On the relationship between individual and population health

The relationship between individual and population health is partially built on the broad dichotomization of medicine into clinical medicine and public health. Potential drawbacks of current views include seeing both individual and population health as absolute and independent concepts. I will argue that the relationship between individual and population health is largely relative and dynamic. Their interrelated dynamism derives from a causally defined life course perspective on health determination starting from an individual’s conception through growth, development and participation in the collective till death, all seen within the context of an adaptive society. Indeed, it will become clear that neither individual nor population health is identifiable or even definable without informative contextualization within the other. For instance, a person’s health cannot be seen in isolation but must be placed in the rich contextual web such as the socioeconomic circumstances and other health determinants of where they were conceived, born, bred, and how they shaped and were shaped by their environment and communities, especially given the prevailing population health exposures over their lifetime. We cannot discuss the “what” and “how much” of individual and population health until we know the cumulative trajectories of both, using appropriate causal language

Patient Perspectives with Abbreviated versus Standard Pre-Test HIV Counseling in the Prenatal Setting: A Randomized-Controlled, Non-Inferiority Trial

In the US, an unacceptably high percentage of pregnant women do not undergo prenatal HIV testing. Previous studies have found increased uptake of prenatal HIV testing with abbreviated pre-test counseling, however little is known about patient decision making, testing satisfaction and knowledge in this setting.A randomized-controlled, non-inferiority trial was conducted from October 2006 through February 2008 at San Francisco General Hospital (SFGH), the public teaching hospital of the City and County of San Francisco. A total of 278 English- and Spanish-speaking pregnant women were randomized to receive either abbreviated or standard nurse-performed HIV test counseling at the initial prenatal visit. Patient decision making experience was compared between abbreviated versus standard HIV counseling strategies among a sample of low-income, urban, ethnically diverse prenatal patients. The primary outcome was the decisional conflict score (DCS) using O'Connor low-literacy scale and secondary outcomes included satisfaction with test decision, basic HIV knowledge and HIV testing uptake. We conducted an intention-to-treat analysis of 278 women--134 (48.2%) in the abbreviated arm (AA) and 144 (51.8%) in the standard arm (SA). There was no significant difference in the proportion of women with low decisional conflict (71.6% in AA vs. 76.4% in SA, p = .37), and the observed mean difference between the groups of 3.88 (95% CI: -0.65, 8.41) did not exceed the non-inferiority margin. HIV testing uptake was very high (97. 8%) and did not differ significantly between the 2 groups (99.3% in AA vs. 96.5% in SA, p = .12). Likewise, there was no difference in satisfaction with testing decision (97.8% in AA vs. 99.3% in SA, p = .36). However, women in AA had significantly lower mean HIV knowledge scores (78.4%) compared to women in SA (83.7%, p<0.01).This study suggests that streamlining the pre-test counseling process, while associated with slightly lower knowledge, does not compromise patient decision making or satisfaction regarding HIV testing.ClinicalTrials.gov NCT00503308

Contribution of Cerebellar Sensorimotor Adaptation to Hippocampal Spatial Memory

Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation

Understanding Streptococcus suis serotype 2 infection in pigs through a transcriptional approach

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus suis </it>serotype 2 (<it>S. suis </it>2) is an important pathogen of pigs. <it>S suis 2 </it>infections have high mortality rates and are characterized by meningitis, septicemia and pneumonia. <it>S. suis </it>2 is also an emerging zoonotic agent and can infect humans that are exposed to pigs or their by-products. To increase our knowledge of the pathogenesis of meningitis, septicemia and pneumonia in pigs caused by <it>S. suis </it>2, we profiled the response of peripheral blood mononuclear cells <b>(</b>PBMC), brain and lung tissues to infection with <it>S. suis </it>2 strain SC19 using the Affymetrix Porcine Genome Array.</p> <p>Results</p> <p>A total of 3,002 differentially expressed transcripts were identified in the three tissues, including 417 unique genes in brain, 210 in lung and 213 in PBMC. These genes showed differential expression (DE) patterns on analysis by visualization and integrated discovery (DAVID). The DE genes involved in the immune response included genes related to the inflammatory response (CD163), the innate immune response (TLR2, TLR4, MYD88, TIRAP), cell adhesion (CD34, SELE, SELL, SELP, ICAM-1, ICAM-2, VCAM-1), antigen processing and presentation (MHC protein complex) and angiogenesis (VEGF), together with genes encoding cytokines (interleukins). Five selected genes were validated by qRT-PCR analysis.</p> <p>Conclusions</p> <p>We studied the response to infection with <it>S. suis </it>2 strain SC19 by microarray analysis. Our findings confirmed some genes identified in previous studies and discovered numerous additional genes that potentially function in <it>S. suis </it>2 infections in vivo. This new information will form the foundation of future investigations into the pathogenesis of <it>S. suis</it>.</p

Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons

The inhibitory GABAergic system has been implicated in multiple neuropsychiatric diseases such as schizophrenia and autism. The Dlx homeobox transcription factor family is essential for development and function of GABAergic interneurons. Mice lacking the Dlx1 gene have postnatal subtype-specific loss of interneurons and reduced IPSCs in their cortex and hippocampus. To ascertain consequences of these changes in the GABAergic system, we performed a battery of behavioral assays on the Dlx1 mutant mice, including zero maze, open field, locomotor activity, food intake, rotarod, tail suspension, fear conditioning assays (context and trace), prepulse inhibition, and working memory related tasks (spontaneous alteration task and spatial working memory task). Dlx1 mutant mice displayed elevated activity levels in open field, locomotor activity, and tail suspension tests. These mice also showed deficits in contextual and trace fear conditioning, and possibly in prepulse inhibition. Their learning deficits were not global, as the mutant mice did not differ from the wild-type controls in tests of working memory. Our findings demonstrate a critical role for the Dlx1 gene, and likely the subclasses of interneurons that are affected by the lack of this gene, in behavioral inhibition and associative fear learning. These observations support the involvement of particular components of the GABAergic system in specific behavioral phenotypes related to complex neuropsychiatric diseases

Sexual Conflict and Sexually Antagonistic Coevolution in an Annual Plant

BACKGROUND: Sexual conflict theory predicts sexually antagonistic coevolution of reproductive traits driven by conflicting evolutionary interests of two reproducing individuals. Most studies of the evolutionary consequences of sexual conflicts have, however, to date collectively investigated only a few species. In this study we used the annual herb Collinsia heterophylla to experimentally test the existence and evolutionary consequences of a potential sexual conflict over onset of stigma receptivity. METHODOLOGY/PRINCIPAL FINDINGS: We conducted crosses within and between four greenhouse-grown populations originating from two regions. Our experimental setup allowed us to investigate male-female interactions at three levels of geographic distances between interacting individuals. Both recipient and pollen donor identity affected onset of stigma receptivity within populations, confirming previous results that some pollen donors can induce stigma receptivity. We also found that donors were generally better at inducing stigma receptivity following pollen deposition on stigmas of recipients from another population than their own, especially within a region. On the other hand, we found that donors did worse at inducing stigma receptivity in crosses between regions. Interestingly, recipient costs in terms of lowered seed number after early fertilisation followed the same pattern: the cost was apparent only if the pollen donor belonged to the same region as the recipient. CONCLUSION/SIGNIFICANCE: Our results indicate that recipients are released from the cost of interacting with local pollen donors when crossed with donors from a more distant location, a pattern consistent with a history of sexually antagonistic coevolution within populations. Accordingly, sexual conflicts may have important evolutionary consequences also in plants

Adaptive Developmental Delay in Chagas Disease Vectors: An Evolutionary Ecology Approach

The developmental time of vector insects is important to their population dynamics, evolutionary biology, epidemiology of the diseases they transmit, and to their responses to global climatic change. In various triatomine species vectors of Chagas disease (Triatominae, Reduviidae), a delay in the molt of a small proportion of individuals has been observed, and from an evolutionary ecology approach, we propose the hypothesis that the developmental delay is an adaptation to environmental stochasticity through a spreading of risk (bet-hedging) diapause strategy. We confirmed, by means of a survey among specialists, the existence of the developmental delay in triatomines. Statistical descriptions of the developmental time of 11 species of triatomines showed some degree of bi-modality in nine of them. We predicted by means of an optimization model which genotype, coding for a given frequency of developmental diapause, is expected to evolve. We identified a series of parameters that can be measured in the field and in the laboratory to test the hypothesis of an optimal diapause frequency. We also discuss the importance of these findings for triatomines in terms of global climatic change and epidemiological consequences such as their resistance to insecticides

A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model

A Social Identity Approach to Sport Psychology: Principles, Practice, and Prospects.

Drawing on social identity theory and self-categorization theory, we outline an approach to sport psychology that understands groups not simply as features of sporting contexts but rather as elements that can be, and often are, incorporated into a person's sense of self and, through this, become powerful determinants of their sport-related behavior. The underpinnings of this social identity approach are outlined, and four key lessons for sport that are indicative of the analytical and practical power of the approach are presented. These suggest that social identity is the basis for sports group (1) behavior, (2) formation and development, (3) support and stress appraisal, and (4) leadership. Building on recent developments within sport science, we outline an agenda for future research by identifying a range of topics to which the social identity approach could fruitfully contribute

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe