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Engagement in research and publication helps medical students develop the skills to improve healthcare through evidence-based medicine. The qualitative evidence-base for the medical student experience of publishing is limited. This study aims to explore medical students' publication practices and understand their experiences of research and publication. The study is based on a mixed-methods convergent design. A survey questionnaire was distributed to medical students in UK medical schools by social media and email communication. We recruited volunteer participants through the survey and interviewed a sample whilst the survey was open. We purposively selected the sample to ensure representation from research-intensive and other universities. Survey results indicated that 21.3% (27/127) of respondents had a publication. The most common publication type was a conference abstract. The main motivation to publish was career progression and the main barriers were lack of opportunity or support to submit an article. There was no significant association between attending a research-intensive university and submitting an article. The interviews revealed that contributing to academic advancement was also a motivation to publish. Participants expressed receiving differing levels of support from supervisors and their institutions. Data from the interviews suggested that the most commonly perceived barriers identified in the survey (lack of opportunity and support to conduct and publish research) may vary in prevalence between different medical schools. Further research is required to explore how different types of support offered by medical schools affect student engagement in publishing research. [ABSTRACT FROM AUTHOR]

Objective: To define novel gene biomarkers for prognosis of head and neck squamous cell carcinoma (HNSCC) patients' survival. Study Design: Retrospective study. Setting: The Cancer Genome Atlas (TCGA) HNSCC RNA‐Seq dataset. Methods: Coexpressed gene clusters were extracted from TCGA RNA‐seq data using our previously published method (EPIG). Kaplan‐Meier estimator was then used for overall survival‐relevant analysis, with patients partitioned into 3 groups based on gene expression levels: female, male_low, and male_high. Results: Male had better overall survival than female and male with higher expression level of Y‐chromosome‐linked (Y‐linked) genes had significantly better survival than those with lower expression levels. In addition, male with a higher expression level of Y‐linked genes showed even better survival when they have a higher level of coexpressed cluster of genes related to B or T cell immune response. Other clinical conditions related to immune responses also consistently showed favorable effects on the Y‐linked genes for survival estimation. Male patients with higher expression level of Y‐linked genes also have significantly higher tumor/normal tissue (T/N) ratio of those genes and higher level of several immune responses related clinical measurements (eg, lymphocyte and TCR related). Male patients with lower expression level of Y‐linked genes benefited from radiation‐only treatment. Conclusions: The favorable role of a cluster of coexpressed Y‐linked genes in HNSCC patients' survival is potentially associated with elevated level of immune responses. These Y‐linked genes could serve as useful prognostic biomarkers for HNSCC patients' survival estimation and treatment. [ABSTRACT FROM AUTHOR]

Summary: In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between pre‐operative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 μg.l−1; functional iron deficiency as ferritin 30–100 μg.l−1 or transferrin saturation < 20%; and the remainder as non‐iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co‐primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri‐operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one‐third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre‐operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l−1, 95%CI 5.3–12.5; moderate in functional iron deficiency, mean difference 2.8 g.l−1, 95%CI −0.1 to 5.7; and with little change seen in those patients who were non‐iron deficient. Subgroup analyses did not suggest that intravenous iron compared with placebo reduced the likelihood of death or blood transfusion at 30 days differentially across subgroups according to baseline ferritin (p = 0.33 for interaction), transferrin saturation (p = 0.13) or in combination (p = 0.45), or for the number of blood transfusions (p = 0.06, 0.29, and 0.39, respectively). There was no beneficial effect of the use of intravenous iron compared with placebo, regardless of the metrics to diagnose iron deficiency, on postoperative complications or length of hospital stay. [ABSTRACT FROM AUTHOR]

Translational Relevance: Evaluation of targeted therapies is urgently needed for the majority of patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC) who progress after immunochemotherapy. Erlotinib, a targeted inhibitor of epidermal growth factor receptor pathway, lacks FDA approval in HNSCC due to inadequate tumor response. This study identifies two potential avenues to improve tumor response to erlotinib among patients with HNSCC. For the first time, this study shows that an increased erlotinib dose of 300 mg in smokers is well-tolerated and produces similar plasma drug concentration as the regular dose of 150 mg in non-smokers, with increased study-specific defined tumor response. The study also highlights the opportunity for improved patient selection for erlotinib treatment by demonstrating that early in-treatment [18]FDG PET/CT is a potential predictor of tumor response, with robust statistical correlations between metabolic changes on early in-treatment PET (4-7 days through treatment) and anatomic response measured by end-of-treatment CT. Purpose: Patients with advanced HNSCC failing immunochemotherapy have no standard treatment options. Accelerating the investigation of targeted drug therapies is imperative. Treatment with erlotinib produced low response rates in HNSCC. This study investigates the possibility of improved treatment response through patient smoking status-based erlotinib dose optimization, and through early in-treatment [18]FDG PET evaluation to differentiate responders from non-responders. Experimental design: In this window-of-opportunity study, patients with operable HNSCC received neoadjuvant erlotinib with dose determined by smoking status: 150 mg (E150) for non-smokers and 300 mg (E300) for active smokers. Plasma erlotinib levels were measured using mass spectrometry. Patients underwent PET/CT before treatment, between days 4-7 of treatment, and before surgery (post-treatment). Response was measured by diagnostic CT andwas defined as decrease inmaximumtumor diameter by ≥ 20% (responders), 10-19% (minimum-responders), and < 10% (non-responders). Results: Nineteen patients completed treatment, ten of whom were smokers. There were eleven responders, five minimum-responders, and three nonresponders. Tumor response and plasma erlotinib levels were similar between the E150 and E300 patient groups. The percentage change on early PET/CT and post-treatment PET/CT compared to pre-treatment PET/CT were significantly correlated with the radiologic response on post-treatment CTs: R=0.63, p=0.0041 and R=0.71, p=0.00094, respectively. Conclusion: This pilot study suggests that early in-treatment PET/CT can predict response to erlotinib, and treatment with erlotinib dose adjusted according to smoking status is well-tolerated and may improve treatment response in HNSCC. These findings could help optimize erlotinib treatment in HNSCC and should be further investigated. [ABSTRACT FROM AUTHOR]

Participation in European surveillance for bloodstream infection (BSI) commenced in Ireland in 1999 with all laboratories (n = 39) participating by 2014. Observational hand hygiene auditing (OHHA) was implemented in 2011. The aim of this study was to evaluate the impact of OHHA on hand hygiene compliance, alcohol hand rub (AHR) procurement and the incidence of sensitive and resistant Staphylococcus aureus and Enterococcus faecium and faecalis BSI. A prospective segmented regression analysis was performed to determine the temporal association between OHHA and outcomes. Observed hand hygiene improved from 74.7% (73.7-75.6) in 2011 to 90.8% (90.1-91.3) in 2016. AHR procurement increased from 20.1 l/ 1000 bed days used (BDU) in 2009 to 33.2 l/1000 BDU in 2016. A pre-intervention reduction of 2% per quarter in the ratio of methicillin sensitive Staphylococcus aureus BSI/BDU stabilized in the time period after the intervention (P < 0.01). The ratio of Methicillin resistant Staphylococcus aureus (MRSA) BSI/BDU was decreasing by 5% per quarter pre-intervention, this slowed to 2% per quarter post intervention, (P < 0.01). There was no significant change in the ratio of vancomycin sensitive (P = 0.49) or vancomycin resistant (P = 0.90) Enterococcus sp. BSI/BDU post intervention. This study shows national OHHA increased observed hand hygiene compliance and AHR procurement, however there was no associated reduction in BSI. [ABSTRACT FROM AUTHOR]

Aim: To refine a FTIR protocol for detection of NaOCl‐induced dentinal collagen changes using an ex vivo irrigation model, and to apply it to determine the collagen change within 0.5 mm of canal or root surfaces, with or without mature roots or periodontal involvement. Methodology: The root canals of extracted human roots were irrigated with control saline (n = 3) or 5% NaOCl (n = 3) and sectioned into transverse disks for FTIR analyses, 0.5 mm from both the canal lumen and root surface, before and after surface treatment with 17% EDTA. Amide I/phosphate and amide II/phosphate absorbance ratios were compared using the Wilcoxon sign rank test. Mature roots without periodontal involvement were irrigated with: saline (n = 7), 5% NaOCl (n = 7) or 5% NaOCl + 17% EDTA (n = 7); those with periodontal involvement (n = 7) or immature roots (n = 7) were irrigated with 5% NaOCl. Dentine disks were then prepared for FTIR analyses. The effects of irrigant/root maturity/periodontal involvement were analysed using linear mixed models. Results: FTIR analyses of the irrigated samples revealed a significant (P < 0.05) reduction in collagen bands near the canal lumen after NaOCl irrigation using surface EDTA‐treated samples. Irrigation with the test solutions resulted in significant (P < 0.0001) dentinal collagen changes in the mature roots, whilst those in the immature roots were significantly (P < 0.05) greater compared with the mature roots with or without periodontal involvement; but there was no difference between the latter groups. Conclusion: EDTA surface treatment of polished dentine surfaces enhanced FTIR detection of NaOCl‐induced collagen changes. Both root maturity and irrigation protocol influenced the ability of NaOCl to alter dentinal collagen up to 0.5 mm from the canal lumen. [ABSTRACT FROM AUTHOR]

Background: The epithelial lining of the human epididymis is critical for sperm maturation. This process requires distinct specialized functions in the head, body, and tail of the duct. These region‐specific properties are maintained by distinct gene expression profiles which are governed by transcription factor networks, non‐coding RNAs, and other factors. Materials and methods: We used genome‐wide protocols including DNase‐seq, RNA‐seq and ChIP‐seq to characterize open (active) chromatin, the transcriptome and occupancy of specific transcription factors (TFs) respectively, in caput, corpus, and cauda segments of adult human epididymis tissue and primary human epididymis epithelial (HEE) cell cultures derived from them. RNA‐seq following TF depletion or activation, combined with gene ontology analysis also determined TF targets. Results: Among regional differentially expressed transcripts were epithelial‐selective transcription factors (TFs), microRNAs, and antiviral response genes. Caput‐enriched TFs included hepatocyte nuclear factor 1 (HNF1) and the androgen receptor (AR), both of which were also predicted to occupy cis‐regulatory elements identified as open chromatin in HEE cells. HNF1 targets were identified genome‐wide using ChIP‐seq, in HEE cells. Next, siRNA‐mediated depletion of HNF1 revealed a pivotal role for this TF in coordinating epithelial water and solute transport in caput epithelium. The importance of AR in HEE cells was shown by AR ChIP‐seq, and by RNA‐seq after synthetic androgen (R1881) treatment. AR has a distinct transcriptional program in the HEE cells and likely recruits different co‐factors (RUNX1 and CEBPβ) in comparison to those used in prostate epithelium. Discussion and Conclusion: Our data identify many transcription factors that regulate the development and differentiation of HEE cells. Moreover, a comparison between immature and adult HEE cells showed key TFs in the transition to fully differentiated function of this epithelium. These data may help identify new targets to treat male infertility and have the potential to open new avenues for male contraception. [ABSTRACT FROM AUTHOR]

Market forces are increasingly forcing manufacturing companies to reduce both the time to market and the design cycle time for new products. These forces have given rise to a new engineering philosophy in which product design and manufacture take place in parallel. Successful implementation of this philosophy depends on the availability of tools which support CAD/CAM integration in a creative way. This paper proposes the use of computer aided process planning (CAPP) as a two-stage procedure: product/process analysis followed by process planning proper. Product/process analysis involves the application of design for manufacturing and assembly techniques via an effective CAD database interface. A prototype two stage computer-based process planning system for robot-based assembly applications is described. [ABSTRACT FROM AUTHOR]

This paper reviews the role of Production Activity Control (PAC) in modern production and inventory management systems. It argues that the PAC system is fundamental to the realisation of computer integrated manufacturing (CIM) at the operational or shop floor level. It presents an architecture for PAC and suggests that to date research has overemphasised one element of PAC, namely the scheduling function, and further has considered scheduling as an isolated problem without reference to the overall PAC system requirement. This, along with the tendency to consider scheduling as a combinatorial problem to be solved using mathematically elegant techniques accounts for the 'theory-practice gap' in scheduling. The paper concludes with some suggestions for further research effort in the PAC area. [ABSTRACT FROM AUTHOR]

Computer solutions have not made a very significant impact on scheduling problems. This reflects the fact that algorithmic solutions are often not appropriate for scheduling problems. Scheduling problems are more amenable to heuristic solution techniques. This paper describes a heuristic system for job scheduling in printed circuit board assembly. The main part of the system is written in Common LISP. [ABSTRACT FROM AUTHOR]

A previous paper (Browne el al. 1981) identified the decision making problems associated with job shop control and presented an objective function for measuring its performance. Given that definition of job shop control and cost- based objective function, simulation modelling offers the best prospect of a solution of the problem of providing a management tool to aid in the decision making associated with job shop control. This paper provides a detailed analysis of the design of such a model. The model, written in the GASP IV simulation language and running on a CDC 7600 computer, is based on the job shop of a major machine tool manufacturer and has been validated against actual job shop performance. [ABSTRACT FROM AUTHOR]

The paper defines batch or job shop production and reviews the functions of production planning and production control in a job shop manufacturing situation. It argues that the separation of planning and control ham resulted in the artificial isolation of the sequencing problem in job shop research. It, attempts to redefine the production control function for a job shop, now called job shop control, and discuss the activities it involves. The major decision-making problems associated with job shop control are highlighted and an objective function of costs to aid in management decision making is evolved. [ABSTRACT FROM AUTHOR]

The objectives of this study were (i) to determine whether blastocyst-induced responses in endometrial explants were detectable after 6- or 24-h co-culture in vitro; (ii) to test if direct contact is required between embryos and the endometrial surface in order to stimulate endometrial gene expression; (iii) to establish the number of blastocysts required to elicit a detectable endometrial response; (iv) to investigate if upregulation of five interferon-stimulated genes (ISGs) in the endometrium was specific to the blastocyst stage and (v) to test if alterations in endometrial gene expression can be induced by blastocyst-conditioned medium. Exposure of endometrial explants to Day 8 blastocysts in vitro for 6 or 24 h induced the expression of ISGs (MX1, MX2, OAS1, ISG15, RSAD2); expression of IFNAR1, IFNAR2, NFKB1, IL1B, STAT1, LGALS3BP, LGALS9, HPGD, PTGES, ITGB1, AKR1C4, AMD1 and AQP4 was not affected. Culture of explants in the presence of more than five blastocysts was sufficient to induce the effect, with maximum expression of ISGs occurring in the presence of 20 blastocysts. This effect was exclusive to blastocyst stage embryos; oocytes, 2-cell embryos or Day 5 morulae did not alter the relative abundance of any of the transcripts examined. Direct contact between blastocysts and the endometrial surface was not required in order to alter the abundance of these transcripts and blastocystconditioned medium alone was sufficient to stimulate a response. Results support the notion that local embryo-maternal interaction may occur as early as Day 8 of pregnancy in cattle. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To explore factors associated with negative insulin appraisals among adults with Type 2 diabetes, including perceived and experienced diabetes stigma. Methods: The second Diabetes MILES – Australia study (MILES‐2) is a national survey of adults with diabetes, focused on behavioural and psychosocial issues. Subgroup analyses were conducted on the responses of 456 adults with insulin‐treated Type 2 diabetes (38% women; mean ± sd age: 61.2 ± 8.8 years; diabetes duration: 14.5 ± 7.5 years; years using insulin: 6.4 ± 5.5). Participants completed validated measures of perceived and experienced diabetes stigma (Type 2 Diabetes Stigma Assessment Scale), insulin appraisals [Insulin Treatment Appraisal Scale (ITAS)] and known correlates of insulin appraisals: diabetes‐specific distress (Problem Areas In Diabetes scale) and diabetes‐specific self‐efficacy (Confidence in Diabetes Self‐care scale). A multiple linear regression was conducted (N = 279) to determine the contribution of those variables found to be associated with ITAS Negative scores. Results: Univariable analyses revealed negative insulin appraisals were associated with demographic and self‐care characteristics (age, employment status, BMI, years using insulin, injections per day), self‐efficacy, diabetes‐specific distress and diabetes stigma (all P < 0.01). Number of injections per day [regression coefficient [95% confidence interval]: 0.74 [0.08, 1.40]; P = 0.028], self‐efficacy [−0.12 [−0.19, −0.06]; P < 0.001] and diabetes stigma [0.39 (0.31, 0.46); P < 0.001) significantly and independently contributed to the final multivariable model, explaining 58% of the variance in ITAS Negative scores. The independent contribution of diabetes‐specific distress was suppressed following the inclusion of diabetes stigma. Conclusions: This study represents the first step in understanding the relationship between perceived and experienced diabetes stigma and negative insulin appraisals, and provides quantitative evidence for the strong, independent relationship between these two important constructs. [ABSTRACT FROM AUTHOR]

