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Assortative mating and differential male mating success in an ash hybrid zone population.

BACKGROUND: The structure and evolution of hybrid zones depend mainly on the relative importance of dispersal and local adaptation, and on the strength of assortative mating. Here, we study the influence of dispersal, temporal isolation, variability in phenotypic traits and parasite attacks on the male mating success of two parental species and hybrids by real-time pollen flow analysis. We focus on a hybrid zone population between the two closely related ash species Fraxinus excelsior L. (common ash) and F. angustifolia Vahl (narrow-leaved ash), which is composed of individuals of the two species and several hybrid types. This population is structured by flowering time: the F. excelsior individuals flower later than the F. angustifolia individuals, and the hybrid types flower in-between. Hybrids are scattered throughout the population, suggesting favorable conditions for their local adaptation. We estimate jointly the best-fitting dispersal kernel, the differences in male fecundity due to variation in phenotypic traits and level of parasite attack, and the strength of assortative mating due to differences in flowering phenology. In addition, we assess the effect of accounting for genotyping error on these estimations. RESULTS: We detected a very high pollen immigration rate and a fat-tailed dispersal kernel, counter-balanced by slight phenological assortative mating and short-distance pollen dispersal. Early intermediate flowering hybrids, which had the highest male mating success, showed optimal sex allocation and increased selfing rates. We detected asymmetry of gene flow, with early flowering trees participating more as pollen donors than late flowering trees. CONCLUSION: This study provides striking evidence that long-distance gene flow alone is not sufficient to counter-act the effects of assortative mating and selfing. Phenological assortative mating and short-distance dispersal can create temporal and spatial structuring that appears to maintain this hybrid population. The asymmetry of gene flow, with higher fertility and increased selfing, can potentially confer a selective advantage to early flowering hybrids in the zone. In the event of climate change, hybridization may provide a means for F. angustifolia to further extend its range at the expense of F. excelsior.

Evolution, Molecular↗

Variation in resistance and virulence in the interaction between Arabidopsis thaliana and a bacterial pathogen.

We examined patterns of variation and the extent of local adaptation in the interaction between the highly selfing annual weed Arabidopsis thaliana and its foliar bacterial pathogen Pseudomonas viridiflava by cross-infecting 23 bacterial isolates with 35 plant lines collected from six fallow or cultivated fields in the Midwest, USA. We used two measures of resistance and virulence: bacterial count in the leaf and symptom development four days after infection. We found variation in resistance in A. thaliana and virulence in P. viridiflava, as well as a significant difference in symptoms between two distinct genetic clades within P. viridiflava. We also observed that both resistance and plant development rate varied with field type of origin (cultivated or fallow), possibly through age-related resistance, a developmentally regulated general form of resistance. Finally, we did not observe local adaptation by host or pathogen, rather we found patterns of variation across populations that depended in part on P. viridiflava clade. These data suggest that the interaction between A. thaliana and P. viridiflava varies across space and is mediated by the selection regime of the host populations and differential performance of the P. viridiflava clades. This is one of a very limited number of studies examining a bacterial pathogen of wild plant populations and one of a few studies to examine patterns of variation in a plant-pathogen association that is not a highly specialized gene-for-gene interaction.

Arabidopsis↗

Population structure of a parasitic plant and its perennial host.

Characterization of host and parasite population genetic structure and estimation of gene flow among populations are essential for the understanding of parasite local adaptation and coevolutionary interactions between hosts and parasites. We examined two aspects of population structure in a parasitic plant, the greater dodder (Cuscuta europaea) and its host plant, the stinging nettle (Urtica dioica), using allozyme data from 12 host and eight parasite populations. First, we examined whether hosts exposed to parasitism in the past contain higher levels of genetic variation. Second, we examined whether host and parasite populations differ in terms of population structure and if their population structures are correlated. There was no evidence that host populations differed in terms of gene diversity or heterozygosity according to their history of parasitism. Host populations were genetically more differentiated (F(ST) = 0.032) than parasite populations (F(ST) = 0.009). Based on these F(ST) values, gene flow was high for both host and parasite. Such high levels of gene flow could counteract selection for local adaptation of the parasite. We found no significant correlation between geographic and genetic distance (estimated as pairwise F(ST)), either for the host or for the parasite. Furthermore, host and parasite genetic distance matrices were uncorrelated, suggesting that sites with genetically similar host populations are unlikely to have genetically similar parasite populations.

Alleles↗

Genomic separation of Salish Sea and Pacific outer coast populations of the keystone sea star Pisaster ochraceus.

Environmental boundaries shape genetic diversity through the interacting effects of geographic distance, local adaptation, and constraints on gene flow. The ochre sea star (Pisaster ochraceus), an intertidal keystone predator, has long been considered to have limited spatial genetic structure along the North American Pacific coast, likely due to its extended larval dispersal period and high potential for gene flow. Here, we characterize spatial genomic variation in Pisaster ochraceus using whole-genome sequencing data from individuals spanning nearly 3000 kilometers of coastline from Alaska to southern California. Analyses of putatively neutral SNPs demonstrate considerable mixing across the latitudinal range, but also reveal substantial structure between outer Pacific coast populations and those within the semi-enclosed Salish Sea, suggesting restricted gene flow and demographic divergence between these regions. Genomic divergence is further supported by evidence of selection, with outlier loci highlighting extended regions of low diversity in the Salish Sea, consistent with recent selective sweeps and potential local adaptation to distinct estuarine conditions. These findings support the role of oceanographic barriers and environmental heterogeneity in shaping population structure in Pisaster ochraceus, challenging earlier expectations of range-wide homogeneity and providing insight into the persistence of this keystone marine species in a rapidly changing world.

Pisaster↗

Spatial variation in susceptibility to infection in a snail-trematode interaction.

Parasites should be better at infecting hosts from sympatric populations than allopatric populations most of the time (parasite local adaptation). In a previous study of a population of snail parasites (Microphallus sp.) from Lake Alexandrina, New Zealand, we found that Microphallus was more infective to snails (Potamopyrgus antipodarum) in shallow water but not in deep water. Here, we repeated the original study and also monitored the development of the parasite. We found that parasites from shallow water were more infective to hosts from shallow water and developed more rapidly in these hosts. In contrast, parasites from deep water were not more infective to hosts from deep water and did not develop more rapidly in them. These results suggest clinal variation in the susceptibility of these snails, with shallow-water snails more susceptible than deep-water snails. We offer 2 possible explanations for these results. First, gene flow in the Microphallus population is primarily from shallow to deep water, leading to an asymmetric pattern of local adaptation. Alternatively, snails from shallow water may be more susceptible for reasons independent of gene flow, perhaps due to differences in host condition between habitats.

Adaptation, Physiological↗

Spatiotemporal allozyme variation in the damselfly, Lestes viridis (Odonata: Zygoptera): gene flow among permanent and temporary ponds.

Several insect species seem to persist not only in permanent but also in temporary ponds where they face particularly harsh conditions and frequent extinctions. Under such conditions, gene flow may prevent local adaptation to temporary ponds and may promote phenotypic plasticity, or maintain apparent population persistence. The few empirical studies on insects suggest the latter mechanism, but no studies so far quantified gene flow including both pond types. We investigated the effects of pond type and temporal variation on population genetic differentiation and gene flow in the damselfly Lestes viridis in northern Belgium. We report a survey of two allozyme loci (Gpi, Pgm) with polyacrylamide gel electrophoresis in 14 populations from permanent and temporary ponds, and compared these results with similar data from the same permanent populations one year before. The data suggested that neither pond-drying regime, nor temporal variation have a substantial effect on population genetic structuring and did not provide evidence for stable population differentiation in L. viridis in northern Belgium. Gene flow estimates were high within permanent and temporary ponds, and between pond types. Our data are consistent with a source-sink metapopulation system where temporary ponds act as sinks in dry years, and are quickly recolonized after local population extinction. This may create a pattern of apparent population persistence of this species in permanent and temporary ponds without clear local adaptation.

Animals↗

Implementing guidelines for venous thromboembolism prophylaxis in a large Italian teaching hospital: lights and shadows.

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) remains a serious complication in hospitalized patients, in spite of several published guidelines (GL) on its prevention. The objective of this study (part of the TRiPSS-2 project) was to evaluate the impact of a locally adapted GL, supported by a multifaceted implementation strategy, in improving VTE prophylaxis in a large teaching hospital. DESIGN AND METHODS: A before and after controlled study was used to evaluate the impact of the recommendations on the appropriateness of prophylaxis. We evaluated the medical charts of two random samples, each of 250 patients, discharged in the first semester of the years 2000 and 2002. The hospital incidence of VTE (1996-2004) was also monitored, through the discharge summaries. RESULTS: Among high risk patients, appropriateness of prophylaxis increased both in medical (from 25% to 41.7%, p=0.0075) and in surgical patients (from 63.7% to 97.1%, p=0.0004). A parallel sharp increase (by 6-8 times) of consumption of elastic stockings was documented. In both medical and surgical patients the incidence of VTE decreased markedly and sustainedly in 2002-2004, with an adjusted odds ratio of 0.68 (95% confidence interval: 0.62-0.75). However, the use of lower than recommended doses of heparins and the increased use of prophylaxis in low risk patients represent unsolved problems. INTERPRETATION AND CONCLUSIONS: Implementing locally adapted GL may be highly effective in improving appropriateness of prophylaxis and in reducing the incidence of VTE; however a careful evaluation of changes is recommended in order to identify unsolved problems or undesired effects.

Adult↗

Reference genome bias in light of species-specific chromosomal reorganization and translocations.

BACKGROUND: Whole-genome sequencing efforts, have during the past decade, unveiled the central role of genomic rearrangements-such as chromosomal inversions-in evolutionary processes, including local adaptation in a wide range of taxa. However, employment of reference genomes from distantly or even closely related species for mapping and the subsequent variant calling can lead to errors and/or biases in the datasets generated for downstream analyses. RESULTS: Here, we capitalize on the recently generated chromosome-anchored genome assemblies for Arctic cod (Arctogadus glacialis), polar cod (Boreogadus saida), and Atlantic cod (Gadus morhua) to evaluate the extent and consequences of reference bias on population sequencing datasets (approx. 15-20 × coverage) for both Arctic cod and polar cod. Our findings demonstrate that the choice of reference genome impacts the mapping statistics, including mapping depth and mapping quality, as well as core population genetic estimates, such as heterozygosity levels, nucleotide diversity (π), and cross-species genetic divergence (DXY). Furthermore, using a more distantly related reference genome can lead to inaccurate detection and characterization of chromosomal inversions, i.e., in terms of size (length) and location (position), due to inter-chromosomal reorganizations between species. Additionally, we observe that some of the verified species-specific inversions are split across multiple genomic regions when mapped against a heterospecific reference. CONCLUSIONS: Inaccurate identification of chromosomal rearrangements as well as biased population genetic measures could potentially lead to erroneous interpretation of species-specific genomic diversity, impede the resolution of local adaptation, and thus, impact predictions of their genomic potential to respond to climatic and other environmental perturbations.

Animals↗

Individual and combined effects of Ca/Mg ratio and water on trait expression in Mimulus guttatus.

Low Ca/Mg ratios (a defining component of serpentine soils) and low water environmental conditions often co-occur in nature and are thought to exert strong selection pressures on natural populations. However, few studies test the individual and combined effects of these environmental factors. We investigated the effects of low Ca/Mg ratio and low water availability on plant leaf, stem, stolon, and floral traits of Mimulus guttatus, a bodenvag species, i.e., a species that occurs in serpentine and non-serpentine areas. We quantified genetic variation and genetic variation for plasticity for these leaf, stem, stolon, and floral traits at three hierarchical levels: field-habitat type, population, and family, and we evaluated the relative importance of local adaptation and plasticity. We chose two populations and 10 families per population from four distinct field "habitat types" in northern California: high Ca/Mg ratio (non-serpentine) and season-long water availability, high Ca/Mg ratio and seasonally drying, low Ca/Mg ratio (serpentine) and season-long water availability, and low Ca/Mg ratio and seasonally drying. Seedlings were planted into greenhouse treatments that mimicked the four field conditions. We only detected genetic variation for stem diameter and length of longest leaf at the field-habitat level, but we detected genetic variation at the family level for nearly all traits. Soil chemistry and water availability had strong phenotypic effects, alone and in combination. Our hypothesis of an association between responses to low water levels and low Ca/Mg ratio was upheld for length of longest leaf, stem diameter, corolla width, and total number of reproductive units, whereas for other traits, responses to Ca/Mg ratio and low water were clearly independent. Our results suggest that traits may evolve independently from Ca/Mg ratios and water availability and that our focal traits were not simple alternative measures of vigor. We found genetic variation for plasticity both at the field-habitat type and family levels for half of the traits studied. Phenotypic plasticity and genetic variation for plasticity appear to be more important than local adaptation in the success of these M. guttatus populations found across a heterogeneous landscape in northern California. Phenotypic plasticity is an important mechanism maintaining the broad ecological breadth of native populations of M. guttatus.

Adaptation, Physiological↗

Isolation of rhizobia from Ontario soils that are effective at fixing nitrogen with common bean (Phaseolus vulgaris).

UNLABELLED: Common bean (Phaseolus vulgaris) is an important crop in Canada and globally. Like other legumes, common bean establishes symbiotic interactions with nitrogen-fixing bacteria called rhizobia. However, nitrogen fixation by rhizobia in association with common bean is often suboptimal, constraining its productivity and necessitating the application of nitrogen fertilizer. To support the development of high-performing, locally adapted rhizobial inoculants for Ontario common bean growers, we isolated 216 common bean-nodulating rhizobia from southern Ontario soils using a nodule trapping approach with four common bean cultivars. Whole genome sequencing followed by phylogenomic analyses of all rhizobial isolates revealed substantial diversity, assigning them to 11 Rhizobium species, including two novel species. Nearly all isolates belong to the symbiovar phaseoli, spanning the nodC γ-a, γ-b, and α alleles, with four isolates belonging to the symbiovar gallica. Soil origin had a significant impact on the species-level community composition recovered during the nodule trapping experiments. In contrast, host trapping cultivar had only a minor influence on the recovered Rhizobium population. Greenhouse assays demonstrated that one of the novel Rhizobium species exhibited the highest average symbiotic effectiveness, although high-quality isolates were found across multiple species. Together, these results revealed a diverse and genomically variable Rhizobium community capable of forming effective symbioses with common bean in southern Ontario soils. Importantly, our genome-sequenced Rhizobium collection will serve as a valuable resource for identifying competitive and high-quality strains for the development of inoculants tailored to Ontario common bean production. IMPORTANCE: Common bean is a globally important food crop, yet its productivity is often limited by suboptimal nitrogen fixation, forcing growers to rely on synthetic fertilizers. Consequently, identifying high‑performing, locally adapted inoculant strains is essential for reducing dependence on synthetic nitrogen fertilizers and improving the sustainability of temperate agroecosystems. Our study provides a genome‑sequenced collection of common bean-nodulating Rhizobium from southern Ontario, revealing substantial species and genomic diversity across sampling locations. Greenhouse studies allowed us to identify multiple isolates that consistently fix nitrogen with, and enhance the growth of, common bean plants. Our findings highlight strong biogeographical structuring of the effective and competitive subpopulations of rhizobial communities and demonstrate that Ontario soils already harbor strains with high symbiotic potential. In addition, our Rhizobium collection represents a foundational resource to support future inoculant development and enables future work on the ecology, evolution, and applied optimization of legume-rhizobium symbioses.

Nanopore↗

MHC studies in nonmodel vertebrates: what have we learned about natural selection in 15 years?

Elucidating how natural selection promotes local adaptation in interaction with migration, genetic drift and mutation is a central aim of evolutionary biology. While several conceptual and practical limitations are still restraining our ability to study these processes at the DNA level, genes of the major histocompatibility complex (MHC) offer several assets that make them unique candidates for this purpose. Yet, it is unclear what general conclusions can be drawn after 15 years of empirical research that documented MHC diversity in the wild. The general objective of this review is to complement earlier literature syntheses on this topic by focusing on MHC studies other than humans and mice. This review first revealed a strong taxonomic bias, whereby many more studies of MHC diversity in natural populations have dealt with mammals than all other vertebrate classes combined. Secondly, it confirmed that positive selection has a determinant role in shaping patterns of nucleotide diversity in MHC genes in all vertebrates studied. Yet, future tests of positive selection would greatly benefit from making better use of the increasing number of models potentially offering more statistical rigour and higher resolution in detecting the effect and form of selection. Thirdly, studies that compared patterns of MHC diversity within and among natural populations with neutral expectations have reported higher population differentiation at MHC than expected either under neutrality or simple models of balancing selection. Fourthly, several studies showed that MHC-dependent mate preference and kin recognition may provide selective factors maintaining polymorphism in wild outbred populations. However, they also showed that such reproductive mechanisms are complex and context-based. Fifthly, several studies provided evidence that MHC may significantly influence fitness, either by affecting reproductive success or progeny survival to pathogens infections. Overall, the evidence is compelling that the MHC currently represents the best system available in vertebrates to investigate how natural selection can promote local adaptation at the gene level despite the counteracting actions of migration and genetic drift. We conclude this review by proposing several directions where future research is needed.

Animals↗

Group interpersonal psychotherapy for depression in rural Uganda: a randomized controlled trial.

CONTEXT: Despite the importance of mental illness in Africa, few controlled intervention trials related to this problem have been published. OBJECTIVES: To test the efficacy of group interpersonal psychotherapy in alleviating depression and dysfunction and to evaluate the feasibility of conducting controlled trials in Africa. DESIGN, SETTING, AND PARTICIPANTS: For this cluster randomized, controlled clinical trial (February-June 2002), 30 villages in the Masaka and Rakai districts of rural Uganda were selected using a random procedure; 15 were then randomly assigned for studying men and 15 for women. In each village, adult men or women believed by themselves and other villagers to have depressionlike illness were interviewed using a locally adapted Hopkins Symptom Checklist and an instrument assessing function. Based on these interviews, lists were created for each village totaling 341 men and women who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression or subsyndromal depression. Interviewers revisited them in order of decreasing symptom severity until they had 8 to 12 persons per village, totaling 284. Of these, 248 agreed to be in the trial and 9 refused; the remainder died or relocated. A total of 108 men and 116 women completed the study and were reinterviewed. INTERVENTION: Eight of the 15 male villages and 7 of the 15 female villages were randomly assigned to the intervention arm and the remainder to the control arm. The intervention villages received group interpersonal psychotherapy for depression as weekly 90-minute sessions for 16 weeks. MAIN OUTCOME MEASURES: Depression and dysfunction severity scores on scales adapted and validated for local use; proportion of persons meeting DSM-IV major depression diagnostic criteria. RESULTS: Mean reduction in depression severity was 17.47 points for intervention groups and 3.55 points for controls (P<.001). Mean reduction in dysfunction was 8.08 and 3.76 points, respectively (P<.001). After intervention, 6.5% and 54.7% of the intervention and control groups, respectively, met the criteria for major depression (P<.001) compared with 86% and 94%, respectively, prior to intervention (P =.04). The odds of postintervention depression among controls was 17.31 (95% confidence interval, 7.63-39.27) compared with the odds among intervention groups. Results from intention-to-treat analyses remained statistically significant. CONCLUSIONS: Group interpersonal psychotherapy was highly efficacious in reducing depression and dysfunction. A clinical trial proved feasible in the local setting. Both findings should encourage similar trials in similar settings in Africa and beyond.

Adult↗

Natural history of Homo erectus.

Our view of H. erectus is vastly different today than when Pithecanthropus erectus was described in 1894. Since its synonimization into Homo, views of the species and its distribution have varied from a single, widely dispersed, polytypic species ultimately ancestral to all later Homo, to a derived, regional isolate ultimately marginal to later hominin evolution. A revised chronostratigraphic framework and recent work bearing either directly or indirectly on reconstructions of life-history patterns are reviewed here and, together with a review of the cranial and postcranial anatomy of H. erectus, are used to generate a natural history of the species. Here I argue that H. erectus is a hominin, notable for its increased body size, that originates in the latest Pliocene/earliest Pleistocene of Africa and quickly disperses into Western and Eastern Asia. It is also an increasingly derived hominin with several regional morphs sustained by intermittent isolation, particularly in Southeast Asia. This view differs from several current views, most especially that which recognizes only a single hominin species in the Pleistocene, H. sapiens, and those which would atomize H. erectus into a multiplicity of taxa. Following Jolly ([2001] Yrbk Phys Anthropol 44:177-204), the regional morphs of H. erectus may be productively viewed as geographically replacing allotaxa, rather than as the focus of unresolvable species debates. Such a view allows us to focus on the adaptations and biology of local groups, including questions of biogeographic isolation and local adaptation. A number of issues remain unresolved, including the significance of diversity in size and shape in the early African and Georgian records.

Adolescent↗

Oxygen transport in the blood of arctic mammals: adaptation to local heterothermia.

The oxygen binding of whole blood from humans and two arctic mammals, reindeer and muskox, has been studied as a function of carbon dioxide and temperature. All bloods display a marked Bohr effect with Bohr coefficients in the range -0.44- -0.73. The Bohr effect is more pronounced at 20 degrees C. The temperature sensitivity of reindeer and muskox blood expressed by the apparent heat of oxygenation, delta H, is almost three times lower than that of human HbA under the same experimental conditions. This thermodynamic difference gives special benefits to arctic mammals with large heterothermy by safeguarding oxygen unloading at very low ambient temperatures.

Acclimatization↗

Localized and adaptive synoviocyte proliferation characteristics in rat knee joint contractures secondary to immobility.

OBJECTIVE: To investigate the proliferative activity of synoviocytes in joint contracture. DESIGN: Experimental controlled trial. SETTING: Laboratory in vivo study. ANIMALS: Adult male Sprague-Dawley rats (avg weight, 340g). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We immobilized the knee joints of 24 rats, in 135 degrees of flexion, for up to 32 weeks. Controls were 24 sham-operated and 5 unoperated rats. On sagittal sections, synoviocytes that stained with a proliferating cell nuclear antigen antibody were counted over the anterior and posterior synovial intima. The length of the synovial intima was also measured. RESULTS: The absolute number of proliferating synoviocytes decreased markedly in the posterior capsule of knee joints immobilized for more than 2 weeks (2.4+/-1.0 vs 22.7+/-7.1 at week 16, P<.05), and so did the synovial intima length (1.4+/-0.1mm vs 8.6+/-0.5mm at week 16, P<.05). No change occurred anteriorly. CONCLUSION: A decreased number of proliferating synoviocytes and increased intima adhesion in the posterior capsule characterized joint contractures. The data further suggest that the synovial intima adapted to the new position of the joint. Phenomena of mechanotransduction could explain the fact that adaptations were restricted to the posterior synovial intima.

Animals↗

Scale-independent shape analysis for quantitative cytology using mathematical morphology.

A system for automatic quantification of morphological changes of cell lines, proposed for cytotoxicity tests of biomaterials, is presented. Light-micrographs of cultured cells are segmented by adaptive thresholding within a local adaptive window. Connected cells in binarized micrographs are separated by a novel morphological multiscale method, treating cells in their size-specific scale and hence resulting in scale-independent separations. Significant shape descriptors correlating well with cell toxicity are extracted from single cells. Size and compactness distributions turned out to be reliable and useful parameters, providing an alternative to the common subjective grading of shape deformations by visual inspection. The system is evaluated for several standardized toxical reference substances and is now in use for clinical biocompatibility testing.

Cell Line↗

Designing an intervention to improve the management of Helicobacter pylori infection.

BACKGROUND: An intervention to improve the testing and treatment of Helicobacter pylori (HP) in patients receiving chronic acid suppression (AS) therapy was developed at Harvard Pilgrim Health Care (HPHC), a mixed-model not-for-profit health maintenance organization. METHODS: Ten full-time primary care physicians (4 staff model and 6 group practice) were interviewed in 1999 about their knowledge, attitudes, and practice regarding dyspepsia, the use of chronic AS drugs, and approaches to HP infection, as well as about the feasibility and acceptability of various potential interventions that might be used in a quality improvement program. RESULTS: Self-reported practice regarding dyspepsia and HP infection were relatively uniform, and physicians were generally aware of current recommendations. Three common misperceptions acted as barriers to optimal HP management: Untreated HP was not considered an important problem; patients who used drugs for chronic AS rarely had HP infection; and chronic use of AS drugs was considered effective and without adverse consequence. All physicians wanted brief educational materials with explicit guidelines, preferably locally adapted and endorsed by local experts. All informants agreed that the main barrier to successful QI interventions was the requirement for any extra time or effort, particularly when directed at populations of patients who do not have symptomatic complaints. DISCUSSION: The interviews revealed the many barriers to improving the management of HP infection and to targeting educational messages and tailoring different methods for facilitating practice change across different managed care settings. Evidence-based components of the intervention program include physician education, a notification/reminder system, and practice-based tools to facilitate change and minimize workload.

Boston↗