National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants.

BACKGROUND: Data for trends in glycaemia and diabetes prevalence are needed to understand the effects of diet and lifestyle within populations, assess the performance of interventions, and plan health services. No consistent and comparable global analysis of trends has been done. We estimated trends and their uncertainties in mean fasting plasma glucose (FPG) and diabetes prevalence for adults aged 25 years and older in 199 countries and territories. METHODS: We obtained data from health examination surveys and epidemiological studies (370 country-years and 2·7 million participants). We converted systematically between different glycaemic metrics. For each sex, we used a Bayesian hierarchical model to estimate mean FPG and its uncertainty by age, country, and year, accounting for whether a study was nationally, subnationally, or community representative. FINDINGS: In 2008, global age-standardised mean FPG was 5·50 mmol/L (95% uncertainty interval 5·37-5·63) for men and 5·42 mmol/L (5·29-5·54) for women, having risen by 0·07 mmol/L and 0·09 mmol/L per decade, respectively. Age-standardised adult diabetes prevalence was 9·8% (8·6-11·2) in men and 9·2% (8·0-10·5) in women in 2008, up from 8·3% (6·5-10·4) and 7·5% (5·8-9·6) in 1980. The number of people with diabetes increased from 153 (127-182) million in 1980, to 347 (314-382) million in 2008. We recorded almost no change in mean FPG in east and southeast Asia and central and eastern Europe. Oceania had the largest rise, and the highest mean FPG (6·09 mmol/L, 5·73-6·49 for men; 6·08 mmol/L, 5·72-6·46 for women) and diabetes prevalence (15·5%, 11·6-20·1 for men; and 15·9%, 12·1-20·5 for women) in 2008. Mean FPG and diabetes prevalence in 2008 were also high in south Asia, Latin America and the Caribbean, and central Asia, north Africa, and the Middle East. Mean FPG in 2008 was lowest in sub-Saharan Africa, east and southeast Asia, and high-income Asia-Pacific. In high-income subregions, western Europe had the smallest rise, 0·07 mmol/L per decade for men and 0·03 mmol/L per decade for women; North America had the largest rise, 0·18 mmol/L per decade for men and 0·14 mmol/L per decade for women. INTERPRETATION: Glycaemia and diabetes are rising globally, driven both by population growth and ageing and by increasing age-specific prevalences. Effective preventive interventions are needed, and health systems should prepare to detect and manage diabetes and its sequelae. FUNDING: Bill & Melinda Gates Foundation and WHO.

High constant incidence rates of second primary cancers of the head and neck: a pooled analysis of 13 cancer registries.

Scanty data are available on the incidence (i.e., the absolute risk) of second cancers of the head and neck (HN) and its pattern with age. We investigated this issue using data from a multicentric study of 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943-2000. A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up. A total of 1,294 of the patients (1.3%) were diagnosed with second HN cancers (342 tongue, 345 mouth, 418 pharynx and 189 larynx). Male incidence rates of first HN cancer steeply increased from 0.68/100,000 at age 30-34 to 46.2/100,000 at age 70-74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30-34 to 16.5/100,000 at age 80-84. However, age-specific incidence of second HN cancers after a first HN cancer in men was around 200-300/100,000 between age 40-44 and age 70-74 and tended to decline at subsequent ages (150/100,000 at age 80-84); in women, incidence of second HN cancers was around 200-300/100,000 between age 45-49 and 80-84. The patterns of age-specific incidence were consistent for different subsites of second HN cancer and sexes; moreover, they were similar for age-specific incidence of first primary HN cancer in patients who subsequently developed a second HN cancer. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age.

Vaccination with a Melan-A peptide selects an oligoclonal T cell population with increased functional avidity and tumor reactivity.

