procedures (37.2%). More than half worried that their endometrioses make them more vulnerable to COVID-19 [54.2%; 95% CI (53.0, 55.4)]. The top three priorities were remarkably consistent around the world: contact with gynaecologists, knowing when procedures would be performed, and support with mental health (20.3% prioritising this aspect during the pandemic and 13.0% as restrictions begin to ease). This study shows the substantial impact the COVID-19 pandemic has had on people with endometriosis and describes how they would like care prioritised moving forwards. The findings regarding significant support needs for mental health add further weight to the growing recognition of attending to such issues as part of good patient-centred care.

©2014 by American Society for Reproductive Medicine.Objective: To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis. Desig

To establish the concurrent validity, acceptability, and sensor optimization of a consumer-grade, wearable, multi-sensor system to capture quantity and quality metrics of mobility and upper limb movements in stroke survivors. Single-session, cross-sectional. Clinical research laboratory. Thirty chronic stroke survivors (age 57 (10) years; 33% female) with mild to severe motor impairments participated. Not Applicable. Participants donned 5 sensors and performed standardized assessments of mobility and upper limb (UL) movement. True/false, positive/negative time in active movement for the UL were calculated and compared to criterion-standards using an accuracy rate. Bland-Altman plots and linear regression models were used to establish concurrent validity of UL movement counts, step counts, and stance time symmetry of MiGo against established criterion-standard measures. Acceptability and sensor optimization were assessed through an end-user survey and decision matrix. Mobility metrics showed excellent association with criterion-standards for step counts (video: r =0.988, P <.001, IMU: r =0.921, P <.001) and stance-time symmetry (r =0.722, P <.001). In the UL, movement counts showed excellent to good agreement (paretic: r =0.849, P <.001, nonparetic: r =0.672, P <.001). Accuracy of active movement time was 85.2% (paretic) and 88.0% (nonparetic) UL. Most participants (63.3%) had difficulty donning/doffing the sensors. Acceptability was high (4.2/5). The sensors demonstrated excellent concurrent validity for mobility metrics and UL movements of stroke survivors. Acceptability of the system was high, but alternative wristbands should be considered. [ABSTRACT FROM AUTHOR]

Uterine leiomyomata (UL) or fibroids are neoplasms of the uterine smooth muscle associated with heavy menstrual bleeding and other female reproductive tract morbidity. Here, the authors identify eight previously undescribed genetic loci for UL and further look into genetic overlap with heavy menstrual bleeding and endometriosis.

Abstract Background Metal sensitivity as a cause for painful joint replacement has become increasingly prevalent; however, there is a lack of reported clinical outcome data from total knee arthroplasty patients with metal allergies. The purpose of this study was to determine whether patients presenting with a painful total knee arthroplasty with a positive metal sensitivity have improved outcomes following revision to a hypoallergenic implant. Methods A retrospective review was conducted for patients that underwent a revision total knee arthroplasty after metal sensitivity testing over a 3-year period from January 1, 2015, to December 31, 2017. Based on the results of sensitivity testing, patients underwent revision total knee arthroplasty to a hypoallergenic component or a standard component. Following revision, patients returned to the clinic at an interval of 6 weeks, 5 months, and 12 months for functional, pain, and satisfaction assessment. Outcomes were compared within and between sensitivity groups. Results Of the included patients, 78.3% (39/46) were positive for metal sensitivity. The most common metal sensitivity was to nickel (79.5%, 32/39). Both non-reactive and reactive patients significantly improved in range of motion after revision arthroplasty. The reactive group saw a 37.8% decrease in pain at 6 weeks post-revision (p

