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Legal measures in support of prevention in Switzerland.

The Swiss health system results from a balance between federal and cantonal (state) legislation. Federal laws were instituted to combat infectious disease, certain other severe or widespread diseases, and alcohol and drug abuse; for the protection against harmful agents or substances; and on health and accident insurance. Cantonal implementation permits adaptation to local situations. In the case of health protection, this interplay of federal standards setting and cantonal implementation has been generally successful, but situations in the areas of immunization and breast cancer screening are presented, where, in the absence of uniform legislative guidance, cultural and political diversity has led to regionally different approaches. Varying levels of preventive action have resulted in measurable differences in mortality and morbidity. Lessons for other countries are discussed, where decentralization of preventive and health care services is being considered.

Health Policy↗

Cyanide removal by Chinese vegetation--quantification of the Michaelis-Menten kinetics.

BACKGROUND: Little is known about metabolism rates of environmental chemicals by vegetation. A good model compound to study the variation of rates among plant species is cyanide. Vascular plants possess an enzyme system that detoxifies cyanide by converting it to the amino acid asparagine. Knowledge of the kinetic parameters, the half-saturation constant (Km) and the maximum metabolic capacity (vmax), is very useful for enzyme characterization and biochemical purposes. The goal of this study is to find the enzyme kinetics (K(M) and vmax) during cyanide metabolism in the presence of Chinese vegetation, to provide quantitative data for engineered phytoremediation, and to investigate the variation of metabolic rates of plants. METHODS: Detached leaves (1.0 g fresh weight) from 12 species out of 9 families were kept in glass vessels with 100 mL of aqueous solution spiked with potassium cyanide at 23 degrees C for 28 h. Four different treatment concentrations of cyanide were used, ranging from 0.44 to 7.69 mg CN/L. The disappearance of cyanide from the aqueous solution was analyzed spectrophotometrically. Realistic values of the half-saturation constant (KM) and the maximum metabolic capacity (vmax) were estimated by a computer program using non-linear regression treatments. As a comparison, Lineweaver-Burk plots were also used to estimate the kinetic parameters. RESULTS AND DISCUSSION: The values obtained for K(M) and vmax varied with plant species. Using non-linear regression treatments, values of vmax and K(M) were found in a range between 6.68 and 21.91 mg CN/kg/h and 0.90 to 3.15 mg CN/L, respectively. The highest vmax was by Chinese elder (Sambucus chinensis), followed by upright hedge-parsley (Torilis japonica). The lowest Vmax was demonstrated by the hybrid willow (Salix matssudana x alba). However, the highest K(M) was found in the water lily (Nymphea teragona), followed by the poplar (Populus deltoides Marsh). The lowest K(M) was demonstrated by corn (Zea mays L.). The values of vmax were normally distributed with a mean of 13 mg CN/kg/h. CONCLUSIONS: Significant removal of cyanide from aqueous solution was observed in the presence of plant materials without phytotoxicity, even at high doses of cyanide. This gives rise to the conclusion that the Chinese plant species used in this study are all able to efficiently metabolize cyanide, although with different maximum metabolic capacities. A second conclusion is that the variation of metabolism rates between species is small. All these plants had a similar K(M), indicating the same enzyme is active in all plants. RECOMMENDATIONS AND OUTLOOK: Detoxification of cyanide with trees seems to be a feasible option for cleaning soils and water contaminated with cyanide. For phytoremediation projects, screening appropriate plant species adapted to local conditions should be seriously considered. More chemicals should be investigated to find common principles of the metabolism of environmental chemicals by plants.

Biodegradation, Environmental↗

Selective peripheral fading: evidence for inhibitory sensory effect of attention.

A circular array of six discs, three green and three orange in alternate positions, was presented against a uniform grey background. Sixteen observers maintained steady fixation at the centre of the array, and were instructed to direct their attention to three discs of one colour and to ignore the three discs of the other colour. In about 10 s (mean = 11.35 s), some discs started to fade away from awareness. Of those starting to fade, most (mean = 81.3%) were those selected for attention. The faded discs remained out of awareness for up to a few seconds (mean = 1.55 s) during which other discs were clearly visible. The fading increased with eccentricity, a defining characteristic of Troxler fading. However, the selectivity of the fading strongly suggests that voluntary attention can have an inhibitory effect on early sensory processing. Were the fading entirely due to local sensory adaptation, the unattended stimuli would have to be equally adapted and yet somehow remain visible for seconds, which is not plausible.

Color Perception↗

Stabilizing selection on genomic divergence in a wild fish population.

Conservation programs use breeding protocols to increase genomic divergence (by mating genetically dissimilar individuals) in an attempt to circumvent population declines resulting from inbreeding depression. However, disruption of either beneficial gene complexes or local genetic adaptations can lead to outbreeding depression, and thus, there should be a reduction in fitness of individuals at either end of the genomic divergence continuum. Although such simultaneous inbreeding and outbreeding depression has been observed in plant populations, it rarely has been demonstrated in animal populations. Here, I use both genetic and phenotypic measures to show that there is stabilizing selection on genomic divergence in a wild population of bluegill sunfish (Lepomis macrochirus). I also show that breeding individuals that exercise mate choice produce offspring that are closer to the optimal level of genomic divergence than random mating alone would predict.

Animals↗

Chromosome speciation: humans, Drosophila, and mosquitoes.

Chromosome rearrangements (such as inversions, fusions, and fissions) may play significant roles in the speciation between parapatric (contiguous) or partly sympatric (geographically overlapping) populations. According to the "hybrid-dysfunction" model, speciation occurs because hybrids with heterozygous chromosome rearrangements produce dysfunctional gametes and thus have low reproductive fitness. Natural selection will, therefore, promote mutations that reduce the probability of intercrossing between populations carrying different rearrangements and thus promote their reproductive isolation. This model encounters a disabling difficulty: namely, how to account for the spread in a population of a chromosome rearrangement after it first arises as a mutation in a single individual. The "suppressed-recombination" model of speciation points out that chromosome rearrangements act as a genetic filter between populations. Mutations associated with the rearranged chromosomes cannot flow from one to another population, whereas genetic exchange will freely occur between colinear chromosomes. Mutations adaptive to local conditions will, therefore, accumulate differentially in the protected chromosome regions so that parapatric or partially sympatric populations will genetically differentiate, eventually evolving into different species. The speciation model of suppressed recombination has recently been tested by gene and DNA sequence comparisons between humans and chimpanzees, between Drosophila species, and between species related to Anopheles gambiae, the vector of malignant malaria in Africa.

Animals↗

Nonrandom mating in Drosophila melanogaster laboratory populations derived from closely adjacent ecologically contrasting slopes at "Evolution Canyon".

Ecological differentiation of natural populations of Drosophila melanogaster, Drosophila simulans, and another drosophilid, Zaprionus tuberculatus, in "Evolution Canyon," Mount Carmel, Israel, is well established. The fitness complex of D. melanogaster includes oviposition temperature preferences, tolerance to high temperature, drought stress and starvation, and different longevity patterns. This remarkable differentiation has evolved despite small interslope distances (only 100-400 m), within easy dispersal distance. The differences between populations are those expected from genetic adaptation to local microclimates. How such differentiation could evolve and be maintained despite the likelihood of genetic exchange between populations is a challenging question. We hypothesized that interslope microclimatic differences caused strong differential selection for stress tolerance, accompanied by behavioral differentiation (habitat choice and reduced migration rate), reinforced by sexual isolation. Here we report highly significant mate choice by flies from different slopes of the canyon, with preference for sexual partners originating from the same slope. No preferences were found when the sexual partners belonged to different isofemale lines from the same slope.

Animals↗

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female↗

Assessment of total energy expenditure in a Chinese population by a physical activity questionnaire: examination of validity.

A physical activity questionnaire from which total daily energy expenditure (TEE) could be estimated was developed for adult Hong Kong Chinese subjects, and its reliability and validity examined. The questionnaire was based on questionnaires used in Caucasians, and adapted for local lifestyle after focus group meetings involving subjects of all age groups. The questionnaire was administered to 94 subjects, consisting of healthy adults, the elderly, and two patient groups (those with renal disease on continuous ambulatory peritoneal dialysis and those with cancer). Seventy-one subjects were reinterviewed within 14 days to test reliability. Validity was examined in 31 normal subjects by measuring the basal metabolic rate (BMR) by indirect calorimetry and multiplying by the physical activity level (PAL) obtained from published studies using the doubly labelled water method and also from FAO/WHO/UNU to obtain the TEE. The intraclass correlation coefficient of reliability rages from 0.7 to 0.8 for all subject groups. The mean estimated TEE from the questionnaire was not significantly different from the mean value derived from measured BMR x PAL. The mean bias ranged from an underestimation of 27 kcal to overestimation of 215 kcal. However, the limits of variability were wide. Age was inversely related to the energy expended for occupational activities, but was positively associated with energy expended in leisure activities. Women spent less energy on occupational and exercise activities, and more on caretaking activities. Those with disease were also less likely to participate in caretaking activities. We conclude that this questionnaire may be a useful tool for future studies where energy expenditure needs to be estimated in various settings in the Hong Kong Chinese population.

