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PubMed2005

Genome-wide scans for loci under selection in humans.

Natural selection, which can be defined as the differential contribution of genetic variants to future generations, is the driving force of Darwinian evolution. Identifying regions of the human genome that have been targets of natural selection is an important step in clarifying human evolutionary history and understanding how genetic variation results in phenotypic diversity, it may also facilitate the search for complex disease genes. Technological advances in high-throughput DNA sequencing and single nucleotide polymorphism genotyping have enabled several genome-wide scans of natural selection to be undertaken. Here, some of the observations that are beginning to emerge from these studies will be reviewed, including evidence for geographically restricted selective pressures (ie local adaptation) and a relationship between genes subject to natural selection and human disease. In addition, the paper will highlight several important problems that need to be addressed in future genome-wide studies of natural selection.

Chromosome Mapping↗
PubMed2003

Impact of the ICD-10 Primary Health Care (PHC) diagnostic and management guidelines for mental disorders on detection and outcome in primary care. Cluster randomised controlled trial.

BACKGROUND: The World Health Organization (WHO) ICD-10 Primary Health Care (PHC) Guidelines for Diagnosis and Management of Mental Disorders (1996) have not been evaluated in a pragmatic randomised controlled trial (RCT). AIMS: To evaluate the effect of local adaptation and dissemination of the guidelines. METHOD: Pragmatic, pair-matched, cluster RCT involving 30 practices. RESULTS: Guideline practices were less sensitive but more specific in identifying morbidity, but these differences were not significant. Guideline patients did not differ from usual-care patients on 12-item General Health Questionnaire scores at 3-month follow-up or in the proportion who were still cases. There were no significant differences in secondary outcomes. CONCLUSIONS: Attempts to influence clinician behaviour through a process of adaptation and extension of guidelines are unlikely to change detection rates or outcomes.

Adult↗
PubMed2001

Evaluation of the performance of diagnosis-related groups and similar casemix systems: methodological issues.

With the increasing recognition and application of casemix for managing and financing healthcare resources, the evaluation of alternative versions of systems such as diagnosis-related groups (DRGs) has been afforded high priority by governments and researchers in many countries. Outside the United States, an important issue has been the perceived need to produce local versions, and to establish whether or not these perform more effectively than the US-based classifications. A discussion of casemix evaluation criteria highlights the large number of measures that may be used, the rationale and assumptions underlying each measure, and the problems in interpreting the results. A review of recent evaluation studies from a number of countries indicates that considerable emphasis has been placed on the predictive validity criterion, as measured by the R2 statistic. However, the interpretation of the findings has been affected greatly by the methods used, especially the treatment and definition of outlier cases. Furthermore, the extent to which other evaluation criteria have been addressed has varied widely. In the absence of minimum evaluation standards, it is not possible to draw clear-cut conclusions about the superiority of one version of a casemix system over another, the need for a local adaptation, or the further development of an existing version. Without the evidence provided by properly designed studies, policy-makers and managers may place undue reliance on subjective judgments and the views of the most influential, but not necessarily best informed, healthcare interest groups.

Acute Disease↗
PubMed2000

Partner notification of pregnant women infected with syphilis in Nairobi, Kenya.

We examined partner notification among syphilitic pregnant women in Nairobi. At delivery, 377 women were found to be rapid plasma reagin (RPR) reactive. Data were available for 94% of the partners of women who were tested during pregnancy; over 67% of the partners had received syphilis treatment while 23% had not sought treatment mainly because they felt healthy. Six per cent of the women had not informed their partners as they feared blame and/or violence. Adverse pregnancy outcome was related to lack of partner treatment during pregnancy (7% versus 19%, odds ratio (OR) 3.0, 95% confidence interval (CI) 0.9-10.0). Our data suggest that messages focusing on the health of the unborn child have a positive effect on partner notification and innovative and locally adapted strategies for partner notification need more attention.

Adult↗
PubMed2005

Towards systematic reviews that inform health care management and policy-making.

OBJECTIVES: To identify ways to improve the usefulness of systematic reviews for health care managers and policy-makers that could then be evaluated prospectively. METHODS: We systematically reviewed studies of decision-making by health care managers and policy-makers, conducted interviews with a purposive sample of them in Canada and the United Kingdom (n = 29), and reviewed the websites of research funders, producers/purveyors of research, and journals that include them among their target audiences (n = 45). RESULTS: Our systematic review identified that factors such as interactions between researchers and health care policy-makers and timing/timeliness appear to increase the prospects for research use among policy-makers. Our interviews with health care managers and policy-makers suggest that they would benefit from having information that is relevant for decisions highlighted for them (e.g. contextual factors that affect a review's local applicability and information about the benefits, harms/risks and costs of interventions) and having reviews presented in a way that allows for rapid scanning for relevance and then graded entry (such as one page of take-home messages, a three-page executive summary and a 25-page report). Managers and policy-makers have mixed views about the helpfulness of recommendations. Our analysis of websites found that contextual factors were rarely highlighted, recommendations were often provided and graded entry formats were rarely used. CONCLUSIONS: Researchers could help to ensure that the future flow of systematic reviews will better inform health care management and policy-making by involving health care managers and policy-makers in their production and better highlighting information that is relevant for decisions. Research funders could help to ensure that the global stock of systematic reviews will better inform health care management and policy-making by supporting and evaluating local adaptation processes such as developing and making available online more user-friendly 'front ends' for potentially relevant systematic reviews.

Canada↗
PubMed2002

Recognition of unsegmented targets invariant under transformations of intensity.

Images taken in noncooperative environments do not always have targets under the same illumination conditions. There is a need for methods to detect targets independently of the illumination. We propose a technique that yields correlation peaks that are invariant under a linear intensity transformation of object intensity. The new locally adaptive contrast-invariant filter accomplishes this by combining three correlations in a nonlinear way. This method is not only intensity invariant but also has good discrimination and resistance to noise. We present simulation results for various intensity transformations with and without random and correlated noise. When the noise is high enough to threaten errors, the method trades off intensity invariance in order to achieve the optimum signal to noise ratio, and the peak to sidelobe ratio in the presence of clutter is always greater than one. In the presence of random disjoint noise, the signal to noise ratio is independent of the target contrast and of the level of the noise.

Journal Article↗
PubMed2003

Nonlinear filter for pattern recognition invariant to illumination and to out-of-plane rotations.

Automatic target recognition in uncontrolled conditions is a difficult task because many parametersare involved. This study deals with the recognition of targets under limited out-of-plane rotations while maintaining invariance to ambient light illumination. Contrast invariance is achieved by using the recently developed locally adaptive contrast-invariant filter, a method that yields correlation peaks whose values are invariant under any linear transformation of intensity. To reduce the sensitivity to the orientation of the object we replace the reference in the nonlinear filter by a synthetic discriminant filter. The range used for out-of-plane rotations was 40 degrees with a depression angle of 20 degrees. We present results for unsegmented targets on complex backgrounds with the presence of false targets.

Journal Article↗
PubMed2000

Nonlinear diffusion filtering of images obtained by planar laser-induced fluorescence spectroscopy.

The application of nonlinear anisotropic diffusion filtering to reduce noise and enhance contours in images obtained by two-dimensional planar laser-induced fluorescence (PLIF) spectroscopy is presented. In this process the diffusion coefficient is locally adapted, becoming negligible as object boundaries are approached. Noise is efficiently removed, and object contours are strongly enhanced. The technique is demonstrated with PLIF images obtained from the OH radical recorded in turbulent flames. We show that nonlinear diffusion is suitable as a preprocessing step, before image segmentation becomes possible, and we demonstrate how the technique is applied for the quantitative extraction of flame reaction boundaries from PLIF data.

Anisotropy↗
PubMed1988

Relationships of oxygen uptake and oxygen delivery in respiratory failure not due to the adult respiratory distress syndrome.

