Drugs-related death soon after hospital discharge among drug treatment clients in Scotland:record linkage, validation and investigation of risk factors.

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting

Projections of the current and future disease burden of hepatitis C virus infection in Malaysia

The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods.An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia

Over 1200 drugs-related deaths and 190,000 opiate-user-years of follow-up : relative risks by sex and age-group

Heroin users/injectors' risk of drugs-related death by sex and current age is weakly estimated both in individual cohorts of under 1000 clients, 5000 person-years or 50 drugs-related deaths and when using cross-sectional data. A workshop in Cambridge analysed six cohorts who were recruited according to a common European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) protocol from drug treatment agencies in Barcelona, Denmark, Dublin, Lisbon, Rome and Vienna in the 1990s; and, as external reference, opiate-user arrestees in France and hepatitis C diagnosed ever-injectors in Scotland in 1993-2001, both followed by database linkage to December 2001. EMCDDA cohorts recorded approximately equal numbers of drugs-related deaths (864) and deaths from other non-HIV causes (865) during 106,152 person-years of follow-up. External cohorts contributed 376 drugs-related deaths (Scotland 195, France 181) and 418 deaths from non-HIV causes (Scotland 221, France 197) during 86,417 person-years of follow-up (Scotland 22,670, France 63,747). EMCDDA cohorts reported 707 drugs-related deaths in 81,367 man-years {8.7 per 1000 person-years, 95% CI: 8.1 to 9.4} but only 157 in 24,785 person-years for females {6.3 per 1000 person-years, 95% CI: 5.4 to 7.4}. Except in external cohorts, relative risks by current age-group were not particularly strong, and more modest in Poisson regression than in cross-sectional analyses: relative risk was 1.2 (95% CI: 1.0-1.4) for 35-44 year olds compared to 15-24 year 3 olds, but 1.4 for males (95%CI: 1.2-1.6), and dramatically lower at 0.44 after the first year of follow-up (95% CI: 0.37-0.52)

Extreme enrichment of Se, Te, PGE and Au in Cu sulfide microdroplets: evidence from LA-ICP-MS analysis of sulfides in the Skaergaard Intrusion, east Greenland

The Platinova Reef, in the Skaergaard Intrusion, east Greenland, is an example of a magmatic Cu–PGE–Au sulfide deposit formed in the latter stages of magmatic differentiation. As is characteristic with such deposits, it contains a low volume of sulfide, displays peak metal offsets and is Cu rich but Ni poor. However, even for such deposits, the Platinova Reef contains extremely low volumes of sulfide and the highest Pd and Au tenor sulfides of any magmatic ore deposit. Here, we present the first LA-ICP-MS analyses of sulfide microdroplets from the Platinova Reef, which show that they have the highest Se concentrations (up to 1200 ppm) and lowest S/Se ratios (190–700) of any known magmatic sulfide deposit and have significant Te enrichment. In addition, where sulfide volume increases, there is a change from high Pd-tenor microdroplets trapped in situ to larger, low tenor sulfides. The transition between these two sulfide regimes is marked by sharp peaks in Au, and then Te concentration, followed by a wider peak in Se, which gradually decreases with height. Mineralogical evidence implies that there is no significant post-magmatic hydrothermal S loss and that the metal profiles are essentially a function of magmatic processes. We propose that to generate these extreme precious and semimetal contents, the sulfides must have formed from an anomalously metal-rich package of magma, possibly formed via the dissolution of a previously PGE-enriched sulfide. Other processes such as kinetic diffusion may have also occurred alongside this to produce the ultra-high tenors. The characteristic metal offset pattern observed is largely controlled by partitioning effects, producing offset peaks in the order Pt+Pd>Au>Te>Se>Cu that are entirely consistent with published D values. This study confirms that extreme enrichment in sulfide droplets can occur in closed-system layered intrusions in situ, but this will characteristically form ore deposits that are so low in sulfide that they do not conform to conventional deposit models for Cu–Ni–PGE sulfides which require very high R factors, and settling of sulfide liquids

Single cell RNA-seq reveals profound transcriptional similarity between Barrett's oesophagus and oesophageal submucosal glands

Barrett’s oesophagus is a precursor of oesophageal adenocarcinoma. In this common condition, squamous epithelium in the oesophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s oesophagus is highly heterogeneous and its relationships to normal tissues are unclear. Here we investigate the cellular complexity of Barrett’s oesophagus and the upper gastrointestinal tract using RNA-sequencing of single cells from multiple biopsies from six patients with Barrett’s oesophagus and two patients without oesophageal pathology. We find that cell populations in Barrett’s oesophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with oesophageal submucosal gland cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s oesophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Effect of the relative shift between the electron density and temperature pedestal position on the pedestal stability in JET-ILW and comparison with JET-C

The electron temperature and density pedestals tend to vary in their relative radial positions, as observed in DIII-D (Beurskens et al 2011 Phys. Plasmas 18 056120) and ASDEX Upgrade (Dunne et al 2017 Plasma Phys. Control. Fusion 59 14017). This so-called relative shift has an impact on the pedestal magnetohydrodynamic (MHD) stability and hence on the pedestal height (Osborne et al 2015 Nucl. Fusion 55 063018). The present work studies the effect of the relative shift on pedestal stability of JET ITER-like wall (JET-ILW) baseline low triangularity (\u3b4) unseeded plasmas, and similar JET-C discharges. As shown in this paper, the increase of the pedestal relative shift is correlated with the reduction of the normalized pressure gradient, therefore playing a strong role in pedestal stability. Furthermore, JET-ILW tends to have a larger relative shift compared to JET carbon wall (JET-C), suggesting a possible role of the plasma facing materials in affecting the density profile location. Experimental results are then compared with stability analysis performed in terms of the peeling-ballooning model and with pedestal predictive model EUROPED (Saarelma et al 2017 Plasma Phys. Control. Fusion). Stability analysis is consistent with the experimental findings, showing an improvement of the pedestal stability, when the relative shift is reduced. This has been ascribed mainly to the increase of the edge bootstrap current, and to minor effects related to the increase of the pedestal pressure gradient and narrowing of the pedestal pressure width. Pedestal predictive model EUROPED shows a qualitative agreement with experiment, especially for low values of the relative shift