Building capacity for injury prevention: a process evaluation of a replication of the Cardiff Violence Prevention Programme in the Southeastern USA

Objectives Violence is a major public health problem in the USA. In 2016, more than 1.6 million assault-related injuries were treated in US emergency departments (EDs). Unfortunately, information about the magnitude and patterns of violent incidents is often incomplete and underreported to law enforcement (LE). In an effort to identify more complete information on violence for the development of prevention programme, a cross-sectoral Cardiff Violence Prevention Programme (Cardiff Model) partnership was established at a large, urban ED with a level I trauma designation and local metropolitan LE agency in the Atlanta, Georgia metropolitan area. The Cardiff Model is a promising violence prevention approach that promotes combining injury data from hospitals and LE. The objective was to describe the Cardiff Model implementation and collaboration between hospital and LE partners. Methods The Cardiff Model was replicated in the USA. A process evaluation was conducted by reviewing project materials, nurse surveys and interviews and ED–LE records. Results Cardiff Model replication centred around four activities: (1) collaboration between the hospital and LE to form a community safety partnership locally called the US Injury Prevention Partnership; (2) building hospital capacity for data collection; (3) data aggregation and analysis and (4) developing and implementing violence prevention interventions based on the data. Conclusions The Cardiff Model can be implemented in the USA for sustainable violent injury data surveillance and sharing. Key components include building a strong ED–LE partnership, communicating with each other and hospital staff, engaging in capacity building and sustainability planning

Gene Therapy in a Humanized Mouse Model of Familial Hypercholesterolemia Leads to Marked Regression of Atherosclerosis

Familial hypercholesterolemia (FH) is an autosomal codominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Homozygous FH patients (hoFH) have severe hypercholesterolemia leading to life threatening atherosclerosis in childhood and adolescence. Mice with germ line interruptions in the Ldlr and Apobec1 genes (Ldlr(-/-)Apobec1(-/-)) simulate metabolic and clinical aspects of hoFH, including atherogenesis on a chow diet.In this study, vectors based on adeno-associated virus 8 (AAV8) were used to deliver the gene for mouse Ldlr (mLDLR) to the livers of Ldlr(-/-)Apobec1(-/-) mice. A single intravenous injection of AAV8.mLDLR was found to significantly reduce plasma cholesterol and non-HDL cholesterol levels in chow-fed animals at doses as low as 3×10(9) genome copies/mouse. Whereas Ldlr(-/-)Apobec1(-/-) mice fed a western-type diet and injected with a control AAV8.null vector experienced a further 65% progression in atherosclerosis over 2 months compared with baseline mice, Ldlr(-/-)Apobec1(-/-) mice treated with AAV8.mLDLR realized an 87% regression of atherosclerotic lesions after 3 months compared to baseline mice. Immunohistochemical analyses revealed a substantial remodeling of atherosclerotic lesions.Collectively, the results presented herein suggest that AAV8-based gene therapy for FH may be feasible and support further development of this approach. The pre-clinical data from these studies will enable for the effective translation of gene therapy into the clinic for treatment of FH

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Environmental Variation, Fish Community Composition, and Brown Trout Survival in the Pigeon River, Ottawa County, Michigan

The Pigeon River, a small coolwater stream in western Michigan, has a history of hydrologic, stream habitat, and water quality degradation that led to the loss of its trout population by the late 1980s. After regulatory and watershed management efforts to reduce point- and nonpoint source pollution in the 1990s, the Michigan Department of Natural Resources reinstituted brown trout (Salmo trutta) stocking in 2003. As part of these efforts, we monitored water quality in the Pigeon River each fall between 1996 and 2008, and conducted stream surveys in 2006 and 2007 to evaluate the fish community and outcome of trout stocking. Water quality tended to improve and stabilize through time, although point- and nonpoint source pollution still contributed to water quality problems. Hydrologic instability, caused by wetland drainage, agricultural land use, and irrigation withdrawals from the lower mainstream, created periods of environmental stress. As a result, the fish community of the Pigeon River was dominated by common tolerant warmwater species, typical of agricultural watersheds in southern Michigan. Nonetheless, brown trout surviving from initial stockings in 2003 and 2004 had attained lengths of between 18 and 24 inches by 2007, suggesting the thermal regime, water quality, stream habitat, and forage base of macroinvertebrates and small fish were suitable to maintain a stocked brown trout population. Continued efforts to improve water quality, protect instream habitat, reduce high stormflows, and maintain adequate summer baseflows are needed to fully restore environmental conditions for the native fish community and stocked brown trout in the Pigeon River

Application of an Optimization/Simulation Model for the Real-Time Flood Operation of River-Reservoir Systems with One-and Two-Dimensional Unsteady Flow Modeling

An application is presented of a new methodology for the real-time operations of river-reservoir systems. The methodology is based upon an optimization/simulation modeling approach that interfaces optimization with a one and/or two-dimensional unsteady flow simulation model (U.S. Army Corps of Engineers HEC-RAS). The approach also includes a model for short-term rainfall forecasting, and the U.S. Army Corps of Engineers HEC-HMS model for rainfall-runoff modeling. Both short-term forecasted rainfall in addition to gaged streamflow data and/or NEXRAD (Next-Generation Radar) can be implemented in the modeling approach. The optimization solution methodology is based upon a genetic algorithm implemented through MATLAB. The application is based upon the May 2010 flood event on the Cumberland River system in the USA, during which releases from Old Hickory dam caused major flooding in the downstream area of Nashville, TN, USA, and allowed the dam to be placed in an emergency operational situation. One of the major features of the modeling effort and the application presented was to investigate the use of different unsteady flow modeling approaches available in the HEC-RAS, including one-dimensional (1D), two-dimensional (2D), and the combined (1D/2D) approach. One of the major results of the application was to investigate the use the different unsteady flow approaches in the modeling approach. The 2D unsteady flow modeling, based upon the diffusion wave approach, was found to be superior for the application to the Cumberland River system. The model application successfully determined real-time operations that would have maintained the flood water surface elevations at the downstream control point in Nashville below the 100-year return period river water surface and maintaining the gate openings at the Old Hickory Dam from reaching an emergency operational situation, which could have caused major losses at the dam

Sustainable Water Allocation in Umarkhed Taluka through Optimization of Reservoir Operation in the Wardha Sub-Basin, India

Climate change is causing shifts in seasonal weather patterns and variation in seasonal time scales in India. Factors including uneven distribution of water, faulty agricultural practices and water policies, low prices of farm products, and debt are leading farmers to commit suicide in Umarkhed Taluka of the Yavatmal District. This study aimed to develop a sustainable solution to water scarcity in the surrounding watershed by introducing optimization modeling in reservoir operation. Past studies have conducted different hydrologic analyses to address the water scarcity issue in this region. However, none of the studies incorporated optimization in their models. This study developed an integrated hydrologic and optimization model that can predict the daily reservoir releases for climate change scenarios from 2020 to 2069 based upon Representative Concentration Pathway (RCP-4.5 and RCP-8.5) climate change scenarios from 2020 to 2069. The integrated simulations were able to deliver around 19% more water than the historical discharge at the most downstream station of the Wardha Watershed. The simulated approaches store less water than the actual unoptimized scenario and deliver water when there is a need at the downstream locations. Finally, because the downstream locations of the Wardha Watershed receive more water, a localized storage system can be developed and a transfer method can be utilized to deliver sufficient water to the Umarkhed Taluka