Both the underlying molecular mechanisms and the kinetics of TCR repertoire selection following vaccination against tumor Ags in humans have remained largely unexplored. To gain insight into these questions, we performed a functional and structural longitudinal analysis of the TCR of circulating CD8(+) T cells specific for the HLA-A2-restricted immunodominant epitope from the melanocyte differentiation Ag Melan-A in a melanoma patient who developed a vigorous and sustained Ag-specific T cell response following vaccination with the corresponding synthetic peptide. We observed an increase in functional avidity of Ag recognition and in tumor reactivity in the postimmune Melan-A-specific populations as compared with the preimmune blood sample. Improved Ag recognition correlated with an increase in the t(1/2) of peptide/MHC interaction with the TCR as assessed by kinetic analysis of A2/Melan-A peptide multimer staining decay. Ex vivo analysis of the clonal composition of Melan-A-specific CD8(+) T cells at different time points during vaccination revealed that the response was the result of asynchronous expansion of several distinct T cell clones. Some of these T cell clones were also identified at a metastatic tumor site. Collectively, these data show that tumor peptide-driven immune stimulation leads to the selection of high-avidity T cell clones of increased tumor reactivity that independently evolve within oligoclonal populations.

Embolic strokes of undetermined source in the athens stroke registry: a descriptive analysis.

BACKGROUND AND PURPOSE: A new clinical construct termed embolic stroke of undetermined source (ESUS) was recently introduced, but no such population has been described yet. Our aim is to provide a detailed descriptive analysis of an ESUS population derived from a large prospective ischemic stroke registry using the proposed diagnostic criteria. METHODS: The criteria proposed by the Cryptogenic Stroke/ESUS International Working Group were applied to the Athens Stroke Registry to identify all ESUS patients. ESUS was defined as a radiologically confirmed nonlacunar brain infarct in the absence of (a) extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the ischemic area, (b) major-risk cardioembolic source, and (c) any other specific cause of stroke. RESULTS: Among 2735 patients admitted between 1992 and 2011, 275 (10.0%) were classified as ESUS. In the majority of ESUS (74.2%), symptoms were maximal at onset. ESUS were of moderate severity (median National Institute Health Stroke Scale score, 5). The most prevalent risk factor was arterial hypertension (64.7%), and 50.9% of patients were dyslipidemic. Among potential causes of the ESUS, covert atrial fibrillation (AF) was the most prevalent: in 30 (10.9%) patients, AF was diagnosed during hospitalization for stroke recurrence, whereas in 50 (18.2%) patients AF was detected after repeated ECG monitoring during follow-up. Also, covert AF was strongly suggested in 38 patients (13.8%) but never recorded. CONCLUSIONS: About 10% of patients with first-ever ischemic stroke met criteria for ESUS; covert paroxysmal AF seems to be a frequent cause of ESUS.

Population genetic structure of the dengue mosquito Aedes aegypti in Venezuela

The mosquito Aedes aegypti is the main vector of dengue in Venezuela. The genetic structure of this vector was investigated in 24 samples collected from eight geographic regions separated by up to 1160 km. We examined the distribution of a 359-basepair region of the NADH dehydrogenase subunit 4 mitochondrial gene among 1144 Ae. aegypti from eight collections. This gene was amplified by the polymerase chain reaction and tested for variation using single strand conformation polymorphism analysis. Seven haplotypes were detected throughout Venezuela and these were sorted into two clades. Significant differentiation was detected among collections and these were genetically isolated by distance.

Changes in antihypertensive drug treatment in the general population: the Colaus Study

