Non-specific filtering of beta-distributed data.

BackgroundNon-specific feature selection is a dimension reduction procedure performed prior to cluster analysis of high dimensional molecular data. Not all measured features are expected to show biological variation, so only the most varying are selected for analysis. In DNA methylation studies, DNA methylation is measured as a proportion, bounded between 0 and 1, with variance a function of the mean. Filtering on standard deviation biases the selection of probes to those with mean values near 0.5. We explore the effect this has on clustering, and develop alternate filter methods that utilize a variance stabilizing transformation for Beta distributed data and do not share this bias.ResultsWe compared results for 11 different non-specific filters on eight Infinium HumanMethylation data sets, selected to span a variety of biological conditions. We found that for data sets having a small fraction of samples showing abnormal methylation of a subset of normally unmethylated CpGs, a characteristic of the CpG island methylator phenotype in cancer, a novel filter statistic that utilized a variance-stabilizing transformation for Beta distributed data outperformed the common filter of using standard deviation of the DNA methylation proportion, or its log-transformed M-value, in its ability to detect the cancer subtype in a cluster analysis. However, the standard deviation filter always performed among the best for distinguishing subgroups of normal tissue. The novel filter and standard deviation filter tended to favour features in different genome contexts; for the same data set, the novel filter always selected more features from CpG island promoters and the standard deviation filter always selected more features from non-CpG island intergenic regions. Interestingly, despite selecting largely non-overlapping sets of features, the two filters did find sample subsets that overlapped for some real data sets.ConclusionsWe found two different filter statistics that tended to prioritize features with different characteristics, each performed well for identifying clusters of cancer and non-cancer tissue, and identifying a cancer CpG island hypermethylation phenotype. Since cluster analysis is for discovery, we would suggest trying both filters on any new data sets, evaluating the overlap of features selected and clusters discovered

Dietary treatment of Crohn’s disease: perceptions of families with children treated by exclusive enteral nutrition, a questionnaire survey

Background: Diet is strongly associated with the aetiology of Crohn’s Disease (CD) and exclusive enteral nutrition (EEN) is the primary induction treatment in paediatric CD. This study explored opinions around the use of EEN and alternative novel, solid food-based diets (SFDs) expressed by paediatric patients with CD, previously treated with EEN and their parents. Methods: This anonymous questionnaire surveyed families of CD patients treated with EEN over 1 year. Two questionnaire forms were completed; one asking the patients’ opinions and another referring to their main carer. This questionnaire explored participants’ demographic characteristics; acceptability of a repeat EEN course to treat a future flare (EEN repeat); their opinion on how difficult EEN would be compared to an example SFD; and their intention to participate in a future clinical trial assessing the therapeutic efficacy of an SFD in CD. Results: Forty-one families of CD patients were approached with 29 sending replies (71%). Most of our participants were positive on completing another EEN course, however the majority would choose an SFD alternative (Patients: 66, Parents:72%). Both patients and their parents rated EEN to be more difficult to adhere to compared to an example SFD (p < 0.05), and their ratings were strongly correlated (EEN:r = 0.83, SFD:r = 0.75, p < 0.001). The majority of our respondents would agree to participate in a clinical trial assessing an SFD’s effectiveness (Patients:79, Parents:72%) for the management of active CD. Conclusions: While patients with CD and their families would accept an EEN repeat, the majority would prefer an SFD alternative. CD families surveyed are supportive of the development of solid food-based dietary treatments

Effect of two semesters of small group problem-based learning (PBL) on expectations of physician assistant students regarding self, others, and facilitator using the PBL Readiness Questionnaire

Purpose: The purpose of this study was to assess changes in expectations and perceptions among physician assistant (PA) program matriculants regarding small group problem-based learning (PBL) from the beginning to the end of the first didactic year. Some of the stress experienced by students entering health science professional programs using PBL may be due to lack of awareness of the goals and norms of PBL which differ from those of traditional lecture-based curricula. A change in student expectations as a result of participation in PBL would indicate that these goals and norms can be learned through participation. Methods: The authors developed the PBL Readiness Questionnaire, a 71-item 10-point Likert scale regarding student expectations of the PBL experience regarding self, others and the facilitator. Questionnaire items were developed using data from a student survey as well as literature on characteristics associated with successful performance in a PBL setting. The questionnaire was administered to 60 PA students at the beginning of the first year fall semester and again at the end of the first year spring semester. Results: Analysis revealed a significant change from pre to posttest on total score as well as on the subscales of Expectations of Self and Expectations of Facilitators. The subscale of Expectations of Others approached significance. Conclusions: The change in Expectations of Facilitator may reflect the different role of facilitator vs. lecturer. Facilitators challenge physician assistant students with questions rather than providing information. The change in Expectations of Self could indicate that physician assistant students do not have accurate expectations of their own role in this type of group setting, and the experience of participating in PBL may positively affect their expectations. An area for future study would be a psychometric analysis of the questionnaire items in order to refine the tool and ascertain the reliability and validity of items and subscales

