Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol�which is a marker of cardiovascular risk�changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95 credible interval 3.7 million�4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world. © 2020, The Author(s), under exclusive licence to Springer Nature Limited

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

The impact of endothelial nitric oxide synthase polymorphisms on long-term renal allograft outcome

A major manifestation of chronic allograft failure (CAF) is the accelerated onset of atherosclerotic lesions within the graft. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been implicated in the pathogenesis of native atherosclerosis. This study tested the hypothesis that polymorphisms in eNOS are associated with susceptibility to CAF after cadaveric renal transplantation. The patient cohort comprised 140 renal transplant recipients who had received their transplants between 1985 and 1997 at the Oxford Transplant Centre and included 61 patients with biopsy-proven CAF and 79 with stable graft function for at least 10 years (long-term survivors, LTS). Genotyping for one polymorphism in the promoter region and two polymorphisms in the coding regions of the eNOS gene was performed by polymerase chain reaction with sequence-specific primers (PCRSSP). No association was found between any genetic variant and the development of CAF, even after stratification for other known risk factors. Statistical analysis revealed that all three polymorphisms were closely linked. We conclude that recipient eNOS gene polymorphisms do not alter the risk of CAF after renal transplantation

Signal nonlinearity measurements and corrections in MWIR and LWIR HgCdTe H2RG arrays for NEO Surveyor

The depletion region around each p-n junction in HgCdTe HAWAII-2RG detector arrays decreases in volume as charge is collected, causing the pixel capacitance to change continuously throughout an integration period. This changing capacitance manifests as a steadily decreasing measured signal rate while observing a constant flux. Ignoring this nonlinear response to signal accumulation can lead to underestimating the number of detected pho- tons by as much as 10%. Presented here are two methods, one simple and one complex, of measuring this signal nonlinearity and a theoretical framework behind a nonlinearity correction method. Additionally, experimental data are compared with simulations to explain methods to reduce noise in the nonlinearity measurement and identify deviations from the expected behavior that merit further study. © SPIE. Downloading of the abstract is permitted for personal use only.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Blooming in H2RG arrays: Laboratory measurements of a second brighter-fatter type effect in HgCdTe infrared detectors

Improved measurement and calibration of detector behaviors will be crucial for future space missions, particularly those aiming to tackle outstanding questions in cosmology and exoplanet research. Similarly, many small detector effects, such as the nearest-neighbor interactions of the brighter-fatter effect and interpixel capacitance, will need to be considered to ensure measured signals are truly astronomical in origin. Laboratory measurements confirming the existence of an additional brighter-fatter type effect in HAWAII-1RG and HAWAII-2RG HgCdTe infrared arrays with cutoff wavelengths ranging from 5.7 to 16.7 μm are presented. This effect is similar in nature to the blooming observed in charge-coupled devices and is characterized by a pixel spontaneously sharing a current with its neighbors upon reaching saturation, serving to make the brightest sources appear fatter. In addition to exploring the cause and mechanism of current sharing for this effect, measurements for several arrays show the magnitude of the shared current is greater than 60% of the incoming photocurrent hitting the saturated pixel. A proof-of-concept correction method for this effect is also described along with the necessary next steps to improve this correction and investigate the amplitude of other nearest-neighbor interactions. © 2021 Society of Photo-Optical Instrumentation Engineers (SPIE).Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Tongue function and its influence on masticatory performance in patients treated for oral cancer: a five-year prospective study

Purpose: The purpose of this study was to observe the impact of oral oncological treatment, including the recovery of several tongue functions (force, mobility, and sensory functions), and to determine the influence of these functions on masticatory performance. Materials and methods: Masticatory performance and tongue force, mobility, and sensory functions were determined in 123 patients with oral cavity cancer. The assessments were performed 4 weeks before treatment and 4 to 6 weeks, 6 months, 1 year, and 5 years after treatment. Generalized estimation equations and mixed model analyses were performed, correcting for previously identified factors in the same population. Results: A significant deterioration in tongue mobility and sensory function was observed in patients with mandible and tongue and/or floor-of-mouth tumors. Better tongue force and sensory function (thermal and tactile) positively influenced masticatory performance, and this effect was stronger where fewer occlusal units were present. The effect of both the tongue force and maximum bite force was weaker in dentate patients in comparison with patients with full dentures. A web-based application was developed to enable readers to explore our results and provide insight into the coherence between the found factors in the mixed model. Conclusions: Tongue function deteriorates after oral oncological treatment, without statistically significant recovery. Adequate bite and tongue forces are especially important for patients with a poor prosthetic state. Patients with sensory tongue function deficits especially benefit from the presence of more occluding pairs

Modulation transfer function measurements of HgCdTe long wavelength infrared arrays for the Near-Earth Object Surveyor

The modulation transfer function (MTF) is a useful measure in image quality analysis and performance budget determination. Sensitive long wavelength infrared (LWIR) detectors for astronomical space telescopes require slight modifications to the existing MTF measurement methods due to the increased prevalence of high dark current pixels. Presented here are the specifics of a modified slanted edge method to determine the MTF in λc > 10 μm HgCdTe detectors to be used with the planned Near-Earth Object Surveyor Mission. The measured MTF at Nyquist using 6 μm light is 0.22 ± 0.02 and is 0.25 ± 0.02 using 10 μm light for both 250 and 350 mV of applied reverse bias. These measurements are from edge spread functions with median signal values around 50% of the well depth, as the MTF is expected to change with signal value due to two brighter-fatter type effects. The expected trends caused by the influences of these two effects and the expected trends with wavelength of absorbed photons are all observed. © 2022 Society of Photo-Optical Instrumentation Engineers (SPIE).Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Tongue function and its influence on masticatory performance in patients treated for oral cancer : a five-year prospective study

Purpose: The purpose of this study was to observe the impact of oral oncological treatment, including the recovery of several tongue functions (force, mobility, and sensory functions), and to determine the influence of these functions on masticatory performance. Materials and methods: Masticatory performance and tongue force, mobility, and sensory functions were determined in 123 patients with oral cavity cancer. The assessments were performed 4 weeks before treatment and 4 to 6 weeks, 6 months, 1 year, and 5 years after treatment. Generalized estimation equations and mixed model analyses were performed, correcting for previously identified factors in the same population. Results: A significant deterioration in tongue mobility and sensory function was observed in patients with mandible and tongue and/or floor-of-mouth tumors. Better tongue force and sensory function (thermal and tactile) positively influenced masticatory performance, and this effect was stronger where fewer occlusal units were present. The effect of both the tongue force and maximum bite force was weaker in dentate patients in comparison with patients with full dentures. A web-based application was developed to enable readers to explore our results and provide insight into the coherence between the found factors in the mixed model. Conclusions: Tongue function deteriorates after oral oncological treatment, without statistically significant recovery. Adequate bite and tongue forces are especially important for patients with a poor prosthetic state. Patients with sensory tongue function deficits especially benefit from the presence of more occluding pairs