Aged↗

Resuscitation in the out-of-hospital setting: medical futility criteria for on-scene pronouncement of death.

The complete and irreversible cessation of life is often difficult to determine with complete confidence in the dynamic environment of out-of-hospital emergency care. As a result, resuscitation efforts often are initiated and maintained by emergency medical services (EMS) providers in many hopeless situations. Medical guidelines are reviewed here to aid EMS organizations with respect to decisions about: 1) initiating or waiving resuscitation efforts; 2) the appropriate duration of resuscitation efforts; and 3) recommended procedures for on-scene or prehospital pronouncement of death (termination of resuscitation). In cases of nontraumatic cardiac arrest, few unassailable criteria, other than certain physical signs of irreversible tissue deterioration, exist for determining medical futility at the initial encounter with the patient. Thus, the general medical recommendation is to attempt to resuscitate all patients, adult or child, in the absence of rigor mortis or dependent lividity. Conversely, wellfounded guidelines now are available for decisions regarding termination of resuscitation in such patients once they have received a trial of advanced cardiac life support. In practice, however, the final decision to proceed with on-scene pronouncement of death for these patients may be determined more by family and provider comfort levels and the specific on-scene environment. For patients with posttraumatic circulatory arrest, the type of injury (blunt or penetrating), the presence of vital signs, and the electrocardiographic findings are used to determine the futility of initiating or continuing resuscitation efforts. In general, patients who are asystolic on-scene are candidates for on-scene pronouncement, regardless of mechanism. With a few exceptions, blunt trauma patients with a clearly associated mechanism of lethal injury are generally candidates for immediate cessation of efforts once they lose their pulses and respirations. Regardless of the medical futility criteria, specialized training of EMS providers and targeted related testing of operational issues need to precede field implementation of on-scene pronouncement policies. Such policies also must be modified and adapted for local issues and resources. In addition, although the current determinations of medical futility, as delineated here, are important to establish for societal needs, the individual patient's right to live must be kept in mind always as new medical advances are developed.

Adolescent↗

Promoting sexual and reproductive health in early adolescence in South Africa and Tanzania: development of a theory- and evidence-based intervention programme.

AIMS: Action to prevent the spread of HIV among young people in Sub-Saharan Africa is needed urgently. In order to be effective, such action should be theory and evidence based and carefully adapted to local cultures and contexts. The present article describes the organization, theoretical basis, and methodological approach of a project that aims at developing and evaluating school-based interventions targeting adolescents aged 12-14 years. METHODS: Researchers from European and African universities have developed interventions that were conducted in three sites: Cape Town and Polokwane (South Africa) and Dar es Salaam (Tanzania). In each site the interventions were evaluated through large-scale field experiments with intervention schools and delayed intervention schools and with baseline and two follow-up data collections. Minimum sample sizes were estimated for each site based on local data and taking into account that the unit of allocation was schools and not individual students (the design effect). During the formative phase as well as within the field experiments, qualitative studies were also conducted. DISCUSSION: The interventions were developed consistent with the Intervention Mapping approach, and the theoretical framework was based on a modified version of the Theory of Planned Behaviour. The limitations of Western social cognition models were recognized, and the theoretical framework has therefore been expanded in two directions: towards integrating cultural processes and towards taking societal factors and constraints into account. CONCLUSION: The project will throw light on the application of social cognition models as well as the usefulness of the Intervention Mapping approach to intervention development in sub-Saharan Africa.

Adolescent↗

Local and global costs of adaptive plasticity to density in Arabidopsis thaliana.

Although phenotypic plasticity is demonstrably adaptive in a range of settings, organisms are not perfectly plastic. Costs of plasticity comprise one factor predicted to counter the evolution of this adaptive strategy, yet evidence of costs is rare. Here, we test the fitness effects of plastic life-history and morphological responses to density and costs of this plasticity in recombinant inbred lines of Arabidopsis thaliana. Several costs of plasticity and homeostasis were detected. Of particular relevance, there was a significant cost of plasticity to active stem-elongation responses, an adaptive trait in many species. There was also a cost of plasticity to apical branch production at both high and low density, which resulted from the greater suppression of basal branching in genotypes with plastic apical branch production relative to genotypes with fixed apical branch production. The presence of a cost in multiple environments (i.e., a global cost) is predicted to counter the evolution of plasticity. Experimental segregating progenies such as the one used here are expected to have higher genetic costs of plasticity than arrays of genotypes sampled from natural populations because selection should remove genotypes with costs resulting from linkage disequilibrium or epistasis. The use of experimental progeny arrays therefore increases the ability to evaluate genetic costs.

Adaptation, Physiological↗

The efficient computation of position-specific match scores with the fast fourier transform.

Historically, in computational biology the fast Fourier transform (FFT) has been used almost exclusively to count the number of exact letter matches between two biosequences. This paper presents an FFT algorithm that can compute the match score of a sequence against a position-specific scoring matrix (PSSM). Our algorithm finds the PSSM score simultaneously over all offsets of the PSSM with the sequence, although like all previous FFT algorithms, it still disallows gaps. Although our algorithm is presented in the context of global matching, it can be adapted to local matching without gaps. As a benchmark, our PSSM-modified FFT algorithm computed pairwise match scores. In timing experiments, our most efficient FFT implementation for pairwise scoring appeared to be 10 to 26 times faster than a traditional FFT implementation, with only a factor of 2 in the acceleration attributable to a previously known compression scheme. Many important algorithms for detecting biosequence similarities, e.g., gapped BLAST or PSIBLAST, have a heuristic screening phase that disallows gaps. This paper demonstrates that FFT algorithms merit reconsideration in these screening applications.

Algorithms↗

Principles for assessing disease management outcomes.

Disease management (DM) is rapidly becoming an important force in the late 20th and early 21st century as a strategy for managing the chronic illness of large populations. Given the increasing visibility of DM programs, the clinical, economic and financial impact of this support are vital to DM program accountability and its acceptance as a solution to the twin challenges of achieving affordable, quality health care. Measuring and reporting outcomes in DM is difficult. DM programs must adapt to local market conditions and customer desires, which in turn limits generalizability, and still account for the overlapping/interlocking/multifaceted nature of the interventions included in any DM program. The Disease Management Association of America convened a Steering Committee to suggest a preferred approach, not a mandated or standardized approach for DM program evaluation. This paper presents the Steering Committee's "Consensus Statement" and "Guiding Principles" for robust evaluation.

Disease Management↗

Decision analysis in the formulary process.

The use of decision analysis as a tool in making formulary decisions is discussed. Decision analysis is best applied in formulary decisions when factors other than acquisition costs are important in determining overall treatment costs for two products. The decision-analysis process assigns probabilities and costs to various treatments and outcomes. In the case of acute myocardial infarction, the decision analyst would gather data on angioplasty and thrombolysis and assign probabilities and costs for each treatment and subsequent endpoints on the basis of clinical trial data. When such data do not exist, estimates may be generated by expert panels. Applying clinical trial data to an individual hospital is not straightforward because of differences between clinical trials and clinical practice. Analysts and clinicians should evaluate any proposed model for its robustness and adaptability to local conditions and practitioner variation. Access to internal hospital data is essential in developing the model. An ideal decision-analysis model includes all important available interventions and defines and discloses the analyst's time frame and financial perspective. After implementation of the formulary decision, the results can be monitored and, if necessary, adjustments can be made in the allocation of resources. Barriers to effective decision analysis include lack of data and differences in sources of cost and outcome data. Despite the current limitations of decision analysis, clinicians and policymakers may find this technique increasingly useful in the complex formulary process.

Angioplasty↗

Selective primary health care: strategies for control of disease in the developing world. XXII. Tetanus: a preventable problem.

Tetanus, although an eminently preventable disease, remains common and uncontrolled in many developing countries. The persistence of tetanus is attributable to health service policies that ignore the disease because of a dearth of reliable epidemiologic and economic information. In many developing countries there have, as yet, been few public or professional demands for preventive action. For the prevention of neonatal tetanus, the immediate priority is immunization timed to produce and maintain protective levels of maternal antitoxin during pregnancy. This strategy should be accompanied by the extension and improvement of scientific standards of midwifery. To protect the rest of the population from wound tetanus, the strategy of first choice consists of continuous multiple-antigen immunization in infancy and childhood. Such a program should be reinforced by the routine administration of a toxoid booster following all accidental wounds as well as before all ritual procedures known to carry risk. These strategies, which are of proven efficacy and adaptable to local conditions of the large populations still in need of protection, together provide powerful justification for the expansion of primary maternal and child health services. Careful measurement of the incidence of neonatal tetanus would provide a good indicator of the degree of effectiveness such services have attained in many rural communities.

Adolescent↗

Locus-specific genetic differentiation at Rw among warfarin-resistant rat (Rattus norvegicus) populations.

Populations may diverge at fitness-related genes as a result of adaptation to local conditions. The ability to detect this divergence by marker-based genomic scans depends on the relative magnitudes of selection, recombination, and migration. We survey rat (Rattus norvegicus) populations to assess the effect that local selection with anticoagulant rodenticides has had on microsatellite marker variation and differentiation at the warfarin resistance gene (Rw) relative to the effect on the genomic background. Initially, using a small sample of 16 rats, we demonstrate tight linkage of microsatellite D1Rat219 to Rw by association mapping of genotypes expressing an anticoagulant-rodenticide-insensitive vitamin K 2,3-epoxide reductase (VKOR). Then, using allele frequencies at D1Rat219, we show that predicted and observed resistance levels in 27 populations correspond, suggesting intense and recent selection for resistance. A contrast of F(ST) values between D1Rat219 and the genomic background revealed that rodenticide selection has overwhelmed drift-mediated population structure only at Rw. A case-controlled design distinguished these locus-specific effects of selection at Rw from background levels of differentiation more effectively than a population-controlled approach. Our results support the notion that an analysis of locus-specific population genetic structure may assist the discovery and mapping of novel candidate loci that are the object of selection or may provide supporting evidence for previously identified loci.

Animals↗

Abundant mtDNA diversity and ancestral admixture in Colombian criollo cattle (Bos taurus).

Various cattle populations in the Americas (known as criollo breeds) have an origin in some of the first livestock introduced to the continent early in the colonial period (16th and 17th centuries). These cattle constitute a potentially important genetic reserve as they are well adapted to local environments and show considerable variation in phenotype. To examine the genetic ancestry and diversity of Colombian criollo we obtained mitochondrial DNA control region sequence information for 110 individuals from seven breeds. Old World haplogroup T3 is the most commonly observed CR lineage in criollo (0.65), in agreement with a mostly European ancestry for these cattle. However, criollo also shows considerable frequencies of haplogroups T2 (0.9) and T1 (0.26), with T1 lineages in criollo being more diverse than those reported for West Africa. The distribution and diversity of Old World lineages suggest some North African ancestry for criollo, probably as a result of the Arab occupation of Iberia prior to the European migration to the New World. The mtDNA diversity of criollo is higher than that reported for European and African cattle and is consistent with a differentiated ancestry for some criollo breeds.

Animals↗

The development of a quality information system: a case study of Mexico.

One of the primary obstacles in the implementation of continuous quality improvement (CQI) programmes in developing countries is the lack of timely and appropriate information for decentralized decision-making. The integrated quality information system (QIS) described herein demonstrates Mexico's unique effort to package four separate, yet mutually reinforcing, tools for the generation and use of quality-related information at all levels of the Mexican national health care system. The QIS is one element of the continuous quality improvement programme administered by the Secretariat of Health in Mexico. Mexico's QIS was designed to be flexible and capable of adapting to local needs, while at the same time allowing for the standardization of health care quality assurance indicators, and subsequent ability to measure and compare the quality performance of health facilities nationwide. The flexibility of the system extends to permit the optimal use of available data by health care managers at all levels of the health care system, as well as the generation of new information in important areas often neglected in more traditional information systems. Mexico's QIS consists of four integrated components: 1) a set of client and provider surveys, to assess specific issues in the quality of health services delivered; 2) client and provider national satisfaction surveys; 3) a sentinel health events strategy; and 4) a national Comparative Performance Evaluation System, for use by the Secretariate of Health for the quality assessment of state and provincial health care services (internal benchmarking). The QIS represents another step in Mexico's ongoing effort to use data for effective decision-making in the planning, monitoring and evaluation of services delivered by the national health care system. The design and application of Mexico's QIS provides a model for decentralized decision-making that could prove useful for developing countries, where the effective use of quality indicators is often limited. Further, the system could serve as a mechanism for motivating positive change in the way information is collected and used in the process of ensuring high quality health care service delivery.

Benchmarking↗