Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Validation of the family focused mental health practice questionnaire in measuring health and social care professionals' family focused practice.

BackgroundParental mental illness is a major public health issue and there is growing evidence that family focused practice can improve outcomes for parents and their families. However, few reliable and valid instruments measure mental health and social care professionals' family focused practice.ObjectivesTo explore the psychometric properties of the Family Focused Mental Health Practice Questionnaire in a population of health and social care professionals.MethodsHealth and Social Care Professionals (n = 836) in Northern Ireland completed an adapted version of the Family Focused Mental Health Practice Questionnaire. Exploratory factor analysis was used to test the structure of the underlying dimensions in the questionnaire. The results, and theoretical considerations, guided construction of a model that could explain variation in respondents' items. This model was then validated using confirmatory factor analysis.ResultsExploratory factor analysis revealed that solutions including 12 to 16 factors provided a good fit to the data and indicated underlying factors that could be meaningfully interpreted in line with existing literature. From these exploratory analyses, we derived a model that included 14 factors and tested this model with Confirmatory Factor Analysis. The results suggested 12 factors that summarized 46 items that were most optimal in reflecting family focused behaviours and professional and organizational factors. The 12 dimensions identified were meaningful and consistent with substantive theories: furthermore, their inter-correlations were consistent with known professional and organizational processes known to promote or hinder family focused practice.ConclusionThis psychometric evaluation reveals that the scale provides a meaningful measure of professionals' family focused practice within adult mental health and children's services, and the factors that hinder and enable practice in this area. The findings, therefore, support the use of this measure to benchmark and further develop family focused practice in both adult mental health and children's services

Land Mine and Clutter Object Discrimination using Wavelet and Time Domain Spatially Distributed Features from Metal Detectors and their Fusion with GPR Features for Hand-Held Units

This paper presents some advances in discrimination and fusion algorithms using metal detector (MD) and ground penetrating radar (GPR) sensors in a robotic wand unit. Previously investigated spatially distributed features are extended and fused with discrete wavelet transform representations of MD data. A multilayer perceptron technique is then applied to discriminate between land mine and land mine-like objects based on the wavelet coefficient and time domain features separately. Using MD wavelet and time domain fusion, the probability of false alarms is reduced by 46.0% and 18.0% over the wavelet and time domain models, respectively, at 0.95 probability of detection. Fusion results are presented for the MD and GPR sensors to demonstrate that the two sensors provide complementary information for significantly reducing the probability of false alarm. Blind test results from a government test facility are presented to evaluate the effectiveness of the algorithms

Advances in EMI and GPR Algorithms in Discrimination Mode Processing for Handheld Landmine Detectors

This paper presents some advancement in the detection algorithms using EMI sensor, GPR sensor and their fusion. In the EMI algorithm, we propose the application of the weighted distributed density (WDD) functions on the wavelet domain and the time domain of the EMI data for feature based detection. A multilayer perceptron technique is then applied to discriminate between mine and clutter objects based on the wavelet domain and time domain features separately. When the results from the two domains are fused together, the probability of false alarms is reduced by a factor of two. The enhancement in the GPR algorithm includes the depth processing which selects a certain data segment below the ground surface for detection, as well as utilizing the phase variation of the signal return across a mine to achieve better detection. Finally, we present fusion results from EMI and GPR sensors to demonstrate that the two sensors provide complementary information and when they are properly fused together the probability of false alarm can be reduced significantly

Proteomic Characterization of Middle Ear Fluid Confirms Neutrophil Extracellular Traps as a Predominant Innate Immune Response in Chronic Otitis Media.

BACKGROUND:Chronic Otitis Media (COM) is characterized by middle ear effusion (MEE) and conductive hearing loss. MEE reflect mucus hypersecretion, but global proteomic profiling of the mucosal components are limited. OBJECTIVE:This study aimed at characterizing the proteome of MEEs from children with COM with the goal of elucidating important innate immune responses. METHOD:MEEs were collected from children (n = 49) with COM undergoing myringotomy. Mass spectrometry was employed for proteomic profiling in nine samples. Independent samples were further analyzed by cytokine multiplex assay, immunoblotting, neutrophil elastase activity, next generation DNA sequencing, and/or immunofluorescence analysis. RESULTS:109 unique and common proteins were identified by MS. A majority were innate immune molecules, along with typically intracellular proteins such as histones and actin. 19.5% percent of all mapped peptide counts were from proteins known to be released by neutrophils. Immunofluorescence and immunoblotting demonstrated the presence of neutrophil extracellular traps (NETs) in every MEE, along with MUC5B colocalization. DNA found in effusions revealed unfragmented DNA of human origin. CONCLUSION:Proteomic analysis of MEEs revealed a predominantly neutrophilic innate mucosal response in which MUC5B is associated with NET DNA. NETs are a primary macromolecular constituent of human COM middle ear effusions