Advanced management protocol of transanal irrigation in order to improve the outcome of pediatric patients with fecal incontinence

Background: Transanal irrigation (TAI) is employed for children with fecal incontinence, but it can present several problems which require a study of their outcomes among different patholo-gies and without a tailored work up. The aim of our study was to evaluate the effectiveness of an advanced protocol in order to tailor TAI, prevent complications, and evaluate outcomes. Methods: We included 70 patients (14 anorectal malformation, 12 Hirschsprung’s disease, 24 neurological impairment, 20 functional incontinence) submitted to a comprehensive protocol with Peristeen®: fecal score, volumetric enema, rectal ultrasound, anorectal 3D manometry, and diary for testing and parameter adjustment. Results: Among the patients, 62.9% needed adaptations to the parameters, mainly volume of irrigated water and number of puffs of balloon. These adaptations were positively correlated with pre-treatment manometric and enema data. In each group, the improvement of score was statistically significant in all cases (p 0.000); the main factor influencing the efficacy was the rate of sphincter anomalies. The ARM group had slower improvement than other groups, whereas functional patients had the best response. Conclusions: Our results showed that TAI should not be standardized for all patients, because each one has different peculiarities; evaluation of patients before TAI with rectal ultrasound, enema, and manometry allowed us to tailor the treatment, highlighting different outcomes among various pathologies, thus improving the efficacy

DeepWeeds: a multiclass weed species image dataset for deep learning

Robotic weed control has seen increased research of late with its potential for boosting productivity in agriculture. Majority of works focus on developing robotics for croplands, ignoring the weed management problems facing rangeland stock farmers. perhaps the greatest obstacle to widespread uptake of robotic weed control is the robust classification of weed species in their natural environment. the unparalleled successes of deep learning make it an ideal candidate for recognising various weed species in the complex rangeland environment. This work contributes the first large, public, multiclass image dataset of weed species from the Australian rangelands; allowing for the development of robust classification methods to make robotic weed control viable. The DeepWeeds dataset consists of 17,509 labelled images of eight nationally significant weed species native to eight locations across northern Australia. This paper presents a baseline for classification performance on the dataset using the benchmark deep learning models, Inception-v3 and ResNet-50. These models achieved an average classification accuracy of 95.1% and 95.7%, respectively. We also demonstrate real time performance of the ResNet-50 architecture, with an average inference time of 53.4 ms per image. These strong results bode well for future field implementation of robotic weed control methods in the Australian rangelands

A randomized phase I study of the safety and immunogenicity of three ascending dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults

Background: Staphylococcus aureus is a common cause of healthcare-acquired morbidity and mortalityand increased healthcare resource utilization. A prophylactic vaccine is being developed that may reducethis disease burden.Methods: Volunteers in good general health aged 50–85 (n = 312) and 18–24 (n = 96) years were random-ized to receive a single intramuscular dose of one of three dose levels of a non-adjuvanted, 3-antigen S.aureus vaccine (SA3Ag) or placebo. SA3Ag antigens included capsular polysaccharides 5 and 8 (CP5 andCP8), each conjugated to cross-reactive material 197 (CRM197), and recombinant clumping factor A (ClfA).Safety, tolerability, and immunogenicity were evaluated.Results: At day 29 post-vaccination, robust immune responses were observed in both age cohorts at allthree SA3Ag dose levels. In the primary analysis population, the 50- to 85-year age stratum, geometricmean-fold-rises in competitive Luminex® immunoassay antibody titers from baseline ranged from 29.2to 83.7 (CP5), 14.1 to 31.0 (CP8), and 37.1 to 42.9 (ClfA), all (P < 0.001) exceeding the pre-defined two-fold rise criteria. Similar rises in opsonophagocytic activity assay titers demonstrated functionality ofthe immune response. Most injection-site reactions were mild in severity and there were no substantial differences (SA3Ag vs. placebo) with regard to systemic or adverse events.Conclusions: In this study of healthy adults aged 50–85 and 18–24 years, SA3Ag elicited a rapid and robustimmune response and was well tolerated, with no notable safety concerns.Michael Nissen, Helen Marshall, Peter Richmond, Sepehr Shakib, Qin Jiang, David Cooper, Denise Rill, James Baber, Joseph Eiden, William Gruber, Kathrin U. Jansen, Emilio A. Emini, Annaliesa S. Anderson, Edward T. Zito, Douglas Girgent

Melanoma cells homing to the brain : an in vitro model

We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0 \u3bcm pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, \u3b1v\u3b23, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion

Alternative Splicing at a NAGNAG Acceptor Site as a Novel Phenotype Modifier

Approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, bypassing the deleterious stop codon can lead to a mild disease outcome. Splicing at NAGNAG tandem splice sites has been reported to result in insertion or deletion (indel) of three nucleotides. We identified such a mechanism as the origin of the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation (2623G>T) in the CFTR gene. Analyses performed on nasal epithelial cell mRNA detected three distinct isoforms, a considerably more complex situation than expected for a single nucleotide substitution. Structure-function studies and in silico analyses provided the first experimental evidence of an indel of a stop codon by alternative splicing at a NAGNAG acceptor site. In addition to contributing to proteome plasticity, alternative splicing at a NAGNAG tandem site can thus remove a disease-causing UAG stop codon. This molecular study reveals a naturally occurring mechanism where the effect of either modifier genes or epigenetic factors could be suspected. This finding is of importance for genetic counseling as well as for deciding appropriate therapeutic strategies

Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

<p>Abstract</p> <p>Background</p> <p>Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission.</p> <p>Methods/design</p> <p>The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) <abbrgrp><abbr bid="B2">2</abbr><abbr bid="B3">3</abbr></abbrgrp>. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes.</p> <p>Trial registration</p> <p>The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.</p

SME Requirements and Guidelines for the Design of Smart and Highly Adaptable Manufacturing Systems

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