Clinical perspectives of emerging pathogens in bleeding disorders.

As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma

Incremental healthcare resource utilization and costs in US patients with Cushing's disease compared with diabetes mellitus and population controls

Abstract Purpose Resource utilization and costs in Cushing's disease (CD) patients have not been studied extensively. We compared CD patients with diabetes mellitus (DM) patients and population-based controls to characterize differences in utilization and costs. Methods Using 2008-2012 MarketScan Ò database, we identified three patient groups: (1) CD patients; (2) DM patients; and (3) population-based control patients without CD. DM and control patients were matched to CD patients by age, gender, region, and review year in a 2:1 ratio. Outcomes included annual healthcare resource utilization and costs. Results There were 1852 CD patients, 3704 DM patients and 3704 controls. Mean age was 42.9 years; 78.2 % were female. CD patients were hospitalized more frequently (19.3 %) than DM patients (11.0 %, p \ .001) or controls (5.6 %, p \ .001). CD patients visited the ED more frequently (25.4 %) than DM patients (21.1 %, p \ .001) or controls (14.3 %, p \ .001). CD patients had more office visits than DM patients (19.1 vs. 10.7, p \ .001) or controls (7.1, p \ .001). CD patients on average filled more prescriptions than DM patients (51.7 vs. 42.7, p \ .001) or controls (20.5, p \ .001). Mean total healthcare costs for CD patients were $26,269 versus$12,282 for DM patients (p \ .001) and $5869 for controls (p \ .001). Conclusions CD patients had significantly higher annual rates of healthcare resource utilization compared to matched DM patients and population controls without CD. CD patient costs were double DM costs and quadruple control costs. This study puts into context the additional burdens of CD over DM, a common, chronic endocrine condition affecting multiple organ systems, and population controls

A biphasic model of lifespan in nematode Caenorhabditis elegans worm

Ageing research focuses on identifying lifespan modifiers and understanding and appropriately interpreting their effects. One of the most relevant quantities being studied is the shape of the survival curve that can reveal crucial information on the mechanism of action. Here, we introduce a bilogistic model to describe the shape of the lifespan curves of Caenorhabditis elegans populations. Using the corrected Akaike information criterion and the RMSE as goodness-of-fit tests, we show that the bilogistic model provides a better fit to the experimental data from nematode worms than other mathematical models and can identify and confirm biphasic lifespan data. Our parametric model offers a method to interpret replicate experiments data in terms of the shape parameters of the lifespan curve and enables robust statistical analysis of intra- and inter-group variance. We apply the model to novel lifespan data from C. elegans and Drosophila melanogaster and provide a rational statistical analysis of lifespan modifiers such as temperature and daf-16/FOXO mutation

Temporal Trends in Smoking and Nicotine Dependence in Relation to Co-occurring Substance Use in the United States, 2005-2016

Background Despite an overall decline in tobacco use in the United States, secular trends of smoking and nicotine dependence with co-occurring substance use are not well characterized. Methods We examined self-reported tobacco and other substance use in 22,245 participants age 21–59 in the United States from six waves of the National Health and Nutrition Examination Survey (NHANES). Using Joinpoint regression, we assessed secular trends of smoking and nicotine dependence as a function of co-occurring use of alcohol, prescription opioids, marijuana/hashish, cocaine/heroin/methamphetamine, or other injection drug use. Multivariable logistic regressions were fitted to identify the potential risk factors. Results During 2005–2016, the prevalence of current smoking decreased (without co-occurring substance use: 17.0 %–12.7 %; with co-occurring use of one substance: 35.3 % to 24.6 %; with co-occurring use of two or more substances: 53.8 %–42.2 %), and moderate-to-severe nicotine dependence decreased as well (8.0 %–4.2 %, 16.0 %–8.8 %, and 23.9 %–15.7 %, respectively). Smoking and nicotine dependence were more likely in those with co-occurring use of one substance (current smoking: odds ratio [OR] = 2.22, 95 % confidence interval [CI] = 2.01–2.45); nicotine dependence: OR = 1.88, 95 % CI = 1.63–2.17) and in those with co-occurring use of two or more substances (current smoking: OR = 5.25, 95 % CI = 4.63–5.95; nicotine dependence: OR = 3.24, 95 % CI = 2.72–3.87). Conclusions Co-occurring substance use was associated with smaller reductions in tobacco use, over time, and with increased odds of nicotine dependence. This suggests that co-occurring substance users should be regarded as a tobacco-related disparity group and prioritized for tobacco control interventions

A biphasic model of lifespan in nematode Caenorhabditis elegans worm.

Ageing research focuses on identifying lifespan modifiers and understanding and appropriately interpreting their effects. One of the most relevant quantities being studied is the shape of the survival curve that can reveal crucial information on the mechanism of action. Here, we introduce a bilogistic model to describe the shape of the lifespan curves of Caenorhabditis elegans populations. Using the corrected Akaike information criterion and the RMSE as goodness-of-fit tests, we show that the bilogistic model provides a better fit to the experimental data from nematode worms than other mathematical models and can identify and confirm biphasic lifespan data. Our parametric model offers a method to interpret replicate experiments data in terms of the shape parameters of the lifespan curve and enables robust statistical analysis of intra- and inter-group variance. We apply the model to novel lifespan data from C. elegans and Drosophila melanogaster and provide a rational statistical analysis of lifespan modifiers such as temperature and daf-16/FOXO mutation

A Comprehensive X-ray Report on AT2019wey

The Galactic low-mass X-ray binary AT2019wey (ATLAS19bcxp, SRGA J043520.9+552226, SRGE J043523.3+552234, ZTF19acwrvzk) was discovered as a new optical transient in Dec 2019, and independently as an X-ray transient in Mar 2020. In this paper, we present comprehensive NICER, NuSTAR, Chandra, Swift, and MAXI observations of AT2019wey from ~1 year prior to the discovery to the end of September 2020. AT2019wey appeared as a ~1 mCrab source and stayed at this flux density for several months, displaying a hard X-ray spectrum that can be modeled as a power-law with photon index Gamma~1.8. In June 2020 it started to brighten, and reached ~20 mCrab in ~2 months. The inclination of this system can be constrained to i≾30 deg by modeling the reflection spectrum. Starting from late-August (~59082 MJD), AT2019wey entered into the hard-intermediate state (HIMS), and underwent a few week-long timescale outbursts, where the brightening in soft X-rays is correlated with the enhancement of a thermal component. Low-frequency quasi-periodic oscillation (QPO) was observed in the HIMS. We detect no pulsation and in timing analysis of the NICER and NuSTAR data. The X-ray states and power spectra of AT2019wey are discussed against the landscape of low-mass X-ray binaries

Molecular Phylodynamics of the Heterosexual HIV Epidemic in the United Kingdom

The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses originating among immigrants from sub-Saharan Africa. The high rate of HIV evolution, combined with the availability of a very high density sample of viral sequences from routine clinical care has allowed the phylodynamics of the epidemic to be investigated for the first time. Sequences of the viral protease and partial reverse transcriptase coding regions from 11,071 patients infected with HIV of non-B subtypes were studied. Of these, 2774 were closely linked to at least one other sequence by nucleotide distance. Including the closest sequences from the global HIV database identified 296 individuals that were in UK-based groups of 3 or more individuals. There were a total of 8 UK-based clusters of 10 or more, comprising 143/2774 (5%) individuals, much lower than the figure of 25% obtained earlier for men who have sex with men (MSM). Sample dates were incorporated into relaxed clock phylogenetic analyses to estimate the dates of internal nodes. From the resulting time-resolved phylogenies, the internode lengths, used as estimates of maximum transmission intervals, had a median of 27 months overall, over twice as long as obtained for MSM (14 months), with only 2% of transmissions occurring in the first 6 months after infection. This phylodynamic analysis of non-B subtype HIV sequences representing over 40% of the estimated UK HIV-infected heterosexual population has revealed heterosexual HIV transmission in the UK is clustered, but on average in smaller groups and is transmitted with slower dynamics than among MSM. More effective intervention to restrict the epidemic may therefore be feasible, given effective diagnosis programmes