Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints

Recent advances in cardiovascular magnetic resonance (CMR) now allow the accurate and reproducible measurement of many aspects of cardiac and vascular structure and function, with prognostic data emerging for several key imaging biomarkers. These biomarkers are increasingly used in the evaluation of new drugs, devices and lifestyle modifications for the prevention and treatment of cardiovascular disease. This review outlines a conceptual framework for the application of imaging biomarkers to clinical trials, highlights several important CMR techniques which are in use in randomised studies, and reviews certain aspects of trial design, conduct and interpretation in relation to the use of CMR

Returning findings within longitudinal cohort studies: the 1958 birth cohort as an exemplar

This is the final version of the article. Available from BioMed Central via the DOI in this record.Population-based, prospective longitudinal cohort studies are considering the issues surrounding returning findings to individuals as a result of genomic and other medical research studies. While guidance is being developed for clinical settings, the process is less clear for those conducting longitudinal research. This paper discusses work conducted on behalf of The UK Cohort and Longitudinal Study Enhancement Resource programme (CLOSER) to examine consent requirements, process considerations and specific examples of potential findings in the context of the 1958 British Birth cohort. Beyond deciding which findings to return, there are questions of whether re-consent is needed and the possible impact on the study, how the feedback process will be managed, and what resources are needed to support that process. Recommendations are made for actions a cohort study should consider taking when making vital decisions regarding returning findings. Any decisions need to be context-specific, arrived at transparently, communicated clearly, and in the best interests of both the participants and the study.JE acknowledges the Economic and Social Research Council for their support for CLOSER [ES/K000357/1]. NW acknowledges the support of the JDRF, the Wellcome Trust and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award [100140]. 58READIE is supported by the Wellcome Trust [WT095219MA] and the Medical Research Council [G1001799]

Ten-Year Trends in Children’s Caloric-Beverage Consumption and Behavioral Intent

Soft drinks, fruit juice and milk are the most common caloric-beverages consumed by adolescents and teens. We report the ten-year trends in the percentage of daily calories consumed in the form of caloric-beverages from a broad sample of fifth-grade students in the United States. This is a major area of concern related to dietary quality and body weight amongst children. The study was conducted from 2001-2011 through the Healthy Hearts for Kids (HH4K) online instructional program. A total of 17,559 students from 1,048 schools in 49 US states participated. Results reveal there were no changes across the ten-year period in reported fruit juice and milk consumption in the past week. There was a significant downward trend in soft drink consumption in the ten-year period. Juice consumption was positively correlated with soft drink and milk consumption in the past week. Soft drink consumption was positively correlated with milk consumption. The intent to drink two or more soft drinks tomorrow was significantly related to soft drink consumption in the last week and to expected soft drink consumption a year from now. The intent to drink two or more soft drinks in a day one year from now was not related to reported soft drink consumption in the last week. The intent to drink two or more soft drinks tomorrow was not correlated with juice consumption in the past week or with milk consumption in the past week. In conclusion, soft drink consumption declined, but there were no changes in consumption of milk and fruit juice. Soft drinks did not appear to displace either milk or fruit juice. These participants appear to be aware that soft drinks are a less healthy choice

Critical information gaps remain in understanding impacts of industrial seismic surveys on marine vertebrates

This is the final version. Available from Inter Research via the DOI in this record. Anthropogenic noise is increasing throughout the world's oceans. One major contributor is industrial seismic surveys-a process typically undertaken to locate and estimate the quantity of oil and gas deposits beneath the seafloor-which, in recent years, has increased in magnitude and scope in some regions. Regulators permit this activity despite widespread uncertainties regarding the potential ecological impacts of seismic surveys and gaps in baseline information on some key species of conservation concern. Research to date suggests that impacts vary, from displacement to direct mortality, but these effects remain poorly understood for most species. Here, we summarize potential effects of seismic surveys, describe key knowledge gaps, and recommend broad-scale research priorities for 3 impacted taxonomic groups: fish, marine mammals, and sea turtles. We also suggest further technological advances, improved mitigation measures, and better policy and management structures to minimize the ecological impacts of seismic surveys in light of scientific uncertainty.Natural Environment Research Counci

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Fractal frontiers in cardiovascular magnetic resonance: towards clinical implementation

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.JCM: Higher Education Funding Council for England and the UK National Institute for Health Research, University College London, Biomedical Research Centre; GC: NIHR BRC University College London. DAB: Intramural research program, National Institutes of Health

Challenges of HIV diagnosis and management in the context of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review

Introduction: Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilisation of ART for immediate treatment and prevention of HIV infection. Discussion: Missed acute HIV infection prevents people living with HIV (PLWH) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. Whilst immediate ART is recommended for all PLWH, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As roll-out of PrEP continues, HIV testing algorithms may need to be modified. Conclusions: With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance is needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable