Interplay of water and reactive elements in oxidation of alumina-forming alloys.

High-temperature alloys are crucial to many important technologies that underpin our civilization. All these materials rely on forming an external oxide layer (scale) for corrosion protection. Despite decades of research on oxide scale growth, many open questions remain, including the crucial role of the so-called reactive elements and water. Here, we reveal the hitherto unknown interplay between reactive elements and water during alumina scale growth, causing a metastable 'messy' nano-structured alumina layer to form. We propose that reactive-element-decorated, hydroxylated interfaces between alumina nanograins enable water to access an inner cathode in the bottom of the scale, at odds with the established scale growth scenario. As evidence, hydride-nanodomains and reactive element/hydrogen (deuterium) co-variation are observed in the alumina scale. The defect-rich alumina subsequently recrystallizes to form a protective scale. First-principles modelling is also performed to validate the RE effect. Our findings open up promising avenues in oxidation research and suggest ways to improve alloy properties.

Reduced display of conformational epitopes in the N-terminal truncated GAD65 isoform: relevance for people with stiff person syndrome or DQ8/8-positive Type 1 diabetes mellitus.

AIMS: To investigate whether the N-terminal truncated glutamic acid decarboxylase 65 (GAD65) isoform is as well recognized by people with stiff person syndrome as it is by people with Type 1 diabetes, and whether conformational GAD65 antibody epitopes are displayed properly by the isoform. METHODS: GAD65 antibody-positive healthy individuals (n=13), people with stiff-person syndrome (n=15) and children with new-onset Type 1 diabetes (n=654) were analysed to determine binding to full-length GAD65 and the N-terminal truncated GAD65 isoform in each of these settings. GAD65 autoantibody epitope specificity was correlated with binding ratios of full-length GAD65/N-terminal truncated GAD65. RESULTS: The N-terminal truncated GAD65 isoform was significantly less recognized in GAD65Ab-positive people with stiff-person syndrome (P=0.002) and in healthy individuals (P=0.0001) than in people with Type 1 diabetes. Moreover, at least two specific conformational GAD65Ab epitopes were not, or were only partially, presented by the N-terminal truncated GAD65 isoform compared to full-length GAD65. Finally, an N-terminal conformational GAD65Ab epitope was significantly less recognized in DQ8/8 positive individuals with Type 1 diabetes (P=0.02). CONCLUSIONS: In people with stiff person syndrome preferred binding to the full-length GAD65 isoform over the N-terminal truncated molecule was observed. This binding characteristic is probably attributable to reduced presentation of two conformational epitopes by the N-terminal truncated molecule. These findings support the notion of disease-specific GAD65Ab epitope specificities and emphasize the need to evaluate the applicability of novel assays for different medical conditions.

Quality of life for up to 18 months after low-energy hip, vertebral, and distal forearm fractures-results from the ICUROS.

This study used data from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) to estimate the quality of life (QoL) impact of fracture. Hip, vertebral, and distal forearm fractures incur substantial QoL losses. Hip and vertebral fracture results in markedly impaired QoL for at least 18 months. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) is a multinational observational study that aims to describe costs and quality of life (QoL) consequences of osteoporotic fractures. To date, 11 countries have participated in the study: Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, the UK, and the USA. The objective of this paper is to describe the QoL impact of hip, vertebral, and distal forearm fracture. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall) and at 4, 12, and 18 months after fracture. Quality of life was measured as health state utility values (HSUVs) derived from the EQ-5D-3L. Complete case analysis was conducted as the base case with available case and multiple imputation performed as sensitivity analyses. Multivariate analysis was performed to explore predictors of QoL impact of fracture. RESULTS: Among 5456 patients enrolled using convenience sampling, 3021 patients were eligible for the base case analysis (1415 hip, 1047 distal forearm, and 559 vertebral fractures). The mean (SD) difference between HSUV before and after fracture for hip, vertebral, and distal forearm fracture was estimated at 0.89 (0.40), 0.67 (0.45), and 0.48 (0.34), respectively (p < 0.001 for all fracture types). Eighteen months after fracture, mean HSUVs were lower than before the fracture in patients with hip fracture (0.66 vs. 0.77 p < 0.001) and vertebral fracture (0.70 vs. 0.83 p < 0.001). Hospitalization and higher recalled pre-fracture QoL were associated with increased QoL impact for all fracture types. CONCLUSIONS: Hip, vertebral, and distal forearm fractures incur substantial loss in QoL and for patients with hip or vertebral fracture, QoL is markedly impaired for at least 18 months.

Assessing pre- and post-zygotic barriers between North Atlantic eels (Anguilla anguilla and A. rostrata).

Elucidating barriers to gene flow is important for understanding the dynamics of speciation. Here we investigate pre- and post-zygotic mechanisms acting between the two hybridizing species of Atlantic eels: Anguilla anguilla and A. rostrata. Temporally varying hybridization was examined by analyzing 85 species-diagnostic single-nucleotide polymorphisms (SNPs; FST ⩾0.95) in eel larvae sampled in the spawning region in the Sargasso Sea in 2007 (N=92) and 2014 (N=460). We further investigated whether genotypes at these SNPs were nonrandomly distributed in post-F1 hybrids, indicating selection. Finally, we sequenced the mitochondrial ATP6 and nuclear ATP5c1 genes in 19 hybrids, identified using SNP and restriction site associated DNA (RAD) sequencing data, to test a previously proposed hypothesis of cytonuclear incompatibility leading to adenosine triphosphate (ATP) synthase dysfunction and selection against hybrids. No F1 hybrids but only later backcrosses were observed in the Sargasso Sea in 2007 and 2014. This suggests that interbreeding between the two species only occurs in some years, possibly controlled by environmental conditions at the spawning grounds, or that interbreeding has diminished through time as a result of a declining number of spawners. Moreover, potential selection was found at the nuclear and the cytonuclear levels. Nonetheless, one glass eel individual showed a mismatch, involving an American ATP6 haplotype and European ATP5c1 alleles. This contradicted the presence of cytonuclear incompatibility but may be explained by that (1) cytonuclear incompatibility is incomplete, (2) selection acts at a later life stage or (3) other genes are important for protein function. In total, the study demonstrates the utility of genomic data when examining pre- and post-zyotic barriers in natural hybrids.

Socioeconomic factors' effect on return to work after first stroke.

OBJECTIVE: The objective of this nationwide study was to analyze how functional status and socioeconomic status affect return to work (RTW) among younger patients with first-time stroke in a Sweden. MATERIAL AND METHODS: This register-based cohort study included employed patients aged 25-55 with first-time stroke between 2008 and 2011 and primary outcome was RTW within 1 year after stroke. Data regarding functional status and employment status were retrieved from the Swedish Stroke Register, Riksstroke, and socioeconomic data (income, education, and country of birth) from Statistics Sweden. RESULTS: We included 2539 patients who had answered the question on RTW, and 1880 (74.0%) had RTW within 12 months. Patients with low income (69.9% in lowest income group vs 79.9% in highest group, P<.001), patients born in countries outside the Nordic countries (Sweden 75.5%, Nordic countries 74.3%, European countries 61.7%, other countries 57.3%, P<.001), and the youngest patients (25-34, 63.1%; 35-44, 75.9%; 45-55, 74.3%; P=.008) were less likely to RTW. Pain, low mood, and answering the questionnaire with help were more common in low socioeconomic groups, and when adjusting for these variables, together with age and sex, income and country of birth were no longer independent predictors for RTW. CONCLUSION: Patients with low socioeconomic status less often RTW 1 year after stroke.Impaired functional status after stroke is more common in patients with lower socioeconomic status and mediates socioeconomic differences in RTW. Improvement of functional status should be targeted to facilitate RTW among stroke patients with low socioeconomic status.

Communication: Band bending at the interface in polyethylene-MgO nanocomposite dielectric.

Polymer nanocomposite dielectrics are promising materials for electrical insulation in high voltage applications. However, the physics behind their performance is not yet fully understood. We use density functional theory to investigate the electronic properties of the interfacial area in magnesium oxide-polyethylene nanocomposite. Our results demonstrate polyethylene conduction band matching with conduction bands of different surfaces of magnesium oxide. Such band bending results in long range potential wells of up to 2.6 eV deep. Furthermore, the fundamental influence of silicon treatment on magnesium oxide surface properties is assessed. We report a reduction of the surface-induced states at the silicon-treated interface. The simulations provide information used to propose a new model for charge trapping in nanocomposite dielectrics.

Bisphenol A concentration in human saliva related to dental polymer-based fillings.

