Journal of internal medicine
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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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Review
Implementation of alternative test strategies for the safety assessment of engineered nanomaterials.
Nanotechnology introduces a new field that requires novel approaches and methods for hazard and risk assessment. For an appropriate scientific platform for safety assessment, nanoscale properties and functions of engineered nanomaterials (ENMs), including how the physicochemical properties of the materials relate to mechanisms of injury at the nano-bio interface, must be considered. Moreover, this rapidly advancing new field requires novel test strategies that allow multiple toxicants to be screened in robust, mechanism-based assays in which the bulk of the investigation can be carried out at the cellular and biomolecular level whilst maintaining limited animal use and is based on the contribution of toxicological pathways to the pathophysiology of disease. ⋯ An ATS is defined here as an alternative to animal experiments or refinement/reduction alternative to traditional animal testing. Secondly, the approach of selecting pathways of toxicity to screen for the pulmonary hazard potential of carbon nanotubes and metal oxides will be discussed, as well as how to use these pathways to perform high-content or high-throughput testing and how the data can be used for hazard ranking, risk assessment, regulatory decision-making and 'safer-by-design' strategies. Finally, the utility and disadvantages of this predictive toxicological approach to ENM safety assessment, and how it can assist the 21st-century vision, will be addressed.
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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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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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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.