A novel mutation in the sulfate transporter gene SLC26A2 (DTDST) specific to the Finnish population causes de la Chapelle dysplasia.

BACKGROUND: Mutations in the sulfate transporter gene SLC26A2 (DTDST) cause a continuum of skeletal dysplasia phenotypes that includes achondrogenesis type 1B (ACG1B), atelosteogenesis type 2 (AO2), diastrophic dysplasia (DTD), and recessive multiple epiphyseal dysplasia (rMED). In 1972, de la Chapelle et al reported two siblings with a lethal skeletal dysplasia, which was denoted "neonatal osseous dysplasia" and "de la Chapelle dysplasia" (DLCD). It was suggested that DLCD might be part of the SLC26A2 spectrum of phenotypes, both because of the Finnish origin of the original family and of radiographic similarities to ACG1B and AO2. OBJECTIVE: To test the hypothesis whether SLC26A2 mutations are responsible for DLCD. METHODS: We studied the DNA from the original DLCD family and from seven Finnish DTD patients in whom we had identified only one copy of IVS1+2T>C, the common Finnish mutation. A novel SLC26A2 mutation was found in all subjects, inserted by site-directed mutagenesis in a vector harbouring the SLC26A2 cDNA, and expressed in sulfate transport deficient Chinese hamster ovary (CHO) cells to measure sulfate uptake activity. RESULTS: We identified a hitherto undescribed SLC26A2 mutation, T512K, homozygous in the affected subjects and heterozygous in both parents and in the unaffected sister. T512K was then identified as second pathogenic allele in the seven Finnish DTD subjects. Expression studies confirmed pathogenicity. CONCLUSIONS: DLCD is indeed allelic to the other SLC26A2 disorders. T512K is a second rare "Finnish" mutation that results in DLCD at homozygosity and in DTD when compounded with the milder, common Finnish mutation.

Changes of overweight and obesity in the adult Swiss population according to educational level, from 1992 to 2007.

In many high income developed countries, obesity is inversely associated with educational level. In some countries, a widening gap of obesity between educational groups has been reported. The aim of this study was to assess trends in body mass index (BMI) and in prevalence of overweight and obesity and their association with educational level in the adult Swiss population. Four cross-sectional National health interview surveys conducted in 1992/93 (n = 14,521), 1997 (n = 12,474), 2002 (n = 18,908) and 2007 (n = 17,879) using representative samples of the Swiss population (age range 18-102 years). BMI was derived from self-reported data. Overweight was defined as BMI > or = 25 and <30 kg/m(2), and obesity as BMI > or = 30 kg/m(2). Mean (+/- standard deviation) BMI increased from 24.7 +/- 3.6 in 1992/3 to 25.4 +/- 3.6 kg/m2 in 2007 in men and 22.8 +/- 3.8 to 23.7 +/- 4.3 kg/m(2) in women. Between 1992/3 and 2007, the prevalence of overweight + obesity increased from 40.4% to 49.5% in men and from 22.3% to 31.3% in women, while the prevalence of obesity increased from 6.3% to 9.4% in men and from 4.9% to 8.5% in women. The rate of increase in the prevalence of obesity was greater between 1992/3 and 2002 (men: +0.26%/year; women: +0.31%/year) than between 2002 and 2007 (men: +0.10%/year; women: +0.10%/year). A sizable fraction (approximately 25%) of the increasing mean BMI was due to increasing age of the participants over time. The increase was larger in low than high education strata of the population. BMI was strongly associated with low educational level among women and this gradient remained fairly constant over time. A weaker similar gradient by educational level was apparent in men, but it tended to increase over time. In Switzerland, overweight and obesity increased between 1992 and 2007 and was associated with low education status in both men and women. A trend towards a stabilization of mean BMI levels was noted in most age categories since 2002. The increase in the prevalence of obesity was larger in low education strata of the population. These findings suggest that obesity preventive measures should be targeted according to educational level in Switzerland.

Population demography and the evolution of helping behaviors.

Limited dispersal may favor the evolution of helping behaviors between relatives as it increases their relatedness, and it may inhibit such evolution as it increases local competition between these relatives. Here, we explore one way out of this dilemma: if the helping behavior allows groups to expand in size, then the kin-competition pressure opposing its evolution can be greatly reduced. We explore the effects of two kinds of stochasticity allowing for such deme expansion. First, we study the evolution of helping under environmental stochasticity that may induce complete patch extinction. Helping evolves if it results in a decrease in the probability of extinction or if it enhances the rate of patch recolonization through propagules formed by fission of nonextinct groups. This mode of dispersal is indeed commonly found in social species. Second, we consider the evolution of helping in the presence of demographic stochasticity. When fecundity is below its value maximizing deme size (undersaturation), helping evolves, but under stringent conditions unless positive density dependence (Allee effect) interferes with demographic stochasticity. When fecundity is above its value maximizing deme size (oversaturation), helping may also evolve, but only if it reduces negative density-dependent competition.

Utilisation de la coronarographie en Suisse: une étude de population. [The use of coronary vessel radiography in Switzerland: a population study].

All patients having undergone a coronarography during 1984 have been surveyed in Switzerland. This retrospective study has used existing data in the 13 centers practicing this diagnostic procedure. 4921 coronarographies were carried out in 1984, amongst 4359 patients. In terms of population-based rates, the national figures are 77 procedures/100,000 residents, and 68 patients/100,000 residents. Female rates are one fourth of the male rates (27/100,000 versus 112/100,000). For both sexes, the highest utilization rates are for the age groups 60-64. Swiss figures are relatively low when compared with other developed countries. However, patterns of utilization are very different within the country: according to the Canton of residence of the patient, the utilization rates (standardized for age and sex) vary from 8/100,000 to 160/100,000. There is a distinct gradient from south-west to north-east, which closely corresponds to the distribution of centers practicing the procedure. More intriguing is the fact that cardiovascular mortality shows an inverse geographical gradient, with the highest mortality in Cantons having the lowest rate of coronarography. Various reasons for the observed variations are discussed, in relation with differences in supply of diagnostic and therapeutic equipments, but also in relation with various patterns of demand related to differential morbidity rates and/or differential patterns of clinical decision.

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study).

To assess the associations between alcohol consumption and cytokine levels (interleukin-1beta - IL-1β; interleukin-6 - IL-6 and tumor necrosis factor-α - TNF-α) in a Caucasian population. Population sample of 2884 men and 3201 women aged 35-75. Alcohol consumption was categorized as nondrinkers, low (1-6 drinks/week), moderate (7-13/week) and high (14+/week). No difference in IL-1β levels was found between alcohol consumption categories. Low and moderate alcohol consumption led to lower IL-6 levels: median (interquartile range) 1.47 (0.70-3.51), 1.41 (0.70-3.32), 1.42 (0.66-3.19) and 1.70 (0.83-4.39) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.01, but this association was no longer significant after multivariate adjustment. Compared to nondrinkers, moderate drinkers had the lowest odds (Odds ratio=0.86 (0.71-1.03)) of being in the highest quartile of IL-6, with a significant (p<0.05) quadratic trend. Low and moderate alcohol consumption led to lower TNF-α levels: 2.92 (1.79-4.63), 2.83 (1.84-4.48), 2.82 (1.76-4.34) and 3.15 (1.91-4.73) pg/ml for nondrinkers, low, moderate and high drinkers, respectively, p<0.02, and this difference remained borderline significant (p=0.06) after multivariate adjustment. Moderate drinkers had a lower odds (0.81 [0.68-0.98]) of being in the highest quartile of TNF-α. No specific alcoholic beverage (wine, beer or spirits) effect was found. Moderate alcohol consumption is associated with lower levels of IL-6 and (to a lesser degree) of TNF-α, irrespective of the type of alcohol consumed. No association was found between IL-1β levels and alcohol consumption.

Breast cancer in younger women in Switzerland 1996-2009 : a longitudinal population-based study

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and a leading cause of death in younger women. METHODS: We analysed incidence, mortality and relative survival (RS) in women with BC aged 20-49 years at diagnosis, between 1996 and 2009 in Switzerland. Trends are reported as estimated annual percentage changes (EAPC). RESULTS: Our findings confirm a slight increase in the incidence of BC in younger Swiss women during the period 1996-2009. The increase was largest in women aged 20-39 years (EAPC 1.8%). Mortality decreased in both age groups with similar EAPCs. Survival was lowest among women 20-39 years (10-year RS 73.4%). We observed no notable differences in stage of disease at diagnosis that might explain these differences. CONCLUSIONS: The increased incidence and lower survival in younger women diagnosed with BC in Switzerland indicates possible differences in risk factors, tumour biology and treatment characteristics that require additional examination.

Effect of biogeographic history on population vulnerability in European amphibians.

The genetic diversity of populations, which contributes greatly to their adaptive potential, is negatively affected by anthropogenic habitat fragmentation and destruction. However, continental-scale losses of genetic diversity also resulted from the population expansions that followed the end of the last glaciation, an element that is rarely considered in a conservation context. We addressed this issue in a meta-analysis in which we compared the spatial patterns of vulnerability of 18 widespread European amphibians in light of phylogeographic histories (glacial refugia and postglacial routes) and anthropogenic disturbances. Conservation statuses significantly worsened with distances from refugia, particularly in the context of industrial agriculture; human population density also had a negative effect. These findings suggest that features associated with the loss of genetic diversity in post-glacial amphibian populations (such as enhanced fixation load or depressed adaptive potential) may increase their susceptibility to current threats (e.g., habitat fragmentation and pesticide use). We propose that the phylogeographic status of populations (i.e., refugial vs. post-glacial) should be considered in conservation assessments for regional and national red lists.

No association between ApoE polymorphism and febrile seizures.

Seizures associated with fever are a common pediatric problem, affecting about 2-7 % of children between 3 months and 5 years of age. Differentiation of febrile seizures from acute symptomatic seizures secondary to central nervous system infections or seizures associated with fever in children with epilepsy is essential to provide appropriate treatment and follow-up care. Here, we tested the hypothesis that children who exhibit simple febrile seizures during early childhood, but do not develop epileptic seizures later in life, might preferentially carry the ApoE2 allele of the gene coding for the apolipoprotein E. We did not find any differences in the distribution of ApoE alleles or genotypes between individuals who exhibited simple febrile seizures (n = 93) and age-matched, typically developing subjects (n = 80). We found that the observed allele and genotype frequencies did not deviate from Hardy-Weinberg equilibrium, which suggests that the frequencies of ApoE alleles and genotypes are stable in the Swiss population from which our samples were derived. Across both groups of subjects (n = 173), we found an ApoE2 allele frequency of 0.064, an ApoE3 frequency of 0.829 and an ApoE4 frequency of 0.107. Our findings are consistent with previous reports of the distribution of ApoE polymorphism for European subjects free of any neurological disorders, and show that the different alleles of the gene coding for the apolipoprotein E are not associated with the occurrence of simple febrile seizures.

Future development of gastrointestinal cancer incidence and mortality rates in Switzerland: a tumour registry- and population-based projection up to 2030.

QUESTIONS UNDER STUDY: Since tumour burden consumes substantial healthcare resources, precise cancer incidence estimations are pivotal to define future needs of national healthcare. This study aimed to estimate incidence and mortality rates of oesophageal, gastric, pancreatic, hepatic and colorectal cancers up to 2030 in Switzerland. METHODS: Swiss Statistics provides national incidences and mortality rates of various cancers, and models of future developments of the Swiss population. Cancer incidences and mortality rates from 1985 to 2009 were analysed to estimate trends and to predict incidence and mortality rates up to 2029. Linear regressions and Joinpoint analyses were performed to estimate the future trends of incidences and mortality rates. RESULTS: Crude incidences of oesophageal, pancreas, liver and colorectal cancers have steadily increased since 1985, and will continue to increase. Gastric cancer incidence and mortality rates reveal an ongoing decrease. Pancreatic and liver cancer crude mortality rates will keep increasing, whereas colorectal cancer mortality on the contrary will fall. Mortality from oesophageal cancer will plateau or minimally increase. If we consider European population-standardised incidence rates, oesophageal, pancreatic and colorectal cancer incidences are steady. Gastric cancers are diminishing and liver cancers will follow an increasing trend. Standardised mortality rates show a diminution for all but liver cancer. CONCLUSIONS: The oncological burden of gastrointestinal cancer will significantly increase in Switzerland during the next two decades. The crude mortality rates globally show an ongoing increase except for gastric and colorectal cancers. Enlarged healthcare resources to take care of these complex patient groups properly will be needed.

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Wellcome Trust.