OBJECTIVES: The aims of this study were to quantify salivary concentrations of bisphenol A (BPA) and to assess if presence of dental composite fillings is associated with higher BPA levels in saliva. MATERIALS AND METHODS: Twenty individuals with six or more tooth surfaces filled with polymer-based dental materials (composite group) and 20 individuals without any polymer-based materials (control group) were included in the study. Saliva was collected in polypropylene tubes and stored at -80 °C before analysis. Concentration of free (unconjugated) and total bisphenol A was determined by liquid chromatography/mass spectrometry (LC/MS). Values below limit of detection (0.1 ng/mL) were set to one-half of the limit of detection. Mann-Whitney U test (one sided; the Exact Tests Option in IBM-SPSS version 21) was used for the statistical analyses. RESULTS: The concentration of BPA in saliva was very low. In the composite group, 8 of 20 samples had detectable concentrations of BPA. In the control group, 3 of 20 samples had detectable concentrations of BPA. Statistical analysis indicated that the concentration of unconjugated BPA was slightly higher in the composite group (p = 0.044) than in the control group. CONCLUSIONS: Presence of dental composites may be associated with slightly higher concentration of unconjugated BPA in saliva. However, additional studies using sensitive analytical methods are needed before firm conclusions can be drawn. Influence from other factors, like food intake and time of the day for saliva sampling, must be considered. CLINICAL RELEVANCE: The relative contribution of existing polymer-based dental fillings to total BPA exposure seems to be low.

Mitigation of acidified salmon rivers - effects of liming on young brown trout Salmo trutta.

In southern Norway, 22 acidified rivers supporting anadromous salmonids were mitigated with lime to improve water quality and restore fish populations. In 13 of these rivers, effects on Salmo trutta and Salmo salar densities were monitored over 10-12 years, grouped into age 0 and age ≥ 1 year fish. These rivers had a mean annual discharge of between 4·9 and 85·5 m3 s-1 , and six of them were regulated for hydro-power production. Salmo salar were lost in six of these rivers prior to liming, and highly reduced in the remaining seven rivers. Post-liming, S. salar became re-established in all six rivers with lost populations, and recovered in the seven other rivers. Salmo trutta occurred in all 13 study rivers prior to liming. Despite the improved water quality, both age 0 and age ≥ 1 year S. trutta densities decreased as S. salar density increased, with an average reduction of >50% after 10 years of liming. For age 0 year S. trutta this effect was less strong in rivers where S. salar were present prior to liming. In contrast, densities of S. trutta increased in unlimed streams above the anadromous stretches in two of the rivers following improved water quality due to natural recovery. Density increases of both age 0 and age ≥ 1 year S. salar showed a positive effect of river discharge. The results suggest that the decline in S. trutta density after liming is related to interspecific resource competition due to the recovery of S. salar. Thus, improved water quality through liming may not only sustain susceptible species, but can have a negative effect on species that are more tolerant prior to the treatment, such as S. trutta.

Early market access of cancer drugs in the EU.

Patient access to new cancer drugs in the EU involves centralised licensing decisions by regulators as well as reimbursement recommendations in the context of national healthcare systems. Differences in assessment criteria and evidence requirements may result in divergent decisions at central and national levels, ultimately compromising effective access to patients. Early access decisions are particularly challenging due to the limited clinical evidence available to conclude on the benefit-risk and relative (cost-) effectiveness of new high-priced cancer drugs. We describe mechanisms to accelerate approval of promising anticancer drugs that fulfil an unmet medical need, review the experience from the European Medicines Agency, compare timelines and outcomes of reimbursement decisions in major EU markets, and discuss shortcomings of the current system, ongoing initiatives, and future steps to facilitate effective early access.

Trans-generational maternal effect: temperature influences egg size of the offspring in Atlantic salmon Salmo salar.

Effect of increased temperature during egg maturation on the mass of single eggs produced by the offspring was investigated experimentally in Atlantic salmon Salmo salar. Mass of eggs produced by next-generation females was larger when their mothers experienced warmer water during the last two months of egg maturation, relative to those that experienced unheated river water. There was no similar trans-generational paternal effect on offspring egg mass.

Environmental change influences the life history of salmon Salmo salar in the North Atlantic Ocean.

