GoMiner: a resource for biological interpretation of genomic and proteomic data

We have developed GoMiner, a program package that organizes lists of 'interesting' genes (for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. GoMiner provides quantitative and statistical output files and two useful visualizations. The first is a tree-like structure analogous to that in the AmiGO browser and the second is a compact, dynamically interactive 'directed acyclic graph'. Genes displayed in GoMiner are linked to major public bioinformatics resources

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.National Institute for Health ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/nrclinonc.2016.7

Current and future trends in tuberculosis incidence in New York City: a dynamic modelling analysis

Background: After steady decline since the 1990s, tuberculosis incidence in New York City and throughout the USA has plateaued. We aimed to explore the major drivers of the flattening of tuberculosis incidence in New York City and to project the future trajectory of the tuberculosis epidemic in the absence of any additional intervention. Methods: We developed a compartmental transmission model of tuberculosis in New York City. The model was parameterised with detailed epidemiological data and stratified by age and nativity (US-born vs foreign-born). We ran the model under five alternative scenarios representing different explanations for recent declines in tuberculosis incidence. We evaluated the relative likelihood of each scenario by comparing its output with available data. We used the most likely scenarios to explore potential mechanisms underlying the recent declines in tuberculosis in New York City and to describe the reasonable range of future epidemic trajectories. Our primary outcome was the projected rate of decline in tuberculosis incidence from 2015 to 2025. Model calibration yielded estimates of future disease incidence and reductions in incidence with 95% credible intervals (CrIs). Findings: Demographic changes and declining tuberculosis transmission alone were insufficient to explain recent trends in tuberculosis incidence in New York City. Only scenarios that assumed contemporary changes in tuberculosis dynamics among foreign-born individuals—a declining rate of reactivation or a decrease in imported subclinical tuberculosis—could accurately describe the trajectory of disease incidence since 2007. In those scenarios, the projected decline in incidence from 2015 to 2025 varied from minimal (2·0% per year [95% CrI 0·4–3·5]) to similar to 2005 to 2009 trends (4·4% per year [2·5–6·4]). The primary factor differentiating optimistic from pessimistic projections was the degree to which improvements in tuberculosis dynamics among the foreign-born population continued into the coming decade. Interpretation: Further progress towards elimination of tuberculosis in New York City requires additional focus on the foreign-born population. Without additional intervention in this group, tuberculosis incidence might not decline further. Funding: None

Do Symptoms of Depression Interact with Substance Use to Affect HIV Continuum of Care Outcomes?

Few studies examine how depression and substance use interact to affect HIV control. In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95-1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74-0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression

The relationship of alcohol and other drug use during the COVID-19 pandemic among people with or at risk of HIV; A cross-sectional survey of people enrolled in Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) cohorts.

BackgroundAlcohol use during the COVID-19 pandemic increased. People living with HIV or at risk for HIV acquisition often have psycho-social and structural barriers or co-occurring substance use making them vulnerable to the adverse effects of alcohol. We describe factors associated with alcohol use during the COVID-19 pandemic in this group.MethodsFrom May 2020 to February 2021, 1984 people enrolled in 6 existing cohort studies completed surveys about alcohol and other drug use during the COVID-19 pandemic. We describe the past-month prevalence of no alcohol use, low-risk use, and hazardous use. We use multinomial regression to describe factors associated with low-risk or hazardous alcohol use relative to no alcohol use.ResultsForty-five percent of participants reported no alcohol use, 33% low-risk use, and 22% hazardous use in the past 30 days. Cannabis and stimulant use were associated with a higher prevalence of low-risk use relative to no use. Tobacco, stimulant, cannabis use and recent overdose were associated with a higher prevalence of hazardous use relative to no use. Substance use treatment and living with HIV were associated with a lower prevalence of low-risk or hazardous use relative to no use.ConclusionsStimulant use was strongly associated with a higher prevalence of hazardous alcohol use while engagement in substance use treatment or living with HIV was associated with a lower prevalence. Ascertaining hazardous alcohol and other drug use, particularly stimulants, in clinical care could identify people at higher risk for adverse outcome and harm reduction counseling

COVID-19 and the HIV continuum in people living with HIV enrolled in Collaborating Consortium of Cohorts Producing NIDA Opportunities (C3PNO) cohorts.

BackgroundThe COVID-19 pandemic disrupted the normal delivery of HIV care, altered social support networks, and caused economic insecurity. People with HIV (PWH) are vulnerable to such disruptions, particularly if they have a history of substance use. We describe engagement in care and adherence to antiretroviral therapy (ART) for PWH during the pandemic.MethodsFrom May 2020 to February 2021, 773 PWH enrolled in 6 existing cohorts completed 1495 surveys about substance use and engagement in HIV care during the COVID-19 pandemic. We described the prevalence and correlates of having missed a visit with an HIV provider in the past month and having missed a dose of ART in the past week.ResultsThirteen percent of people missed an HIV visit in the past month. Missing a visit was associated with unstable housing, food insecurity, anxiety, low resiliency, disruptions to mental health care, and substance use including cigarette smoking, hazardous alcohol use, cocaine, and cannabis use. Nineteen percent of people reported missing at least one dose of ART in the week prior to their survey. Missing a dose of ART was associated with being a man, low resiliency, disruptions to mental health care, cigarette smoking, hazardous alcohol use, cocaine, and cannabis use, and experiencing disruptions to substance use treatment.ConclusionsSocial determinants of health, substance use, and disruptions to mental health and substance use treatment were associated with poorer engagement in HIV care. Close attention to continuity of care during times of social disruption is especially critical for PWH