Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk. Interpretation Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID

Hurricane Gustav (2008) Waves and Storm Surge: Hindcast, Synoptic Analysis, and Validation in Southern Louisiana

Hurricane Gustav (2008) made landfall in southern Louisiana on 1 September 2008 with its eye never closer than 75 km to New Orleans, but its waves and storm surge threatened to flood the city. Easterly tropical-storm-strength winds impacted the region east of the Mississippi River for 12-15 h, allowing for early surge to develop up to 3.5 m there and enter the river and the city's navigation canals. During landfall, winds shifted from easterly to southerly, resulting in late surge development and propagation over more than 70 km of marshes on the river's west bank, over more than 40 km of Caernarvon marsh on the east bank, and into Lake Pontchartrain to the north. Wind waves with estimated significant heights of 15 m developed in the deep Gulf of Mexico but were reduced in size once they reached the continental shelf. The barrier islands further dissipated the waves, and locally generated seas existed behind these effective breaking zones. The hardening and innovative deployment of gauges since Hurricane Katrina (2005) resulted in a wealth of measured data for Gustav. A total of 39 wind wave time histories, 362 water level time histories, and 82 high water marks were available to describe the event. Computational models-including a structured-mesh deepwater wave model (WAM) and a nearshore steady-state wave (STWAVE) model, as well as an unstructured-mesh "simulating waves nearshore'' (SWAN) wave model and an advanced circulation (ADCIRC) model-resolve the region with unprecedented levels of detail, with an unstructured mesh spacing of 100-200 m in the wave-breaking zones and 20-50 m in the small-scale channels. Data-assimilated winds were applied using NOAA's Hurricane Research Division Wind Analysis System (H*Wind) and Interactive Objective Kinematic Analysis (IOKA) procedures. Wave and surge computations from these models are validated comprehensively at the measurement locations ranging from the deep Gulf of Mexico and along the coast to the rivers and floodplains of southern Louisiana and are described and quantified within the context of the evolution of the storm

A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000 : 1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m−2×three administrations with a serum carboxypeptidase G2 level of 0.05 U ml−1. Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems

The decline and rise of neighbourhoods: the importance of neighbourhood governance

There is a substantial literature on the explanation of neighbourhood change. Most of this literature concentrates on identifying factors and developments behind processes of decline. This paper reviews the literature, focusing on the identification of patterns of neighbourhood change, and argues that the concept of neighbourhood governance is a missing link in attempts to explain these patterns. Including neighbourhood governance in the explanations of neighbourhood change and decline will produce better explanatory models and, finally, a better view about what is actually steering neighbourhood change

Identifying risks for male street gang affiliation: a systematic review and narrative synthesis

Gang violence has increased in recent years. Individuals are becoming gang affiliated younger, and many have suffered historic maltreatment. Subsequent exposure to violence can result in profound consequences, including acute psychological harm. This review aims to identify predictive risk factors for male street gang affiliation. A systematic literature search was conducted utilising PsycINFO, PsycARTICLES, Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews and the Social Policy and Practice databases (from the databases’ inception to 03/04/15). From this search, n=244 peer-reviewed papers were included in an initial scoping review, and n=102 thereafter met criteria for a systematic review; a narrative synthesis follows. Gang members have typically faced numerous historic adversities across multiple domains; individual, family, peers, school and community. Cumulative factors generated an independent risk. The meta-narrative described an overarching failure to safeguard vulnerable individuals, with the motivation for gang affiliation hypothetically arising from an attempt to have their basic needs met. Clinical and research recommendations were made to inform early intervention policy and practice

A Biological Model for Influenza Transmission: Pandemic Planning Implications of Asymptomatic Infection and Immunity

Background: The clinical attack rate of influenza is influenced by prior immunity and mixing patterns in the host population, and also by the proportion of infections that are asymptomatic. This complexity makes it difficult to directly estimate R0 from the attack rate, contributing to uncertainty in epidemiological models to guide pandemic planning. We have modelled multiple wave outbreaks of influenza from different populations to allow for changing immunity and asymptomatic infection and to make inferences about R0. \ud \ud Data and Methods. On the island of Tristan da Cunha (TdC), 96% of residents reported illness during an H3N2 outbreak in 1971, compared with only 25% of RAF personnel in military camps during the 1918 H1N1 pandemic. Monte Carlo Markov Chain (MCMC) methods were used to estimate model parameter distributions. \ud \ud Findings. We estimated that most islanders on TdC were non-immune (susceptible) before the first wave, and that almost all exposures of susceptible persons caused symptoms. The median R0 of 6.4 (95% credibility interval 3.7–10.7) implied that most islanders were exposed twice, although only a minority became ill in the second wave because of temporary protection following the first wave. In contrast, only 51% of RAF personnel were susceptible before the first wave, and only 38% of exposed susceptibles reported symptoms. R0 in this population was also lower [2.9 (2.3–4.3)], suggesting reduced viral transmission in a partially immune population. \ud \ud Interpretation: Our model implies that the RAF population was partially protected before the summer pandemic wave of 1918, arguably because of prior exposure to interpandemic influenza. Without such protection, each symptomatic case of influenza would transmit to between 2 and 10 new cases, with incidence initially doubling every 1–2 days. Containment of a novel virus could be more difficult than hitherto supposed

A Population Genetic Approach to Mapping Neurological Disorder Genes Using Deep Resequencing

Deep resequencing of functional regions in human genomes is key to identifying potentially causal rare variants for complex disorders. Here, we present the results from a large-sample resequencing (n = 285 patients) study of candidate genes coupled with population genetics and statistical methods to identify rare variants associated with Autism Spectrum Disorder and Schizophrenia. Three genes, MAP1A, GRIN2B, and CACNA1F, were consistently identified by different methods as having significant excess of rare missense mutations in either one or both disease cohorts. In a broader context, we also found that the overall site frequency spectrum of variation in these cases is best explained by population models of both selection and complex demography rather than neutral models or models accounting for complex demography alone. Mutations in the three disease-associated genes explained much of the difference in the overall site frequency spectrum among the cases versus controls. This study demonstrates that genes associated with complex disorders can be mapped using resequencing and analytical methods with sample sizes far smaller than those required by genome-wide association studies. Additionally, our findings support the hypothesis that rare mutations account for a proportion of the phenotypic variance of these complex disorders

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015