Geometric Back-Propagation in Morphological Neural Networks

This paper provides a definition of back-propagation through geometric correspondences for morphological neural networks. In addition, dilation layers are shown to learn probe geometry by erosion of layer inputs and outputs. A proof-of-principle is provided, in which predictions and convergence of morphological networks significantly outperform convolutional networks

Reducing the Effects of PCR Amplification and Sequencing Artifacts on 16S rRNA-Based Studies

The advent of next generation sequencing has coincided with a growth in interest in using these approaches to better understand the role of the structure and function of the microbial communities in human, animal, and environmental health. Yet, use of next generation sequencing to perform 16S rRNA gene sequence surveys has resulted in considerable controversy surrounding the effects of sequencing errors on downstream analyses. We analyzed 2.7×10[superscript 6] reads distributed among 90 identical mock community samples, which were collections of genomic DNA from 21 different species with known 16S rRNA gene sequences; we observed an average error rate of 0.0060. To improve this error rate, we evaluated numerous methods of identifying bad sequence reads, identifying regions within reads of poor quality, and correcting base calls and were able to reduce the overall error rate to 0.0002. Implementation of the PyroNoise algorithm provided the best combination of error rate, sequence length, and number of sequences. Perhaps more problematic than sequencing errors was the presence of chimeras generated during PCR. Because we knew the true sequences within the mock community and the chimeras they could form, we identified 8% of the raw sequence reads as chimeric. After quality filtering the raw sequences and using the Uchime chimera detection program, the overall chimera rate decreased to 1%. The chimeras that could not be detected were largely responsible for the identification of spurious operational taxonomic units (OTUs) and genus-level phylotypes. The number of spurious OTUs and phylotypes increased with sequencing effort indicating that comparison of communities should be made using an equal number of sequences. Finally, we applied our improved quality-filtering pipeline to several benchmarking studies and observed that even with our stringent data curation pipeline, biases in the data generation pipeline and batch effects were observed that could potentially confound the interpretation of microbial community data.National Institutes of Health (U.S.) (1R01HG005975-01)National Science Foundation (U.S.) (award #0743432)National Institutes of Health (U.S.) (grant NIHU54HG004969

Peer-assisted learning in the prehospital educational setting in South Africa

Abstract:Clinical learning is an important component of health professions training. Peer-assisted learning (PAL) involves students who work in the clinical learning domain, often with their peers. There is a paucity of literature related to PAL in the South African (SA) context. Objectives. To explore the perspectives of SA prehospital emergency care personnel regarding PAL. Methods. A cross-sectional design used a purpose-designed online survey to gather data from qualified prehospital emergency care personnel. Participation was invited by emailing persons registered on a privately managed database. The questionnaire was available for 2 months after the initial email had been sent. The questionnaire used Likert-type scales to measure participant perceptions of specific aspects related to PAL. An open-ended question gathered data on participant perceptions of PAL. Results. Participants recognised PAL as a contributor to improved theoretical and practical academic performance, increased confidence, better debriefing and creating a platform for future relationships, both professionally and socially. Most participants reported a positive relationship with their PAL partners. The presence of a PAL partner made participants more comfortable during hostile or unsafe situations. Conclusions. PAL was positively viewed by participants and the environment created by PAL was perceived to enhance learning, debriefing and confidence and to improve theoretical and practical assessment results. We recommend that students are included in the PAL partner allocation process. Further research should include PAL in a larger spread of health professions in the African setting

Context matters! The relationship between mother-reported family nutrition climate, general parenting, food parenting practices and children’s BMI

Background: Efforts to explain children’s nutrition behavior or weight often involve investigating the parent-child relationship, typically studying the associations between food parenting practices (FPPs) and child outcomes. However, these behaviors are embedded in a broader system: general parenting (GP, the general emotional climate at home), and the family health climate (an aspect of the broader family system in the context of health). In the current study, we combined the parent-child measures of parenting (FPPs and GP) and the nutritional dimension of the family health climate (family nutrition climate, FNC) to get a broader view of how these concepts are interrelated. The current study had two aims: predicting FPPs using GP and FNC as predictor variables, and investigating the relationship between FPPs and children’s weight in different groups of parents, based on low and high GP and FNC scores. Methods: We collected cross-sectional data via an online survey panel. Mothers of 267 children aged 5–12 years filled out a questionnaire assessing demographics (e.g., children’s weight and height), GP, FPPs, and FNC. Bivariate correlation coefficients were calculated between all constructs. Structural equation modeling was performed to test the hypothesized relationships between GP, FNC and FPPs. Hereafter, different groups of parents were identified, using median split, based on a low or high score on GP or a low or high score on FNC. Bivariate correlation coefficients were calculated between FPPs and children’s BMI z-score for these different groups. Results: GP and FNC were consistently positively correlated (all r’s ≥.177), and both concepts were positively associated with healthy FPPs (all r’s ≥.214). In families with a positive context (i.e. scoring high on GP and on FNC), healthy FPPs were associated with lower BMI z-scores of the children (r -.229). This association was not found for children with a more negative family context. Conclusions: FNC and GP are valuable additional concepts to investigate relationships between FPPs and child outcomes. We recommend that more studies, next to investigating the parent-child system, include a measure of the broader family system, in order to get a broader view of the mechanisms explaining child health behaviors and weight status

