Birth order and childhood type 1 diabetes risk: A pooled analysis of 31 observational studies

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results: Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second-or later born children became apparent [fully adjusted OR=0.90 95% confidence interval (CI) 0.83-0.98; P=0.02] but this association varied markedly between studies (I 2=67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children <5years of age (n=25 studies, maternal age adjusted OR=0.84 95% CI 0.75, 0.93; I 2=23%). Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged <5 years. This finding could reflect increased exposure to infections in early life in later born children. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.

Optimal glycaemic control, pre-eclampsia and gestational hypertension in women with type 1 diabetes in the Diabetes and Pre-Eclampsia Intervention Trial

OBJECTIVE
To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes.

RESEARCH DESIGN AND METHODS
Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1–6.9%), moderate (7.0–7.9%), and poor (=8.0%) glycemic control, respectively.

RESULTS
Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C =8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values =6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values =7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension.

CONCLUSIONS
Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.

Disordered eating attitudes among female adolescents with Type 1 Diabetes: Role of mothers.

Previous research has demonstrated that disordered eating among adolescent females with type 1 diabetes (T1D) is related to the weight loss and eating attitudes of their mothers. The present research sought to examine the extent to which female adolescents’ perceptions of their mother’s weight loss and eating attitudes and behaviours explained the adolescents’ disordered eating attitudes and behaviours. Female adolescents with T1D and their mothers completed self-report questionnaires during outpatient clinic visits. Adolescents’ perceptions of their mother’s frequency of dieting behaviour and the importance of thinness to their mother were significant covariates of the adolescents’ body dissatisfaction and drive for thinness. Attitudes about disordered eating were also explained by different elements of family cohesion and mothers’ attitudes to weight loss. Routinely assessing perceptions of family and maternal attitudes and adopting a systemic approach to the care of adolescent females with T1D may help with the identification and management of these at-risk individuals.

Characterization of Nickel Germanide Schottky Contacts for the Fabrication of Germanium p-channel MOSFETs

Nickel germanide Schottky contacts, formed by rapid thermal annealing of thin nickel films, have been characterized on n-type germanium wafers for a range of RTA temperatures. The highest Schottky barrier heights for electrons (= 0.6-0.7 eV) were obtained for RTA temperatures of approximately 300°C. For this RTA schedule, the corresponding barrier height for holes is close to zero, ideal for Schottky contacted p-channel germanium MOSFETs. When the RTA temperature was increased to 400oC, a dramatic reduction in electron barrier height (< 0.1 eV) was observed. This RTA schedule, therefore, appears ideal for ohmic source/drain contacts to n channel germanium MOSFETs. From sheet resistance measurements and XRD characterization, nickel germanide formation was found to occur at 300oC and above. The NiGe phase was dominant for RTA temperatures up to at least 435oC.

Identification of a major GpVI-binding locus in human type III collagen

We have analyzed the adhesion of human and murine platelets, and of recombinant human and murine GpVI ectodomains, to synthetic triple-helical collagen-like peptides. These included 57 peptides derived from the sequence of human type III collagen and 9 peptides derived from the cyanogen bromide fragment of bovine type III collagen, alpha 1(III)CB4. We have identified several peptides that interact with GpVI, in particular a peptide designated III-30 with the sequence GAOGLRGGAGPOG-PEGGKGAAGPOGPO. Both human and murine platelets bound to peptide III-30 in a GpVI-dependent manner. III-30 also supported binding of recombinant GpVI ectodomains. Cross-linked III-30 induced aggregation of human and murine platelets, although with a lower potency than collagen-related peptide. Modifications of the peptide sequence indicated that the hydroxyproline residues play a significant role in supporting its GpVI reactivity. However, many peptides containing OGP/ GPO motifs did not support adhesion to GpVI. These data indicate that the ability of a triple-helical peptide to bind GpVI is not solely determined by the presence or spatial arrangement of these OGP/GPO motifs within the peptides.

Rotating massive main-sequence stars II. Simulating a population of LMC early B-type stars as a test of rotational mixing

Context. Rotational mixing in massive stars is a widely applied concept, with far-reaching consequences for stellar evolution, nucleosynthesis, and stellar explosions.

An Investigation into the Dissolution Properties of Celecoxib Melt Extrudates: Understanding the Role of Polymer Type and Concentration in Stabilizing Supersaturated Drug Concentrations

In this study, the dissolution properties of celecoxib (CX) solid dispersions manufactured from Eudragit 4155F and polyvinylpyrrolidone (PVP) were evaluated. Hot-melt extrusion (HME) technology was used to prepare amorphous solid dispersions of drug/polymer binary systems at different mass ratios. The drug concentrations achieved from the dissolution of PVP and Eudragit 4155F solid dispersions in phosphate buffer, pH 7.4 (PBS 7.4) were significantly greater than the equilibrium solubility of CX (1.58 µg/mL). The degree of supersaturation increased significantly as the polymer concentration within the solid dispersion increased. The maximum drug concentration achieved by PVP solid dispersions did not significantly exceed the apparent solubility of amorphous CX. The predominant mechanism for achieving supersaturated CX concentrations in PBS 7.4 was attributed to stabilization of amorphous CX during dissolution. Conversely, Eudragit 4155F solid dispersions showed significantly greater supersaturated drug solutions particularly at high polymer concentrations. For example, at a drug/polymer ratio of 1:9, a concentration of 100 µg/mL was achieved after 60 min that was stable (no evidence of drug recrystallization) for up to 72 h. This clearly identifies the potential of Eudragit 4155F to act as a solubilizing agent for CX. These findings were in good agreement with the results from solubility performed using PBS 7.4 in which Eudragit 4155F had been predissolved. In these tests, Eudragit 4155F significantly increased the equilibrium solubility of CX. Solution 1H NMR spectra were used to identify drug/polymer interactions. Deshielding of CX aromatic protons (H-1a and H-1b) containing the sulfonamide group occurred as a result of dissolution of Eudragit 4155F solid dispersions, whereas deshielding of H-1a protons and shielding of H-1b protons occurred as a result of the dissolution of PVP solid dispersions. In principle, it is reasonable to suggest that the different drug/polymer interactions observed give rise to the variation in dissolution observed for the two polymer/drug systems.