Abstract Background There is lack of population level data on prevalence and distribution of common benign women’s health conditions such as endometriosis, uterine fibroids, polycystic ovary syndrome from the Eastern Mediterranean region despite their significant consequences on quality of life. In particular, there is complete absence of any health statistics from Northern Cyprus, which is an emerging region in Europe. The Cyprus Women’s Health Research (COHERE) Initiative is the first large-scale cross-sectional study in the region, aiming to determine the relative burden of benign women’s health conditions and related co-morbidities in women living in Northern Cyprus. Methods The COHERE Initiative is a cross-sectional study aiming to recruit 8000 women aged 18–55 years and residing for at least the past 5 years in Northern Cyprus. The study is composed of two main steps: (1) Baseline recruitment, including (i) completion of a detailed health questionnaire, which is an expanded version of the World Endometriosis Research Foundation (WERF) Endometriosis Phenome Harmonisation Project (EPHect) standardised questionnaire, including questions on demographics, menstrual history, hormone use, pregnancy, pain (pelvic pain, bladder and bowel pain, migraine), medical history, family history of illnesses, medication use, life-style factors in relation to a wide range of reproductive and endocrine conditions, resource use (ii) measurement of weight, height, waist/hip circumference and blood pressure, (iii) collection of saliva samples for genotyping. (2) Gynaecology clinic follow up, including a pelvic ultrasound scan (USS). There is also a follow-up food frequency questionnaire (FFQ) targeted to all women taking part in the baseline recruitment with an aim to collect more detailed data on dietary habits. Discussion The COHERE Initiative will generate prevalence rates for conditions, define the clinical profiles for women’s health conditions, and estimate the economic burden of these conditions in Northern Cyprus. The results will also provide insights into the current status of health-care among women living in a currently under-investigated region. The genetic findings will inform future gene mapping studies for investigation of the heritable component of conditions in this population/region. Moreover, the results will be compared with other centres collecting data using EPHect tools globally and will help determine population differences and similarities in disease patterns and clinical profiles. The COHERE Initiative will serve as a resource to conduct hypothesis-driven follow-up studies investigating effect of the ‘Mediterranean life-style’ as well as genetic factors on common benign women’s health conditions that maybe specific to Eastern Mediterranean populations.

District heating systems have a great potential for supporting the energy transition towards a renewa-ble energy system, and could also be an option in less dense populated urban districts and rural communities with a medium heat density. In these cases, distributed thermal energy storages at each building could improve the overall system performance by enabling a leaner sizing of the piping sys-tems due to peak-shaving and reducing the heat losses of the distribution grid. But how can distribut-ed storages already be considered within the design of the district heating network itself? And what are the quantitative benefits with respect to the district heating piping system? This paper answers these questions and presents an open-source optimisation approach for designing the piping network of a district heating system. This includes the optimisation of the network topology, the dimensioning of the pipes, and the consideration of distributed storage options. A linear mixed-integer program-ming model with a high spatial resolution including heat storages at each customer has been imple-mented. Within the QUARREE100 project, the approach is demonstrated on a real world case of an existing district with 129 houses in the provincial town Heide in Northern Germany. In the scenario with 1 m³ heat storages, the thermal losses of the district heating network can be reduced by 10.2 % and the total costs by 13.1 %.

Introduction: High prevalence of gynecological conditions in women of Middle Eastern origin is reported, likely due to regional risk factors and mediators. The objective of this systematic review and meta-analysis is to investigate the prevalence of polycystic ovary syndrome (PCOS), endometriosis, uterine fibroids, and adenomyosis in women of Middle Eastern origin.Methods: MEDLINE, EMBASE, PsycINFO, Global Health, and Google Scholar databases were searched from database inception until 14 February 2021 to identify relevant studies. Peer-reviewed research articles that reported the prevalence of PCOS, endometriosis, uterine fibroids, and adenomyosis in the Middle Eastern population were written in English or Arabic. The primary outcome was the estimated pooled prevalence of PCOS, endometriosis, uterine fibroids, and adenomyosis in the Middle Eastern populations. The secondary outcome was to assess the evidence in the data for the presence of heterogeneity, by conducting subtype-pooled analysis of prevalence estimates of the conditions. Total weighted prevalence was calculated via Freeman–Tukey arcsine transformation and heterogeneity through the I2 statistic. Quality control was performed using GRADE criteria.Results: A total of 47 studies, 26 on PCOS, 12 on endometriosis, eight on uterine fibroids, and seven on adenomyosis, were included. The pooled prevalence of PCOS diagnosed according to the NIH criteria was 8.9% (95% CI: 6.5–11.7; prevalence range: 4.0–27.6%), with a higher prevalence from the Gulf Arab states (18.8%, 95% CI: 9.5–30.3; range: 12.1–27.6%). According to the Rotterdam criteria, the pooled prevalence of PCOS was 11.9% (95% CI: 7.1–17.7; range: 3.4–19.9%) with studies limited to the Persian and Levant regions. Endometriosis was diagnosed in 12.9% (95% CI: 4.2–25.4; range: 4.2–21.0%) of women undergoing laparoscopy, for any indication. Uterine fibroid and adenomyosis prevalence of women was 30.6% (95% CI: 24.9–36.7; range: 18.5–42.6%) and 30.8% (95% CI: 27.1–34.6, range: 25.6–37.7%), respectively. Heterogeneity was present between studies due to statistical and methodological inconsistencies between studies, and quality of evidence was low due to sample size and unrepresentative participant selection.Conclusion: This is the first review that has reported the prevalence of gynecological diseases in the Middle Eastern population, suggesting that gynecological morbidity is a public health concern. Due to the health disparities in women, further research is required to understand the relative roles of environmental and genetic factors in the region to serve as a benchmark for evaluation and comparative purposes with other populations.