Annual mean total length (LT) of wild one-sea-winter (1SW) Atlantic salmon Salmo salar of the Norwegian River Imsa decreased from 63 to 54 cm with a corresponding decrease in condition factor (K) for cohorts migrating to sea from 1976 to 2010. The reduction in LT is associated with a 40% decline in mean individual mass, from 2 to 1·2 kg. Hatchery fish reared from parental fish of the same population exhibited similar changes from 1981 onwards. The decrease in LT correlated negatively with near-surface temperatures in the eastern Norwegian Sea, thought to be the main feeding area of the present stock. Furthermore, S. salar exhibited significant variations in the proportion of cohorts attaining maturity after only one winter in the ocean. The proportion of S. salar spawning as 1SW fish was lower both in the 1970s and after 2000 than in the 1980s and 1990s associated with a gradual decline in post-smolt growth and smaller amounts of reserve energy in the fish. In wild S. salar, there was a positive association between post-smolt growth and the sea survival back to the River Imsa for spawning. In addition, among smolt year-classes, there were significant positive correlations between wild and hatchery S. salar in LT, K and age at maturity. The present changes may be caused by ecosystem changes following the collapse and rebuilding of the pelagic fish abundance in the North Atlantic Ocean, a gradual decrease in zooplankton abundance and climate change with increasing surface temperature in the Norwegian Sea. Thus, the observed variation in the life-history traits of S. salar appears primarily associated with major changes in the pelagic food web in the ocean.

Do adolescents who are night owls have a higher risk of dental caries? - a case-control study.

OBJECTIVE: The aim was to evaluate the association between circadian rhythm and the risk of caries in adolescents, as well as their dietary and toothbrushing habits. METHODS: A group of 196 adolescents (15 and 16 years old) were divided into two equal groups based on caries risk (case = high risk; and control = low risk). Before their dental examinations, they were asked to complete a questionnaire. The questionnaire included questions on circadian rhythm, dietary and oral self-care habits, and demographic variables. The participants were divided into three circadian types: evening types who are alert in the evening and tired in the morning; morning types who are the opposite; and neutral types who are neither particularly alert in the evening nor extremely tired in the morning. RESULTS: The most common sleep-cycle group type was neutral (50%). After this came evening types (37%) and finally morning types (13%). Morning and neutral types reported more frequently than evening types that they had breakfast every morning and brushed their teeth twice a day. More evening types were categorized as at high risk of caries. Circadian rhythm, breakfast habits and toothbrushing frequency were associated with a high risk of caries. The predicted probability of being at high risk of caries was almost four times higher for evening types than for morning types (OR 3.8; 95% CI 1.3-10.9). CONCLUSION: Adolescents who belonged to the evening circadian rhythm group brushed their teeth more seldom, ate breakfast less regularly and had a higher risk of caries than morning types. A patient's circadian rhythm should be considered when planning oral health education for adolescents with a high risk of caries.

Signatures of natural selection between life cycle stages separated by metamorphosis in European eel.

BACKGROUND: Species showing complex life cycles provide excellent opportunities to study the genetic associations between life cycle stages, as selective pressures may differ before and after metamorphosis. The European eel presents a complex life cycle with two metamorphoses, a first metamorphosis from larvae into glass eels (juvenile stage) and a second metamorphosis into silver eels (adult stage). We tested the hypothesis that different genes and gene pathways will be under selection at different life stages when comparing the genetic associations between glass eels and silver eels. RESULTS: We used two sets of markers to test for selection: first, we genotyped individuals using a panel of 80 coding-gene single nucleotide polymorphisms (SNPs) developed in American eel; second, we investigated selection at the genome level using a total of 153,423 RAD-sequencing generated SNPs widely distributed across the genome. Using the RAD approach, outlier tests identified a total of 2413 (1.57%) potentially selected SNPs. Functional annotation analysis identified signal transduction pathways as the most over-represented group of genes, including MAPK/Erk signalling, calcium signalling and GnRH (gonadotropin-releasing hormone) signalling. Many of the over-represented pathways were related to growth, while others could result from the different conditions that eels inhabit during their life cycle. CONCLUSIONS: The observation of different genes and gene pathways under selection when comparing glass eels vs. silver eels supports the adaptive decoupling hypothesis for the benefits of metamorphosis. Partitioning the life cycle into discrete morphological phases may be overall beneficial since it allows the different life stages to respond independently to their unique selection pressures. This might translate into a more effective use of food and niche resources and/or performance of phase-specific tasks (e.g. feeding in the case of glass eels, migrating and reproducing in the case of silver eels).

Doubly Reactive INS-IGF2 Autoantibodies in Children with Newly Diagnosed Autoimmune (type 1) Diabetes.