The effect of prednisolone on endometrial uterine NK cell concentrations and pregnancy outcome in women with reproductive failure. A retrospective cohort study

This retrospective study of prospectively collected data examines the effect of prednisolone therapy on raised uterine Natural Killer cell (uNK) concentrations and pregnancy outcomes in women with recurrent miscarriage (RM) and recurrent implantation failure (RIF) after IVF/ICSI treatment. 136 women diagnosed with RRF who had a timed midluteal endometrial biopsy taken for uNK cell analysis were included. Women with high uNK cell concentrations (n = 45) were treated with prednisolone (10 mg/day) for one month, after which a second biopsy was taken for repeat uNK cell analysis. Women for whom prednisolone caused a decrease in uNK cell concentrations continued on prednisolone until 12 weeks of pregnancy. Pregnancy outcomes (live birth, miscarriage and implantation rates) and pregnancy complications were compared for women who received prednisolone and those who did not. Results showed that the prevalence of high uNK cells was 33.1%. Prednisolone significantly decreased the uNK cell concentration (P < 0.001), however reduction to normal limits was achieved in only 48.3% of patients. There was no difference in any of the pregnancy outcomes or complications between women who had received prednisolone and those who had not. In conclusion, this study showed a relatively high prevalence of raised uNK cells in women with recurrent reproductive failure and confirmed the effect of prednisolone on reducing uNK cell concentrations. We found however no evidence for a significant beneficial effect for prednisolone therapy on pregnancy outcomes. Until the results of an adequately powered RCT become available however, these findings should be considered preliminary

Measurement of uterine natural killer cell percentage in the periimplantation endometrium from fertile women and women with recurrent reproductive failure: establishment of a reference range

Background Uterine natural killer cells are the major leukocytes present in the periimplantation endometrium. Previous studies have found controversial differences in uterine natural killer cell percentage in women with recurrent reproductive failure compared with fertile controls. Objective We sought to compare the uterine natural killer cell percentage in women with recurrent reproductive failure and fertile controls. Study Design This was a retrospective study carried out in university hospitals. A total of 215 women from 3 university centers participated in the study, including 97 women with recurrent miscarriage, 34 women with recurrent implantation failure, and 84 fertile controls. Endometrial biopsy samples were obtained precisely 7 days after luteinization hormone surge in a natural cycle. Endometrial sections were immunostained for CD56 and cell counting was performed by a standardized protocol. Results were expressed as percentage of positive uterine natural killer cell/total stromal cells. Results The median uterine natural killer cell percentage in Chinese ovulatory fertile controls in natural cycles was 2.5% (range 0.9-5.3%). Using 5th and 95th percentile to define the lower and upper limits of uterine natural killer cell percentage, the reference range was 1.2-4.5%. Overall, the groups with recurrent reproductive failure had significantly higher uterine natural killer cell percentage than the controls (recurrent miscarriage: median 3.2%, range 0.6-8.8%; recurrent implantation failure: median 3.1%, range 0.8-8.3%). However, there was a subset of both groups (recurrent miscarriage: 16/97; recurrent implantation failure: 6/34) that had lower uterine natural killer cell percentage compared to fertile controls. Conclusion A reference range for uterine natural killer cell percentage in fertile women was established. Women with recurrent reproductive failure had uterine natural killer cell percentages both above and below the reference range

Preparing Nurses for Roles in End-of-Life Decision-Making

Abstract PREPARING NURSES FOR ROLES IN END-OF-LIFE DECISION-MAKING by Susan K. Laird, MSN, RN Purpose: This DNP quality improvement project provided an educational intervention for senior nursing students to facilitate learning better ways to support patients and families dealing with end-of-life decision-making. Background/Significance: Aging patients often present with multiple co-morbidities, yet fewer than 37% of patients have advance directives in place and have made their wishes known to family members who will be faced with end-of-life decisions. On the front lines with dying patients and family members, nurses are poised to provide information and support to this population, yet they are not adequately prepared to do so. PICO: Will education and training in end-of-life issues improve nursing students’ knowledge and confidence so that they will be better prepared to provide care for patients and families facing end-of-life decision-making when they enter the workforce? Methods: For this quasi-experimental study, participants were given a pre-test, a classroom presentation of six original educational modules developed by the DNP student, followed by a post-test, a questionnaire and a participant evaluation. The pre/post-tests were identical, containing questions addressing attitudes and knowledge. The modules addressed cultural issues, family dynamics, and communications skills. Results: Fifty-four students participated in the class. Participants demonstrated statistically significant increases in knowledge and changes in attitudes after the educational intervention. Implications: It is the goal of this study to provide and evaluate educational materials and trainings which potentially contribute to the increase of knowledge for nursing students and for nurses already in their practice settings. By providing a broader exposure to challenges facing patients and their families facing end-of-life issues earlier in and throughout the nursing curriculum, nursing students may enter the clinical setting with increased confidence and improved comfort levels in their own abilities which may in turn lead to better overall patient care

