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IntroductionWe hypothesized that at least half of incident hemodialysis (HD) patients on 3-times weekly dialysis could safely start on an incremental, 2-times weekly HD schedule if residual kidney function (RKF) had been considered.MethodsRKF is assessed in all our HD patients. This single-center, retrospective cohort study of incident adult HD patients, who survived ≥6 months on a 3-times weekly HD regimen and had a timed urine collection within 3 months of starting HD, assessed each patient's theoretical ability to achieve adequate urea clearance, ultrafiltration rate, and hemodynamic stability if on 2-times weekly HD.ResultsOf the 410 patients in the cohort, we found that 112 (27%) could have optimally and 107 (26%) could have been appropriately considered for 2-times weekly incremental HD. In general, diuretics were underutilized in >50% of subjects who had adequate RKF urea clearance. The optimal 2-times weekly patients had better potassium and phosphorus control. The correlation coefficient of calculated residual kidney urea clearance with 24-hour urine volume and with kinetic model residual kidney clearance was 0.68 and 0.99, respectively.DiscussionMore than 50% of incident HD patients with RKF have adequate kidney urea clearance to be considered for 2-times weekly HD. When additionally ultrafiltration volume and blood pressure stability are taken into account, more than one-fourth of the total cohort could optimally start HD in an incremental fashion.

This article describes the process used to develop and assess an NSF-funded instructional innovation: an online collection (https://www.CAUSEweb.org/smiles/) of 28 interactive songs of high esthetic quality designed to span literature-based learning objectives of introductory statistics that develop statistical literacy and reasoning. The interactive songs are also designed to reduce statistics anxiety and require little time or instructor expertise. The songs are interactive in that the interface solicits (and provides hints and feedback on) student contributions (concepts or examples) and then plays back the song with student inputs integrated and highlighted. After providing a brief background, this article describes requirements, challenges, and opportunities in educational songwriting for the mathematical sciences, then describes the intervention and how its special nature affected the development process. Pilot studies at a research university and at a majority Black two-year college showed that students found the innovation to be a good tool to help their learning, reduce their anxiety about statistics, have an easy to follow interface, and use high quality songs. Analysis of log files from the use of the software shows some evidence of better performance on assessments after use and informs improvements of the automated feedback. Supplemental materials for this article are available online.

Blood pressure (BP) is a complex trait that is the consequence of an interaction between genetic and environmental determinants. Previous studies have demonstrated increased BP in mice with global deletion of TASK-1 channels contemporaneous with diverse dysregulation of aldosterone production. In humans, genome-wide association studies in ≈100 000 individuals of European, East Asian, and South Asian ancestry identified a single nucleotide polymorphism (SNP) in KCNK3 (the gene encoding TASK-1) associated with mean arterial pressure. The current study was motivated by the hypotheses that (1) association of KCNK3 SNPs with BP and related traits extends to blacks and Hispanics, and (2) KCNK3 SNPs exhibit associations with plasma renin activity and aldosterone levels. We examined baseline BP measurements for 7840 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), and aldosterone levels and plasma renin activity in a subset of 1653 MESA participants. We identified statistically significant association of the previously reported KCNK3 SNP (rs1275988) with mean arterial pressure in MESA blacks (P=0.024) and a nearby SNP (rs13394970) in MESA Hispanics (P=0.031). We discovered additional KCNK3 SNP associations with systolic BP, mean arterial pressure, and hypertension. We also identified statistically significant association of KCNK3 rs2586886 with plasma aldosterone level in MESA and demonstrated that global deletion of TASK-1 channels in mice produces a mild-hyperaldosteronism, not associated with a decrease in renin. Our results suggest that genetic variation in the KCNK3 gene may contribute to BP variation and less severe hypertensive disorders in which aldosterone may be one of several causative factors.

OBJECTIVE: Patients with early multiple sclerosis (MS) have stereotyped attack severity and recovery. We sought to determine if polymorphisms in MS susceptibility genes are associated with these attack features or with the risk of a second attack. METHODS: 503 white subjects evaluated within a year of MS onset were included in the study. The severity of and recovery from the first two attacks were determined based on published definitions. Seventeen MS susceptibility genes were genotyped at the UCSF MS Genetics laboratory. Each polymorphism was evaluated in multivariate ordinal models, adjusted for the other polymorphisms, for its association with attack severity and recovery. We also assessed if these polymorphisms were associated with increased risk of a second attack. RESULTS: The MPHOSPH9 polymorphism was associated with greater attack severity (odds ratios [OR] = 1.47, 95% CI [1.11, 1.94], p = 0.008), while the RGS1 and TNFRSF1A polymorphisms tended to be associated with reduced attack severity. The CD6 polymorphism tended to be associated with increased odds of worse attack recovery (OR = 1.25, 95% CI [0.93, 1.68], p = 0.13). In those who were HLA-DRB1-negative, the EVI5 polymorphism was associated with attacks of less severity; in HLA-DRB1 positive patients, EVI5 was associated with attacks of greater severity and worse recovery. The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event within a year. CONCLUSIONS: Some MS susceptibility polymorphisms may be associated with attack severity, recovery, or frequency. Further characterization of these genes may lead to a better understanding of MS pathogenesis and to a more individualized treatment approach.

OBJECTIVE: The anatomic location of subsequent relapses in early multiple sclerosis (MS) appears to be predicted by the first attack location. We sought to determine if genetic polymorphisms associated with MS susceptibility are associated with attack location. METHODS: 17 genome-wide association study-identified MS susceptibility polymorphisms were genotyped in 503 white, non-Hispanic patients seen within a year of MS onset. Their association with the CNS location of the first two MS attacks was assessed in multivariate repeated measures analyses (generalized estimating equations with robust standard errors). RESULTS: The IL12A polymorphism was independently associated with increased odds of attacks involving the spinal cord (OR = 1.52, 95% CI 1.11, 2.07, p = 0.009), as was the IRF8 polymorphism (OR = 2.40, 95% CI [1.04, 5.50], p = 0.040). The IL7R polymorphism was associated with reduced odds of attacks involving the brainstem/cerebellum (OR = 0.46, 95% CI 0.22, 0.97, p = 0.041), as were the TNFRSF1A and IL12A polymorphisms. The CD6 polymorphism conferred reduced odds of optic neuritis as an attack location (OR = 0.69, 95% CI [0.49, 0.97], p = 0.034). Several other genes showed trends for association with attack location. CONCLUSIONS: Some of the MS susceptibility genes may be associated with MS attack location. The IL12A polymorphism is of particular interest given that interferon beta therapy appears to influence IL12 levels. These findings may lead to improved understanding of MS pathogenesis and treatment.