Previous studies have suggested that oxygen uptake (VO2) may be dependent on oxygen delivery (QO2) at most levels of QO2 in patients with the adult respiratory distress syndrome (ARDS); however, the adequacy of substrate delivery in patients with non-ARDS respiratory failure is unclear. The purpose of the present study was to examine the relationship between VO2 and QO2 in a group of critically ill patients (n = 10) with non-ARDS respiratory failure (ie, cardiac pulmonary edema, chronic obstructive pulmonary disease [COPD], or pneumonia). For comparison, these relationships were also examined in a group of patients (n = 6) with ARDS. The data indicate that VO2 is dependent on QO2 in both patients with ARDS and non-ARDS respiratory failure. In contrast, regional venous oxygen tension differences varied considerably between the two groups of patients, indicating differences in local adaptations to critical reductions in QO2. Finally, over a similar range of QO2, oxygen extraction was greater in patients with ARDS compared to patients with non-ARDS respiratory failure (r = -0.67 and slope = -0.62 vs r = -0.45 and slope = -0.35; p less than 0.05). These data suggest that a linear relationship between VO2 and QO2 is not unique to patients with ARDS and may not predict regional adaptations to critical reductions in substrate availability.

Hemodynamics↗
PubMed2006

Clinical diagnostic and sociocultural dimensions of deliberate self-harm in Mumbai, India.

Patients' accounts complement psychiatric assessment of deliberate self-harm (DSH). In this study we examined psychiatric disorders, and sociocultural and cross-cultural features of DSH. SCID diagnostic interviews and a locally adapted EMIC interview were used to study 196 patients after DSH at a general hospital in Mumbai, India. Major depression was the most common diagnosis (38.8%), followed by substance use disorders (16.8%), but 44.4% of patients did not meet criteria for an enduring Axis-I disorder (no diagnosis, V-code, or adjustment disorder). Psychache arising from patient-identified sociocultural contexts and stressors complements, but does not necessarily fulfill, criteria for explanatory psychiatric disorders.

Adolescent↗
PubMed2005

High-diversity genes in the Arabidopsis genome.

High-diversity genes represent an important class of loci in organismal genomes. Since elevated levels of nucleotide variation are a key component of the molecular signature for balancing selection or local adaptation, high-diversity genes may represent loci whose alleles are selectively maintained as balanced polymorphisms. Comparison of 4300 random shotgun sequence fragments of the Arabidopsis thaliana Ler ecotype genome with the whole genomic sequence of the Col-0 ecotype identified 60 genes with putatively high levels of intraspecific variability. Eleven of these genes were sequenced in multiple A. thaliana accessions, 3 of which were found to display elevated levels of nucleotide polymorphism. These genes encode the myb-like transcription factor MYB103, a putative soluble starch synthase I, and a homeodomain-leucine zipper transcription factor. Analysis of these genes and 4-7 flanking genes in 14-20 A. thaliana ecotypes revealed that two of these loci show other characteristics of balanced polymorphisms, including broad peaks of nucleotide diversity spanning multiple linked genes and an excess of intermediate-frequency polymorphisms. Scanning genomes for high-diversity genomic regions may be useful in approaches to adaptive trait locus mapping for uncovering candidate balanced polymorphisms.

Alleles↗
PubMed2006

A tuberculosis outbreak in a private-home family child care center in San Francisco, 2002 to 2004.

BACKGROUND: Child care facilities are well known as sites of infectious disease transmission, and California child care facility licensure requirements include annual tuberculosis (TB) screening for on-site adults. In April 2004, we detected an adult with TB living in a private-home family child care center (child care center A). METHODS: We reviewed patient medical records and conducted a contact investigation. The investigation included all persons at the child care center, the workplace and leisure contacts of the adult patient with TB, and the household contacts of secondary case patients. Contact names were obtained through patient interviews. A positive tuberculin skin test result was defined as induration of > or =5 mm. DNA fingerprints of Mycobacterium tuberculosis isolates were analyzed. Outbreak cases were those that had matching DNA fingerprint patterns or were linked epidemiologically, if DNA fingerprint results were not available. RESULTS: Between August 2002 and July 2004, we detected 11 outbreak cases, including 9 (82%) among children (<18 years of age). All 11 outbreak patients lived or were cared for at child care center A. The 9 pediatric TB patients were young (<7 years of age), United States-born children of foreign-born parents, and 4 (44%) had positive cultures for M tuberculosis. Including isolates recovered from the 2 adult patients, all 6 M tuberculosis isolates shared identical, 7-band, DNA fingerprint patterns. The contact investigation identified 3 (33%) of the 9 pediatric cases; 2 (22%) presented with illness and 4 (44%) were detected by primary care providers during routine TB screening. Excluding case subjects, 36 (54%) of 67 named contacts had latent TB infection. CONCLUSIONS: Provider adherence to locally adapted pediatric TB screening recommendations proved critical to outbreak control. TB screening compliance by the child care center and more aggressive source-case investigation by the TB program might have prevented or abated this large pediatric TB outbreak.

