Clinical Utility of Microarrays: Current Status, Existing Challenges and Future Outlook

Microarray-based clinical tests have become powerful tools in the diagnosis and treatment of diseases. In contrast to traditional DNA-based tests that largely focus on single genes associated with rare conditions, microarray-based tests are ideal for the study of diseases with underlying complex genetic causes. Several microarray based tests have been translated into clinical practice such as MammaPrint and AmpliChip CYP450. Additional cancer-related microarray-based tests are either in the process of FDA review or under active development, including Tissue of Tumor Origin and AmpliChip p53. All diagnostic microarray testing is ordered by physicians and tested by a Clinical Laboratories Improvement Amendment-certified (CLIA) reference laboratory. Recently, companies offering consumer based microarray testing have emerged. Individuals can order tests online and service providers deliver the results directly to the clients via a password-protected secure website. Navigenics, 23andMe and deCODE Genetics represent pioneering companies in this field. Although the progress of these microarray-based tests is extremely encouraging with the potential to revolutionize the recognition and treatment of common diseases, these tests are still in their infancy and face technical, clinical and marketing challenges. In this article, we review microarray-based tests which are currently approved or under review by the FDA, as well as the consumer-based testing. We also provide a summary of the challenges and strategic solutions in the development and clinical use of the microarray-based tests. Finally, we present a brief outlook for the future of microarray-based clinical applications.     

Penicillium marneffei Infection: Knowledge, Gaps, and Future Directions

Penicilliosis is a disease caused by Penicillium marneffei, a fungus endemic to Southeast Asia. Prior to the HIV/AIDS epidemic, infection was exceedingly rare, but penicilliosis is currently one of the most common opportunistic infections in persons with HIV/AIDS in some Asian countries. This paper describes the clinical manifestations, diagnosis, and epidemiology of this emerging opportunistic infection and will focus on some gaps in our knowledge and directions for future research.     

Amoeboid Chemotaxis: Future Challenges and Opportunities

Chemotaxis is the directed movement of a cell towards a gradient of chemicals such as chemokines or growth factors. This phenomenon can be studied in organisms ranging from bacteria to mammalian cells, and here we will focus on eukaryotic amoeboid chemotaxis. Chemotactic responses are mediated by two major classes of receptors: GPCR''s and RTK''s, with multiple pathways signaling downstream of them, certain ones functioning in parallel. In this review we address two important features of amoeboid chemotaxis that will be important for further advances in the field. First, the application of in vivo imaging will be critical for providing insight into the functional requirements for chemotactic responses. We will briefly cover a number of systems in which in vivo imaging is providing new insights. Second, due to the network-type design of signaling pathways of eukaryotic chemotaxis, more refined phenotypic analysis will be necessary, and we will discuss recent analyses of the role of the phosphoinositide 3-kinase pathway in this light. We will close with some speculations regarding future applications of more detailed in vivo analysis and mechanistic understanding of eukaryotic amoeboid chemotaxis.Key Words: chemotaxis, signaling, in vivo models, development, phospholipase, phosphoinositide 3-kinase     

Wiki Surveys: Open and Quantifiable Social Data Collection

In the social sciences, there is a longstanding tension between data collection methods that facilitate quantification and those that are open to unanticipated information. Advances in technology now enable new, hybrid methods that combine some of the benefits of both approaches. Drawing inspiration from online information aggregation systems like Wikipedia and from traditional survey research, we propose a new class of research instruments called wiki surveys. Just as Wikipedia evolves over time based on contributions from participants, we envision an evolving survey driven by contributions from respondents. We develop three general principles that underlie wiki surveys: they should be greedy, collaborative, and adaptive. Building on these principles, we develop methods for data collection and data analysis for one type of wiki survey, a pairwise wiki survey. Using two proof-of-concept case studies involving our free and open-source website www.allourideas.org, we show that pairwise wiki surveys can yield insights that would be difficult to obtain with other methods.     

Assessing Coverage,Equity and Quality Gaps in Maternal and Neonatal Care in Sub-Saharan Africa: An Integrated Approach

BackgroundGaps in coverage, equity and quality of health services hinder the achievement of the Millennium Development Goals 4 and 5 in most countries of sub-Saharan Africa as well as in other high-burden countries, yet few studies attempt to assess all these dimensions as part of the situation analysis. We present the base-line data of a project aimed at simultaneously addressing coverage, equity and quality issues in maternal and neonatal health care in five districts belonging to three African countries.MethodsData were collected in cross-sectional studies with three types of tools. Coverage was assessed in three hospitals and 19 health centres (HCs) utilising emergency obstetric and newborn care needs assessment tools developed by the Averting Maternal Death and Disability program. Emergency obstetrics care (EmOC) indicators were calculated. Equity was assessed in three hospitals and 13 HCs by means of proxy wealth indices and women delivering in health facilities were compared with those in the general population to identify inequities. Quality was assessed in three hospitals using the World Health Organization’s maternal and neonatal quality of hospital care assessment tool which evaluates the whole range of aspects of obstetric and neonatal care and produces an average score for each main area of care.ResultsAll the three hospitals qualified as comprehensive EmOC facilities but none of the HCs qualified for basic EmOC. None of the districts met the minimum requisites for EmOC indicators. In two out of three hospitals, there were major quality gaps which were generally greater in neonatal care, management of emergency and complicated cases and monitoring. Higher access to care was coupled by low quality and good quality by very low access. Stark inequities in utilisation of institutional delivery care were present in all districts and across all health facilities, especially at hospital level.ConclusionOur findings confirm the existence of serious issues regarding coverage, equity and quality of health care for mothers and newborns in all study districts. Gaps in one dimension hinder the potential gains in health outcomes deriving from good performances in other dimensions, thus confirm the need for a three-dimensional profiling of health care provision as a basis for data-driven planning.     

Financial Risk Protection and Universal Health Coverage: Evidence and Measurement Challenges

Financial risk protection is a key component of universal health coverage (UHC), which is defined as access to all needed quality health services without financial hardship. As part of the PLOS Medicine Collection on measurement of UHC, the aim of this paper is to examine and to compare and contrast existing measures of financial risk protection. The paper presents the rationale behind the methodologies for measuring financial risk protection and how this relates to UHC as well as some empirical examples of the types of measures. Additionally, the specific challenges related to monitoring inequalities in financial risk protection are discussed. The paper then goes on to examine and document the practical challenges associated with measurement of financial risk protection. This paper summarizes current thinking on the area of financial risk protection, provides novel insights, and suggests future developments that could be valuable in the context of monitoring progress towards UHC.

This paper is part of the PLOS Universal Health Coverage Collection.

Key Summary Points

• Health payments are a heavy financial burden for millions around the world. Financial risk protection is concerned with safeguarding people against the financial hardship associated with paying for health services.
• Two commonly applied concepts capture the lack of financial risk protection. The first, catastrophic health expenditure, occurs when a household''s out-of-pocket (OOP) payments are so high relative to its available resources that the household foregoes the consumption of other necessary goods and services. The second concept, impoverishment, occurs when OOP payments push households below or further below the poverty line, a threshold under which even the most basic standard of living is not ensured.
• Headcount indicators, which measure the number of people affected, alone do not give the full picture of the problem. Additional measures of the intensity of financial hardship provide useful insights into the nature of OOP payments in different settings.
• Robust monitoring of financial risk protection requires reliable household expenditure surveys ideally conducted every 2 to 5 years.

     

Plant Conservation in the Future: New Challenges, New Opportunities

Throughout the world, plant diversity is being reduced rapidly by the extinction of species and of local differentiated populations. In presenting possible solutions to this very serious problem Ⅰ will first briefly describe the factors that have led to the development of China's wealth of biodivenity; then examine the causes of extinction,with an emphasis on the situation in China; and conclude with recommendations on how to most effectively conserve plants in this huge and botanically diverse country.     

Fungal Vaccines and Immunotherapeutics: Current Concepts and Future Challenges

Purpose of review

The remarkable advances in modern medicine have paradoxically resulted in a rapidly expanding population of immunocompromised patients displaying extreme susceptibility to life-threatening fungal infections. There are currently no licensed vaccines, and the prophylaxis and therapy of fungal infections in at-risk individuals remains challenging, contributing to undesirable mortality and morbidity rates. The design of successful antifungal preventive approaches has been hampered by an insufficient understanding of the dynamics of the host-fungus interaction and the mechanisms that underlie heterogenous immune responses to vaccines and immunotherapy.

Recent findings

Recent advances in proteomics and glycomics have contributed to the identification of candidate antigens for use in subunit vaccines, novel adjuvants, and delivery systems to boost the efficacy of protective vaccination responses that are becoming available, and several targets are being exploited in immunotherapeutic approaches.

Summary

We review some of the emerging concepts as well as the inherent challenges to the development of fungal vaccines and immunotherapies to protect at-risk individuals.