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A template for improved prevention and control of cardiovascular disease in sub-Saharan Africa.

Cardiovascular disease (CVD) is rapidly becoming an important public health problem in sub-Saharan Africa, yet the response so far is often minimal and inadequate. While there is, undoubtedly, a 'double burden of disease' (persisting infectious diseases co-existing with emerging non-communicable disease), this is hardly reflected in current health planning, possibly due to a limited appreciation of the changing pattern of CVD and CVD risk factor exposure. In a situation where there are also considerable budget constraints and well-established infectious disease priorities, it is difficult to implement effective interventions for prevention or treatment of CVD. Yet such planning is urgently needed and a template for a comprehensive programme, adaptable to local situations, is presented here. The first step is to raise awareness and create evidence-based commitment among policy-makers, which could lead to the establishment of a multi-sectoral CVD unit at national level. Programmes need to focus on prevention of modifiable risk factors at population level, involving a wide range of institutions and individuals. Recommended strategies include decentralizing the design and implementation of programmes, with appropriate standardized surveillance of major risk factors, all complemented by operational, epidemiological and basic research.

Africa South of the Sahara↗

The epidemiology and control of measles in Yaoundé, Cameroun, 1968-1975.

Surveillance data on measles in Yaoundé during the 8 years from 1968-1975 have been reviewed. Measles epidemics occurred in every year except 1969-1970, the period of the attach phase of the Smallpox Eradication and Measles Control Programme. Subsequent biennial mass measles immunisation campaigns and maintenance measles immunisation at the child health centre failed to interrupt epidemic transmission. 70-80% of cases were under 24 months of age. Annual outbreaks occurred during the first half of each year, but smaller numbers of cases continued throughout the year. The outbreaks came to an end despite 32-41% of 6 through 36 month old children remaining susceptible. The seasonality of measles was not simply related to the annual rainfall pattern. Rather it is hypothesised that measles seasonality depends on the movement of young children with their mothers during the annual agricultural cycles. Measles immunisation programmes must be adapted to local epidemiological and cultural conditions in order to interrupt transmission.

Age Factors↗

Approaches to improve iron bioavailability from complementary foods.

The importance of trace element bioavailability in the etiology of nutritional deficiencies, for example in the etiology of iron deficiency and iron deficiency anemia, can be expected to be most pronounced in individuals with high requirements. Of special concern is the situation in poor communities where infants and young children are consuming monotonous, cereal-based diets. Traditionally, cereal-based gruels are often one of the first semisolid foods to be introduced into the infant's diet. These foods can be expected to have low energy and nutrient density as well as low bioavailability of iron due to the presence of phytic acid. Ascorbic acid is a potent enhancer of non-heme iron absorption that can overcome the inhibiting effect of phytic acid when present in high enough quantities. However, home prepared complementary foods based on cereals and legumes contain negligible amounts of ascorbic acid unless ascorbic acid-rich foods are mixed with the cereal or consumed at the same time. Different approaches to improve iron bioavailability from plant-based complementary foods, e.g., by enzymatic degradation of phytic acid and/or by increased consumption of ascorbic acid-rich foods, should be explored and adapted to local conditions. In addition, there is a need to evaluate efficacy and effectiveness of strategies to increase the dietary intake of bioavailable iron by dietary diversification and food fortification under realistic conditions.

Ascorbic Acid↗

Development of a universally applicable household food insecurity measurement tool: process, current status, and outstanding issues.

The United States Public Law 480 Title II food aid program is the largest U.S. government program directed at reducing hunger, malnutrition, and food insecurity in the developing world. USAID and Title II implementing partners face challenges in measuring the success of Title II programs in reducing household food insecurity because of the technical difficulty and cost of collecting and analyzing data on traditional food security indicators, such as per capita income and caloric adequacy. The Household Food Insecurity Access Scale (HFIAS) holds promise as an easier and more user-friendly approach for measuring the access component of household food security. To support the consistent and comparable collection of the HFIAS, efforts are under way to develop a guide with a standardized questionnaire and data collection and analysis instructions. A set of domains have been identified that is deemed to capture the universal experience of the access component of household food insecurity across countries and cultures. Based on these domains, a set of questions has been developed with wording that is deemed to be universally appropriate, with minor adaptation to local contexts. These underlying suppositions, based on research in multiple countries, are being verified by potential users of the guide. The key remaining issue relates to the process for creating a categorical indicator of food insecurity status from the HFIAS.

Anxiety↗

Genome scans of DNA variability in humans reveal evidence for selective sweeps outside of Africa.

The last 50,000-150,000 years of human history have been characterized by rapid demographic expansions and the colonization of novel environments outside of sub-Saharan Africa. Mass migrations outside the ancestral species range likely entailed many new selection pressures, suggesting that genetic adaptation to local environmental conditions may have been more prevalent in colonizing populations outside of sub-Saharan Africa. Here we report a test of this hypothesis using genome-wide patterns of DNA polymorphism. We conducted a multilocus scan of microsatellite variability to identify regions of the human genome that may have been subject to continent-specific hitchhiking events. Using published polymorphism data for a total of 624 autosomal loci in multiple populations of humans, we used coalescent simulations to identify candidate loci for geographically restricted selective sweeps. We identified a total of 13 loci that appeared as outliers in replicated population comparisons involving different reference samples for Africa. A disproportionate number of these loci exhibited reduced levels of relative variability in non-African populations alone, suggesting that recent episodes of positive selection have been more prevalent outside of sub-Saharan Africa.

Africa↗

Setting up and running a familial cancer clinic.

This article is based on the author's own experience of establishing and running a familial cancer clinic over the past 9 years. There are certainly other ways of doing it, depending on the clinical context--resources, involvement of colleagues from other specialities--and each clinic should be adapted to local circumstances. As the familial component of the common cancers such as breast and colorectal cancers is increasingly recognised, and DNA-based predictive testing becomes a possibility, the future demand for genetic advice is likely to increase dramatically. This will almost certainly require a re-appraisal of the way in which familial cancer services are provided, which is discussed in the final section.

Ambulatory Care↗

Ecotypic differentiation of gas exchange responses and leaf anatomy in a tropical forest understory shrub from areas of contrasting rainfall regimes.

Many studies have documented genetic differentiation of physiological ecotypes along environmental gradients in the temperate zone, but this topic has received little attention in tropical plants. We collected cuttings of Psychotria horizontalis (Rubiaceae) from Atlantic and Pacific coastal areas in central Panama, which differed twofold in annual rainfall, and grew them under common conditions in a screened, open-air growing house for 14 months. Plants from the wetter (Atlantic) region showed significantly higher stomatal conductance, but photosynthetic rates were similar in both groups, leading to higher water use efficiency in plants from the drier (Pacific) region. Responses of stomatal conductance to atmospheric humidity were similar in both groups. Anatomical studies show that plants from the wetter region had a higher mesophyll surface area per unit leaf area (A(mes)/A(leaf)) than plants from the drier region (17.2 versus 13.9), and also had a higher stomatal density (161.5 versus 98.0 mm(-2)) and fewer trichomes (2.0 versus 18.7 mm(-2)). The proportion of palisade cell surface area that was exposed to intercellular airspaces is higher in plants from the Pacific coast than from the Atlantic coast, such that the total palisade cell surface area exposed to the intercellular airspaces is similar in plants from the two regions (A(mes)/A(leaf) = 1.7). Paired plants transplanted into natural forest understory conditions showed considerable variability among sites, but plants from the drier region consistently had lower stomatal conductance than plants from the wetter region. After 20 months in the field, plant growth was similar regardless of plant origin, but plants of Pacific coast origin had longer roots and more (but smaller) leaves than plants of Atlantic coast origin. Stomatal density in field-grown plants was higher in plants of Atlantic (135.9 mm(-2)) than Pacific (90.1 mm(-2)) origin. An understanding of genetically based adaptations to local environmental conditions is important for predicting the consequences of climatic change and forest fragmentation.

Journal Article↗

The etiology and management of genital ulcers in the Dominican Republic and Peru.