Tracking of structural and functional cardiac measures from infancy into school-age

Objective Cardiac structure and function are important predictors for cardiovascular disease in adults. Not much is known about tracking of cardiac measures, other than left ventricular mass, from early life onwards. We examined whether and to what extent cardiac measures track from infancy into school-age. Methods We performed a population-based prospective cohort study among 1072 children. Aortic root diameter, left atrial diameter, left ventricular mass, relative wall thickness and fractional shortening were measured repeatedly by echocardiography. We explored tracking between infancy (1.5, six and 24 months) and school-age (six and 10 years). Results Of all cardiac measures, aortic root diameter, left atrial diameter and left ventricular mass were significantly correlated between infancy and school-age (r = 0.10-0.42, all p-values < 0.01), with the strongest correlations between 24 months and 10 years. Of the different structures, aortic root diameter showed the strongest correlations. Approximately 30% of children who were in the lowest or highest quartile of a measure at the age of 1.5 months remained in that quartile at the age of 10 years. When analysing the effects of the infant cardiac measures on the same outcomes at 10 years in conditional regression models, we observed ef

Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study

Fecal microbiota transplant is increasingly used to treat recurrent or relapsing Clostridium difficile infection. In this randomized controlled study, using a frozen inoculum from unrelated donors was safe and effective, whether administered by nasogastric tube or by colonoscopy. Background. Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration. Methods. Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires. Results. A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2–16) relapses prior to study enrollment, with 5 (range, 3–15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5–10) the day prior to FMT to 2 (IQR, 1–2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2–6) before transplant to 8 (IQR, 5–9) after transplant. No serious or unexpected adverse events occurred. Conclusions. In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration. Clinical Trials Registration. NCT01704937.National Institute of Allergy and Infectious Diseases (U.S.) (HHSN272200900018C)

Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

Contains fulltext : 109282.pdf (publisher's version ) (Open Access)BACKGROUND: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD). The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial. METHODS/DESIGN: This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, alpha1-microglobulin, KIM-1, H-FABP, MCP-1) and serum (fibroblast growth factor 23) biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed. DISCUSSION: We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response. TRIAL REGISTRATION NUMBER: Clinical trials.gov NCT01354405

The Human Microbiome Project: A Community Resource for the Healthy Human Microbiome

The Human Microbiome Project (HMP) [1],[2] is a concept that was long in the making. After the Human Genome Project, interest grew in sequencing the “other genome" of microbes carried in and on the human body [3],[4]. Microbial ecologists, realizing that >99% of environmental microbes could not be easily cultured, developed approaches to study microorganisms in situ [5], primarily by sequencing the 16S ribosomal RNA gene (16S) as a phylogenetic and taxonomic marker to identify members of microbial communities [6]. The need to develop corresponding new methods for culture-independent studies [7],[8] in turn precipitated a sea change in the study of microbes and human health, inspiring the new term “metagenomics" [9] both to describe a technological approach—sequencing and analysis of the genes from whole communities rather than from individual genomes—and to emphasize that microbes function within communities rather than as individual species. This shift from a focus on individual organisms to microbial interactions [10] culminated in a National Academy of Science report [11], which outlined challenges and promises for metagenomics as a way of understanding the foundational role of microbial communities both in the environment and in human health.National Institutes of Health (U.S.) (grant U54HG004969)National Institutes of Health (U.S.) (grant U54HG004973)National Institutes of Health (U.S.) (grant U54AI084844)National Institutes of Health (U.S.) (grant U01HG004866)National Institutes of Health (U.S.) (grant R01HG005969)National Institutes of Health (U.S.) (grant R01HG004872)United States. Army Research Office (grant W911NF-11-1-0473)National Science Foundation (U.S.) (NSF DBI-1053486)Howard Hughes Medical Institute (Early Career Scientist

The Treatment-Naive Microbiome in New-Onset Crohn\u27s Disease

Inflammatory bowel diseases (IBDs), including Crohn\u27s disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD