Observational human studies in allergic diseases: design concepts and highlights of recent National Institute of Allergy and Infectious Diseases-funded research.

PURPOSE OF REVIEW: To present and discuss key design concepts for optimizing the impact of observational studies in the field of allergy and to highlight recent findings from NIAID-funded research networks. RECENT FINDINGS: We discuss three concepts. First, the benefit of prospective, longitudinal observational studies exemplified by recent findings on the seasonal nature of all rhinitis phenotypes in children with asthma and the protective effects of high house dust allergen content during the first year of life on the development of asthma at age 7 years. Second, the benefit of detailed (deep) phenotyping exemplified by the identification of a MALT1 gene variant as a strong genetic link to peanut allergy and the determination that atopic dermatitis with food allergy constitutes a distinct cutaneous endotype, compared with atopic dermatitis alone. Third, the benefit of hypothesis-generating research combined with prospective design and deep phenotyping as exemplified by the unveiling of potential pathophysiologic pathways leading to asthma exacerbations in children, after a 'cold'. SUMMARY: Observational studies can be highly impactful if designed well. Longitudinal study design, deep phenotyping, and hypothesis-generating research are three major design concepts that should be considered in the development of these studies.

Building the strategic national stockpile through the NIAID Radiation Nuclear Countermeasures Program.

The possibility of a public health radiological or nuclear emergency in the United States remains a concern. Media attention focused on lost radioactive sources and international nuclear threats, as well as the potential for accidents in nuclear power facilities (e.g., Windscale, Three Mile Island, Chernobyl, and Fukushima) highlight the need to address this critical national security issue. To date, no drugs have been licensed to mitigate/treat the acute and long-term radiation injuries that would result in the event of large-scale, radiation, or nuclear public health emergency. However, recent evaluation of several candidate radiation medical countermeasures (MCMs) has provided initial proof-of-concept of efficacy. The goal of the Radiation Nuclear Countermeasures Program (RNCP) of the National Institute of Allergy and Infectious Diseases (National Institutes of Health) is to help ensure the government stockpiling of safe and efficacious MCMs to treat radiation injuries, including, but not limited to, hematopoietic, gastrointestinal, pulmonary, cutaneous, renal, cardiovascular, and central nervous systems. In addition to supporting research in these areas, the RNCP continues to fund research and development of decorporation agents targeting internal radionuclide contamination, and biodosimetry platforms (e.g., biomarkers and devices) to assess the levels of an individual's radiation exposure, capabilities that would be critical in a mass casualty scenario. New areas of research within the program include a focus on special populations, especially pediatric and geriatric civilians, as well as combination studies, in which drugs are tested within the context of expected medical care management (e.g., antibiotics and growth factors). Moving forward, challenges facing the RNCP, as well as the entire radiation research field, include further advancement and qualification of animal models, dose conversion from animal models to humans, biomarker identification, and formulation development. This paper provides a review of recent work and collaborations supported by the RNCP.

The NIH-NIAID schistosomiasis resource center.

A bench scientist studying schistosomiasis must make a large commitment to maintain the parasite's life cycle, which necessarily involves a mammalian (definitive) host and the appropriate species of snail (intermediate host). This is often a difficult and expensive commitment to make, especially in the face of ever-tightening funds for tropical disease research. In addition to funding concerns, investigators usually face additional problems in the allocation of sufficient lab space to this effort (especially for snail rearing) and the limited availability of personnel experienced with life cycle upkeep. These problems can be especially daunting for the new investigator entering the field. Over 40 years ago, the National Institutes of Health-National Institute of Allergy and Infectious Diseases (NIH-NIAID) had the foresight to establish a resource from which investigators could obtain various schistosome life stages without having to expend the effort and funds necessary to maintain the entire life cycle on their own. This centralized resource translated into cost savings to both NIH-NIAID and to principal investigators by freeing up personnel costs on grants and allowing investigators to divert more funds to targeted research goals. Many investigators, especially those new to the field of tropical medicine, are only vaguely, if at all, aware of the scope of materials and support provided by this resource. This review is intended to help remedy that situation. Following a short history of the contract, we will give a brief description of the schistosome species provided, provide an estimate of the impact the resource has had on the research community, and describe some new additions and potential benefits the resource center might have for the ever-changing research interests of investigators.

HIV vaccine research: the way forward.

The need to broaden research directed at answering fundamental questions in HIV vaccine discovery through laboratory, nonhuman primate (NHP), and clinical research has recently been emphasized. In addition, the importance of attracting and retaining young researchers, developing better NHP models, and more closely linking NHP and clinical research is being stressed. In an era of a level budget for biomedical research at the U.S. National Institutes of Health (NIH), HIV/AIDS vaccine research efforts will need to be carefully prioritized such that resources to energize HIV vaccine discovery can be identified. This article summarizes progress and challenges in HIV vaccine research, the priorities arising from a recent summit at NIAID, and the actions needed, some already under way, to address those priorities.