Induced endometrial trauma (endometrial scratch) in the mid-luteal menstrual cycle phase preceding first cycle IVF/ICSI versus usual IVF/ICSI therapy: study protocol for a randomised controlled trial

Endometrial trauma commonly known as endometrial scratch (ES) has been shown to improve pregnancy rates in women with a history of repeated implantation failure undergoing in vitro fertilisation (IVF), with or without intracytoplasmic sperm injection (ICSI). However, the procedure has not yet been fully explored in women having IVF/ICSI for the first time. This study aims to examine the effect of performing an ES in the mid-luteal phase prior to a first-time IVF/ICSI cycle on the chances of achieving a clinical pregnancy and live birth. If ES can influence this success rate, there would be a significant cost saving to the National Health Service through decreasing the number of IVF/ICSI cycles necessary to achieve a pregnancy, increase the practice of single embryo transfer and consequently have a large impact on risks and costs associated with multiple pregnancies. This 30-month, UK, multicentre, parallel group, randomised controlled trial includes a 9-month internal pilot and health economic analysis recruiting 1044 women from 16 fertility units. It will follow up participants to identify if IVF/ICSI has been successful and live birth has occurred up to 6 weeks post partum. Primary analysis will be on an intention-to-treat basis. A substudy of endometrial samples obtained during the ES will assess the role of immune factors in embryo implantation. Main trial recruitment commenced on January 2017 and is ongoing.Participants randomised to the intervention group will receive the ES procedure in the mid-luteal phase of the preceding cycle prior to first-time IVF/ICSI treatment versus usual IVF/ICSI treatment in the control group, with 1:1 randomisation. The primary outcome is live birth rate after completed 24 weeks gestation. South Central-Berkshire Research Ethics Committee approved the protocol. Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences. ISRCTN23800982; Pre-results

Endometrial transcriptome in recurrent miscarriage and recurrent implantation failure

The endometrium becomes receptive to the embryo only in the mid-luteal phase, but not other stages of the menstrual cycle. Endometrial factors play an important role in implantation. Women with recurrent miscarriage and recurrent implantation failure have both been reported to have altered expression of receptivity markers during the window of implantation. We aimed to compare the gene expression profiles of the endometrium in the window of implantation among women with unexplained recurrent implantation failures (RIF) and unexplained recurrent miscarriages (RM) by RNA sequencing (RNA-Seq). In total 20 patients (9 RIF and 11 RM) were recruited. In addition 4 fertile subjects were included as reference. Endometrium samples were precisely timed on the 7th day after luteal hormone surge (LH+7). All the 24 samples were extracted for total RNA. The transcriptome was determined by RNA-Seq in first 14 RNA samples (5 RIF, 6 RM, and 3 fertile). Differentially expressed genes between RM and RIF were validated by quantitative real time PCR (qPCR) in all 24 RNA samples (9 RIF, 11 RM and 4 fertile). Complementary and coagulation cascades pathway was the significantly up-regulated in RIF while down-regulated in RM. Differentially expressed genes C3, C4, C4BP, DAF, DF and SERPING1 in complement and coagulation cascade pathway between RM and RIF were further validated by qPCR. This study identified differential molecular pathways in endometrium between RIF and RM, which potentially affect the implantation process

Assessing expectations of Physician Assistant program applicants using the Problem-Based Learning Readiness Questionnaire: Effect of a 1-hour PBL experience

Purpose: Physician Assistant (PA) programs using problem-based learning (PBL) and other self-directed learning pedagogies must inform applicants of the nature of this type of curriculum. The purpose of this study is to determine if the author-composed PBL Readiness Questionnaire can detect changes in applicant expectations of self, others, and facilitators following a one-hour PBL experience. Method: Applicants to a Physician Assistant program took part in a one-hour PBL experience as part of their admissions interview process and 729 completed the PBL Readiness Questionnaire before and after the experience. Results: Analysis of variance showed a significant increase in pre versus post total score (p = .000). Multivariate analysis of variance of pre versus post subscale scores of expectations of self, others, and facilitators was also significant (p = 0.000). Conclusions: The PBL Readiness Questionnaire significantly changed applicant expectations of self, others, and facilitators in the direction consistent with PBL pedagogy. PA programs using problem-based learning and/or other self-directed learning pedagogies could use this scale to detect changes in applicant expectations following admissions processes. Future studies could determine effectiveness of scores in predicting student outcomes. Keywords: problem-based learning, admissions, small group learning, pedagogy, case based learnin