Search

Hereditary chronic kidney disease (CKD) appears to be more frequent than the clinical perception. Exome sequencing (ES) studies in CKD cohorts could identify pathogenic variants in ~10% of individuals. Tubulointerstitial kidney diseases, showing no typical clinical/histologic finding but tubulointerstitial fibrosis, are particularly difficult to diagnose. We used a targeted panel (29 genes) and MUC1-SNaPshot to sequence 271 DNAs, selected in defined disease entities and age cutoffs from 5217 individuals in the German Chronic Kidney Disease cohort. We identified 33 pathogenic variants. Of these 27 (81.8%) were in COL4A3/4/5, the largest group being 15 COL4A5 variants with nine unrelated individuals carrying c.1871G>A, p.(Gly624Asp). We found three cysteine variants in UMOD, a novel missense and a novel splice variant in HNF1B and the homoplastic MTTF variant m.616T>C. Copy-number analysis identified a heterozygous COL4A5 deletion, and a HNF1B duplication/deletion, respectively. Overall, pathogenic variants were present in 12.5% (34/271) and variants of unknown significance in 9.6% (26/271) of selected individuals. Bioinformatic predictions paired with gold standard diagnostics for MUC1 (SNaPshot) could not identify the typical cytosine duplication (c.428dupC) in any individual, implying that ADTKD-MUC1 is rare. Our study shows that >10% of selected individuals carry disease-causing variants in genes partly associated with tubulointerstitial kidney diseases. COL4A3/4/5 genes constitute the largest fraction, implying they are regularly overlooked using clinical Alport syndrome criteria and displaying the existence of phenocopies. We identified variants easily missed by some ES pipelines. The clinical filtering criteria applied enriched for an underlying genetic disorder.

Global attention continues to focus on the quality of teaching, teacher quality, teacher education programs and the preparation of graduates who are ready to teach. This self-study research focuses on one aspect of the preparation and assessment of graduates for teaching: the marking and moderation of a Teaching Assessment Performance (TPA), a mandated assessment tool implemented in Australian universities and education institutions that is used as one key determinant to assess graduate readiness for the profession. While there is a developing field of research related to the implementation and effectiveness of TPAs, less is known about the teacher educator expertise required to mark and moderate these assessments. The purpose of this self-study, conducted at Federation University, a regional university in Australia, aimed to identify and examine teacher educator marker and moderator experience and expertise through the establishment of a professional learning community (PLC). Using audio-recorded transcripts of team meetings and teacher educator vignettes, the data were analysed using NVivo and were individually and collectively categorised and coded. Reflecting in and on our practice, we focused on critical moments, interactions, and experiences to interrogate the data. The key themes included: (1) collaboration through marking and moderation; (2) reflection through critical engagement; (3) growth as a teacher educator and (4) enactment in teacher educator practice. This self-study of practice, using a PLC, enabled us to make our often-tacit knowledge, understanding and expertise explicit, and provided frameworks and structures for enacting this new knowledge in practice.

BACKGROUND: Autosomal recessive renal tubular dysgenesis is a rare, usually fatal inherited disorder of the renin-angiotensis system (RAS). Herein, we report an adolescent individual experiencing an unknown chronic kidney disease and aim to provide novel insights into disease mechanisms. METHODS: Exome sequencing for a gene panel associated with renal disease was performed. The RAS was assessed by comprehensive biochemical analysis in blood. Renin expression was determined in primary tubular cells by quantitative polymerase chain reaction and in situ hybridization on kidney biopsy samples. Allele frequencies of heterozygous and biallelic deleterious variants were determined by analysis of the Genomics England 100,000 Genomes Project. RESULTS: The patient was delivered prematurely after oligohydramnios was detected during pregnancy. Postnatally, he recovered from third-degree acute kidney injury but developed chronic kidney disease stage G3b over time. Exome sequencing revealed a previously reported pathogenic homozygous missense variant, p.(Arg375Gln), in the AGT (angiotensinogen) gene. Blood AGT concentrations were low, but plasma renin concentration and gene expression in kidney biopsy, vascular, and tubular cells revealed strong upregulation of renin. Angiotensin II and aldosterone in blood were not abnormally elevated. CONCLUSIONS: Renal tubular dysgenesis may present as chronic kidney disease with a variable phenotype, necessitating broad genetic analysis for diagnosis. Functional analysis of the RAS in a patient with AGT mutation revealed novel insights regarding compensatory upregulation of renin in vascular and tubular cells of the kidney and in plasma in response to depletion of AGT substrate as a source of Ang II (similarly observed with hepatic AGT silencing for the treatment of hypertension). [ABSTRACT FROM AUTHOR]

Resilient systems can absorb and recover from disturbances and adapt to changed conditions to maintain system functionality. Uncertainty about the meaning of resilience and the attributes it requires has limited the application of resilience thinking in biosecurity. However, considering increasing pressures from trade, travel and climate change, enhancing the resilience of biosecurity systems is likely to be critical to reduce the impacts of pests and diseases on economies, societies and environments.Here we provide a pathway for resilience thinking into risk management. Based on a literature review we discuss its benefits, develop an operational definition of resilience for biosecurity systems and identify the fundamental attributes that support resilience.We show that resilient biosecurity systems can anticipate disturbances, cope with low‐probability high‐impact events and adapt to new and changing circumstances. The status of biosecurity system resilience can be measured using evaluative rubrics, which give decision‐makers an overall performance rating and insight into system weaknesses. General measures, objective functions and simulation approaches are potential avenues for quantifying biosecurity system resilience in practice.Policy implications: Adopting resilience thinking into biosecurity risk management has the potential to reduce the damages caused by invading pests and diseases. If resilience thinking is used alongside traditional risk analysis, then regulators can more effectively address and prepare for the systemic consequences of high‐impact incursions and outbreaks of pests and diseases, which are unpredictable, low‐probability events. However, the design of resilience‐enhancing measures should be guided by economic principles and consider the rate of return of these measures over time. [ABSTRACT FROM AUTHOR]

Male prison rape and sexual assaults remains a serious and sensitive issue in many countries. Human rights groups claim that sexual assaults among male prisoners have reached pandemic proportions and need to be stopped. Researchers for many years have studied the causes of male sexual assault in prison and offered numerous recommendations on its prevention. Few, however, have presented evidence for a decline in male prisoner sexual assaults and investigated the reasons for the decline. This article provides evidence from population-based surveys of a steady decrease in male prisoner sexual assaults in New South Wales (NSW) between 1996 and 2009. The authors conducted in-depth interviews with former and current inmates, and using a "systems" approach they discuss the complexity of sexual assaults in prison, incorporating a multiplicity of perspectives. In particular, they bring together different sources of data and discuss this in relation to changes in power structures and control in a modern prison, the attitudes of older and younger prisoners, the concept of "duty of care," introduction of prison drug programs, and prisoner attitudes toward gender and sexuality. In anthropology, the term "system" is used widely for describing sociocultural phenomena of a given society in a holistic manner without reducing the complexity of a given community. (Contains 2 tables.)