Life course socioeconomic circumstances and cardiovascular disease risk in Central and Eastern Europe

This thesis investigated the influences of early life socioeconomic circumstances (SEC) on cardiovascular disease (CVD) risk in Russia, Poland and the Czech Republic. Early life SEC are inversely associated with CVD risk factors and outcomes in western countries, but the same relationships have not been evaluated in Central and Eastern Europe. CVD is a major cause of morbidity and mortality in this region. I used data from the first round of the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study, which randomly selected men and women aged 45 to 69 years from population registers in Novosibirsk (Russia), Krakow (Poland) and six towns in the Czech Republic. Nearly 29,000 people were recruited, with an overall response rate of 61%. Blood pressure (systolic and diastolic blood pressure, hypertension), lipids (total and HDL cholesterol), adiposity (BMI, waist circumference, waist to hip ratio), smoking habits (starting and quitting) and CVD risk, as measured by SCORE, were assessed in relation to retrospectively collected direct and proxy measures of early life SEC. The reliability of adult anthropometric measures (height, leg length and trunk length) as proxy markers of early life SEC was confirmed by investigating the relationships with three direct measures of early life SEC (maternal and paternal education and household ownership of six assets at age ten years). Higher childhood SEC were linked to an increased likelihood of women starting smoking, a decreased likelihood of men quitting smoking, and reduced adiposity in both genders. The remaining CVD risk factors and overall CVD risk did not appear to be consistently influenced by childhood SEC. The results of the thesis suggest that early life socioeconomic influences on classical CVD risk may not be consistent across cultures, and that they may vary by the stage of the epidemiological transition and by local context

Phenotypic spectrum in osteogenesis imperfecta due to mutations in TMEM38B: unravelling a complex cellular defect.

Context: Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Objectives: Clinical and bone material phenotype description and osteoblast differentiation studies. Design and Setting: Natural history study in paediatric research centres. Patients: Eight patients with type XIV OI. Main Outcome Measures: Clinical examinations included: bone mineral density, radiographs, echocardiography and muscle biopsy. Bone biopsy samples (n=3) were analysed using histomorphometry, quantitative backscattered electron microscopy and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Results: The clinical phenotype of type XIV OI ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband L1-L4 bone density Z-score was reduced (median -3.3 [range -4.77 to +0.1; n=7]), and increased by +1.7 (1.17 to 3.0; n=3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased late and mineralization-related markers. Predominance of TRIC-B over TRIC-A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. Conclusions: OI type XIV has a bone histology, matrix mineralization and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities

Database of diazotrophs in global ocean: abundance, biomass and nitrogen fixation rates

Marine N2 fixing microorganisms, termed diazotrophs, are a key functional group in marine pelagic ecosystems. The biological fixation of dinitrogen (N2) to bioavailable nitrogen provides an important new source of nitrogen for pelagic marine ecosystems and influences primary productivity and organic matter export to the deep ocean. As one of a series of efforts to collect biomass and rates specific to different phytoplankton functional groups, we have constructed a database on diazotrophic organisms in the global pelagic upper ocean by compiling about 12 000 direct field measurements of cyanobacterial diazotroph abundances (based on microscopic cell counts or qPCR assays targeting the nifH genes) and N2 fixation rates. Biomass conversion factors are estimated based on cell sizes to convert abundance data to diazotrophic biomass. The database is limited spatially, lacking large regions of the ocean especially in the Indian Ocean. The data are approximately log-normal distributed, and large variances exist in most sub-databases with non-zero values differing 5 to 8 orders of magnitude. Reporting the geometric mean and the range of one geometric standard error below and above the geometric mean, the pelagic N2 fixation rate in the global ocean is estimated to be 62 (52–73) Tg N yr?1 and the pelagic diazotrophic biomass in the global ocean is estimated to be 2.1 (1.4–3.1) Tg C from cell counts and to 89 (43–150) Tg C from nifH-based abundances. Reporting the arithmetic mean and one standard error instead, these three global estimates are 140 ± 9.2 Tg N yr?1, 18 ± 1.8 Tg C and 590 ± 70 Tg C, respectively. Uncertainties related to biomass conversion factors can change the estimate of geometric mean pelagic diazotrophic biomass in the global ocean by about ±70%. It was recently established that the most commonly applied method used to measure N2 fixation has underestimated the true rates. As a result, one can expect that future rate measurements will shift the mean N2 fixation rate upward and may result in significantly higher estimates for the global N2 fixation. The evolving database can nevertheless be used to study spatial and temporal distributions and variations of marine N2 fixation, to validate geochemical estimates and to parameterize and validate biogeochemical models, keeping in mind that future rate measurements may rise in the future. The database is stored in PANGAEA (doi:10.1594/PANGAEA.774851)

Bounds on the possible evolution of the Gravitational Constant from Cosmological Type-Ia Supernovae

Recent high-redshift Type Ia supernovae results can be used to set new bounds on a possible variation of the gravitational constant $G$. If the local value of $G$ at the space-time location of distant supernovae is different, it would change both the kinetic energy release and the amount of $^{56}$Ni synthesized in the supernova outburst. Both effects are related to a change in the Chandrasekhar mass $M_{Ch} \propto G^{-3/2}$. In addition, the integrated variation of $G$ with time would also affect the cosmic evolution and therefore the luminosity distance relation. We show that the later effect in the magnitudes of Type Ia supernovae is typically several times smaller than the change produced by the corresponding variation of the Chandrasekhar mass. We investigate in a consistent way how a varying $G$ could modify the Hubble diagram of Type Ia supernovae and how these results can be used to set upper bounds to a hypothetical variation of $G$. We find G/G_0 \la 1.1 and G'/G \la 10^{-11} yr^{-1} at redshifts $z\simeq 0.5$. These new bounds extend the currently available constrains on the evolution of $G$ all the way from solar and stellar distances to typical scales of Gpc/Gyr, i.e. by more than 15 orders of magnitudes in time and distance.Comment: 9 pages, 4 figures, Phys. Rev. D. in pres

Ionization and scintillation response of high-pressure xenon gas to alpha particles

High-pressure xenon gas is an attractive detection medium for a variety of applications in fundamental and applied physics. In this paper we study the ionization and scintillation detection properties of xenon gas at 10 bar pressure. For this purpose, we use a source of alpha particles in the NEXT-DEMO time projection chamber, the large scale prototype of the NEXT-100 neutrinoless double beta decay experiment, in three different drift electric field configurations. We measure the ionization electron drift velocity and longitudinal diffusion, and compare our results to expectations based on available electron scattering cross sections on pure xenon. In addition, two types of measurements addressing the connection between the ionization and scintillation yields are performed. On the one hand we observe, for the first time in xenon gas, large event-by-event correlated fluctuations between the ionization and scintillation signals, similar to that already observed in liquid xenon. On the other hand, we study the field dependence of the average scintillation and ionization yields. Both types of measurements may shed light on the mechanism of electron-ion recombination in xenon gas for highly-ionizing particles. Finally, by comparing the response of alpha particles and electrons in NEXT-DEMO, we find no evidence for quenching of the primary scintillation light produced by alpha particles in the xenon gas