The COVID-19 lockdown has significantly disrupted the higher education environment within the Netherlands and led to changes in available study-related resources and study demands of students. These changes in study resources and study demands, the uncertainty and confusion about educational activities, the developing fear and anxiety about the disease, and the implementation of the COVID-19 lockdown measures may have a significant impact on the mental health of students. As such, this study aimed to investigate the trajectory patterns, rate of change, and longitudinal associations between study resources–demands and mental health of 141 university students from the Netherlands before and during the COVID-19 lockdown. The present study employed a longitudinal design and a piecewise latent growth modeling strategy to investigate the changes in study resources and mental health over a 3 month period. The results showed that moderate levels of student resources significantly decreased before, followed by a substantial rate of increase during, lockdown. In contrast, study demands and mental health were reported to be moderate and stable throughout the study. Finally, the growth trajectories of study resources–demands and mental health were only associated before the lockdown procedures were implemented. Despite growing concerns relating to the negative psychological impact of COVID-19 on students, our study shows that the mental health during the initial COVID-19 lockdown remained relatively unchanged.

BackgroundBayesian estimation with informative priors permits updating previous findings with new data, thus generating cumulative knowledge. To reduce subjectivity in the process, the present study emphasizes how to systematically weigh and specify informative priors and highlights the use of different aggregation methods using an empirical example that examined whether observed mother-adolescent positive and negative interaction behavior mediate the associations between maternal and adolescent internalizing symptoms across early to mid-adolescence in a 3-year longitudinal multi-method design.MethodsThe sample consisted of 102 mother-adolescent dyads (39.2% girls, Mage T1 = 13.0). Mothers and adolescents reported on their internalizing symptoms and their interaction behaviors were observed during a conflict task. We systematically searched for previous studies and used an expert-informed weighting system to account for their relevance. Subsequently, we aggregated the (power) priors using three methods: linear pooling, logarithmic pooling, and fitting a normal distribution to the linear pool by means of maximum likelihood estimation. We compared the impact of the three differently specified informative priors and default priors on the prior predictive distribution, shrinkage, and the posterior estimates.ResultsThe prior predictive distributions for the three informative priors were quite similar and centered around the observed data mean. The shrinkage results showed that the logarithmic pooled priors were least affected by the data. Most posterior estimates were similar across the different priors. Some previous studies contained extremely specific information, resulting in bimodal posterior distributions for the analyses with linear pooled prior distributions. The posteriors following the fitted normal priors and default priors were very similar. Overall, we found that maternal, but not adolescent, internalizing symptoms predicted subsequent mother-adolescent interaction behavior, whereas negative interaction behavior seemed to predict subsequent internalizing symptoms. Evidence regarding mediation effects remained limited.ConclusionA systematic search for previous information and an expert-built weighting system contribute to a clear specification of power priors. How information from multiple previous studies should be included in the prior depends on theoretical considerations (e.g., the prior is an updated Bayesian distribution), and may also be affected by pragmatic considerations regarding the impact of the previous results at hand (e.g., extremely specific previous results).

Endometriosis affects 10% of women worldwide and is one of the most common causes of chronic pelvic pain and infertility. However, causal mechanisms of this disease remain unknown due to its heterogeneous presentation. In order to successfully study its phenotypic variation, large sample sizes are needed. Pooling of data across sites is not always feasible given the large variation in the complexity and quality of the data collected. The World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonization Project (EPHect) have developed an endometriosis participant questionnaire (EPQ) to harmonize non-surgical clinical participant characteristic data relevant to endometriosis research, allowing for large-scale collaborations in English-speaking populations. Although the WERF EPHect EPQs have been translated into different languages, no study has examined the cross-cultural translation and adaptation for content and face validity. In order to investigate this, we followed the standard guidelines for cross-cultural adaptation and translation of the minimum version of the EPQ (EPQ-M) using 40 patients who underwent laparoscopic surgery in Turkey and 40 women in Northern Cyprus, aged between 18 and 55. We assessed the consistency by using cognitive testing and found the EPHect EPQ-M to be comprehensive, informative, and feasible in these two Turkish-speaking populations. The translated and adapted questionnaire was found to be epidemiologically robust, taking around 30–60 min to complete; furthermore, participants reported a similar understanding of the questions, showing that common perspectives were explored. Results from the cognitive testing process led to minor additions to some items such as further descriptive and/or visuals in order to clarify medical terminology. This paper illustrates the first successful cross-cultural translation and adaptation of the EPHect EPQ-M and should act as a tool to allow for further studies that wish to use this questionnaire in different languages. Standardized tools like this should be adopted by researchers worldwide to facilitate collaboration and aid in the design and conduction of global studies to ultimately help those affected by endometriosis and its associated symptoms.

The trend toward large-scale collaborative studies gives rise to the challenge of combining data from different sources efficiently. Here, we demonstrate how Bayesian evidence synthesis can be used to quantify and compare support for competing hypotheses and to aggregate this support over studies. We applied this method to study the ordering of multi-informant scores on the ASEBA Self Control Scale (ASCS), employing a multi-cohort design with data from four Dutch cohorts. Self-control reports were collected from mothers, fathers, teachers and children themselves. The available set of reporters differed between cohorts, so in each cohort varying components of the overarching hypotheses were evaluated. We found consistent support for the partial hypothesis that parents reported more self-control problems than teachers. Furthermore, the aggregated results indicate most support for the combined hypothesis that children report most problem behaviors, followed by their mothers and fathers, and that teachers report the fewest problems. However, there was considerable inconsistency across cohorts regarding the rank order of children’s reports. This article illustrates Bayesian evidence synthesis as a method when some of the cohorts only have data to evaluate a partial hypothesis. With Bayesian evidence synthesis, these cohorts can still contribute to the aggregated results.

Two of the most commonly used solid biomass sources for fuel are wood chips and wood pellets. The calorific value and the moisture content of those biofuels determine the efficiency of the CHP and the biorefinery plants. Therefore, with the increased shift towards a biobased economy, the biomass cost and its physical properties must be precisely determined. Most of the current standards are lacking and provide neither enough details about the issues caused by the biomass heterogeneity nor with the variation in experimental practice. Phenomena such as data scattering, poor repeatability and wide uncertainty, are mostly observed during the measurements of the calorific value and the moisture content. To overcome such issues, an interlaboratory comparison between three national metrology institutes using bomb calorimetry has taken place. The comparison helped to identify the root causes behind the poor reproducibility of the wood samples. Factors such as the equilibrium moisture content of the biomass, the pellet mass, the applied pressure to form the pellet, the handling techniques and the determination errors are highlighted and analyzed. The final results paved the way to provide an enhanced detailed experimental practice where the repeatability and reproducibility have been strongly improved. Moreover, the detailed uncertainty sources and calculations are presented. It has been found that by fulfilling the recommended approach the measurement repeatability improved by up to 50–80%, while the final uncertainty improved by 10–30%. This enhancement leads to a maximum relative expanded uncertainty of around ±1% (coverage factor of k = 2 and a confidence level of 95%).

