Membranous nephropathy in the UK Biobank

Background Despite MN being one of the most common causes of nephrotic syndrome worldwide, its biological and environmental determinants are poorly understood in large-part due to it being a rare disease. Making use of the UK Biobank, a unique resource holding a clinical dataset and stored DNA, serum and urine for ~500,000 participants, this study aims to address this gap in understanding. Methods The primary outcome was putative MN as defined by ICD-10 codes occurring in the UK Biobank. Univariate relative risk regression modelling was used to assess the associations between the incidence of MN and related phenotypes with sociodemographic, environmental exposures, and previously described increased-risk SNPs. Results 502,507 patients were included in the study of whom 100 were found to have a putative diagnosis of MN; 36 at baseline and 64 during the follow-up. Prevalence at baseline and last follow-up were 72 and 199 cases/million respectively. At baseline, as expected, the majority of those previously diagnosed with MN had proteinuria, and there was already evidence of proteinuria in patients diagnosed within the first 5 years of follow-up. The highest incidence rate for MN in patients was seen in those homozygous for the high-risk alleles (9.9/100,000 person-years). Conclusion It is feasible to putatively identify patients with MN in the UK Biobank and cases are still accumulating. This study shows the chronicity of disease with proteinuria present years before diagnosis. Genetics plays an important role in disease pathogenesis, with the at-risk group providing a potential population for recall

Re-architecting datacenter networks and stacks for low latency and high performance

Modern datacenter networks provide very high capacity via redundant Clos topologies and low switch latency, but transport protocols rarely deliver matching performance. We present NDP, a novel data-center transport architecture that achieves near-optimal completion times for short transfers and high flow throughput in a wide range of scenarios, including incast. NDP switch buffers are very shallow and when they fill the switches trim packets to headers and priority forward the headers. This gives receivers a full view of instantaneous demand from all senders, and is the basis for our novel, high-performance, multipath-aware transport protocol that can deal gracefully with massive incast events and prioritize traffic from different senders on RTT timescales. We implemented NDP in Linux hosts with DPDK, in a software switch, in a NetFPGA-based hardware switch, and in P4. We evaluate NDP's performance in our implementations and in large-scale simulations, simultaneously demonstrating support for very low-latency and high throughput

Common Risk Variants in AHI1 Are Associated With Childhood Steroid Sensitive Nephrotic Syndrome

Introduction: Steroid-sensitive nephrotic syndrome (SSNS) is the most common form of kidney disease in children worldwide. Genome-wide association studies (GWAS) have demonstrated the association of SSNS with genetic variation at HLA-DQ/DR and have identified several non-HLA loci that aid in further understanding of disease pathophysiology. We sought to identify additional genetic loci associated with SSNS in children of Sri Lankan and European ancestry. Methods: We conducted a GWAS in a cohort of Sri Lankan individuals comprising 420 pediatric patients with SSNS and 2339 genetic ancestry matched controls obtained from the UK Biobank. We then performed a transethnic meta-analysis with a previously reported European cohort of 422 pediatric patients and 5642 controls. Results: Our GWAS confirmed the previously reported association of SSNS with HLA-DR/DQ (rs9271602, P = 1.12 × 10−27, odds ratio [OR] = 2.75). Transethnic meta-analysis replicated these findings and identified a novel association at AHI1 (rs2746432, P = 2.79 × 10−8, OR = 1.37), which was also replicated in an independent South Asian cohort. AHI1 is implicated in ciliary protein transport and immune dysregulation, with rare variation in this gene contributing to Joubert syndrome type 3. Conclusions: Common variation in AHI1 confers risk of the development of SSNS in both Sri Lankan and European populations. The association with common variation in AHI1 further supports the role of immune dysregulation in the pathogenesis of SSNS and demonstrates that variation across the allele frequency spectrum in a gene can contribute to disparate monogenic and polygenic diseases

Surgical approach of posterior fossa tumor (bone aneurysmal cyst): A case report

An aneurysmal bone cyst is an expansible osteolytic lesion with a thin wall, containing blood-filled cystic cavities. The term aneurismal is derived from its radiographic appearance. Local hemodynamic alterations related to venous obstruction or arteriovenous fistulae that occur after an injury are important in the pathogenesis of an aneurismal bone cyst. The lesion is a component of, or arises within, a preexisting bone tumor in about one third of cases; this finding further substantiates the fact that aneurismal bone cysts occur in an abnormal bone as a result of associated hemodynamic changes. The authors would like to present a case and the problems which they had during the surgical procedures.&nbsp

You do not have to act to be impulsive: Brain resting-state activity predicts performance and impulsivity on the Balloon Analogue Risk Task

Objective: Impulsivity is a key, trait-like feature of the decision-making process. As personality traits are stable over time, we hypothesized that resting-state (RS) neural activity would predict individual impulsivity. Methods: Thirty-five healthy individuals underwent fMRI scan during RS and subsequently performed the Balloon Analogue Risk Task (BART). In BART, impulsivity was inversely correlated to monetary earnings. A group-level whole-brain regression assessed the relationship between earnings at BART and RS evaluated by the Hurst Exponent, regional homogeneity; low frequency oscillation (LFO), (including the Amplitude of Low Frequency Fluctuations – ALFF– and the fractional Amplitude of Low Frequency Fluctuations –fALFF) and the Default Mode Network (DMN) functional connectivity. Results: ALFF significantly correlates with total earnings in the ventral part of the ACC/MPFC (FWE corrected p < 0.05 (uncorrected p value <0.0005; cluster size: ≥10 voxels), while H significantly correlates with total earnings in the anterior insula and the part opercularis of the inferior frontal gyrus. Conclusions: These results suggest that impulsivity and ability to change strategies according to external cues are trait characteristics shaped in the RS's functional architecture that can be detected also when individuals are not engaged in decision-making tasks

Emotion regulation difficulties in the relation between stress-related insomnia symptoms and brain response to emotional faces: An fMRI study

The aim of the current study was to investigate whether the experience of insomnia symptoms per se and symptoms of insomnia due to stress are associated with an increased brain response to the presentation of emotional faces. In addition, we also examined whether the effect of these sleep difficulties on emotional reactivity at the brain level depends on the experience of emotion regulation (ER) difficulties. The current sample consisted of 37 individuals (20 females, 17 males) selected from a larger group of 120 respondents who completed a survey about sleep problems and ER difficulties. Our results indicate that the tendency to experience stress-related insomnia symptoms but not insomnia symptoms per se modulates brain responses to emotional facial expressions, especially in areas of the parietal cortex, insula, and surrounding opercular voxels. Furthermore, difficulties in ER might play an important role, as the effect of stress-related insomnia symptoms on most of these brain regions disappears when controlling for difficulties in ER. However, an effect in the insula was maintained during the presentation of angry faces, suggesting that stress-related insomnia symptoms may increase the brain response to anger in the insula relatively independent from difficulties in ER. These findings suggest that individuals affected by stress-related insomnia symptoms show an enhanced brain response when presented with emotional stimuli (either positive or negative) in brain areas associated with hyperarousal, which could represent a possible ER deficit in these individuals. Thus, interventions that focus on targeting ER difficulties might be effective in reducing the hyperarousal state in individuals affected by stress-related insomnia symptoms

HPV strain distribution in patients with genital warts in a female population sample

The incidence of human papillomavirus (HPV) in the human cancer domain is still a subject of intensive study. In this study, we examined cervical swab samples from 713 females with genital warts, and tested the samples for high‑and low‑risk genital HPV. HPV genotyping was assessed using a Genotyping test that detects HPV by the amplification of target DNA using polymerase chain reaction and nucleic acid hybridization. In total, we detected 37 anogenital HPV DNA genotypes [6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73 (MM9), 81, 82 (MM4), 83 (MM7), 84 (MM8), IS39 and CP6108] and investigated the incidence of these genotypes in the patients with genital warts. We found differences in the distribution of high‑/low‑risk strains and the incidence of high‑risk strains was found to occur mainly in females under 35 years of age. The data from our study suggest that a detailed oral, rectal and genital identification of high‑risk strains should be performed to visualize the entire pattern of possible triggers of carcinogenesis. © 2016, Spandidos Publications. All rights reserved