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2nd Asia-Pacific regional meeting of the International Working Group on Harmonization of Dementia Drug Guidelines: meeting report.

The 2nd Asia-Pacific regional meeting of the International Working Group on Harmonization of Dementia Drug Guidelines (IWGH) was held in Beijing, China in late 2002. Representatives from over a dozen countries convened to present data on dementia within the region and to share information on locally adapted outcome measures for use in dementia clinical trials. The IWGH recognized the competency and capability of many Asian sites and endorsed their inclusion in future multicenter clinical dementia research activities.

Asia↗

Prevalence of influenza vaccination in a high-risk population: impact of age and race.

Participants in a Nashville Davidson County survey were queried regarding influenza vaccination, with the goal of developing strategies to improve vaccination coverage in the county. The Metropolitan Public Health Department used a locally adapted version of the Behavioral Risk Factor Surveillance System in a random-digit-dialing phone survey with a sample of 7901 residents of Davidson County, Tennessee, about health-related behaviors. Out of 7233 fully completed surveys, data for 7016 were analyzed. Thirty-six percent of the respondents were male; 17% were aged 18-24, 40% were aged 25-44, 26% were aged 45-64, and 16% were aged 65 or older. Seventy-six percent were white. Forty-five percent reported a chronic illness, increasing their risk for complications from influenza; 11% had asthma, 7% diabetes, 25% hypercholesterolemia, and 28% hypertension. Predictors for receipt of influenza vaccine were older age, presence of a primary care provider, health insurance, and employment. Those with chronic diseases were more likely to be vaccinated when compared to the general population. Among those 65 and older, blacks were less likely to be vaccinated (OR = 0.57, CI = 0.43, 0.76). The substantial disparity in receipt of influenza vaccine reflects the lack of recommendations and policies for vaccination coverage and suggests the need for greater community-based efforts to improve the preventive health behaviors of healthcare professionals and the public. In addition, new vaccine delivery strategies and systematic vaccination marketing efforts may be needed to increase influenza vaccination rates in communities of color and other underserved populations.

Adolescent↗

Implementing practice guidelines for appropriate antimicrobial usage: a systematic review.

BACKGROUND: Antimicrobial resistance is increasing, apparently in part as a result of the inappropriate use of antimicrobial agents. OBJECTIVES: To conduct a systematic review of guideline implementation studies for improving appropriate use of antimicrobial agents and to determine which implementation methods appear to improve the outcome of appropriate antimicrobial use. RESEARCH DESIGN: The Medline database was searched for comparative studies on guideline implementation of appropriate antimicrobial use in common infections. Estimates of treatment effects and costs were included. The community-acquired infections selected were otitis media, respiratory illnesses, pharyngitis, and sinusitis. The nosocomial infections selected were urinary tract infections and surgical wound infections. Antiretroviral treatment studies and vancomycin usage studies were also included. Other computer-assisted antibiotic control studies not selected in the above topics were included. RESULTS: Forty studies were found that documented the effectiveness of implementation methods in encouraging appropriate antimicrobial use. The available evidence showed that multifaceted implementation methods were most successful. Individual implementation methods that appeared to be useful were academic detailing, feedback from nurses, pharmacists, or physicians, local adaptation of a guideline, small-group interactive sessions, and computer-assisted care.

Adult↗

Occupational therapy and physiotherapy for the patient with burns: principles and management guidelines.

Clinical practice guidelines are a tool to assist with clinical decision making. They provide information about the care for a condition and make recommendations based on research evidence, which can be adapted locally. A focus group within the Allied Health Interest Group of the Australian and New Zealand Burn Association has compiled the "Occupational Therapy and Physiotherapy for the Patient with Burns--Principles and Management Guidelines." These guidelines are designed as a practical guide to the relevant clinical knowledge and therapy intervention techniques required for effective patient management. Content areas include respiratory management, edema management, splinting and positioning, physical function (mobility, function, exercise), scar management, and psychosocial and mutual elements. The document has undergone extensive review by members of the Australian and New Zealand Burn Association to ensure clarity, internal consistency, and acceptability. The guidelines have been endorsed by the Australian and New Zealand Burn Association. An abridged version of the guidelines is included in this article, with the full document available from www.anzba.org.au.

Burns↗

Schizophrenia and the cultural epidemiology of stigma in Bangalore, India.

Illness-related stigma is a complex and important issue, and its social impact contributes to a hidden burden of many health problems. Mitigating effects of stigma are a priority for mental health policy, especially for schizophrenia. Although numerous studies document its impact on patients and their families, health studies of stigma typically regard it in global terms without adequate attention to the conceptual and practical importance of sociocultural contexts and the particular features of illness that evoke stigma. Research at a psychiatric referral center in Bangalore, India, studied the cultural epidemiology of schizophrenia and stigma in interviews with family caretakers of 60 patients, using a locally adapted EMIC interview and the Positive and Negative Symptom Scale. An index of 13 stigma queries based on Goffman's formulation covered relevant aspects and proved to be internally consistent (Cronbach alpha = 0.81). Multivariate statistical regression and qualitative analysis of narratives were used to analyze this stigma index and identify explanatory variables based on cultural patterns of distress (PD), perceived causes (PC), and previous help seeking (HS). Significant variables included suspiciousness and inappropriate sexual behavior (PD), heredity and bad deeds (PC), and informal help seeking (HS). Previous allopathic help seeking was negatively associated with stigma. Analysis of coded text segments from respondent narratives showed how these variables were related to family-perceived stigma, with reference to marriage practices, moral meanings of schizophrenia, and ways in which effective allopathic care minimized stigma. Findings identify features of schizophrenia-related stigma in India, contribute to comparative culture studies, and inform practical approaches to mitigate stigma through community awareness and improved mental health services.

Culture↗

Somatization revisited: diagnosis and perceived causes of common mental disorders.

The assessment of somatoform disorders is complicated by persistent theoretical and practical questions of classification and assessment. Critical rethinking of professional concepts of somatization suggests the value of complementary assessment of patients' illness explanatory models of somatoform and other common mental disorders. We undertook this prospective study to assess medically unexplained somatic symptoms and their patient-perceived causes of illness and to show how patients' explanatory models relate to professional diagnoses of common mental disorders and how they may predict the short-term course of illness. Tertiary care patients (N=186) with prominent somatoform symptoms were evaluated with the Structured Clinical Interview for DSM-IV, a locally adapted Explanatory Model Interview to elicit patients' illness experience (priority symptoms) and perceived causes, and clinical self-report questionnaires. The self-report questionnaires were administered at baseline and after 6 months. Diagnostic overlap between somatoform, depressive, and anxiety disorders occurred frequently (79.6%). Patients explained pure somatoform disorders mainly with organic causal attributions; they explained pure depressive and/or anxiety disorders mainly with psychosocial perceived causes, and patients in the diagnostic overlap group typically reported mixed causal attributions. In this last group, among patients with similar levels of symptom severity, organic perceived causes were related to a lower physical health sum score on the MOS Short Form, and psychosocial perceived causes were related to less severe depressive symptoms, assessed with the Hospital Anxiety and Depression Scale at 6 months. Among patients meeting criteria for comorbid somatoform with anxiety and/or depressive disorders, complementary assessment of patient-perceived causes, a key element of illness explanatory models, was related to levels of functional impairment and short-term prognosis. For such patients, causal attributions may be particularly useful to clarify clinically significant features of common mental disorders and thereby contribute to clinical assessment.

Adult↗

Genetic population structure of the prosobranch snail Potamopyrgus antipodarum (Gray) in Denmark using PCR-RAPD fingerprints.

Parthenogenetic species are often more widely distributed geographically than their sexual relatives. This success in colonizing can be explained either by dispersal of one or a few clones of wide physiological tolerance or by the distribution of many locally adapted clones. Here we test the hypothesis that successfully invading clones of Potamopyrgus antipodarum (Gray) are composed of a few broadly adapted genotypes by using polymerase chain reaction random amplified polymorphic DNA (PCR-RAPD) fingerprinting on six different populations of P. antipodarum from Denmark and three morphotypes of P. antipodarum from Britain. We detected two genotypes of P. antipodarum in six populations examined across Denmark using four decamer primers. The two genotypes were found to be morphologically and genetically indistinguishable from British P. antipodarum. In five of the six Danish populations only one genotype was found; at the remaining site, the two genotypes occurred sympatrically. The present study suggests that P. antipodarum successfully invaded Europe by the proliferation of very few clones.

Animals↗

Genetic diversity in Leavenworthia populations with different inbreeding levels.

Levels of neutral genetic diversity within and between populations were compared between outcrossing (self-incompatible) and inbreeding populations in the annual plant genus Leavenworthia. Two taxonomically independent comparisons are possible, since self-incompatibility has been lost twice in the group of species studied. Within inbred populations of L.uniflora and L.crassa, no DNA sequence variants were seen among the alleles sampled, but high diversity was seen in alleles from populations of the outcrosser L. stylosa, and in self-incompatible L. crassa populations. Diversity between populations was seen in all species. Although total diversity values were lower in the sets of inbreeding populations, between-population values were as high or higher, than those in the outcrossing taxa. Possible reasons for these diversity patterns are discussed. As the effect of inbreeding appears to be a greater than twofold reduction in diversity, we argue that some process such as selection for advantageous mutations, or against deleterious mutations, or bottlenecks occurring predominantly in the inbreeders, appears necessary to account for the findings. If selection for advantageous mutations is responsible, it appears that it must be some form of local adaptive selection, rather than substitution of alleles that are advantageous throughout the species. This is consistent with the finding of high between-population diversity in the inbreeding taxa.

Genetic Variation↗

Lifetime success and interactions of farm salmon invading a native population.

Farm Atlantic salmon escape and invade rivers throughout the North Atlantic annually, which has generated growing concern about their impacts on native salmon populations. A large-scale experiment was therefore undertaken in order to quantify the lifetime success and interactions of farm salmon invading a Norwegian river. Sexually mature farm and native salmon were genetically screened, radio tagged and released into the River Imsa where no other salmon had been allowed to ascend. The farm fishes were competitively and reproductively inferior, achieving less than one-third the breeding success of the native fishes. Moreover, this inferiority was sex biased, being more pronounced in farm males than females, resulting in the principal route of gene flow involving native males mating with farm females. There were also indications of selection against farm genotypes during early survival but not thereafter. However, evidence of resource competition and competitive displacement existed as the productivity of the native population was depressed by more than 30%. Ultimately, the lifetime reproductive success (adult to adult) of the farm fishes was 16% that of the native salmon. Our results indicate that such annual invasions have the potential for impacting on population productivity, disrupting local adaptations and reducing the genetic diversity of wild salmon populations.

Animals↗

Waiting time to parapatric speciation.

Using a weak migration and weak mutation approximation, I studied the average waiting time to parapatric speciation. The description of reproductive isolation used is based on the classical Dobzhansky model and its recently proposed multilocus generalizations. The dynamics of parapatric speciation are modelled as a biased random walk performed by the average genetic distance between the residents and immigrants. If a small number of genetic changes is sufficient for complete reproductive isolation, mutation and random genetic drift alone can cause speciation on the time-scale of ten to 1,000 times the inverse of the mutation rate over a set of loci underlying reproductive isolation. Even relatively weak selection for local adaptation can dramatically decrease the waiting time to speciation. The actual duration of the parapatric speciation process (that is the duration of intermediate forms in the actual transition to a state of complete reproductive isolation) is shorter by orders of magnitude than the overall waiting time to speciation. For a wide range of parameter values, the actual duration of parapatric speciation is of the order of one over the mutation rate. In general, parapatric speciation is expected to be triggered by changes in the environment.

Animals↗

Modelling infection as a two-step process combining gene-for-gene and matching-allele genetics.

The genetic basis of infection determines the dynamics of host-parasite coevolution and associated phenomena such as local adaptation and the evolution of sex and recombination. Here, we present parasite resistance as a two-step process in which hosts must first detect parasites and then eradicate them; failure at either step results in infection. The model incorporates 'matching-allele' (MA) genetics for detection and 'gene-for-gene' (GFG) genetics for eradication. We found that the oscillatory dynamics were similar to pure GFG genetics when the cost of 'virulence' alleles was low, but resembled pure MA genetics when the cost was high. The magnitude of the cost that switched the dynamics from GFG dominated to MA dominated depended on the genetic architecture of defence (i.e. the number of GFG and MA loci).

Alleles↗

Temporal variation in feeding morphology and size-structured population dynamics in fishes.

Considerable variation in morphology associated with resource use is a classic example of local adaptation to the environment. We demonstrate that a temporal change in feeding morphology might occur within a population. In a 5-year natural field experiment, we estimated gill raker morphology, resource density and population dynamics of the roach and its competitor, the perch. Despite a variation in density of zooplankton resources and perch across years, no change in roach density was observed. However, gill raker morphology in roach covaried with size structure of the zooplankton resource across years. A laboratory experiment confirmed that gill raker morphology has a great effect on roach foraging efficiency on zooplankton and that there is a functional trade-off with regard to zooplankton foraging. We suggest that the response in gill raker structure is an adaptation to deal with the rapid population dynamics of zooplankton, which are in turn mediated by changes in the size structure of the competing perch.

Adaptation, Physiological↗

Regional heterogeneity and gene flow maintain variance in a quantitative trait within populations of lodgepole pine.

Genetic variation is of fundamental importance to biological evolution, yet we still know very little about how it is maintained in nature. Because many species inhabit heterogeneous environments and have pronounced local adaptations, gene flow between differently adapted populations may be a persistent source of genetic variation within populations. If this migration-selection balance is biologically important then there should be strong correlations between genetic variance within populations and the amount of heterogeneity in the environment surrounding them. Here, we use data from a long-term study of 142 populations of lodgepole pine (Pinus contorta) to compare levels of genetic variation in growth response with measures of climatic heterogeneity in the surrounding region. We find that regional heterogeneity explains at least 20% of the variation in genetic variance, suggesting that gene flow and heterogeneous selection may play an important role in maintaining the high levels of genetic variation found within natural populations.

Climate↗

A particle-dynamics study of dissipation in colliding clouds of ultracold fermions.

We present a numerical study of the micro-dynamical roots of dissipation in two colliding mesoscopic clouds of point-like fermions as a function of the scattering length and of temperature approaching full quantum degeneracy. This study, which is motivated by current experiments on ultracold gaseous mixtures of fermionic atoms inside magnetic traps, combines the solution of the coupled Vlasov-Landau equations for the Wigner distribution functions with a locally adaptive importance-sampling technique for handling collisional interactions. The results illustrate the consequences of genuinely quantum collisional phenomena, and in particular the role of Pauli blocking in the transition to hydrodynamic behaviour. We also compare the computed quantum collision rate as a function of temperature in the weak-coupling case with theoretical results assuming that equilibrium distributions determine the quantum collision integral.

Journal Article↗

Rapid genome-wide introgression reveals fitness advantage of immigrant genotypes.

Evolutionary biology has long recognized the tendency for populations to be locally adapted to their ancestral habitat, resulting in higher resident fitness. However, immigrants can also introduce beneficial alleles. The resulting adaptive introgression is usually inferred retrospectively, rather than as a contemporary process. Here, we document exceptionally rapid ongoing adaptive introgression in a lake population of threespine stickleback (Gasterosteus aculeatus). In the first generations after a discrete immigration event, all chromosomes exhibited large increases in immigrant ancestry due to linkage disequilibrium. After a decade, the extent of introgression varied across the genome. The fastest-evolving genes included Spi1b, which enables an increased fibrosis defense against a previously common tapeworm, whose prevalence then declined dramatically. This case study highlights the capacity for immigration to supply beneficial alleles that drive rapid genome-wide evolution.

Journal Article↗

Identifying loci under positive selection in complex population histories.

Detailed modeling of a species' history is of prime importance for understanding how natural selection operates over time. Most methods designed to detect positive selection along sequenced genomes, however, use simplified representations of past histories as null models of genetic drift. Here, we present the first method that can detect signatures of strong local adaptation across the genome using arbitrarily complex admixture graphs, which are typically used to describe the history of past divergence and admixture events among any number of populations. The method-called graph-aware retrieval of selective sweeps (GRoSS)-has good power to detect loci in the genome with strong evidence for past selective sweeps and can also identify which branch of the graph was most affected by the sweep. As evidence of its utility, we apply the method to bovine, codfish, and human population genomic data containing panels of multiple populations related in complex ways. We find new candidate genes for important adaptive functions, including immunity and metabolism in understudied human populations, as well as muscle mass, milk production, and tameness in specific bovine breeds. We are also able to pinpoint the emergence of large regions of differentiation owing to inversions in the history of Atlantic codfish.

Animals↗

Golden Indica and Japonica rice lines amenable to deregulation.

As an important step toward free access and, thus, impact of GoldenRice, a freedom-to-operate situation has been achieved for developing countries for the technology involved. Specifically, to carry the invention beyond its initial "proof-of-concept" status in a Japonica rice (Oryza sativa) cultivar, we report here on two transformed elite Indica varieties (IR64 and MTL250) plus one Japonica variety Taipei 309. Indica varieties are predominantly consumed in the areas with vitamin A deficiency. To conform with regulatory constraints, we changed the vector backbone, investigated the absence of beyond-border transfer, and relied on Agrobacterium tumefaciens-mediated transformation to obtain defined integration patterns. To avoid an antibiotic selection system, we now rely exclusively on phosphomannose isomerase as the selectable marker. Single integrations were given a preference to minimize potential epigenetic effects in subsequent generations. These novel lines, now in the T(3) generation, are highly valuable because they are expected to more readily receive approval for follow-up studies such as nutritional and risk assessments and for breeding approaches leading to locally adapted variety development.

Agrobacterium tumefaciens↗

X-ray diffraction topography using a diffractometer with a bendable monochromator at a synchrotron radiation source.

The different properties of laboratory- and synchrotron-based double-crystal setups for X-ray topographic applications are discussed as a basis for the realization of a versatile instrument allowing the investigation of all kinds of crystals with high strain sensitivity and without any reduction in image size. It appears that the use of a bendable highly perfect monochromator (silicon) achieves this goal, through the local adaptation of Bragg angles, to compensate either dispersion or a bending of the sample.

Journal Article↗