Water supply authorities (WSAs) can influence the behaviour of water users and are influential actors in water governance. Despite this, their decision-making processes and the details of their ...interactions with other water users are seldom explored empirically in water management research. We undertook an exploratory qualitative study using semi-structured interviews and purposive sampling with WSA officials across different institutions in south-eastern Australia. Thematic analysis revealed different water allocation decision-making phases and key factors influencing each phase. The findings highlight that the decisions made by WSAs are not only based on predefined rules, but are affected by many factors.
Mitochondria play a key role in common neurodegenerative diseases and contain their own genome: mtDNA. Common inherited polymorphic variants of mtDNA have been associated with several ...neurodegenerative diseases, and somatic deletions of mtDNA have been found in affected brain regions. However, there are conflicting reports describing the role of rare inherited variants and somatic point mutations in neurodegenerative disorders, and recent evidence also implicates mtDNA levels. To address these issues we studied 1363 post mortem human brains with a histopathological diagnosis of Parkinson's disease (PD), Alzheimer's disease (AD), Frontotemporal dementia - Amyotrophic Lateral Sclerosis (FTD-ALS), Creutzfeldt Jacob disease (CJD), and healthy controls. We obtained high-depth whole mitochondrial genome sequences using off target reads from whole exome sequencing to determine the association of mtDNA variation with the development and progression of disease, and to better understand the development of mtDNA mutations and copy number in the aging brain. With this approach, we found a surprisingly high frequency of heteroplasmic mtDNA variants in 32.3% of subjects. However, we found no evidence of an association between rare inherited variants of mtDNA or mtDNA heteroplasmy and disease. In contrast, we observed a reduction in the amount of mtDNA copy in both AD and CJD. Based on these findings, single nucleotide variants of mtDNA are unlikely to play a major role in the pathogenesis of these neurodegenerative diseases, but mtDNA levels merit further investigation.
There are a multitude of well recognized hip and groin injuries that commonly affect athletes; however, a more recently recognized and possibly often overlooked cause of hip pain is that of ...femoroacetabular impingement (FAI). FAI is characterized by abutment of the femoral neck against the acetabular rim, which may occur by two mechanisms known as 'CAM' or 'pincer' impingement, although most commonly by a mixture of both. CAM impingement is characterized by abutment of the femoral neck against the acetabulum due to a morphological abnormality of the femoral head-neck junction. Pincer impingement occurs where an abnormality of the acetabulum results in impingement against an often normal femoral neck. Both CAM and pincer impingement are known to result in pathological consequences of cartilage delamination and labral lesions, leading to significant pain and disruption to athletic performance and activities of daily living in athletes. There are currently several methods of assessing the degree of impingement by use of CT and magnetic resonance imaging scans, which can be used in conjunction with magnetic resonance arthrography and arthroscopy to assess the damage caused to the underlying structures of the hip. Both open and arthroscopic surgical methods are used, with recent reports in athletes showing excellent results for lifestyle improvement and frequency of returning to sport. In cases of hip and groin pain in athletes, it is important to remember to look for typical history, and examination and imaging findings that may suggest a diagnosis of hip impingement. This article goes some way to explaining the principles, consequences and management of FAI.
Background: Despite investigation, 95% of thyroid nodules are ultimately benign. Radiomics is a field that uses radiological features to inform individualized patient care. We aimed to evaluate the ...diagnostic utility of radiomics in classifying undetermined thyroid nodules into benign and malignant using ultrasonography (US). Methods: A diagnostic test accuracy systematic review and meta-analysis was performed in accordance with PRISMA guidelines. Sensitivity, specificity, and area under curve (AUC) delineating benign and malignant lesions were recorded. Results: Seventy-five studies including 26,373 patients and 46,175 thyroid nodules met inclusion criteria. Males accounted for 24.6% of patients, while 75.4% of patients were female. Radiomics provided a pooled sensitivity of 0.87 (95% CI: 0.86−0.87) and a pooled specificity of 0.84 (95% CI: 0.84−0.85) for characterizing benign and malignant lesions. Using convolutional neural network (CNN) methods, pooled sensitivity was 0.85 (95% CI: 0.84−0.86) and pooled specificity was 0.82 (95% CI: 0.82−0.83); significantly lower than studies using non-CNN: sensitivity 0.90 (95% CI: 0.89−0.90) and specificity 0.88 (95% CI: 0.87−0.89) (p < 0.05). The diagnostic ability of radiologists and radiomics were comparable for both sensitivity (OR 0.98) and specificity (OR 0.95). Conclusions: Radiomic analysis using US provides a reproducible, reliable evaluation of undetermined thyroid nodules when compared to current best practice.
Given the central role of genetic factors in the pathogenesis of common neurodegenerative disorders, it is critical that mechanistic studies in human tissue are interpreted in a genetically ...enlightened context. To address this, we performed exome sequencing and copy number variant analysis on 1511 frozen human brains with a diagnosis of Alzheimer's disease (AD, n = 289), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS, n = 252), Creutzfeldt-Jakob disease (CJD, n = 239), Parkinson's disease (PD, n = 39), dementia with Lewy bodies (DLB, n = 58), other neurodegenerative, vascular, or neurogenetic disorders (n = 266), and controls with no significant neuropathology (n = 368). Genomic DNA was extracted from brain tissue in all cases before exome sequencing (Illumina Nextera 62 Mb capture) with variants called by FreeBayes; copy number variant (CNV) analysis (Illumina HumanOmniExpress-12 BeadChip); C9orf72 repeat expansion detection; and APOE genotyping. Established or likely pathogenic heterozygous, compound heterozygous, or homozygous variants, together with the C9orf72 hexanucleotide repeat expansions and a copy number gain of APP, were found in 61 brains. In addition to known risk alleles in 349 brains (23.9% of 1461 undergoing exome sequencing), we saw an association between rare variants in GRN and DLB. Rare CNVs were found in <1.5% of brains, including copy number gains of PRPH that were overrepresented in AD. Clinical, pathological, and genetic data are available, enabling the retrieval of specific frozen brains through the UK Medical Research Council Brain Banks Network. This allows direct access to pathological and control human brain tissue based on an individual's genetic architecture, thus enabling the functional validation of known genetic risk factors and potentially pathogenic alleles identified in future studies.
Early identification of people at risk of developing COPD is crucial for implementing preventive strategies. We aimed to systematically review and assess the performance of all published models that ...predicted development of COPD. A search was conducted to identify studies that developed a prediction model for COPD development. The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies was followed when extracting data and appraising the selected studies. Of the 4,481 records identified, 30 articles were selected for full-text review, and only four of these were eligible to be included in the review. The only consistent predictor across all four models was a measure of smoking. Sex and age were used in most models; however, other factors varied widely. Two of the models had good ability to discriminate between people who were correctly or incorrectly classified as at risk of developing COPD. Overall none of the models were particularly useful in accurately predicting future risk of COPD, nor were they good at ruling out future risk of COPD. Further studies are needed to develop new prediction models and robustly validate them in external cohorts.
Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of ...onset, but these studies have not been validated in large sporadic case series.
We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity. Individuals with two or more variants within a relevant disease gene panel were defined as 'oligogenic'.
The majority of oligogenic variant combinations consisted of a highly penetrant allele or known risk factor in combination with another rare but likely benign allele. The presence of oligogenic variants did not influence the age of onset or disease severity. After controlling for the single known major risk allele, the frequency of oligogenic variants was no different between cases and controls.
A priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a known genetic risk factor, and it is the burden of these variants in combination with rare benign alleles that is likely to be responsible for some oligogenic associations. Controlling for this bias is essential in studies investigating a potential role for oligogenic variation in neurodegenerative diseases.
Nurse leaders must use behaviors that foster effective teams. The purpose of this study was to determine the behavioral style by 3,396 nurse leaders who attended leadership and communication ...continuing education courses. Sessions included identifying behavioral style preferences using the DiSC
®
Personal Profile Instrument. Of the four behavioral dimensions, Dominance, Influence, Steadiness, and Conscientiousness, 73% scored highest in Dominance and Conscientiousness. The remaining 27% scored highest in preferences for Influence and Steadiness. Nursing leaders may benefit from awareness of differences in behavioral style preferences to enhance communication and team effectiveness, as well as improve satisfaction among team members.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
To systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders.
In this study we developed a pipeline to identify somatic ...variants from exome sequencing data in 1461 diseased and control human brains. Eighty-eight percent of the DNA samples were extracted from the cerebellum. Identified somatic variants were validated by targeted amplicon sequencing and/or PyroMark® Q24.
We observed somatic coding variants present in >10% of sampled cells in at least 1% of brains. The mutational signature of the detected variants showed a predominance of C>T variants most consistent with arising from DNA mismatch repair, occurred frequently in genes that are highly expressed within the central nervous system, and with a minimum somatic mutation rate of 4.25 × 10
per base pair per individual.
These findings provide proof-of-principle that deleterious somatic variants can affect sizeable brain regions in at least 1% of the population, and thus have the potential to contribute to the pathogenesis of common neurodegenerative diseases.
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