Background and aims: there is little information regar ding changes in antihypertensive drug treatment in Switzerland. We aimed at assessing those changes in a population-based, prospective study. Methods: 768 hypertensive subjects (372 women, 397 men) followed for 5 years. Subjects were defined as continuers (no change), switchers (one antihypertensive class replace by another), combiners (one antihypertensive class added) and discontinuers (stopped treatment). Results: Analysis of all patients (mono or combination therapy) showed that 54.6% were continuers, 27.2% combiners, 12.9% switchers and 5.3 % discontinuers. Similar findings were obtained for participants on monotherapy only: 42.2% continuers, 36.7% combiners, 13.4% switchers and 7.7% discontinuers. Combiners had higher systolic and diastolic blood pressure values at baseline than the other groups (p<0.001), while no difference were found for personal and family history and other clinical and biological variables. Compared to continuers, combiners and switchers improved their blood pressure status at follow-up: 26.7% of combiners and 26.3% of switchers improved, versus 17.7% of continuers and 7.3% of discontinuers (p<0.001). Among participants on monotherapy at baseline, continuation was greatest for angiotensin II type 1 receptor blocking agents (ARBs, 53.1%), angiotensin-converting enzyme inhibitors (44.4%) and β-blockers (41.8%). Only one quarter of participants treated with diuretic or calcium channel blockers at baseline remained so at follow-up. Conclusion: Antihypertensivedrug treatment is very stable in Switzerland. There are no big differences in persistence between antihypertensive classes, even if ARBs had the most favorable utilization pattern. Changes are only due to blood pressure level and improve blood pressure status.

Evolution of life history traits in a natural population of the shrew Crocidura russula

Abstract Life history traits encompass all the decisions concerning fitness an individual is faced with during his life. The study of these traits is crucial to understand the factors shaping the biology of living organisms. Up until now, most of the information on the evolution of life history traits comes from laboratory studies. While these studies are interesting to test the effect of specific parameters, their conclusions are difficult to extrapolate to natural populations. Investigating the evolution of life history traits in natural populations is of great interest. This may be tricky because it requires information on reproduction, survival and morphology of individuals. Mark-recapture methods allow most of this information to be obtained. However, when direct observations of a species are not possible due to its ecology, indirect methods must be used to infer lifetime reproductive success. In this case, molecular markers are particularly helpful in assessing the genetic relationships between individuals and allow the construction of a pedigree. This thesis focuses on a natural population of a small insectivorous mammal, the greater white-toothed shrew, Crocidura russula. Because of its hidden lifestyle, the two complementary techniques mentioned above were combined to gather information on this population. The data were used to explore diverse aspects of evolutionary biology. We demonstrated that the high genetic variance displayed by the species was not maintained by its mating system because this shrew was less monogamous than previously thought. The large genetic diversity was most likely promoted by gene flow from the neighborhood. Dispersal was thus a central topic in this thesis. We showed that dispersal was not driven by inbreeding avoidance. In addition, we did not find any inbreeding depression in the population. Dispersal was promoted by a high number of vacant territories in the population for both sexes, meaning that territory acquisition played an important role in driving dispersal. Moreover, dispersal propensity was shown to have a genetic basis and, once achieved, to have no effect on individual fitness. Body mass was found to be a life history trait strongly influenced by sexual and viability selection in both sexes. Larger individuals had higher access to reproduction through territory acquisition and defense than lighter ones. By contrast, intermediate size individuals were favored by viability selection presumably because of ecological constraints and metabolic costs. Finally, we demonstrated that the majority of the life history traits in our shrew population has the potential to evolve because they maintained substantial amounts of additive genetic variance. Nonetheless, life history traits had no significant heritability due to their high level of nonadditive or environmental variance. Résumé Les traits d'histoire de vie comprennent toutes les décisions auxquelles un individu est confronté au cours de sa vie et qui concernent sa valeur adaptative. L'étude de ces traits est cruciale pour comprendre les facteurs qui façonnent la biologie des êtres vivants. Jusqu'à ce jour, la majorité des informations sur l'évolution des traits d'histoire de vie provient d'études réalisées en laboratoire. Alors que ces études sont intéressantes pour tester l'effet de paramètres spécifiques, leurs conclusions sont difficilement extrapolables aux populations naturelles. Il est particulièrement intéressant d'étudier l'évolution des traits d'histoire de vie dans des populations naturelles. Toutefois, ces études peuvent se révéler difficiles parce qu'elles requièrent des informations sur la reproduction, la survie et la morphologie des individus. Des méthodes de marquage-recapture permettent d'obtenir ces informations. Cependant, lorsque l'écologie de l'espèce rend les obervations directes impossibles, des méthodes indirectes doivent être utilisées pour obtenir le succès reproducteur des individus. Dans ce cas, les marqueurs moléculaires sont particulièrement utiles pour évaluer les relations génétiques entre individus et permettre la construction d'un pedigree. Cette thèse porte sur une population naturelle d'un petit mammifère insectivore, la musaraigne musette, Crocidura russula. Parce que cette espèce présente un mode de vie souterrain, les deux techniques complémentaires mentionnées ci-dessus ont été combinées pour acquérir les informations nécessaires. Les données ont été utilisées pour explorer divers aspects de biologie evolutive. Nous avons montré que la grande quantité de variance génétique trouvée chez cette espèce n'est pas maintenue par son système d'appariement. Celle-ci s'est en effet avérée être moins monogame que ce qui était admis jusqu'ici. Sa grande diversité génétique est plutôt entretenue par le flux de gènes provenant du voisinage. La dispersion a donc été un sujet phare dans cette thèse. Nous avons montré qu'elle n'est pas provoquée par un évitement de la consanguinité et nous n'avons pas trouvé de dépression de consanguité dans notre population. L'acquisition d'un territoire joue par contre un rôle important dans la dispersion. En outre, la dispersion possède une base génétique chez cette espèce. De plus, une fois qu'ils ont dispersé, les individus n'ont pas une valeur adaptative differente d'individus philopatriques. Le poids s'est avéré être un trait d'histoire de vie fortement influencé par la sélection sexuelle et de viabilité chez les deux sexes. Les gros individus ont accès à la reproduction parce qu'ils acquièrent et défendent un territoire plus facilement que les plus légers. Au contraire, les individus de taille intermédiaire sont favorisés par la sélection de viabilité, certainement à cause de contraintes écologiques et de coûts métaboliques. Finalement, nous avons montré que la majorité des traits d'histoire de vie dans notre population a le potentiel d'évoluer parce qu'elle maintient des quantités considérables de variance génétique additive. Néanmoins, l'héritabilité de ces traits d'histoire de vie n'est pas significative à cause de la grande quantité de variance non-additive ou environmentale associée à ces traits.

An analysis of the impact of the Schistosomiasis Control Programme in Brazil

The impact of the Schistosomiasis Control Programme (PCE) in Brazil was analyzed, covering the period 1976 to 2003, using the following indicators: percentage of Schistosoma mansoni carriers detected among the population examined in the coproscopic surveys (PPS): mortality rate for schistosomiasis, per 100,000 inhabitants (TME): hospitalization rate for schistosomiasis, per 100,000 inhabitants (TIE): average age of deaths caused by schistosomiasis (IMOE). There was a 38.5% reduction in the PPS after the introduction of the PCE, attributed to the treatment of carriers. Even in hyper-endemic municipalities, such as Conde and Cuitegí, in the state of Paraíba, the PPS fell more than 50% after the first year of treatment. The parasitic burden of the carriers also decreased in the two municipalities. The TME was reduced by 63.4% and the TIE by 77.3%. The mortality rate was highest among the 50-and-above age group. The country×s IMOE rose 32.3%. The IMOE was seen to be much lower in the state of Minas Gerais, where the PCE was only initiated in 1983, with very limited coverage.

Parasitism in Kansas in the 1800s: a glimpse to the past through the analysis of grave sediments from Meadowlark cemetery

During the excavations of the XIX century Meadowlark cemetery (Manhattan, Kansas, US), samples of sediments were taken from around five skeletons, and analyzed to detect intestinal parasites. No helminth eggs were found, but immunological ELISA tests for Entamoeba histolytica were positive in three samples. The immunological techniques have been successfully used in paleoparasitology to detect protozoan infections. Amoebiasis could have been a severe disease in the past, especially where poor sanitary conditions prevailed, and there is evidence that this cemetery may have been used in a situation where poor sanitary conditions may have prevailed. The presence of this protozoan in US during the late XIX century gives information on the health of the population and provides additional data on the parasite's evolution since its appearance in the New World.