BACKGROUND: Clinical diagnosis of genital ulcers is difficult, and diagnostic tests are least available in settings where rates of disease are highest. The World Health Organization (WHO) has developed protocols for the syndromic management of genital ulcers in resource-poor settings. However, because risk factors, patterns and causes of disease, and antimicrobial susceptibilities differ from region to region and over time, they must be adapted to local situations. GOAL: The goal of this study was to determine etiologic factors, evaluate syndromic management, and compare polymerase chain reaction (PCR) testing with other diagnostic alternatives for genital ulcers among patients attending sexually transmitted disease clinics in the Dominican Republic and Peru. STUDY DESIGN: Eighty-one men with genital ulcers in the Dominican Republic and 63 in Peru underwent identical interviews and identical multiplex PCR (M-PCR) tests of genital lesion specimens for etiologic diagnoses. Algorithms for managing genital ulcers were developed. RESULTS: In the Dominican Republic, 5% were M-PCR-positive for, 26% for, and 43% for herpes simplex virus (HSV); in Peru, 10%, 5%, and 43%, respectively, were positive. The WHO algorithm for treating syphilis and chancroid had a sensitivity of 100%, a positive predictive value (PPV) of 24%, and an overtreatment rate of 76%. A modified algorithm for treating only those without vesicular lesions had 88% sensitivity and a 27% PPV, and the overtreatment rate was reduced to 58%. CONCLUSION: HSV caused 43% of genital ulcers in these populations. The modified algorithm had lower sensitivity but a reduced overtreatment rate. M-PCR testing was more sensitive than standard tests and more specific and sensitive than clinical diagnosis.

Adolescent↗

The management of irritable bowel syndrome: a European, primary and secondary care collaboration.

OBJECTIVE: To develop recommendations for the diagnosis and management of irritable bowel syndrome for European doctors delivering primary care. These recommendations can be adapted by local medical groups according to their language, custom and health-care systems. METHODS: Twenty-one general practitioners and gastroenterologists from Europe attended a workshop planned by a steering committee. After a state-of-the-art symposium, four working groups considered the following aspects of irritable bowel syndrome management: what to tell the patient, diagnosis, non-medical treatment and psychosocial management. Current and future drug management was reviewed by the steering committee. The resulting recommendations were considered at two plenary sessions during the meeting, and by circulation of the material during development of the manuscript. RESULTS: The process permitted a unique dialogue between general practitioners and gastroenterologists, in which it was necessary to reconcile the specialists' emphasis on thoroughness with the practical, epidemiological and economic realities of primary care. Despite this dichotomy, consensus was achieved. CONCLUSIONS: European general practitioners and gastroenterologists have produced recommendations that emphasize education of the patient, a positive symptom-based diagnosis, diet and lifestyle advice, psychological support and a critical analysis of current specific psychological and pharmacological treatments.

Colonic Diseases, Functional↗

The gastric mucosa in gastric cancer patients in a low-incidence area.

BACKGROUND AND AIMS: Atrophic gastritis, intestinal metaplasia, and pyloric metaplasia are frequent precursors of noncardial intestinal-type gastric adenocarcinoma in populations in which both gastric cancer and Helicobacter pylori infection are common. We hypothesized that such lesions would be less prevalent in European gastric cancer patients. METHODS: Slides from patients who underwent gastrectomy for adenocarcinoma between 1997 and 2004 were reviewed. Tumors were categorized as intestinal or diffuse; non-neoplastic mucosa was evaluated for gastritis, atrophy, intestinal metaplasia and pyloric metaplasia. RESULTS: We studied 81 patients: 48 Swiss (mean age 68.5 years); 17 Italians (mean age 67.8 years); and 16 Iberians (mean age 54.8 years; P<0.001). Twelve tumors were proximal (all intestinal type), 12 in the corpus (six intestinal-type), and 57 antral (30 intestinal type). Patients with diffuse cancers were younger than those with intestinal type (P<0.05). Nineteen patients (23.4%) had a normal stomach; 30% of T1 tumors and 90% of T4s arose in a normal stomach (P<0.02). H. pylori gastritis was found in 47 patients (58%); they did not differ in age, sex, national origin, cancer location or type from those without gastritis. Intestinal metaplasia correlated with H. pylori gastritis (P=0.002). Pyloric metaplasia was infrequent and limited to rare microfoci. CONCLUSIONS: A quarter of the patients had a normal stomach, and pyloric metaplasia was distinctly uncommon. Approaches to prevention and early detection of gastric cancer based on bioptic or serological demonstration of atrophy and metaplasia could overlook at least 25% of the people at risk in certain populations and may need to be adapted to local conditions.

Adenocarcinoma↗

An evaluation of sexually transmitted infection case management in health facilities in 4 border provinces of Cambodia.

BACKGROUND: Cambodia has reported the highest prevalence of HIV in the general population in Asia. Sex work and high sexually transmitted infection (STI) prevalences are thought to be major contributory factors. GOAL: The goal of this study was to assess standards of STI care through a survey of public sector health facilities in 4 border provinces of Cambodia. METHODS: Healthcare facilities providing STI care were identified. Interviews were held with healthcare providers and STI patients and a manual check made of the STI register and standard medical history forms for female sex workers (SWs) registered with the 100% condom use program. Clinical management was assessed for SWs, women with vaginal discharge, and men with urethral discharge. Advice about condom use, partner notification, STI and HIV education, and availability of STI drugs were reviewed. RESULTS: Seven percent of all patients seeking health care at health centers (HCs) had STI-related problems. Coverage of sex workers was high in 3 provinces. Drug stock outs, particularly cefixime, occurred at all levels of assessment. In STI clinics, almost all (99-100%) cervicitis and urethritis cases were diagnosed and treated correctly. In HCs with integrated STI services, according to national guidelines, cervicitis was diagnosed in 65% of women with vaginal discharge of whom 47% were diagnosed correctly, and in these, 88% were treated correctly. Sixty-six percent of SWs seen at STI clinics were diagnosed with cervicitis and 54% at follow up. CONCLUSIONS: STI services should be expanded further to health centers not currently offering STI care. Overtreatment for cervicitis in both SWs at reattendance and low-risk women with vaginal discharge are continuing problems. The WHO/UNAIDS STI service indicator criteria had limited application for the assessment of SW services but were adapted for local needs. Attendance of SWs in designated STI clinics appears to be a useful indicator for the acceptability and efficiency of the current national STI program.

Ambulatory Care Facilities↗

Agricultural use of water.

Irrigation for agricultural purposes is one of the essential claims on available water resources. Those resources have not been adequately utilized in many countries for a variety of reasons. Where finance has been allocated to irrigation schemes, the schemes have tended to be large-scale, and the performance often disappointing. Alternatively, small-scale irrigation schemes, while receiving less support and encouragement, can often be more effective. For both large-scale and small-scale irrigation schemes, the responses of individual farmers and village communities are critical factors. More technologies need to be developed that are adapted to local needs, resources and aspirations within the context of current socio-economic practices. Obviously, the wider the range of technologies available, the more likely it will be that the technology most appropriate to existing conditions will be identified and used.

Agriculture↗

Blending in with the crowd: social parasites integrate into their host colonies using a flexible chemical signature.

Social parasites are able to exploit their host's communication code and achieve social integration. For colony foundation, a newly mated slave-making ant queen must usurp a host colony. The parasite's brood is cared for by the hosts and newly eclosed slave-making workers integrate to form a mixed ant colony. To elucidate the social integration strategy of the slave-making workers, Polyergus rufescens, behavioural and chemical analyses were carried out. Cocoons of P. rufescens were introduced into subcolonies of four potential host species: Formica subgenus Serviformica (Formica cunicularia and F. rufibarbis, usual host species; F. gagates, rare host; F. selysi, non-natural host). Slave-making broods were cared for and newly emerged workers showed several social interactions with adult Formica. We recorded the occurrence of abdominal trophallaxis, in which P. rufescens, the parasite, was the donor. Social integration of P. rufescens workers into host colonies appears to rely on the ability of the parasite to modify its cuticular hydrocarbon profile to match that of the rearing species. To study the specific P. rufescens chemical profile, newly emerged callows were reared in isolation from the mother colony (without any contact with adult ants). The isolated P. rufescens workers exhibited a chemical profile closely matching that of the primary host species, indicating the occurrence of local host adaptation in the slave-maker population. However, the high flexibility in the ontogeny of the parasite's chemical signature could allow for host switching.