BackgroundRobotic arm therapy devices that incorporate actuated assistance can enhance arm recovery, motivate patients to practice, and allow therapists to deliver semi-autonomous training. However, because such devices are often complex and actively apply forces, they have not achieved widespread use in rehabilitation clinics or at home. This paper describes the design and pilot testing of a simple, mechanically passive device that provides robot-like assistance for active arm training using the principle of mechanical resonance.MethodsThe Resonating Arm Exerciser (RAE) consists of a lever that attaches to the push rim of a wheelchair, a forearm support, and an elastic band that stores energy. Patients push and pull on the lever to roll the wheelchair back and forth by about 20 cm around a neutral position. We performed two separate pilot studies of the device. In the first, we tested whether the predicted resonant properties of RAE amplified a user’s arm mobility by comparing his or her active range of motion (AROM) in the device achieved during a single, sustained push and pull to the AROM achieved during rocking. In a second pilot study designed to test the therapeutic potential of the device, eight participants with chronic stroke (35 ± 24 months since injury) and a mean, stable, initial upper extremity Fugl-Meyer (FM) score of 17 ± 8 / 66 exercised with RAE for eight 45 minute sessions over three weeks. The primary outcome measure was the average AROM measured with a tilt sensor during a one minute test, and the secondary outcome measures were the FM score and the visual analog scale for arm pain.ResultsIn the first pilot study, we found people with a severe motor impairment after stroke intuitively found the resonant frequency of the chair, and the mechanical resonance of RAE amplified their arm AROM by a factor of about 2. In the second pilot study, AROM increased by 66% ± 20% (p = 0.003). The mean FM score increase was 8.5 ± 4 pts (p = 0.009). Subjects did not report discomfort or an increase in arm pain with rocking. Improvements were sustained at three months.ConclusionsThese results demonstrate that a simple mechanical device that snaps onto a manual wheelchair can use resonance to assist arm training, and that such training shows potential for safely increasing arm movement ability for people with severe chronic hemiparetic stroke.

In 5 of the 6 large Dutch developmental cohorts investigated here, lower SES adolescents are underrepresented and higher SES adolescents overrepresented. With former studies clearly revealing differences between SES strata in adolescent social competence and behavioral control, this misrepresentation may contribute to an overestimation of normative adolescent competence. Using a raking procedure, we used national census statistics to weigh the cohorts to be more representative of the Dutch population. Contrary to our expectations, in all cohorts, little to no differences between SES strata were found in the two outcomes. Accordingly, no differences between weighted and unweighted mean scores were observed across all cohorts. Furthermore, no clear change in correlations between social competence and behavioral control was found. These findings are most probably explained by the fact that measures of SES in the samples were quite limited, and the low SES participants in the cohorts could not be considered as representative of the low SES groups in the general population. Developmental outcomes associated with SES may be affected by a raking procedure in other cohorts that have a sufficient number and sufficient variation of low SES adolescents.

Longitudinal data from multiple cohorts may be analyzed by Bayesian research synthesis. Here, we illustrate this approach by investigating the development of self-control between age 13 and 19 and the role of sex therein in a multi-cohort, longitudinal design. Three Dutch cohorts supplied data: the Netherlands Twin Register (NTR; N = 21,079), Research on Adolescent Development and Relationships-Young (RADAR-Y; N = 497), and Tracking Adolescents’ Individual Lives Survey (TRAILS; N = 2229). Self-control was assessed by one measure in NTR and RADAR-Y, and three measures in TRAILS. In each cohort, we evaluated evidence for competing informative hypotheses regarding the development of self-control. Subsequently, we aggregated this evidence over cohorts and measures to arrive at a robust conclusion that was supported by all cohorts and measures. We found robust evidence for the hypothesis that on average self-control increases during adolescence (i.e., maturation) and that individuals with lower initial self-control often experience a steeper increase in self-control (i.e., a pattern of recovery). From self-report, boys have higher initial self-control levels at age 13 than girls, whereas parents report higher self-control for girls.