The splice variant INS-IGF2 entails the preproinsulin signal peptide, the insulin B-chain, eight amino acids of the C-peptide and 138 unique amino acids from an ORF in the IGF2 gene. The aim of this study was to determine whether levels of specific INS-IGF2 autoantibodies (INS-IGF2A) were related to age at diagnosis, islet autoantibodies, HLA-DQ or both, in patients and controls with newly diagnosed type 1 diabetes. Patients (n = 676), 0-18 years of age, diagnosed with type 1 diabetes in 1996-2005 and controls (n = 363) were analysed for specific INS-IGF2A after displacement with both cold insulin and INS-IGF2 to correct for non-specific binding and identify double reactive sera. GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, ZnT8QA and HLA-DQ genotypes were also determined. The median level of specific INS-IGF2A was higher in patients than in controls (P < 0.001). Irrespective of age at diagnosis, 19% (126/676) of the patients had INS-IGF2A when the cut-off was the 95th percentile of the controls (P < 0.001). The risk of INS-IGF2A was increased among HLA-DQ2/8 (OR = 1.509; 95th CI 1.011, 2.252; P = 0.045) but not in 2/2, 2/X, 8/8, 8/X or X/X (X is neither 2 nor 8) patients. The association with HLA-DQ2/8 suggests that this autoantigen may be presented on HLA-DQ trans-heterodimers, rather than cis-heterodimers. Autoantibodies reactive with both insulin and INS-IGF2A at diagnosis support the notion that INS-IGF2 autoimmunity contributes to type 1 diabetes.

Prenatal exposure to environmental chemical contaminants and asthma and eczema in school-age children.

BACKGROUND: Emerging evidence suggests that prenatal or early-life exposures to environmental contaminants may contribute to an increased risk of asthma and allergies in children. We aimed to the explore associations of prenatal exposures to a large set of environmental chemical contaminants with asthma and eczema in school-age children. METHODS: We studied 1024 mother-child pairs from Greenland and Ukraine from the INUENDO birth cohort. Data were collected by means of an interview-based questionnaire when the children were 5-9 years of age. Questions from the ISAAC study were used to define asthma, eczema, and wheeze. We applied principal components analysis (PCA) to sixteen contaminants in maternal serum sampled during pregnancy, including perfluoroalkyl substances (PFASs), metabolites of diethylhexyl (DEHP) and diisononyl (DiNP) phthalates, PCB-153, and p,p'-DDE. Scores of five principal components (PCs) explaining 70% of the variance were included in multiple logistic regression models. RESULTS: In a meta-analysis that included both populations, the PC2 score, reflecting exposure to DiNP, was negatively associated with current eczema (OR 0.71, 95% CI 0.52-0.96). Other associations were not consistent between the two populations. In Ukrainian children, the PC3 score (DEHP) was positively associated with current wheeze (adjusted OR 1.56, 95% CI 1.03-2.37), whereas the PC5 score, dominated by perfluorooctanoic acid (PFOA), was inversely associated with current wheeze (OR 0.64, 0.41-0.99). In Greenlandic children, a negative association of PC4 (organochlorines) with ever eczema (OR 0.78, 0.61-0.99) was found. CONCLUSIONS: We found limited evidence to support a link between prenatal exposure to environmental chemical contaminants and childhood asthma and eczema.

Extremely preterm infants who are small for gestational age have a high risk of early hypophosphatemia and hypokalemia.

AIM: Electrolyte balances have not been sufficiently evaluated in extremely preterm infants after early parenteral nutrition. We investigated the risk of early hypophosphatemia and hypokalemia in extremely preterm infants born small for gestational age (SGA) who received nutrition as currently recommended. METHODS: This prospective, observational cohort study included all consecutive extremely preterm infants born at 24-27 weeks who received high amino acids and lipid perfusion from birth. We evaluated the electrolyte levels of SGA infants and infants born appropriate for gestational age (AGA) during the first five days of life. RESULTS: The 12 SGA infants had lower plasma potassium levels from Day One compared to the 36 AGA infants and were more likely to have hypokalemia (58% vs 17%, p = 0.001) and hypophosphatemia (40% vs 9%, p < 0.01) during the five-day observation period. After adjusting for perinatal factors, SGA remained significantly associated with hypophosphatemia (odds ratio 1.39, confidence intervals 1.07-1.81, p = 0.01). CONCLUSION: Extremely preterm infants born SGA who were managed with currently recommended early parenteral nutrition had a high risk of early hypokalemia and hypophosphatemia. Potassium and phosphorus intakes should be set at sufficient levels from birth onwards, especially in SGA infants.

Sexual size dimorphism in anadromous brown trout Salmo trutta.

Anadromous trout Salmo trutta exhibits sexual size dimorphism (SSD ); females were larger than males in populations where male mean total length (LT ) at maturity was below 49 cm and females were smaller than males when mean male LT was above 49 cm, the slope of the regression of female on male LT was 0·59. In streams with mean annual discharge below 41 m(3) s(-1) , flow added significantly to a model with SSD as the dependent variable and male mean LT at maturity as the first predictor variable. There was a slight increase in SSD with increasing latitude, which may result from an increase in male size with increasing latitude.

Body mass index in young school-age children in relation to organochlorine compounds in early life: a prospective study.

OBJECTIVE: To investigate the association between maternal pregnancy and estimated postnatal serum concentrations of the organochlorines 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and body mass index (BMI) z-scores in 5- to 9-year-old children. METHODS: Maternal sera from the INUENDO birth cohort (2002-2004) comprising mother-child pairs (N=1109) from Greenland, Warsaw (Poland), and Kharkiv (Ukraine) were analysed for CB-153 and p,p'-DDE, using gas chromatography-mass-spectrometry, and were grouped into tertiles for statistical analyses. A toxicokinetic model was used to estimate the first 12 months cumulative exposure to the compounds. Associations between these compounds and child age- and sex-specific BMI z-scores were calculated at follow-up (2010-2012), using multiple linear regression analysis. RESULTS: No clear associations between pregnancy CB-153 and p,p'-DDE and child BMI were observed (the pooled differences in BMI z-score (95% confidence interval) comparing 3rd tertile to 1st tertile were -0.07 (-0.32 to 0.18) and -0.10 (-0.30 to 0.10) kg m(-2), respectively). For postnatal CB-153 and p,p'-DDE and BMI, the overall differences in BMI z-score comparing 3rd tertile to 1st tertile were 0.12 (-0.15 to 0.39) and -0.03 (-0.20 to 0.27) kg m(-2), respectively. CONCLUSIONS: This follow-up study of Greenlandic, Polish and Ukrainian populations showed no clear association between pregnancy and postnatal exposure to p,p'-DDE and CB-153 and BMI at the age of 5-9 years.

Genome-wide single-generation signatures of local selection in the panmictic European eel.

Next-generation sequencing and the collection of genome-wide data allow identifying adaptive variation and footprints of directional selection. Using a large SNP data set from 259 RAD-sequenced European eel individuals (glass eels) from eight locations between 34 and 64(o) N, we examined the patterns of genome-wide genetic diversity across locations. We tested for local selection by searching for increased population differentiation using F(ST) -based outlier tests and by testing for significant associations between allele frequencies and environmental variables. The overall low genetic differentiation found (F(ST) = 0.0007) indicates that most of the genome is homogenized by gene flow, providing further evidence for genomic panmixia in the European eel. The lack of genetic substructuring was consistent at both nuclear and mitochondrial SNPs. Using an extensive number of diagnostic SNPs, results showed a low occurrence of hybrids between European and American eel, mainly limited to Iceland (5.9%), although individuals with signatures of introgression several generations back in time were found in mainland Europe. Despite panmixia, a small set of SNPs showed high genetic differentiation consistent with single-generation signatures of spatially varying selection acting on glass eels. After screening 50 354 SNPs, a total of 754 potentially locally selected SNPs were identified. Candidate genes for local selection constituted a wide array of functions, including calcium signalling, neuroactive ligand-receptor interaction and circadian rhythm. Remarkably, one of the candidate genes identified is PERIOD, possibly related to differences in local photoperiod associated with the >30° difference in latitude between locations. Genes under selection were spread across the genome, and there were no large regions of increased differentiation as expected when selection occurs within just a single generation due to panmixia. This supports the conclusion that most of the genome is homogenized by gene flow that removes any effects of diversifying selection from each new generation.

Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study.

STUDY QUESTION: Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? SUMMARY ANSWER: The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. WHAT IS KNOWN ALREADY: PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. STUDY DESIGN, SIZE, DURATION: A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: ≤24 days, long cycle: ≥32 days) and irregularities (≥7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95% CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95% CI: 0.8; 3.5)]. The overall response rate was 45.3% with considerable variation between countries (91.3% in Greenland, 69.1% in Poland and 26.3% in Ukraine). LIMITATIONS, REASONS FOR CAUTION: Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS: The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. STUDY FUNDING/COMPETING INTEREST(S): Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), www.inuendo.dk. The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study (www.inuendo.dk/clear) supported by the European Commission's 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.