Going into the groin: Injection into the femoral vein among people who inject drugs in three urban areas of England

Background: There have been increasing concerns about injection into the femoral vein – groin injecting – among people who inject drugs in a number of countries, though most studies have been small. The extent, reasons and harms associated with groin injecting are examined. Method: Participants were recruited using respondent driven sampling (2006–2009). Weighted data was examined using bivariate analyses and logistic regression. Results: The mean age was 32 years; 25% were women (N = 855). During the preceding 28 days, 94% had injected heroin and 13% shared needles/syringes. Overall, 53% reported ever groin injecting, with 9.8% first doing so at the same age as starting to inject. Common reasons given for groin injecting included: “Can’t get a vein elsewhere” (68%); “It is discreet” (18%); and “It is quicker” (14%). During the preceding 28 days, 41% had groin injected, for 77% this was the only body area used (for these “It is discreet” was more frequently given as a reason). In the multivariable analysis, groin injection was associated with: swabbing injection sites; saving filters for reuse; and receiving opiate substitution therapy. It was less common among those injecting into two body areas, and when other people (rather than services) were the main source of needles. Groin injection was more common among those with hepatitis C and reporting ever having deep vein thrombosis or septicaemia. Conclusions: Groin injection was common, often due to poor vascular access, but for some it was out of choice. Interventions are required to reduce injecting risk and this practice

Not in the vein: 'missed hits', subcutaneous and intramuscular injections and associated harms among people who inject psychoactive drugs in Bristol, United Kingdom

Background: The extent of intentional or accidental subcutaneous and intramuscular injections and the factors associated with these have rarely been studied among people who inject drugs, yet these may play an important role in the acquisition bacterial infections. This study describes the extent of these, and in particular the factors and harms associated with accidental subcutaneous and intramuscular injections (i.e. ‘missed hits’). Methods: People who inject drugs were recruited using respondent driven sampling. Weighted data was examined using bivariate analyses and logistic regression. Results: The participants mean age was 33 years (31% aged under 30-years), 28% were women, and the mean time since first injection was 12 years (N = 329). During the preceding three months, 97% had injected heroin, 71% crack-cocaine, and 16% amphetamines; 36% injected daily. Overall, 99% (325) reported that they aimed to inject intravenously; only three aimed to inject subcutaneously and one intramuscularly. Of those that aimed to inject intravenously, 56% (181) reported ever missing a vein (for 51 this occurred more than four times month on average). Factors associated with ‘missed hits’ suggested that these were the consequence of poor vascular access, injection technique and/or hygiene. ‘Missed hits’ were twice as common among those reporting sores/open wounds, abscesses, or redness, swelling and tenderness at injection sites. Conclusion: Intentional subcutaneous and intramuscular injections are rare in this sample. ‘Missed hits’ are common and appear to be associated with poor injection practice. Interventions are required to reduce risk through improving injecting practice and hygiene

Cumulative burden of depression and all-cause mortality in women living with human immunodeficiency virus

Background Research linking depression to mortality among people living with human immunodeficiency virus (PLWH) has largely focused on binary "always vs never" characterizations of depression. However, depression is chronic and is likely to have cumulative effects on mortality over time. Quantifying depression as a cumulative exposure may provide a better indication of the clinical benefit of enhanced depression treatment protocols delivered in HIV care settings. Methods Women living with HIV (WLWH), naive to antiretroviral therapy, from the Women's Interagency HIV Study were followed from their first visit in or after 1998 for up to 10 semiannual visits (5 years). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. An area-under-the-curve approach was used to translate CES-D scores into a time-updated measure of cumulative days with depression (CDWD). We estimated the effect of CDWD on all-cause mortality using marginal structural Cox proportional hazards models. Results Overall, 818 women contributed 3292 woman-years over a median of 4.8 years of follow-up, during which the median (interquartile range) CDWD was 366 (97-853). Ninety-four women died during follow-up (2.9 deaths/100 woman-years). A dose-response relationship was observed between CDWD and mortality. Each additional 365 days spent with depression increased mortality risk by 72% (hazard ratio, 1.72; 95% confidence interval, 1.34-2.20). Conclusions In this sample of WLWH, increased CDWD elevated mortality rates in a dose-response fashion. More frequent monitoring and enhanced depression treatment protocols designed to reduce CDWD may interrupt the accumulation of mortality risk among WLWH

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Isotopic Grand Unification with the Inclusion of Gravity (revised version)

We introduce a dual lifting of unified gauge theories, the first characterized by the isotopies, which are axiom- preserving maps into broader structures with positive-definite generalized units used for the representation of matter under the isotopies of the Poincare' symmetry, and the second characterized by the isodualities, which are anti-isomorphic maps with negative-definite generalized units used for the representation of antimatter under the isodualities of the Poincare' symmetry. We then submit, apparently for the first time, a novel grand unification with the inclusion of gravity for matter embedded in the generalized positive-definite units of unified gauge theories while gravity for antimatter is embedded in the isodual isounit. We then show that the proposed grand unification provides realistic possibilities for a resolution of the axiomatic incompatibilities between gravitation and electroweak interactions due to curvature, antimatter and the fundamental space-time symmetries.Comment: 20 pages, Latex, revised in various details and with added reference

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available