Journal of internal medicine
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The aim of the present study was to determine whether serum urate (sUA) concentration is positively associated with subclinical atherosclerosis, independent of body mass index (BMI), amongst generally healthy adults. ⋯ sUA may be an early biomarker for subclinical atherosclerosis in young adults; starting in early middle age, sUA predicts subclinical atherosclerosis independently of BMI.
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Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. ⋯ In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.
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Using the principles of public health genomics, we examined the opportunities and challenges of implementing personalized prevention programmes for cancer at the population level. Our model-based estimates indicate that polygenic risk stratification can potentially improve the effectiveness and cost-effectiveness of screening programmes. However, compared with 'one-size-fits-all' screening programmes, personalized screening adds further layers of complexity to the organization of screening services and raises ethical, legal and social challenges. Before polygenic inheritance is translated into population screening strategy, evidence from empirical research and engagement with and education of the public and the health professionals are needed.
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Review
Lessons from postgenome-wide association studies: functional analysis of cancer predisposition loci.
In the last few years, genome-wide association studies (GWASs) have identified hundreds of predisposition loci for several types of human cancers. Recent progress has been made in determining the underlying mechanisms through which different single-nucleotide polymorphisms (SNPs) affect predisposition to cancer. ⋯ Most common variants associated with cancer risk are localized in nonprotein-coding regions highlighting transcriptional regulation as a common theme in the mechanism of cancer predisposition. Here, we outline strategies to functionally dissect predisposition loci and discuss their limitations as well as challenges for future studies.
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Developing new pharmacotherapies for autism spectrum disorder (ASD) is a challenge. ASD has a complex genetic architecture, several neurobiological phenotypes and multiple symptom domains. However, new opportunities are emerging that could lead to the development of 'targeted' and individualized pharmacological interventions. ⋯ The establishment of animal models and cellular assays is important for developing and testing new pharmacological targets before initiating large-scale clinical trials. Finally, we present the European Autism Interventions - A Multicentre Study for Developing New Medications (EU-AIMS) Initiative, which was set up in the context of the EU Innovative Medicines Initiative as the first European platform for integrated translational research in ASD. The EU-AIMS Initiative consists of academic and industrial partners working in collaboration to deliver a more 'personalized' approach to diagnosing and treating ASD in the future.