Aims To develop and validate a self-report measure designed to assess perceived and experienced stigma for adults with Type 1 diabetes: the Type 1 Diabetes Stigma Assessment Scale (DSAS-1). Methods A large item-pool (64 items) was drafted based on qualitative data from interviews with 27 adults with Type 1 diabetes. Eleven adults with Type 1 diabetes completed the draft questionnaire (responding to items using a five-point Likert scale), and participated in cognitive debriefing interviews. Based on their feedback, the item-pool was reduced and refined. Adults with Type 1 diabetes ( N=898) completed an online survey including the draft stigma questionnaire (41 items) and other validated measures. Psychometric validation included principal components analysis and confirmatory factor analysis (split samples), internal consistency reliability assessment and Spearman's rho correlations. Results Scale reduction techniques resulted in 19 items ( α=0.93). An unforced three-factor solution suggested three subscales: Treated Differently (six items, α=0.89); Blame and Judgement (six items, α=0.88); and Identity Concerns (seven items, α=0.89). This was corroborated with a confirmatory factor analysis, which demonstrated reasonable model fit with the three factors; less so for a single-factor model. Satisfactory concurrent, convergent and discriminant validity were demonstrated. Conclusions The 19-item DSAS-1 is a valid and reliable measure of the perceptions and experiences of Type 1 diabetes stigma. This novel, relatively brief measure has satisfactory psychometric properties. The DSAS-1 is now available for investigations into the nature and magnitude of the relationships between diabetes stigma and diabetes self-care behaviours and outcomes. [ABSTRACT FROM AUTHOR]

Background: Circulating miRNAs (ci-miRNAs) are endogenous, non-coding RNAs emerging as potential diagnostic biomarkers. Equine miRNAs have been previously identified including subsets of tissue-specific miRNAs. In order to investigate ci-miRNAs as diagnostic tools, normal patterns of expression for different scenarios including responses to exercise need to be identified. Human studies have demonstrated that many ci-miRNAs are up-regulated following exercise with changes in expression patterns in skeletal muscle. However, technical challenges such as haemolysis impact on accurate plasma ci-miRNA quantification, with haemolysis often occurring naturally in horses following moderateto- intense exercise. The objectives of this study were to identify plasma ci-miRNA profiles and skeletal muscle miRNAs before and after exercise in Thoroughbreds (Tb), and to evaluate for the presence and effect of haemolysis on plasma ci-miRNA determination. Resting and post-exercise plasma ci-miRNA profiles and haemolysis were evaluated in twenty 3 year-old Tbs in sprint training. Resting and post-exercise skeletal muscle miRNA abundance was evaluated in a second cohort of eleven 2 year-old Tbs just entering sprint training. Haemolysis was further quantified in resting blood samples from twelve Tbs in sprint training. A human plasma panel containing 179 miRNAs was used for profiling, with haemolysis assessed spectrophotometrically. Data was analysed using a paired Student's t-test and Pearson's rank correlation. Results: Plasma ci-miRNA data for 13/20 horses and all skeletal muscle miRNA data passed quality control. From plasma, 52/179 miRNAs were detected at both time-points. Haemolysis levels were greater than the threshold for accurate quantification of ci-miRNAs in 18/25 resting and all post-exercise plasma samples. Positive correlations (P < 0.05) between haemolysis and miRNA abundance were detected for all but 4 miRNAs, so exercise-induced changes in plasma ci-miRNA expression could not be quantified. In skeletal muscle samples, 97/179 miRNAs were detected with 5 miRNAs (miR-21-5p, let-7d-3p, let-7d-5p, miR-30b-5p, miR-30e-5p) differentially expressed (DE, P < 0.05) between time-points. Conclusions: The degree of haemolysis needs to be determined prior to quantifying plasma ci-miRNA expression from horses in high-intensity exercise training. Identification of DE miRNAs in skeletal muscle indicates modification of miRNA expression may contribute to adaptive training responses in Tbs. Using a human plasma panel likely limited detection of equine-specific miRNAs. [ABSTRACT FROM AUTHOR]