Adolescent↗
PubMed2001

Recent studies on Schistosoma intercalatum: taxonomic status, puzzling distribution and transmission foci revisited.

Schistosoma intercalatum, which causes human rectal schistosomiasis in Africa, still presents a great interest for its imprecise taxonomic status and its puzzling distribution in Africa. Two geographically isolated strains of S. intercalatum are recognized, the Lower Guinea strain and the Congo strain, which differ from each other in a number of morphological, biological and biochemical characteristics. Recent molecular data using RAPD markers indicate high divergence between the two strains, with values of Nei and Li's similarity index allowing recognition of two genetically distinct taxa: experiments on pre- and post-isolating mechanisms are in progress in order to re-evaluate the taxonomic status of this polytypic species. With regard to its geographical distribution, S. intercalatum is characterized by the existence of two stable endemic areas (localized in Lower Guinea and North East of Democratic Republic of Congo) which correspond to the historical areas of species discovery, and the emergence during the last 15 years of new foci of the Lower Guinea strain outside previously known endemic areas. The absence of local adaptation of the Lower Guinea strain to its intermediate host, supported by experimental studies, may help to facilitate the spread of this strain. Nevertheless, the present restricted distribution of this species remains puzzling, because its potential snail hosts (bulinids) are widely distributed throughout much of Africa. Recent experimental and epidemiological studies suggest that interspecific sexual interactions between human schistosomes could have a role in limiting the distribution of S. intercalatum: the competitive sexual processes acting among human schistosomes show that S. haematobium and S. mansoni are always competitively dominant over S. intercalatum. These epidemiological observations lead the authors to distinguish three kinds of transmission foci for S. intercalatum.

Africa↗
PubMed2001

Source-sink dynamics between transgenic and non-transgenic habitats and their role in the evolution of resistance.

The interaction of population dynamics and movement among two habitat types (toxic transgenic fields and nontoxic refuge fields) on the evolution of insecticide resistance was examined in two different simulation models. The two models were developed to test the hypothesis that increasing habitat grain from fine-grained to coarse-grained, and the resultant increase in nonrandom mating, would increase the rate of local adaptation, here the evolution of resistance. The first model, a complex, stochastic spatially explicit model, altered habitat grain by varying adult dispersal rates between habitat patches. In contrast to the expectation that increasing patch isolation and increasing the coarseness of the habitats would increase the rate of resistance evolution, intermediate levels of dispersal actually delayed resistance by as much as fivefold over the range of dispersal levels observed. Source-sink dynamics related to ovipositional patterns and the related population dynamics appear to explain the results. A simple deterministic model was developed to abstract out the separate impacts of mating and ovipositional behaviors. This model showed qualitatively the same results, although under similar assumptions it predicted much longer delays in resistance evolution. In this model, nonrandom mating alone always increased the rate at which insects adapted to transgenic crops, but nonrandom mating in combination with nonrandom oviposition could significantly delay resistance evolution. Differences between the two models may be due to the population regulation incorporated in the spatially explicit model. The models clearly suggest that resistance management programs using untreated refuges should not over-emphasize random mating at the cost of making the habitat too fine-grained.

Animals↗
PubMed2006

Evolving metacommunities: toward an evolutionary perspective on metacommunities.

