Avandia (TM) - From molecule to market for type 2 diabetes.

Type 2 diabetes is a disease fast approaching epidemic proportions throughout the world. From insulin sensitizers to PPARg agonists, the lecture will outline the successful medicinal chem. and biol. strategy underpinning the discovery and selection of Avandia, an innovative new medicine for this disease.

Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes: A meta-analysis of observational studies

Aims/hypothesis: The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders.
Methods: After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies.
Results: Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p<0.001). There was little evidence of heterogeneity between studies (p=0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p=0.01).
Conclusions/interpretation: This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.

Atopy, home environment and the risk of childhood-onset type 1 diabetes: a population-based case-control study

Background: The marked increases in the incidence of type 1 diabetes in recent decades strongly suggest the role of environmental influences. These environmental influences remain largely unknown.

No association between routinely recorded infections in early life and subsequent risk of childhood-onset Type 1 diabetes: a matched case-control study using the UK General Practice Research Database

Aims To determine whether children with infections in early life (recorded routinely in general practice) have a reduced risk of Type 1 diabetes, as would be expected from the hygiene hypothesis.

Dust and the Type II-Plateau Supernova 2004et

We present mid-infrared (MIR) observations of the Type II-plateau supernova (SN) 2004et, obtained with the Spitzer Space Telescope between 64 and 1406 days past explosion. Late-time optical spectra are also presented. For the period 300-795 days past explosion, we argue that the spectral energy distribution (SED) of SN 2004et comprises (1) a hot component due to emission from optically thick gas, as well as free-bound radiation; (2) a warm component due to newly formed, radioactively heated dust in the ejecta; and (3) a cold component due to an IR echo from the interstellar-medium dust of the host galaxy, NGC 6946. There may also have been a small contribution to the IR SED due to free-free emission from ionized gas in the ejecta. We reveal the first-ever spectroscopic evidence for silicate dust formed in the ejecta of a supernova. This is supported by our detection of a large, but progressively declining, mass of SiO. However, we conclude that the mass of directly detected ejecta dust grew to no more than a few times 10(-4) M-circle dot. We also provide evidence that the ejecta dust formed in comoving clumps of fixed size. We argue that, after about two years past explosion, the appearance of wide, box-shaped optical line profiles was due to the impact of the ejecta on the progenitor circumstellar medium and that the subsequent formation of a cool, dense shell was responsible for a later rise in the MIR flux. This study demonstrates the rich, multifaceted ways in which a typical core-collapse supernova and its progenitor can produce and/or interact with dust grains. The work presented here adds to the growing number of studies that do not support the contention that SNe are responsible for the large mass of observed dust in high-redshift galaxies.

Extensive optical and near-infrared observations of the nearby, narrow-lined type Ic SN 2007gr: days 5 to 415

We present photometric and spectroscopic observations at optical and near-infrared wavelengths of the nearby type Ic supernova 2007gr. These represent the most extensive data-set to date of any supernova of this sub-type, with frequent coverage from shortly after discovery to more than one year post-explosion. We deduce a rise time to B-band maximum of 11.5 +/- 2.7 d. We find a peak B-band magnitude of M-B = -16.8, and light curves which are remarkably similar to the so-called "hypernova" SN 2002ap. In contrast, the spectra of SNe 2007gr and 2002ap show marked differences, not least in their respective expansion velocities. We attribute these differences primarily to the density profiles of their progenitor stars at the time of explosion i.e. a more compact star for SN 2007gr compared to SN 2002ap. From the quasi-bolometric light curve of SN 2007gr, we estimate that 0.076 +/- 0.010 M-circle dot of Ni-56 was produced in the explosion. Our near-infrared (IR) spectra clearly show the onset and disappearance of the first overtone of carbon monoxide (CO) between similar to 70 to 175 d relative to B-band maximum. The detection of the CO molecule implies that ionised He was not microscopically mixed within the carbon/oxygen layers. From the optical spectra, near-IR light curves, and colour evolution, we find no evidence for dust condensation in the ejecta out to about +400 d. Given the combination of unprecedented temporal coverage, and high signal-to-noise data, we suggest that SN 2007gr could be used as a template object for supernovae of this sub-class.

Spitzer measurements of atomic and molecular abundances in the Type IIPSN 2005af

We present results based on mid-infrared (3.6-30 mm) observations with the Spitzer Space Telescope of the nearby Type IIP supernova 2005af. We report the first ever detection of the SiO molecule in a Type IIP supernova. Together with the detection of the CO fundamental, this is an exciting finding as it may signal the onset of dust condensation in the ejecta. From a wealth of fine-structure lines we provide abundance estimates for stable Ni, Ar, and Ne that, via spectral synthesis, may be used to constrain nucleosynthesis models.

Spectroscopy of the type Ia supernova SN 2002er: Days-11 to+215

We present an extensive set of optical spectroscopy of the nearby type Ia supernova, SN 2002er, with 24 epochs spanning -11 to +34 days. Its spectral evolution is fairly typical of a type Ia supernova although it suffers high extinction. Nevertheless, there are differences in the spectral evolution when compared to coeval spectra of other normal type Ia supernova with comparable decline-rate parameters. Modelling of the photospheric phase spectra using a homogeneous abundance distribution in the atmosphere provides a fair match to the observations, but only by pushing the adopted distance and risetime close to the observational limits. Future improvements here will require models with a more realistic stratified abundance distribution. From simple modelling of a nebular spectrum obtained at +215 d, we infer a Ni-56 mass of 0.69 M-circle dot, consistent with that derived from the light curve.

Worldwide childhood type 1 diabetes incidence - what can we learn from epidemiology?

Type 1 diabetes is the most common form of diabetes in most part of the world, although reliable data are still unavailable in several countries. Wide variations exist between the incidence rates of different populations, incidence is lowest in China and Venezuela (0.1 per 100 000 per year) and highest in Finland and Sardinia (37 per 100 000 per year). In most populations girls and boys are equally affected. In general, the incidence increases with age, the incidence peak is at puberty. After the pubertal years, the incidence rate significantly drops in young women, but remains relatively high in young adult males up to the age 29-35 years. Prospective national and large international registries (DIAMOND and EURODIAB) demonstrated an increasing trend in incidence in most regions of the world over the last few decades and increases seem to be the highest in the youngest age group. Analytical epidemiological studies have identified environmental risk factors operating early in life which might have contributed to the increasing trend in incidence. These include enteroviral infections in pregnant women, older maternal age (39-42 years), preeclampsia, cesarean section delivery, increased birthweight, early introduction of cow's milk proteins and an increased rate of postnatal growth (weight and height). Optimal vitamin D supplementation during early life has been shown to be protective. Some of these environmental risk factors such as viruses may initiate autoimmunity toward the beta cell, other exposures may put on overload on the already affected beta cell and thus accelerate the disease process.

Secular trends, disease maps and ecological analyses of the incidence of childhood onset type 1 diabetes in Northern Ireland, 1989-2003

Aims To investigate secular trends in the incidence of Type 1 diabetes in Northern Ireland over the period 1989-2003. To highlight geographical variations in the incidence of Type 1 diabetes by producing disease maps and to compare incidence rates by relevant area characteristics.

Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: A randomized controlled clinical trial

OBJECTIVE: This study was undertaken to compare preprandial and postprandial capillary glucose monitoring in pregnant women with type 1 diabetes.