Background National guidelines state that patients with breast cancer undergoing mastectomy in England should be offered immediate breast reconstruction ( IR), unless precluded by their fitness for surgery or the need for adjuvant therapies. Methods A national study investigated factors that influenced clinicians' decision to offer IR, and collected data on case mix, operative procedures and reconstructive decision-making among women with breast cancer having a mastectomy with or without IR in the English National Health Service between 1 January 2008 and 31 March 2009. Multivariable logistic regression was used to examine the relationship between whether or not women were offered IR and their characteristics (tumour burden, functional status, planned radiotherapy, planned chemotherapy, perioperative fitness, obesity, smoking status and age). Results Of 13 225 women, 6458 (48·8 per cent) were offered IR. Among factors the guidelines highlighted as relevant to decision-making, the three most strongly associated with the likelihood of an offer were tumour burden, planned radiotherapy and performance status. Depending on the combination of their values, the probability of an IR offer ranged from 7·4 to 85·1 per cent. A regression model that included all available factors discriminated well between whether or not women were offered IR ( c-statistic 0·773), but revealed that increasing age was associated with a fall in the probability of an IR offer beyond that expected from older patients' tumour and co-morbidity characteristics. Conclusion Clinicians are broadly following guidance on the offer of IR, except with respect to patients' age. [ABSTRACT FROM AUTHOR]

Aims To examine the prevalence and correlates of suicidal ideation (SI) in a community-based sample of adults with Type 1 or Type 2 diabetes. Methods Participants were 3338 adults aged 18-70 years with Type 1 diabetes ( n = 1376) or Type 2 diabetes (non-insulin: n = 1238; insulin: n = 724) from a national survey administered to a random sample registered with the National Diabetes Services Scheme. Depression and SI were assessed using the Patient Health Questionnaire, and diabetes-specific distress with the Problem Areas In Diabetes scale. Separate logistic regression analyses by diabetes type/treatment were used to determine relative contribution to SI. Results Overall, we observed a SI rate of 14% in our sample. Participants with Type 2 diabetes using insulin reported more frequent depressive symptoms, and were more likely to report recent SI (19%) compared with those with either Type 1 diabetes or Type 2 diabetes not using insulin (14 and 12%, respectively). After controlling for depression, there was little difference in the prevalence of SI between diabetes types/treatments, but higher diabetes-specific distress significantly increased the odds of SI. Conclusions As SI is a significant risk factor for a suicide attempt, the findings have implications for healthcare professionals, pointing to the importance of adequate screening and action plans for appropriate follow-up of those reporting depression. Our findings are also indicative of the psychological toll of diabetes more generally, and the need to integrate physical and mental healthcare for people with diabetes. [ABSTRACT FROM AUTHOR]

Background: Research suggests that variation in laboratory requesting patterns may indicate unnecessary test use. Requesting patterns for serum immunoglobulins vary significantly between general practitioners (GPs). This study aims to explore GP's views on testing to identify the determinants of behaviour and recommend feasible intervention strategies for improving immunoglobulin test use in primary care.Methods: Qualitative semi-structured interviews were conducted with GPs requesting laboratory tests at Cork University Hospital or University Hospital Kerry in the South of Ireland. GPs were identified using a Health Service Executive laboratory list of GPs in the Cork-Kerry region. A random sample of GPs (stratified by GP requesting patterns) was generated from this list. GPs were purposively sampled based on the criteria of location (urban/rural); length of time qualified; and practice size (single-handed/group). Interviews were carried out between December 2014 and February 2015. Interviews were transcribed verbatim using NVivo 10 software and analysed using the framework analysis method. Emerging themes were mapped to the theoretical domains framework (TDF), which outlines 12 domains that can enable or inhibit behaviour change. The behaviour change wheel and behaviour change technique (BCT) taxonomy were then used to identify potential intervention strategies.Results: Sixteen GPs were interviewed (ten males and six females). Findings suggest that intervention strategies should specifically target the key barriers to effective test ordering, while considering the context of primary care practice. Seven domains from the TDF were perceived to influence immunoglobulin test ordering behaviours and were identified as 'mechanisms for change' (knowledge, environmental context and resources, social/professional role and identity, beliefs about capabilities, beliefs about consequences, memory, attention and decision-making processes and behavioural regulation). Using these TDF domains, seven BCTs emerged as feasible 'intervention content' for targeting GPs' ordering behaviour. These included instructions on how to effectively request the test (how to perform behaviour), information on GPs' use of the test (feedback on behaviour), information about patient consequences resulting from not doing the test (information about health consequences), laboratory/consultant-based advice/education (credible source), altering the test ordering form (restructuring the physical environment), providing guidelines (prompts/cues) and adding interpretive comments to the results (adding objects to the environment). These BCTs aligned to four intervention functions: education, persuasion, environmental restructuring and enablement.Conclusions: This study has effectively applied behaviour change theory to identify feasible strategies for improving immunoglobulin test use in primary care using the TDF, 'behaviour change wheel' and BCT taxonomy. The identified BCTs will form the basis of a theory-based intervention to improve the use of immunoglobulin tests among GPs. Future research will involve the development and evaluation of this intervention. [ABSTRACT FROM AUTHOR]

Nearly all of the annual 287,000 global maternal deaths are preventable. Hypertensive disorders of pregnancy (HDP) are among the major causes. A novel fixed-dose combination pill or polypill to prevent cardiovascular disease is a promising strategy for prevention of HDP. The aim of this study was to identify eligible candidates for a polypill for the prevention of HDP. A comprehensive review of systematic reviews on drug and dietary interventions to prevent HDP was conducted. Interventions were evaluated based on efficacy, dose, route of administration, and side effects. Fourteen interventions were assessed. Low-dose aspirin and calcium were identified as candidates for a polypill, with risk reduction estimations for pregnancy-induced hypertension and preeclampsia ranging between 10 and 62 %, depending on patient population characteristics including a priori risk, and gestation age at start of intervention. Their effect may be augmented through the addition of vitamin D, vitamin B, and folic acid. The effect and optimal composition needs to be evaluated in future trials. Given the persistent burden of maternal and perinatal mortality associated with HDP, prevention of these disorders is key-especially in low-resource settings. The polypill approach with a combination of aspirin, calcium, vitamin D, vitamin B, and folic acid is a promising strategy to improve maternal and perinatal health outcomes. [ABSTRACT FROM AUTHOR]

To compare gene expression among bovine tissues, large bovine RNA-seq datasets were used, comprising 280 samples from 10 different bovine tissues (uterine endometrium, granulosa cells, theca cells, cervix, embryos, leucocytes, liver, hypothalamus, pituitary, muscle) and generating 260 Gbases of data. Twin approaches were used: an information-theoretic analysis of the existing annotated transcriptome to identify the most tissue-specific genes and a de-novo transcriptome annotation to evaluate general features of the transcription landscape. Expression was detected for 97% of the Ensembl transcriptome with at least one read in one sample and between 28% and 66% at a level of 10 tags per million (TPM) or greater in individual tissues. Over 95% of genes exhibited some level of tissue-specific gene expression. This was mostly due to different levels of expression in different tissues rather than exclusive expression in a single tissue. Less than 1% of annotated genes exhibited a highly restricted tissue-specific expression profile and approximately 2% exhibited classic housekeeping profiles. In conclusion, it is the combined effects of the variable expression of large numbers of genes (73%-93% of the genome) and the specific expression of a small number of genes (<1% of the transcriptome) that contribute to determining the outcome of the function of individual tissues. [ABSTRACT FROM AUTHOR]