The Type Ic SN 2007gr: a census of the ejecta from late-time optical-infrared spectra

Nebular spectra of supernovae (SNe) offer an unimpeded view of the inner region of the ejecta, where most nucleosynthesis takes place. Optical spectra cover most, but not all, of the emitting elements and therefore offer only a partial view of the products of the explosion. Simultaneous optical-infrared spectra, on the other hand, contain emission lines of all important elements, from C and O through to the intermediate mass elements (IME) Mg, Si, S, Ca and to Fe and Ni. In particular, Si and S are best seen in the IR. The availability of IR data makes it possible to explore in greater detail the results of the explosion. SN 2007gr is the first Type Ic SN for which such data are available. Modelling the spectra with a non-local thermodynamic equilibrium (NLTE) code reveals that the inner ejecta contain similar to 1M(circle dot) of material within a velocity of approximate to 4500 km s(-1). The same mass of Ni-56 derived from the light-curve peak (0.076M(circle dot)) was used to power the spectrum, yielding consistent results. Oxygen is the dominant element, contributing similar to 0.8M(circle dot). The C/O ratio is

SUPERNOVA 2009kf: AN ULTRAVIOLET BRIGHT TYPE IIP SUPERNOVA DISCOVERED WITH PAN-STARRS 1 AND GALEX

We present photometric and spectroscopic observations of a luminous Type IIP Supernova (SN) 2009kf discovered by the Pan-STARRS 1 (PS1) survey and also detected by the Galaxy Evolution Explorer. The SN shows a plateau in its optical and bolometric light curves, lasting approximately 70 days in the rest frame, with an absolute magnitude of M-V = - 18.4 mag. The P-Cygni profiles of hydrogen indicate expansion velocities of 9000 km s(-1) at 61 days after discovery which is extremely high for a Type IIP SN. SN 2009kf is also remarkably bright in the near-ultraviolet (NUV) and shows a slow evolution 10-20 days after optical discovery. The NUV and optical luminosity at these epochs can be modeled with a blackbody with a hot effective temperature (T similar to 16,000 K) and a large radius (R similar to 1 x 10(15) cm). The bright bolometric and NUV luminosity, the light curve peak and plateau duration, the high velocities, and temperatures suggest that 2009kf is a Type IIP SN powered by a larger than normal explosion energy. Recently discovered high-z SNe (0.7

Optical and infrared observations of SN 2002dj: some possible common properties of fast-expanding Type Ia supernovae

As part of the European Supernova Collaboration, we obtained extensive photometry and spectroscopy of the Type Ia supernova (SN Ia) SN 2002dj covering epochs from 11 d before to nearly two years after maximum. Detailed optical and near-infrared observations show that this object belongs to the class of the high-velocity gradient events as indicated by Si, S and Ca lines. The light curve shape and velocity evolution of SN 2002dj appear to be nearly identical to SN 2002bo. The only significant difference is observed in the optical to near-infrared colours and a reduced spectral ernission beyond 6500 A. For high-velocity gradient SNe Ia, we tentatively identify a faster rise to maximum, a more pronounced inflection in the V and R light curves after maximum and a brighter, slower declining late-time B light curve as common photometric properties of this class of object. They also seem to be characterized by a different colour and colour evolution with respect to 'normal' SNe Ia. The usual light Curve shape parameters do not distinguish these events. Stronger, more blueshifted absorption features of intermediate-mass elements and lower temperatures are the most prominent spectroscopic features of SNe Ia displaying high-velocity gradients. It appears that these events burn more intermediate-mass elements in the outer layers. Possible connections to the metallicity of the progenitor star are explored.

ESC observations of SN 2005cf - I. Photometric evolution of a normal Type Ia supernova

We present early-time optical and near-infrared photometry of supernova (SN) 2005cf. The observations, spanning a period from about 12 d before to 3 months after maximum, have been obtained through the coordination of observational efforts of various nodes of the European Supernova Collaboration and including data obtained at the 2-m Himalayan Chandra Telescope. From the observed light curve we deduce that SN 2005cf is a fairly typical SN Ia with a post-maximum decline [Delta m(15)(B)(true) = 1.12] close to the average value and a normal luminosity of M-B,M-max = -19.39 +/- 0.33. Models of the bolometric light curve suggest a synthesized Ni-56 mass of about 0.7 M-circle dot. The negligible host galaxy interstellar extinction and its proximity make SN 2005cf a good Type Ia SN template.

SN2003du: 480 days in the life of a normal type Ia supernova

Aims. We present a study of the optical and near-infrared (NIR) properties of the Type Ia Supernova (SNIa) 2003du.