The metacommunity framework predicts that local coexistence depends on the outcome of local species interactions and regional migration. In analogous fashion, spatial structure among populations can shape species interactions through evolutionary mechanisms. Yet, most metacommunity theories assume that populations do not evolve. Here, we evaluate how evolution shapes local species coexistence and exclusion within the multiscale and multispecies context embodied by the metacommunity framework. In general, coexistence in joint ecological-evolutionary models requires low to intermediate dispersal rates that can promote maintenance of both regional species and genetic diversity. These conditions support a set of key mechanisms that modify patterns of species coexistence including local adaptation, gene storage effects, genetic rescue effects, spatial genetic subsidies, and metacommunity evolution. Multispecies extensions indicate that correlated selection can further alter the outcome of interspecific interactions depending on the magnitude and direction of correlations and shape of fitness trade-offs. We suggest that an evolving metacommunity perspective has the potential to generate novel predictions about community structure and function by incorporating the genetic and species diversity that characterize natural communities. In adopting such a perspective, we seek to facilitate understanding about the interactions between evolutionary and metacommunity dynamics.

Biological Evolution↗
PubMed2006

Mutualistic stability in the arbuscular mycorrhizal symbiosis: exploring hypotheses of evolutionary cooperation.

The 450-million-year-old symbiosis between the majority of land plants and arbuscular mycorrhizal fungi (AMF) is one of the most ancient, abundant, and ecologically important mutualisms on Earth. Yet, the evolutionary stability of mycorrhizal associations is still poorly understood, as it follows none of the constraints thought to stabilize cooperation in other well-known mutualisms. The capacity of both host and symbiont to simultaneously interact with several partners introduces a unique dilemma; detecting and punishing those exploiting the mutualism becomes increasingly difficult if these individuals can continue to access resources from alternative sources. Here, we explore four hypotheses to explain evolutionary cooperation in the arbuscular mycorrhizal symbiosis: (1) pseudo-vertical transmission and spatial structuring of plant and fungal populations leading to local adaptation of partners; (2) luxury resource exchange in which plants trade surplus carbon for excess fungal nutrients; (3) partner choice allowing partners to associate with better cooperators; and (4) host and symbiont sanctions which actively reward good partners and punish less cooperative ones. We propose that mycorrhizal cooperation is promoted by an exchange of surplus resources between partners and enforced through sanctions by one or both partners. These mechanisms may allow plant and fungal genotypes to discriminate against individuals employing exploitative strategies, promoting patterns of partner choice. Together these selection pressures provide a framework for understanding the stabilization of mycorrhizal cooperation over evolutionary time.

Biological Evolution↗
PubMed1989

Evaluation of production and reproduction of sheep, goat and alpaca genotypes in the Small Ruminant Collaborative Research Support Program.

Research has been conducted as part of the Small Ruminant Collaborative Research Support Program (SR-CRSP) on evaluation of genetic resources and methods of effecting genetic improvement of small ruminants in the participating countries. In Kenya, the focus has been on development of a dual-purpose goat for milk and meat production in farming areas, utilizing two locally adapted breeds, Galla and East African, and two imported dairy breeds, Anglo-Nubian and Toggenburg, into a single stock. That research now has reached the stage of field testing. In Morocco, the performance of a highly prolific breed of sheep, the D'Man, and of a less prolific but larger breed, commonly raised under extensive management, the Sardi, and of their F1, F2 and backcross progeny has been evaluated for several reproduction and growth traits. Prolificacy of the D'Man was transmitted additively, but there was favorable heterosis for age at puberty, fertility and growth rate, resulting in substantial heterosis in total performance. In Indonesia, a high degree of variability in prolificacy in sheep appears to be due to segregation of a gene with large effect on ovulation rate, similar in some respects to the Booroola gene. In Peru, work has involved evaluation of effectiveness of current selection programs and estimation of phenotypic and genetic parameters, in unimproved and improved types of sheep, with a limited amount of work also on alpacas. Fiber production is the principal economic trait in alpacas. There also has been work on evaluation of hair sheep in Brazil, Kenya and Indonesia.

Animals↗