Symbolic trephinations and population structure

The sample examined consists of 19 skulls with symbolic trephinations and 86 skulls without trepanations dated from the X century. Skulls were all excavated in the Great Hungarian Plain in the Carpathian Basin, which was occupied by the Hungarian conquerors at the end of the IX century. The variations of 12 cranial dimensions of the trephined skulls were investigated and compared to the skulls without trepanations after performing a discriminant analysis. The classification results evince that the variability of non-trephined skulls shows a more homogeneous and a more characteristic picture of their own group than the trephined samples, which corresponds to the notion, formed by archaeological evidence and written historical sources, of a both ethnically and socially differing population of the Hungarian conquerors. According to historical research, a part of the population was of Finno-Ugric origin, while the military leading layer of society can be brought into connection with Turkic ethnic groups. All the same, individuals dug up with rich grave furniture and supposed to belong to this upper stratum of society are primarily characterized by the custom of symbolic trephination, and, as our results demonstrate, craniologically they seem to be more heterogeneous.

A population genetics study of Anopheles darlingi (Diptera: Culicidae) from Colombia based on random amplified polymorphic DNA-polymerase chain reaction and amplified fragment lenght polymorphism markers

The genetic variation and population structure of three populations of Anopheles darlingi from Colombia were studied using random amplified polymorphic markers (RAPDs) and amplified fragment length polymorphism markers (AFLPs). Six RAPD primers produced 46 polymorphic fragments, while two AFLP primer combinations produced 197 polymorphic fragments from 71 DNA samples. Both of the evaluated genetic markers showed the presence of gene flow, suggesting that Colombian An. darlingi populations are in panmixia. Average genetic diversity, estimated from observed heterozygosity, was 0.374 (RAPD) and 0.309 (AFLP). RAPD and AFLP markers showed little evidence of geographic separation between eastern and western populations; however, the F ST values showed high gene flow between the two western populations (RAPD: F ST = 0.029; Nm: 8.5; AFLP: F ST = 0.051; Nm: 4.7). According to molecular variance analysis (AMOVA), the genetic distance between populations was significant (RAPD:phiST = 0.084; AFLP:phiST = 0.229, P < 0.001). The F ST distances and AMOVAs using AFLP loci support the differentiation of the Guyana biogeographic province population from those of the Chocó-Magdalena. In this last region, Chocó and Córdoba populations showed the highest genetic flow.

Population genetic structure of the major malaria vector Anopheles darlingi (Diptera: Culicidae) from the Brazilian Amazon, using microsatellite markers

The population genetic structure of Anopheles darlingi, the major human malaria vector in the Neotropics, was examined using seven microsatellite loci from nine localities in central and western Amazonian Brazil. High levels of genetic variability were detected (5-25 alleles per locus; H E = 0.519-0.949). There was deviation from Hardy-Weinberg Equilibrium for 59.79% of the tests due to heterozygote deficits, while the analysis of linkage disequilibrium was significant for only two of 189 (1.05%) tests, most likely caused by null alleles. Genetic differentiation (F ST = 0.001-0.095; Nm = 4.7-363.8) indicates that gene flow is extensive among locations < 152 km apart (with two exceptions) and reduced, but not absent, at a larger geographic scale. Genetic and geographic distances were significantly correlated (R² = 0.893, P < 0.0002), supporting the isolation by distance (IBD) model. The overall estimate of Ne was 202.4 individuals under the linkage disequilibrium model, and 8 under the heterozygote excess model. Analysis of molecular variance showed that nearly all variation (~ 94%) was within sample locations. The UPGMA phenogram clustered the samples geographically, with one branch including 5/6 of the state of Amazonas localities and the other branch the Acre, Rondônia, and remaining Amazonas localities. Taken together, these data suggest little genetic structure for An. darlingi from central and western Amazonian Brazil. These findings also imply that the IBD model explains nearly all of the differentiation detected. In practical terms, populations of An. darlingi at distances < 152 km should respond similarly to vector control measures, because of high gene flow.

Association between social relationships and survival of Swiss octogenarians. A five-year prospective, population-based study.

BACKGROUND AND AIMS: Data from the literature reveal the contrasting influences of family members and friends on the survival of old adults. On one hand, numerous studies have reported a positive association between social relationships and survival. On the other, ties with children may be associated with an increased risk of disability, whereas ties with friends or other relatives tend to improve survival. A five-year prospective, population-based study of 295 Swiss octogenarians tested the hypothesis that having a spouse, siblings or close friends, and regular contacts with relatives or friends are associated with longer survival, even at a very old age. METHODS: Data were collected through individual interviews, and a Cox regression model was applied to assess the effects of kinship and friendship networks on survival, after adjusting for socio-demographic and health-related variables. RESULTS: Our analyses indicate that the presence of a spouse in the household is not significantly related to survival, whereas the presence of siblings at baseline improves the oldest old's chances of surviving five years later. Moreover, the existence of close friends is a central component in the patterns of social relationships of oldest adults, and one which is significantly associated with survival. Overall, the protective effect of social relationships on survival is more related to the quality of those relationships (close friends) than to the frequency of relationships (regular contacts). CONCLUSIONS: We hypothesize that the existence of siblings or close friends may beneficially affect survival, due to the potential influence on the attitudes of octogenarians regarding health practices and adaptive strategies.

Sexually transmitted infections, bacterial vaginosis, and candidiasis in women of reproductive age in rural Northeast Brazil: a population-based study

Population-based data on sexually transmitted infections (STI), bacterial vaginosis (BV), and candidiasis reflect the epidemiological situation more accurately than studies performed in specific populations, but such data are scarce. To determine the prevalence of STI, BV, and candidiasis among women of reproductive age from a resource-poor community in Northeast Brazil, a population-based cross sectional study was undertaken. All women from seven hamlets and the centre of Pacoti municipality in the state of Ceará, aged 12 to 49 years, were invited to participate. The women were asked about socio-demographic characteristics and genital symptoms, and thereafter examined gynaecologically. Laboratory testing included polymerase chain reaction (PCR) for human papillomavirus (HPV), ligase chain reaction (LCR) for Chlamydia trachomatis and Neisseria gonorrhoeae, ELISA for human immunodeficiency virus (HIV), venereal disease research laboratory (VDRL) and fluorescent treponema antibody absorption test (FTA-ABS) for syphilis, and analysis of wet mounts, gram stains and Pap smears for trichomoniasis, candidiasis, and BV. Only women who had initiated sexual life were included in the analysis (n = 592). The prevalences of STI were: HPV 11.7% (95% confidence interval: 9.3-14.7), chlamydia 4.5% (3.0-6.6), trichomoniasis 4.1% (2.7-6.1), gonorrhoea 1.2% (0.5-2.6), syphilis 0.2% (0.0-1.1), and HIV 0%. The prevalence of BV and candidiasis was 20% (16.9-23.6) and 12.5% (10.0-15.5), respectively. The most common gynaecological complaint was lower abdominal pain. STI are common in women in rural Brazil and represent an important health threat in view of the HIV pandemic.

Population structure of the malaria vector Anopheles darlingi in Rondônia, Brazilian Amazon, based on mitochondrial DNA

Anopheles darlingi is the most important Brazilian malaria vector, with a widespread distribution in the Amazon forest. Effective strategies for vector control could be better developed through knowledge of its genetic structure and gene flow among populations, to assess the vector diversity and competence in transmitting Plasmodium. The aim of this study was to assess the genetic diversity of An. darlingi collected at four locations in Porto Velho, by sequencing a fragment of the ND4 mitochondrial gene. From 218 individual mosquitoes, we obtained 20 different haplotypes with a diversity index of 0.756, equivalent to that found in other neotropical anophelines. The analysis did not demonstrate significant population structure. However, haplotype diversity within some populations seems to be over-represented, suggesting the presence of sub-populations, but the presence of highly represented haplotypes complicates this analysis. There was no clear correlation among genetic and geographical distance and there were differences in relation to seasonality, which is important for malarial epidemiology.