Effect of Progressive Weight Loss on Lactate Metabolism: A Randomized Controlled Trial.

OBJECTIVE:Lactate is an intermediate of glucose metabolism that has been implicated in the pathogenesis of insulin resistance. This study evaluated the relationship between glucose kinetics and plasma lactate concentration ([LAC]) before and after manipulating insulin sensitivity by progressive weight loss. METHODS:Forty people with obesity (BMI = 37.9 ± 4.3 kg/m2 ) were randomized to weight maintenance (n = 14) or weight loss (n = 19). Subjects were studied before and after 6 months of weight maintenance and before and after 5%, 11%, and 16% weight loss. A hyperinsulinemic-euglycemic clamp procedure in conjunction with [6,6-2 H2 ]glucose tracer infusion was used to assess glucose kinetics. RESULTS:At baseline, fasting [LAC] correlated positively with endogenous glucose production rate (r = 0.532; P = 0.001) and negatively with insulin sensitivity, assessed as the insulin-stimulated glucose disposal (r = -0.361; P = 0.04). Progressive (5% through 16%) weight loss caused a progressive decrease in fasting [LAC], and the decrease in fasting [LAC] after 5% weight loss was correlated with the decrease in endogenous glucose production (r = 0.654; P = 0.002) and the increase in insulin sensitivity (r = -0.595; P = 0.007). CONCLUSIONS:This study demonstrates the interrelationships among weight loss, hepatic and muscle glucose kinetics, insulin sensitivity, and [LAC], and it suggests that [LAC] can serve as an additional biomarker of glucose-related insulin resistance

Hepatitis B surface antigen in urine of hemodialysis patients

Hepatitis B surface antigen in urine of hemodialysis patients. As part of an extensive epidemiological survey of chronic hemodialysis patients in Michigan, hepatitis B surface antigen (HBsAg) was identified in the sera of 79 of 701 (11%) patients. Of these patients, 59 were carriers of HBsAg for three or more months. Urine samples were collected from 36 of 39 HBsAg carriers having urinary output. Of these samples, 19 (52%) were positive for HBsAg by radioimmunoassay; this was confirmed by specific antibody neutralization. The HBsAg was not identified in the urine of seven hemodialysis patients who were lacking serum HBsAg or in urine samples from three HBsAg sero-carriers who had normal renal function. Patients undergoing maintenance hemodialysis appear to constitute a large reservoir of HBsAg chronic carriers. This study indicates that a minimum of 50% of persistent HBsAg carriers who are producing urine have detectable. HBsAg in single, randomly timed, unconcentrated urine specimen. These data suggest that urine may represent a potential vehicle for transmission in nonparenterally acquired hepatitis B.Antigène de surface de l'hépatite B dans l'urine de malades en hémodialyse. Dans le cadre d'une large enquête épidémiologique à propos des malades en hémodialyse chronique dans le Michigan, l'antigène de surface de l'hépatite B (HBsAg) a été identifié dans le sérum de 79 parmi 701 malades (11%). Parmi ces malades, 59 étaient des porteurs de HBsAg depuis 3 mois ou plus. L'urine de 36 des 39 porteurs de HBsAg, qui avaient une diurèse, a été recueillie. Parmi ces 36 urines, 19 (52%) sont positives pour HBsAg par radio-immunologie, ce qui est confirmé par la neutralisation au moyen d'anticorps spécifique. Le HBsAg n'apas été identifié dans l'urine de 7 malades en hémodialyse qui n'avaient pas le HBsAg sérique et dans l'urine de 3 porteurs de HBsAg dont les fonctions rénales étaient normales. Les malades soumis à l'hémodialyse itérative paraissent constituer un grand réservoir de porteurs chroniques de HBsAg. Cette étude indique qu'au minimum 50% des porteurs chroniques de HBsAg qui ont une diurèse, ont un HBsAg détectable dans un échantillon unique d'urine, prélevé au hasard, non concentré. Ces résultats suggèrent que l'urine peut être un véhicule de transmission de l'hépatite B acquise par voie non parentérale

Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?

Rare and ultra-rare diseases (URDs) are often chronic and life-threatening conditions that have a profound impact on sufferers and their families, but many are notoriously difficult to detect. Niemann-Pick disease type C (NP-C) serves to illustrate the challenges, benefits and pitfalls associated with screening for ultra-rare inborn errors of metabolism (IEMs). A comprehensive, non-systematic review of published information from NP-C screening studies was conducted, focusing on diagnostic methods and study designs that have been employed to date. As a key part of this analysis, data from both successful studies (where cases were positively identified) and unsuccessful studies (where the chosen approach failed to identify any cases) were included alongside information from our own experiences gained from the planning and execution of screening for NP-C. On this basis, best-practice recommendations for ultra-rare IEM screening are provided. Twenty-six published screening studies were identified and categorised according to study design into four groups: 1) prospective patient cohort and family-based secondary screenings (18 studies);2) analyses of archived 'biobank' materials (one study);3) medical chart review and bioinformatics data mining (five studies);and 4) newborn screening (two studies). NPC1/NPC2 sequencing was the most common primary screening method (Sanger sequencing in eight studies and next-generation sequencing [gene panel or exome sequencing] in five studies), followed by biomarker analyses (usually oxysterols) and clinical surveillance. Historically, screening for NP-C has been based on single-patient studies, small case series, and targeted cohorts, but the emergence of new diagnostic methods over the last 5-10 years has provided opportunities to screen for NP-C on a larger scale. Combining clinical, biomarker and genetic diagnostic methods represents the most effective way to identify NP-C cases, while reducing the likelihood of misdiagnosis. Our recommendations are intended as a guide for planning screening protocols for ultra-rare IEMs in general

The Zwicky Transient Facility Alert Distribution System

The Zwicky Transient Facility (ZTF) survey generates real-time alerts for optical transients, variables, and moving objects discovered in its wide-field survey. We describe the ZTF alert stream distribution and processing (filtering) system. The system uses existing open-source technologies developed in industry: Kafka, a real-time streaming platform, and Avro, a binary serialization format. The technologies used in this system provide a number of advantages for the ZTF use case, including (1) built-in replication, scalability, and stream rewind for the distribution mechanism; (2) structured messages with strictly enforced schemas and dynamic typing for fast parsing; and (3) a Python-based stream processing interface that is similar to batch for a familiar and user-friendly plug-in filter system, all in a modular, primarily containerized system. The production deployment has successfully supported streaming up to 1.2 million alerts or roughly 70 GB of data per night, with each alert available to a consumer within about 10 s of alert candidate production. Data transfer rates of about 80,000 alerts/minute have been observed. In this paper, we discuss this alert distribution and processing system, the design motivations for the technology choices for the framework, performance in production, and how this system may be generally suitable for other alert stream use cases, including the upcoming Large Synoptic Survey Telescope.Comment: Published in PASP Focus Issue on the Zwicky Transient Facility (doi: 10.1088/1538-3873/aae904). 9 Pages, 2 Figure

Cataclysmic Variables in the First Year of the Zwicky Transient Facility

Using selection criteria based on amplitude, time, and color, we have identified 329 objects as known or candidate cataclysmic variables (CVs) during the first year of testing and operation of the Zwicky Transient Facility. Of these, 90 are previously confirmed CVs, 218 are strong candidates based on the shape and color of their light curves obtained during 3–562 days of observation, and the remaining 21 are possible CVs but with too few data points to be listed as good candidates. Almost half of the strong candidates are within 10 deg of the galactic plane, in contrast to most other large surveys that have avoided crowded fields. The available Gaia parallaxes are consistent with sampling the low mass transfer CVs, as predicted by population models. Our follow-up spectra have confirmed Balmer/helium emission lines in 27 objects, with four showing high-excitation He ii emission, including candidates for an AM CVn, a polar, and an intermediate polar. Our results demonstrate that a complete survey of the Galactic plane is needed to accomplish an accurate determination of the number of CVs existing in the Milky Way

Processing Images from the Zwicky Transient Facility

The Zwicky Transient Facility is a new robotic-observing program, in which a newly engineered 600-MP digital camera with a pioneeringly large field of view, 47~square degrees, will be installed into the 48-inch Samuel Oschin Telescope at the Palomar Observatory. The camera will generate $\sim 1$~petabyte of raw image data over three years of operations. In parallel related work, new hardware and software systems are being developed to process these data in real time and build a long-term archive for the processed products. The first public release of archived products is planned for early 2019, which will include processed images and astronomical-source catalogs of the northern sky in the $g$ and $r$ bands. Source catalogs based on two different methods will be generated for the archive: aperture photometry and point-spread-function fitting.Comment: 6 pages, 4 figures, submitted to RTSRE Proceedings (www.rtsre.org

Attitudes to Interprofessional Education Among Health Science Students Engaging in a Multidisciplinary Workshop Series

Introduction: Interprofessional education (IPE) provides an opportunity for students from single-professions to interact with other disciplines. Student attitude to IPE can impact engagement and change in attitude may provide an indicator of the impact of IPE. This study examines pre-workshop attitudes to IPE and change in attitude following a series of three IPE workshops. Methods: Preworkshop attitudes were examined using the Readiness for Interprofessional Learning Scale (RIPLS) and the Interprofessional Education Perception Scale (IEPS). The IEPS was repeated at the start of Workshop 1 and at the end of Workshop 3. Data were analyzed using linear regression analysis and linear mixed methods for repeated measures. Results: 405 students participated (pre-workshop n=122; workshop 1 n=244; workshop 3 n=236). Pre-workshop attitudinal scores were high. While male gender and studying medicine negatively predicted attitude across some domains, previous experience of a joint patient treatment session on clinical placement positively predicted attitude in the domain of Perception of Actual Cooperation (standardised Beta 0.283, p=0.005). Attitude to IPE improved across all domains of the IEPS from online preparation to the end of workshop 3 (pCompetency and Autonomy, and in the domain of Perceived Need for Cooperation improved only following online preparation, while the domain of Perception of Actual Cooperation improved following both online preparation and participation in the workshops. Discussion: The results presented reflect positively on student readiness for IPE. Attitudes were further improved following engagement in a structured series of IPE workshops

A New Class of Changing-Look LINERs

We report the discovery of six active galactic nuclei (AGN) caught "turning on" during the first nine months of the Zwicky Transient Facility (ZTF) survey. The host galaxies were classified as LINERs by weak narrow forbidden line emission in their archival SDSS spectra, and detected by ZTF as nuclear transients. In five of the cases, we found via follow-up spectroscopy that they had transformed into broad-line AGN, reminiscent of the changing-look LINER iPTF 16bco. In one case, ZTF18aajupnt/AT2018dyk, follow-up HST UV and ground-based optical spectra revealed the transformation into a narrow-line Seyfert 1 (NLS1) with strong [Fe VII, X, XIV] and He II 4686 coronal lines. Swift monitoring observations of this source reveal bright UV emission that tracks the optical flare, accompanied by a luminous soft X-ray flare that peaks ~60 days later. Spitzer follow-up observations also detect a luminous mid-infrared flare implying a large covering fraction of dust. Archival light curves of the entire sample from CRTS, ATLAS, and ASAS-SN constrain the onset of the optical nuclear flaring from a prolonged quiescent state. Here we present the systematic selection and follow-up of this new class of changing-look LINERs, compare their properties to previously reported changing-look Seyfert galaxies, and conclude that they are a unique class of transients well-suited to test the uncertain physical processes associated with the LINER accretion state.Comment: Submitted to ApJ, 31 pages, 17 Figures (excluding Appendix due to file size constraints but will be available in electronic version

Positive psychosocial factors may protect against perceived stress in people with systemic lupus erythematosus with and without trauma history

Objective: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. Methods: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. Results: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (−0.67 (−0.94 to –0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011).Conclusion: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events