Evaluation of Bayesian point-based system on the variant classification of hereditary cancer predisposition genes.

Purpose: To assess the differences in variant classifications using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology 2015 guidelines and the Bayesian point-based classification system (here referred to as the point system) in 115 hereditary cancer predisposition genes and explore variant sub-tiering by the point system.

Methods: Germline variant classifications for 721 pediatric patients from an in-house panel were retrospectively evaluated using the 2 scoring systems.

Results: A total of 2376 unique variants were identified, with ∼23.

The role of the haematopoietic stem cell niche in development and ageing.

Blood production depends on rare haematopoietic stem cells (HSCs) and haematopoietic stem and progenitor cells (HSPCs) that ultimately take up residence in the bone marrow during development. HSPCs and HSCs are subject to extrinsic regulation by the bone marrow microenvironment, or niche. Studying the interactions between HSCs and their niche is critical for improving ex vivo culturing conditions and genetic manipulation of HSCs, which is pivotal for improving autologous HSC therapies and transplantations.

International Consensus Statement on the Radiological Screening of Contact Children in the Context of Suspected Child Physical Abuse.

Importance: Physical abuse is a common but preventable cause of long-term childhood morbidity and mortality. Despite the strong association between abuse in an index child and abuse in contact children, there is no guidance outlining how to screen the latter, significantly more vulnerable group, for abusive injuries. Consequently, the radiological assessment of contact children is often omitted, or variably performed, allowing occult injuries to go undetected and increasing the risk of further abuse.

Misattributed parentage identified through diagnostic exome sequencing: Frequency of detection and reporting practices.

Access to genetic testing, namely, diagnostic exome sequencing (DES), has significantly improved, subsequently increasing the likelihood of discovering incidental findings, such as misattributed relationships and specifically misattributed parentage (MP). Until the recently published ACMG statement, there had been no consensus for laboratories and clinicians to follow when addressing such findings. Family-based genomic testing is valuable for accurate variant interpretation but has the potential to uncover misattributed familial relationships.

Ferric iron reductases and their contribution to unicellular ferrous iron uptake.

Iron is a necessary element for nearly all forms of life, and the ability to acquire this trace nutrient has been identified as a key virulence factor for the establishment of infection by unicellular pathogens. In the presence of O, iron typically exists in the ferric (Fe) oxidation state, which is highly unstable in aqueous conditions, necessitating its sequestration into cofactors and/or host proteins to remain soluble. To counter this insolubility, and to compete with host sequestration mechanisms, many unicellular pathogens will secrete low molecular weight, high-affinity Fe chelators known as siderophores.

ACR Appropriateness Criteria® Radiologic Management of Iliofemoral Venous Thrombosis.

Iliofemoral venous thrombosis carries a high risk for pulmonary embolism, recurrent deep vein thrombosis, and post-thrombotic syndrome complicating 30% to 71% of those affected. The clinical scenarios in which iliofemoral venous thrombosis is managed may be diverse, presenting a challenge to identify optimum therapy tailored to each situation. Goals for management include preventing morbidity from venous occlusive disease, and morbidity and mortality from pulmonary embolism.

R and Shiny for Cost-Effectiveness Analyses: Why and When? A Hypothetical Case Study.

Introduction: Health economics models are typically built in Microsoft Excel owing to its wide familiarity, accessibility and perceived transparency. However, given the increasingly rapid and analytically complex decision-making needs of both the pharmaceutical industry and the field of health economics and outcomes research (HEOR), the demands of cost-effectiveness analyses may be better met by the programming language R.

Objective: This case study provides an explicit comparison between Excel and R for contemporary cost-effectiveness analysis.

Kaposi Sarcoma Inflammatory Cytokine Syndrome Presenting as Infection: A Case Report.

Kaposi sarcoma inflammatory cytokine syndrome is a rare and fatal malignancy that is challenging to treat. The syndrome appears in individuals who are both human immunodeficiency virus and human herpesvirus 8 positive. The diagnosis of disease is challenging because its presentation mimics sepsis and it has a high mortality rate.

Pilot study of global endocrine disrupting activity in Iowa public drinking water utilities using cell-based assays.

Some anthropogenic substances in drinking water are known or suspected endocrine disrupting compounds (EDCs), but EDCs are not routinely measured. We conducted a pilot study of 10 public drinking water utilities in Iowa, where common contaminants (e.g.

'Rapid transit' constipation in children: a possible genesis for irritable bowel syndrome.

Children with chronic idiopathic constipation (CIC) often end up at the surgeon when medical treatments have failed. This opinion piece discusses a recently described pattern of CIC called 'Rapid transit constipation (RTC)' first identified in 2011 as part of surgical workup. RTC was identified using a nuclear medicine gastrointestinal transit study (NMGIT or nuclear transit study) to determine the site of slowing within the bowel and to inform surgical treatment.

ACR Appropriateness Criteria Radiologic Management of Venous Thromboembolism-Inferior Vena Cava Filters.

Venous thromboembolism (VTE)-deep vein thrombosis and pulmonary embolism-is a common cause of morbidity and mortality. The mainstay of VTE prophylaxis and therapy is anticoagulation. In select patients with VTE, inferior vena cava (IVC) filters are used to prevent pulmonary embolism by trapping emboli as they pass from the lower extremity venous system through the IVC.

Creatinine-based estimation of glomerular filtration rate in patients with a Fontan circulation.

Background: Patients with a Fontan circulation are at risk of renal dysfunction. We analyzed cross-sectional data in pediatric and adult Fontan patients in order to assess the accuracy of commonly used serum creatinine-based methods in estimating glomerular filtration rate (GFR).

Methods: A total of 124 Fontan patients (58 children, 66 adults) were enrolled across three study centers.

The natural history of asymptomatic central venous catheter-related thrombosis in critically ill children.

Asymptomatic central venous catheter (CVC)-related thrombosis in children varies in incidence from 5% to 69%. The rate of acute and long-term complications, such as postthrombotic syndrome (PTS), from asymptomatic CVC-related thrombosis is unknown. This article reports the outcomes of a prospective study of 189 children in pediatric intensive care that aimed to determine the frequency of asymptomatic CVC-related thrombosis during hospital admission, and the incidence of residual CVC-related thrombosis and clinically significant PTS 2 years later.

Oxytocin receptor is regulated by Peg3.

Mouse Peg3 encodes a DNA-binding protein involved in the milk letdown process. In the current study, we tested whether PEG3 controls the expression of the oxytocin receptor gene. According to the results, PEG3 directly binds to a genomic region within the 3rd exon of Oxtr, which contains a DNA-binding motif for PEG3.

Hepatic and renal end-organ damage in the Fontan circulation: A report from the Australian and New Zealand Fontan Registry.

Background: Hepatic and renal dysfunction have been observed in survivors of the Fontan procedure, however their incidence and associated factors remain poorly defined.

Methods: A total of 152 participants from a Registry of 1528 patients underwent abdominal ultrasound, transient elastography (FibroScan), serum fibrosis score (FibroTest), in vivo Tc-99m DTPA measurement of glomerular filtration rate (mGFR), and urine albumin-creatinine ratio (ACR).

Results: Mean age and time since Fontan were 19.

Aligned Carbon Nanotube Synaptic Transistors for Large-Scale Neuromorphic Computing.

This paper presents aligned carbon nanotube (CNT) synaptic transistors for large-scale neuromorphic computing systems. The synaptic behavior of these devices is achieved via charge-trapping effects, commonly observed in carbon-based nanoelectronics. In this work, charge trapping in the high- k dielectric layer of top-gated CNT field-effect transistors (FETs) enables the gradual analog programmability of the CNT channel conductance with a large dynamic range ( i.

Preinfusion polyfunctional anti-CD19 chimeric antigen receptor T cells are associated with clinical outcomes in NHL.

After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (IL-15) elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines, including interferon-γ, IL-17A, IL-8, and macrophage inflammatory protein 1α.

MRπ: Inside the meat pie.

Meat pies have been adopted as one of Australia's favourite foods, and considered an icon by many. The hand-held convenience of the pie has made them a culinary necessity while watching sport, also beloved in Australia. An enduring question about the meat pie is what exactly is inside.

Application of Physiologically Based Pharmacokinetic (PBPK) Modeling Within a Bayesian Framework to Identify Poor Metabolizers of Efavirenz (PM), Using a Test Dose of Efavirenz.

Poor metabolisers of CYP2B6 (PM) require a lower dose of efavirenz because of serious adverse reactions resulting from the higher plasma concentrations associated with a standard dose. Treatment discontinuation is a common consequence in patients experiencing these adverse reactions. Such patients benefit from appropriate dose reduction, where efficacy can be achieved without the serious adverse reactions.