An Exploration of Methods to Resolve Inconsistent Self-Reporting of Chronic Conditions and Impact on Multimorbidity in the Canadian Longitudinal Study on Aging

OBJECTIVES: To quantify inconsistent self-reporting of chronic conditions between the baseline (2011-2015) and first follow-up surveys (2015-2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity.METHODS: Community-dwelling adults aged 45-85 years in the baseline and first follow-up surveys were included ( n = 45,184). At each survey, participants self-reported whether they ever had a physician diagnosis of 35 chronic conditions. Identifiable inconsistent responses were enumerated. RESULTS: 32-40% of participants had at least one inconsistent response across all conditions. Illness-related information (e.g., taking medication) resolved most inconsistent responses (&gt;93%) while computer-assisted software asking participants to confirm their inconsistent disease status resolved ≤53%. Using these adjudication methods, multimorbidity prevalence at follow-up increased by ≤1.6% compared to the prevalence without resolving inconsistent responses.DISCUSSION: Inconsistent self-reporting of chronic conditions is common but may not substantially affect multimorbidity prevalence. Future research should validate methods to resolve inconsistencies.</p

Evolution of Black Holes in the Galaxy

In this article we consider the formation and evolution of black holes, especially those in binary stars where radiation from the matter falling on them can be seen. We consider a number of effects introduced by some of us, which are not traditionally included in binary evolution of massive stars. These are (i) hypercritical accretion, which allows neutron stars to accrete enough matter to collapse to a black hole during their spiral-in into another star. (ii) the strong mass loss of helium stars, which causes their evolution to differ from that of the helium core of a massive star. (iii) The direct formation of low-mass black holes (M\sim2\msun) from single stars, a consequence of a significant strange-matter content of the nuclear-matter equation of state at high density. We discuss these processes here, and then review how they affect various populations of binaries with black holes and neutron stars.Comment: 46 pages, 1 figure, to be published in Physics Repor

X-ray Emission from Nitrogen-Type Wolf-Rayet Stars

We summarize new X-ray detections of four nitrogen-type Wolf-Rayet (WR) stars obtained in a limited survey aimed at establishing the X-ray properties of WN stars across their full range of spectral subtypes. None of the detected stars is so far known to be a close binary. We report Chandra detections of WR 2 (WN2), WR 18 (WN4), and WR 134 (WN6), and an XMM-Newton detection of WR79a (WN9ha). These observations clearly demonstrate that both WNE and WNL stars are X-ray sources. We also discuss Chandra archive detections of the WN6h stars WR 20b, WR 24, and WR 136 and ROSAT non-detections of WR 16 (WN8h) and WR 78 (WN7h). The X-ray spectra of all WN detections show prominent emission lines and an admixture of cool (kT 2 keV) plasma. The hotter plasma is not predicted by radiative wind shock models and other as yet unidentified mechanisms are at work. Most stars show X-ray absorption in excess of that expected from visual extinction (Av), likely due to their strong winds or cold circumstellar gas. Existing data suggest a falloff in X-ray luminosity toward later WN7-9 subtypes, which have higher Lbol but slower, denser winds than WN2-6 stars. This provides a clue that wind properties may be a more crucial factor in determining emergent X-ray emission levels than bolometric luminosity.Comment: 42 pages, 5 tables, 10 figure

A 2.3-Day Periodic Variability in the Apparently Single Wolf-Rayet Star WR 134: Collapsed Companion or Rotational Modulation?

We present the results of an intensive campaign of spectroscopic and photometric monitoring of the peculiar Wolf-Rayet star WR 134 from 1989 to 1997. This unprecedentedly large data set allows us to confirm unambiguously the existence of a coherent 2.25 +/- 0.05 day periodicity in the line-profile changes of He II 4686, although the global pattern of variability is different from one epoch to another. This period is only marginally detected in the photometric data set. Assuming the 2.25 day periodic variability to be induced by orbital motion of a collapsed companion, we develop a simple model aiming at investigating (i) the effect of this strongly ionizing, accreting companion on the Wolf-Rayet wind structure, and (ii) the expected emergent X-ray luminosity. We argue that the predicted and observed X-ray fluxes can only be matched if the accretion on the collapsed star is significantly inhibited. Additionally, we performed simulations of line-profile variations caused by the orbital revolution of a localized, strongly ionized wind cavity surrounding the X-ray source. A reasonable fit is achieved between the observed and modeled phase-dependent line profiles of He II 4686. However, the derived size of the photoionized zone substantially exceeds our expectations, given the observed low-level X-ray flux. Alternatively, we explore rotational modulation of a persistent, largely anisotropic outflow as the origin of the observed cyclical variability. Although qualitative, this hypothesis leads to greater consistency with the observations.Comment: 34 pages, 16 figures. Accepted by the Astrophysical Journa