Genetic studies have recently highlighted the importance of fat distribution, as well as overall adiposity, in the pathogenesis of obesity-associated diseases. Using a large study (n = 1,288) from 4 independent cohorts, we aimed to investigate the relationship between mean adipocyte area and obesity-related traits, and identify genetic factors associated with adipocyte cell size. To perform the first large-scale study of automatic adipocyte phenotyping using both histological and genetic data, we developed a deep learning-based method, the Adipocyte U-Net, to rapidly derive mean adipocyte area estimates from histology images. We validate our method using three state-of-the-art approaches; CellProfiler, Adiposoft and floating adipocytes fractions, all run blindly on two external cohorts. We observe high concordance between our method and the state-of-the-art approaches (Adipocyte U-net vs. CellProfiler: R2visceral = 0.94, P < 2.2 × 10-16, R2subcutaneous = 0.91, P < 2.2 × 10-16), and faster run times (10,000 images: 6mins vs 3.5hrs). We applied the Adipocyte U-Net to 4 cohorts with histology, genetic, and phenotypic data (total N = 820). After meta-analysis, we found that mean adipocyte area positively correlated with body mass index (BMI) (Psubq = 8.13 × 10-69, βsubq = 0.45; Pvisc = 2.5 × 10-55, βvisc = 0.49; average R2 across cohorts = 0.49) and that adipocytes in subcutaneous depots are larger than their visceral counterparts (Pmeta = 9.8 × 10-7). Lastly, we performed the largest GWAS and subsequent meta-analysis of mean adipocyte area and intra-individual adipocyte variation (N = 820). Despite having twice the number of samples than any similar study, we found no genome-wide significant associations, suggesting that larger sample sizes and a homogenous collection of adipose tissue are likely needed to identify robust genetic associations.

Introduction Millions of women suffer from the consequences of endometriosis and uterine fibroids, with fibroids the cause for over 50% of hysterectomies in the USA, and direct costs for their treatment estimated at between US$4 and US$9 billion. Endometriosis commonly affects millions of women worldwide predominantly during reproductive age, with severe menstrual and non-menstrual pain and subfertility the main symptoms. Due to the ‘unhappy triad’ of endometriosis—lack of awareness, lack of clinically relevant biomarkers and the unspecific nature of symptoms—women wait on average for 8–12 years before the definitive endometriosis diagnosis is made. Treatment options for both conditions are not satisfactory at the moment, especially with a view to preserving fertility for the women and families affected. In the Fibroids and Endometriosis Oxford (FENOX) study, we combine the investigation of fibroids and endometriosis, and plan to collect high-quality tissue samples and medical data of participants over a time frame of 5 years after surgical intervention.Methods and analysis Biological samples such as blood, saliva, urine, fat, peritoneal fluid and—if found—endometrial tissue or fibroids as well as detailed clinical and intraoperative data will be collected from women undergoing surgery and participating in the study after informed consent. We plan to recruit up to 1200 participants per disease arm (ie, endometriosis and uterine fibroids) over 5 years. Participants will fill in detailed and validated questionnaires on their medical history and quality of life, with follow-ups for 5 years. Enrolment started on 2 April 2018, and FENOX will close on 31 March 2028. We will analyse the biological samples using state-of-the-art molecular biology methods and correlate the findings with the medical records and questionnaire data.Ethics and dissemination The findings will be published in high-ranking journals in the field and presented at national and international conferences.Trial registration number ISRCTN13560263.

Abstract Background Systems biology takes a holistic approach by handling biomolecules and their interactions as big systems. Network based approach has emerged as a natural way to model these systems with the idea of representing biomolecules as nodes and their interactions as edges. Very often the input data come from various sorts of omics analyses. Those resulting networks sometimes describe a wide range of aspects, for example different experiment conditions, species, tissue types, stimulating factors, mutants, or simply distinct interaction features of the same network produced by different algorithms. For these scenarios, synchronous visualization of more than one distinct network is an excellent mean to explore all the relevant networks efficiently. In addition, complementary analysis methods are needed and they should work in a workflow manner in order to gain maximal biological insights. Results In order to address the aforementioned needs, we have developed a Synchronous Network Data Integration (SyNDI) framework. This framework contains SyncVis, a Cytoscape application for user-friendly synchronous and simultaneous visualization of multiple biological networks, and it is seamlessly integrated with other bioinformatics tools via the Galaxy platform. We demonstrated the functionality and usability of the framework with three biological examples - we analyzed the distinct connectivity of plasma metabolites in networks associated with high or low latent cardiovascular disease risk; deeper insights were obtained from a few similar inflammatory response pathways in Staphylococcus aureus infection common to human and mouse; and regulatory motifs which have not been reported associated with transcriptional adaptations of Mycobacterium tuberculosis were identified. Conclusions Our SyNDI framework couples synchronous network visualization seamlessly with additional bioinformatics tools. The user can easily tailor the framework for his/her needs by adding new tools and datasets to the Galaxy platform.

