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, nineteen 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 biologic pathways.

The Johns Hopkins Precursors Study, a long-term prospective study, was used to study the relation between self-reported sleep disturbances and subsequent clinical depression and psychiatric distress. A total of 1,053 men provided information on sleep habits during medical school at The Johns Hopkins University (classes of 1948-1964) and have been followed since graduation. During a median follow-up period of 34 years (range 1-45), 101 men developed clinical depression (cumulative incidence at 40 years, 12.2%), including 13 suicides. In Cox proportional hazards analysis adjusted for age at graduation, class year, parental history of clinical depression, coffee drinking, and measures of temperament, the relative risk of clinical depression was greater in those who reported insomnia in medical school (relative risk (RR) 2.0, 95% confidence interval (CI) 1.2-3.3) compared with those who did not and greater in those with difficulty sleeping under stress in medical school (RR 1.8, 95% CI 1.2-2.7) compared with those who did not report difficulty. There were weaker associations for those who reported poor quality of sleep (RR 1.6, 95% CI 0.9-2.9) and sleep duration of 7 hours or less (RR 1.5, 95% CI 0.9-2.3) with development of clinical depression. Similar associations were observed between reports of sleep disturbances in medical school and psychiatric distress assessed in 1988 by the General Health Questionnaire. These findings suggest that insomnia in young men is indicative of a greater risk for subsequent clinical depression and psychiatric distress that persists for at least 30 years.

Clinical depression appears to be an independent risk factor for incident coronary artery disease for several decades after the onset of the clinical depression.

No abstract

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation. The goals were to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the Sensitization in Transplantation: Assessment of Risk (STAR) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, and highlighted gaps in knowledge are intended to spur research that will inform the next STAR Working Group meeting in 2019.

Fluid intelligence is important for successful functioning in the modern world, but much evidence suggests that fluid intelligence is largely immutable after childhood. Recently, however, researchers have reported gains in fluid intelligence after multiple sessions of adaptive working memory training in adults. The current study attempted to replicate and expand those results by administering a broad assessment of cognitive abilities and personality traits to young adults who underwent 20 sessions of an adaptive dual n-back working memory training program and comparing their post-training performance on those tests to a matched set of young adults who underwent 20 sessions of an adaptive attentional tracking program. Pre- and post-training measurements of fluid intelligence, standardized intelligence tests, speed of processing, reading skills, and other tests of working memory were assessed. Both training groups exhibited substantial and specific improvements on the trained tasks that persisted for at least 6 months post-training, but no transfer of improvement was observed to any of the non-trained measurements when compared to a third untrained group serving as a passive control. These findings fail to support the idea that adaptive working memory training in healthy young adults enhances working memory capacity in non-trained tasks, fluid intelligence, or other measures of cognitive abilities.

Summary Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli – spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia, and may reveal a difference in brain functions that ultimately results in a specific reading impairment.

Background Self-care training can reduce hospitalization for heart failure (HF), and more intensive intervention may benefit more vulnerable patients, including those with low literacy. Methods and Results A 1-year, multisite, randomized controlled comparative effectiveness trial with 605 patients with HF. Those randomized to single session received a 40-minute in-person, literacy-sensitive training; the multisession group received the same initial training and then ongoing telephone-based support. The primary outcome was combined incidence of all-cause hospitalization or death; secondary outcomes included HF-related hospitalization and HF-related quality of life (HFQOL) with pre-specified stratification by literacy. Overall, the incidence of all-cause hospitalization and death did not differ between intervention groups (incidence rate ratio (IRR)=1.01 (95% Confidence Interval (CI): 0.83, 1.22). The effect of multisession training compared with single session training differed by literacy group: among low literacy, multisession yielded lower incidence of all-cause hospitalization and death: IRR=0.75 (0.45,1.25); and among higher literacy, multisession yielded higher incidence: IRR=1.22 (0.99,1.50) (interaction p=0.048). For HF-related hospitalization: among low literacy, multisession yielded lower incidence: IRR=0.53 (95% CI: 0.25,1.12); and among higher literacy, multisession yielded higher incidence: IRR=1.32 (95% CI: 0.92,1.88) (interaction p=0.005). HFQOL improved more for patients receiving multisession compared with single session at 1 and 6 months, but the difference at 12 months was smaller. Effects on HFQOL did not differ by literacy. Conclusions Overall, an intensive multisession intervention did not change clinical outcomes compared with a single session intervention. People with low literacy appear to benefit more from multisession than people with higher literacy. Clinical Trial Registration Information ClinicalTrials.gov; Identifier: NCT00378950.