Animals↗

Infection rate of Aedes aegypti mosquitoes with dengue virus depends on the interaction between temperature and mosquito genotype.

Dengue fever is the most prevalent arthropod-transmitted viral disease worldwide, with endemic transmission restricted to tropical and subtropical regions of different temperature profiles. Temperature is epidemiologically relevant because it affects dengue infection rates in Aedes aegypti mosquitoes, the major vector of the dengue virus (DENV). Aedes aegypti populations are also known to vary in competence for different DENV genotypes. We assessed the effects of mosquito and virus genotype on DENV infection in the context of temperature by challenging Ae. aegypti from two locations in Vietnam, which differ in temperature regimes, with two isolates of DENV-2 collected from the same two localities, followed by incubation at 25, 27 or 32&#xb0;C for 10 days. Genotyping of the mosquito populations and virus isolates confirmed that each group was genetically distinct. Extrinsic incubation temperature (EIT) and DENV-2 genotype had a direct effect on the infection rate, consistent with previous studies. However, our results show that the EIT impacts the infection rate differently in each mosquito population, indicating a genotype by environment interaction. These results suggest that the magnitude of DENV epidemics may not only depend on the virus and mosquito genotypes present, but also on how they interact with local temperature. This information should be considered when estimating vector competence of local and introduced mosquito populations during disease risk evaluation.

Aedes↗

Phenotypic and genotypic diversity of fluorescent pseudomonads isolated from field-grown sugar beet.

A sample of 30 fluorescent pseudomonads isolated from the phyllosphere of sugar beet throughout a single growing season and shown to be closely related on the basis of fatty acid methyl ester (FAME) analysis was subjected to detailed phenotypic and genotypic characterization. Phenotypic traits were assessed on the basis of biochemical properties, assimilation of sole carbon sources, FAME analysis, organic pyrolysate content (MS-pyrolysis), and total cellular protein profiles. With the exception of total cellular protein profiles, numerical analysis of the data revealed two main clusters, each of which was divided into several subclusters. Numerical analysis of total cellular protein data failed to differentiate isolates into two main clusters, but nevertheless grouped isolates into six subclusters. On the basis of biochemical and carbon source assimilation profiles, 19 isolates were identified as Pseudomonas fluorescens biovar V, eight isolates as P. fluorescens biovar III and three isolates as P. syringae pathovar syringae. In general, all methods of phenotypic analysis grouped isolates according to time of sampling and leaf type. Genome analysis was undertaken by pulsed-field gel electrophoresis (PFGE) of PacI, SpeI, SwaI and XbaI macrorestriction fragments and revealed the presence of eight distinct genomic (clonal) groups. These groups correlated closely with the clusters generated by numerical analysis of phenotypic data, but there was no correlation between macrorestriction fragment profile and isolate identification; in fact the variation in macrorestriction fragment patterns within P. fluorescens biovars was as great as the variation detected between biovars, and between P. fluorescens and P. syringae. Statistical evaluation of macrorestriction fragment patterns revealed two examples of recent strain divergence: one was due to the presence of a 400 kbp plasmid within one isolate of a collection of nine otherwise genomically identical isolates, and the other was observed between two phenotypically similar isolates sampled 220 d apart. Genetic variation was expressed in terms of nucleotide diversity (pi) and pairwise comparisons yielded values ranging from 0.0029 to 0.1517. The mean intrapopulation genetic variation was high (0.0993), but limited genetic variation was detected among isolates sampled on each occasion. Taken together this suggests a population comprised of a variety of apparently distantly related clones (genomic groups), each adapted to local conditions. Genome sizes were estimated from the sum of SpeI restriction fragments and ranged from 4.2 to 5.5 Mbp. Examination of the distribution of XbaI, SpeI, SwaI and PacI restriction endonuclease sites showed that the distribution of SpeI sites differed significantly from the expected (random) distribution.

Bacterial Proteins↗

Optimal noise-aided signal transmission through populations of neurons.

Metabolic considerations and neurophysiological measurements indicate that biological neural systems prefer information transmission via many parallel low intensity channels, compared to few high intensity ones [S. B. Laughlin et al., Nature Neurosci. 1, 36 (1998)]. Furthermore, cortical neurons are exposed to a considerable amount of synaptic background activity, which increases the neurons' conductance and leads to a fluctuating membrane potential that, on average, is close to the threshold [A. Destexhe and D. Paré, J. Neurophysiol. 81, 1531 (1999)]. Recent studies have shown that noise can improve the transmission of subthreshold signals in populations of neurons, e.g., if their response is pooled. In general, the optimal noise level depends on the stimulus distribution and on the number of neurons in the population. In this contribution we show that for a large enough number of neurons the latter dependency becomes weak, such that the optimal noise level becomes almost independent of the number of neurons in the population. First we investigate a binary threshold model of neurons. We derive an analytic expression for the optimal noise level at each single neuron, which-for a large enough population size-depends only on quantities that are locally available to a single neuron. Using numerical simulations, we then verify the weak dependence of the optimal noise level on population size in a more realistic framework using leaky integrate-and-fire as well as Hodgkin-Huxley-type model neurons. Next we construct a cost function, where quality of information transmission is traded against its metabolic costs. Again we find that-for subthreshold signals-there is an optimal noise level which maximizes this cost. This noise level, however, is almost independent of the number of neurons, even for small population sizes, as numerical simulations using the Hodgkin-Huxley model show. Since the dependence of the optimal noise level on population size is weak for large enough populations, local neural adaptation is sufficient to adjust the level of noise to its optimal value.

Animals↗

Diffusive diffraction of the local ESR pulse-gradient spin-echo signal in a restricted one-dimensional conductor.

The diffusive motion of the conducting electrons in the one-dimensional organic conductor FA2PF6 (FA, Fluoranthene) is studied with the ESR pulse-gradient spin-echo (PGSE) signal combined with spatial density ESR imaging. A local measurement of the short restricted regions reveals diffraction patterns in the local PGSE data. A model calculation adapted to the local measurements provides a highly accurate quantitative description of the results. The appearance of these patterns provides information about the diffusive motion of the charge at the crystal boundaries.

Journal Article↗

How fluctuating competition and phenotypic plasticity mediate species divergence.

Causal evidence linking resource competition to species divergence is scarce. In this study, we coupled field observations with experiments to ask if the degree of character displacement reflects the intensity of competition between two closely related spadefoot toads (Spea bombifrons and S. multiplicata). Tadpoles of both species develop into either a small-headed omnivorous morph, which feeds mostly on detritus, or a large-headed carnivorous morph, which specializes on and whose phenotype is induced by fairy shrimp. Previously, we found that S. multiplicata are inferior competitors for fairy shrimp and are less likely to develop into carnivores in sympatry with S. bombifrons. We compared four key trophic characters in S. multiplicata across natural ponds where the frequency of S. bombifrons varied. We found that S. multiplicata became increasingly more omnivore-like as the relative abundance of S. bombifrons increased. Moreover, in controlled laboratory populations, S. multiplicata became increasingly more omnivore-like and S. bombifrons became increasingly more carnivore-like as we increased the relative abundance of the other species. Phenotypic plasticity helped mediate this divergence: S. multiplicata became increasingly less likely to eat shrimp and develop into carnivores in the presence of S. bombifrons, a superior predator on shrimp. However, divergence also reflected differences in canalized traits: When reared under common conditions, S. multiplicata tadpoles became increasingly less likely to produce carnivores as their natal pond decreased in elevation. Presumably, this pattern reflected selection against carnivores in lower-elevation ponds, because S. bombifrons became increasingly more common with decreasing elevation. Local genetic adaptation to the presence of S. bombifrons was remarkably fine grained, with differences in carnivore production detected between populations a few kilometers apart. Our results suggest that the degree of character displacement potentially reflects the intensity of competition between interacting species and that both phenotypic plasticity and fine-scale genetic differentiation can mediate this response. Moreover, these results provide causal evidence linking resource competition to species divergence.

Animals↗