Beef in an Optimal Lean Diet study: effects on lipids, lipoproteins, and apolipoproteins123

Background: A Step I diet with lean beef compared with lean white meat both decrease LDL cholesterol. To our knowledge, no studies have evaluated a low–saturated fatty acid (SFA) (<7% calories) diet that contains lean beef

Building connectomes using diffusion MRI: why, how and but

Why has diffusion MRI become a principal modality for mapping connectomes in vivo? How do different image acquisition parameters, fiber tracking algorithms and other methodological choices affect connectome estimation? What are the main factors that dictate the success and failure of connectome reconstruction? These are some of the key questions that we aim to address in this review. We provide an overview of the key methods that can be used to estimate the nodes and edges of macroscale connectomes, and we discuss open problems and inherent limitations. We argue that diffusion MRI-based connectome mapping methods are still in their infancy and caution against blind application of deep white matter tractography due to the challenges inherent to connectome reconstruction. We review a number of studies that provide evidence of useful microstructural and network properties that can be extracted in various independent and biologically-relevant contexts. Finally, we highlight some of the key deficiencies of current macroscale connectome mapping methodologies and motivate future developments

Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection

ABSTRACT: Background: Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming. Nonetheless, few in silico assessments of the effect of nutritional conditions on Mtb’s vulnerability and metabolic adaptation have been carried out. Results: A genome-scale model (GEM) of Mtb, modified from the H37Rv iOSDD890, was used to explore the metabolic reprogramming of two Mtb knockout mutants (pfkA- and icl-mutants), lacking key enzymes of central carbon metabolism, while exposed to changing nutritional conditions (oxygen, and carbon and nitrogen sources). A combination of shadow pricing, sensitivity analysis, and flux distributions patterns allowed us to identify metabolic behaviors that are in agreement with phenotypes reported in the literature. During hypoxia, at high glucose consumption, the Mtb pfkA-mutant showed a detrimental growth effect derived from the accumulation of toxic sugar phosphate intermediates (glucose-6-phosphate and fructose-6-phosphate) along with an increment of carbon fluxes towards the reductive direction of the tricarboxylic acid cycle (TCA). Furthermore, metabolic reprogramming of the icl-mutant (icl1&icl2) showed the importance of the methylmalonyl pathway for the detoxification of propionyl-CoA, during growth at high fatty acid consumption rates and aerobic conditions. At elevated levels of fatty acid uptake and hypoxia, we found a drop in TCA cycle intermediate accumulation that might create redox imbalance. Finally, findings regarding Mtb-mutant metabolic adaptation associated with asparagine consumption and acetate, succinate and alanine production, were in agreement with literature reports. Conclusions: This study demonstrates the potential application of genome-scale modeling, flux balance analysis (FBA), phenotypic phase plane (PhPP) analysis and shadow pricing to generate valuable insights about Mtb metabolic reprogramming in the context of human granulomas

Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis—a review

This review deals with podocyte proteins that play a significant role in the structure and function of the glomerular filter. Genetic linkage studies has identified several genes involved in the development of nephrotic syndrome and contributed to the understanding of the pathophysiology of glomerular proteinuria and/or focal segmental glomerulosclerosis. Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin β2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome. In addition, the role of the proteins which have shown to be important for the structure and functions by gene knockout studies in mice, are also discussed. Furthermore, some rare syndromes with glomerular involvement, in which molecular defects have been recently identified, are briefly described. In summary, this review updates the current knowledge of genetic causes of congenital and childhood nephrotic syndrome and provides new insights into mechanisms of glomerular dysfunction