Abstract Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.

Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.

The goal of this study is to develop a dynamic model for a Carbon Capture (CC) process that can be integrated with a water electrolysis facility. The possibility of operating the post-combustion CC plant dynamically is investigated. The final model successfully tracks the parallel hydrogen production, providing the stoichiometric required CO2 stream for the subsequent methanol reactor. A dynamic model is used to configure controllers and to test the unit performance and stream conditions for various set points. Through the transient operation, the required feed gas is provided while optimizing the solvent and energy requirements. It is found that the slowest acting stage is the reboiler with a time constant of 3.8 h. Other process variables stabilize much quicker, requiring only a few minutes to reach steady-state conditions. The hydrogen-tracking scenario shows that the carbon capture plant can successfully operate under varying conditions with a maximum CO2 output increase of 7% of the minimum flowrate in the representative 24 h simulation time. The output CO2 stream is maintained at the desired >98% purity, 25 °C temperature, and 1.85 bar pressure, which allows to successfully perform hydrogen tracking operations.

Genome-wide association studies in the fields of reproductive medicine and endocrinology are yielding robust genetic variants associated with disease. Integrated genomic, transcriptomic, and epigenomic molecular profiling studies are common methodologies used to understand the biologic pathways perturbed by these variants. However, molecular profiling resources do not include the tissue most relevant to many female reproductive traits, the endometrium, while the parameters influencing variability of results from its molecular profiling are unclear. We investigated the sources of DNA methylation and RNA expression profile variability in endometrium (n = 135), endometriotic disease tissue (endometriosis), and subcutaneous abdominal fat samples from 24 women, quantifying between-individual, within-tissue (cellular heterogeneity), and technical variation. DNA samples (n = 96) were analyzed using Illumina HumanMethlylation450 BeadChip arrays; RNA samples (n = 39) were analyzed using H12-expression arrays. Variance-component analyses showed that, for the top 10–50% variable DNA methylation/RNA expression sites, between-individual variation far exceeded within-tissue and technical variation. Menstrual-phase accounted for most variability in methylation/expression patterns in endometrium (Pm = 7.8 × 10−3, Pe = 8.4 × 10−5) but not in fat and endometriotic tissue; age was significantly associated with DNA methylation profile of endometrium (Pm = 9 × 10−5) and endometriotic disease tissue (Pm = 2.4 × 10−5); and smoking was significantly associated with DNA methylation in adipose tissue (Pm = 1.8 × 10−3). Hierarchical cluster analysis showed significantly different methylation signatures between endometrium and endometriotic tissue enriched for WNT signaling, angiogenesis, cadherin signaling, and gonadotropin-releasing-hormone-receptor pathways. Differential DNA methylation/expression analyses suggested detection of a limited number of sites with large fold changes (FC > 4), but power calculations accounting for different sources of variability showed that for robust detection >500 tissue samples are required. These results enable appropriate study design for large-scale expression and methylation tissue-based profiling relevant to many reproductive and endocrine traits.

Abstract Background The Royal College of Ophthalmologists (RCOphth) and the College of Ophthalmology of Eastern Central and Southern Africa (COECSA) are collaborating to cascade a Training the Trainers (TTT) Programme across the COECSA Region. Within the VISION 2020 Links Programme, it aims to develop a skilled motivated workforce who can deliver high quality eye care. It will train a lead, faculty member and facilitator in 8 countries, who can cascade the programme to local trainers. Methods In phase 1 (2013/14) two 3-day courses were run for 16/17 selected delegates, by 3 UK Faculty. In phase 2 (2015/16) 1 UK Faculty Member ran 3 shorter courses, associated with COECSA events (Congress and Examination). A COECSA Lead was appointed after the first course, and selected delegates were promoted as Facilitators then Faculty Members on successive courses. They were given appropriate materials, preparation, training and mentoring. Results In 4 years the programme has trained 87 delegates, including 1 COECSA Lead, 4 Faculty Members and 7 Facilitators. Delegate feedback on the course was very good and Faculty were impressed with the progress made by delegates. A questionnaire completed by delegates after 6–42 months demonstrated how successfully they were implementing new skills in teaching and supervision. The impact was assessed using the number of eye-care workers that delegates had trained, and the number of patients seen by those workers each year. The figures suggested that approaching 1 million patients per year were treated by eye-care workers who had benefited from training delivered by those who had been on the courses. Development of the Programme in Africa initially followed the UK model, but the need to address more extensive challenges overseas, stimulated new ideas for the UK courses. Conclusions The Programme has developed a pyramid of trainers capable of cascading knowledge, skills and teaching in training with RCOphth support. The third phase will extend the number of facilitators and faculty, develop on-line preparatory and teaching materials, and design training processes and tools for its assessment. The final phase will see local cascade of the TTT Programme in all 8 countries, and sustainability as UK support is withdrawn.

Abstract The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle. Our study showed that the overall methylome remains relatively stable during this stage of the menstrual cycle, with small-scale changes affecting 5% of the studied CpG sites (22,272 out of studied 437,022 CpGs, FDR

Endometriosis is a major cause of infertility. Molecular mechanisms underlying the disease involve genetic and environmental risk factors. In a meta-analysis of eleven GWA studies, Sapkota and colleagues identify five novel risk loci, implicating steroid sex hormone pathways in the pathogenesis.

Biological, genetic, and socio-demographic factors are all important in explaining reproductive behavior, yet these factors are typically studied in isolation. In this study, we explore an innovative sociogenomic approach, which entails including key socio-demographic (marriage, education, occupation, religion, cohort) and genetic factors related to both behavioral [age at first birth (AFB), number of children ever born (NEB)] and biological fecundity-related outcomes (endometriosis, age at menopause and menarche, polycystic ovary syndrome, azoospermia, testicular dysgenesis syndrome) to explain childlessness. We examine the association of all sets of factors with childlessness as well as the interplay between them. We derive polygenic scores (PGS) from recent genome-wide association studies (GWAS) and apply these in the Health and Retirement Study (N = 10,686) and Wisconsin Longitudinal Study (N = 8,284). Both socio-demographic and genetic factors were associated with childlessness. Whilst socio-demographic factors explain 19–46% in childlessness, the current PGS explains

Flue gases from coal, gas, or oil-fired power plants, as well as many heavy industries, are claimed as primary sources of CO2 emissions. Although CO2 capture and storage can play a role in decreasing CO2, its cost is preventing it from the broad application. Converting flue gases into methanol offers a change to mitigate CO2 emissions and a way to produce useful chemicals. In this study, two novel technologies including bi- and tri-reforming are analyzed for methanol production from CO2. The environmental and economic results are examined as two significant factors for green design. Preliminary evaluations pointed out that the reforming-based routes can be considered as a hopeful method for CO2 treatment during the transition stage from a carbon-based- to the carbon-free program.

Background: INTERBIO-21st is Phase II of the INTERGROWTH-21st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.

The Earth System Governance project is a global research alliance that explores novel, effective governance mechanisms to cope with the current transitions in the biogeochemical systems of the planet. A decade after its inception, this article offers an overview of the project's new research framework (which is built upon a review of existing earth system governance research), the goal of which is to continue to stimulate a pluralistic, vibrant and relevant research community. This framework is composed of contextual conditions (transformations, inequality, Anthropocene and diversity), which capture what is being observed empirically, and five sets of research lenses (architecture and agency, democracy and power, justice and allocation, anticipation and imagination, and adaptiveness and reflexivity). Ultimately the goal is to guide and inspire the systematic study of how societies prepare for accelerated climate change and wider earth system change, as well as policy responses.