The promoter polymorphism -232C/G of the PCK1 gene is associated with type 2 diabetes in a UK-resident South Asian population

Background: The PCK1 gene, encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), has previously been implicated as a candidate gene for type 2 diabetes (T2D) susceptibility. Rodent models demonstrate that over-expression of Pck1 can result in T2D development and a single nucleotide polymorphism (SNP) in the promoter region of human PCK1 (-232C/G) has exhibited significant association with the disease in several cohorts. Within the UK-resident South Asian population, T2D is 4 to 6 times more common than in indigenous white Caucasians. Despite this, few studies have reported on the genetic susceptibility to T2D in this ethnic group and none of these has investigated the possible effect of PCK1 variants. We therefore aimed to investigate the association between common variants of the PCK1 gene and T2D in a UK-resident South Asian population of Punjabi ancestry, originating predominantly from the Mirpur area of Azad Kashmir, Pakistan. \ud \ud Methods: We used TaqMan assays to genotype five tagSNPs covering the PCK1 gene, including the -232C/G variant, in 903 subjects with T2D and 471 normoglycaemic controls. \ud \ud Results: Of the variants studied, only the minor allele (G) of the -232C/G SNP demonstrated a significant association with T2D, displaying an OR of 1.21 (95% CI: 1.03 - 1.42, p = 0.019). \ud \ud Conclusion: This study is the first to investigate the association between variants of the PCK1 gene and T2D in South Asians. Our results suggest that the -232C/G promoter polymorphism confers susceptibility to T2D in this ethnic group. \ud \ud Trial registration: UKADS Trial Registration: ISRCTN38297969

Limitation of dimethylsulfoniopropionate synthesis at high irradiance in natural phytoplankton communities of the Tropical Atlantic

Predictions of the ocean-atmosphere flux of dimethyl sulfide will be improved by understanding what controls seasonal and regional variations in dimethylsulfoniopropionate (DMSP) production. To investigate the influence of high levels of irradiance including ultraviolet radiation (UVR), on DMSP synthesis rates (μDMSP) and inorganic carbon fixation (μPOC) by natural phytoplankton communities, nine experiments were carried out at different locations in the low nutrient, high light environment of the northeastern Tropical Atlantic. Rates of μDMSP and μPOC were determined by measuring the incorporation of inorganic 13C into DMSP and particulate organic carbon. Based on measurements over discrete time intervals during the day, a unique μDMSP vs. irradiance (P vs. E) relationship was established. Comparison is made with the P vs. E relationship for μPOC, indicating that light saturation of μDMSP occurs at similar irradiance to μPOC and is closely coupled to carbon fixation on a diel basis. Photoinhibition during the middle of the day was exacerbated by exposure to UVR, causing an additional 55–60% inhibition of both μDMSP and μPOC at the highest light levels. In addition, decreased production of DMSP in response to UVR-induced photoxidative stress, contrasted with the increased net synthesis of photoprotective xanthophyll pigments. Together these results indicate that DMSP production by phytoplankton in the tropical ocean is not regulated in the short term by the necessity to control increasing photooxidative stress as irradiance increases during the day. The study provides new insight into the regulation of resource allocation into this biogeochemically important, multi-functional compatible solute

Entangled-State Cycles of Atomic Collective-Spin States

We study quantum trajectories of collective atomic spin states of $N$ effective two-level atoms driven with laser and cavity fields. We show that interesting ``entangled-state cycles'' arise probabilistically when the (Raman) transition rates between the two atomic levels are set equal. For odd (even) $N$, there are $(N+1)/2$ ($N/2$) possible cycles. During each cycle the $N$-qubit state switches, with each cavity photon emission, between the states $(|N/2,m>\pm |N/2,-m>)/\sqrt{2}$, where $|N/2,m>$ is a Dicke state in a rotated collective basis. The quantum number $m$ ($>0$), which distinguishes the particular cycle, is determined by the photon counting record and varies randomly from one trajectory to the next. For even $N$ it is also possible, under the same conditions, to prepare probabilistically (but in steady state) the Dicke state $|N/2,0>$, i.e., an $N$-qubit state with $N/2$ excitations, which is of particular interest in the context of multipartite entanglement.Comment: 10 pages, 9 figure

Stationary Black Holes: Uniqueness and Beyond

The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.Comment: Major update of the original version by Markus Heusler from 1998. Piotr T. Chru\'sciel and Jo\~ao Lopes Costa succeeded to this review's authorship. Significantly restructured and updated all sections; changes are too numerous to be usefully described here. The number of references increased from 186 to 32

Improving prevention, monitoring and management of diabetes among ethnic minorities: contextualizing the six G’s approach

Objective: People from Black, Asian and Minority Ethnic (BAME) groups are known to have an increased risk of devel-oping diabetes and face greater barriers to accessing healthcare resources compared to their ‘white British’ counter-parts. The extent of these barriers varies by demographics and different socioeconomic circumstances that people find themselves in. The purpose of this paper is to present and discuss a new framework to understand, disentangle and tackle these barriers so that improvements in the effectiveness of diabetes interventions for BAME communities can be achieved. Results: The main mediators of lifestyle behavioural change are gender, generation, geography, genes, God/religion, and gaps in knowledge and economic resources. Dietary and cultural practices of these individuals significantly vary according to gender, generation, geographical origin and religion. Recognition of these factors is essential in increas-ing knowledge of healthy eating, engagement in physical activity and utilisation of healthcare services. Use of the six G’s framework alongside a community centred approach is crucial in developing and implementing culturally sensi-tive interventions for diabetes prevention and management in BAME communities. This could improve their health outcomes and overall wellbeing

Discovery of the Onset of Rapid Accretion by a Dormant Massive Black Hole

Massive black holes are believed to reside at the centres of most galaxies. They can be- come detectable by accretion of matter, either continuously from a large gas reservoir or impulsively from the tidal disruption of a passing star, and conversion of the gravitational energy of the infalling matter to light. Continuous accretion drives Active Galactic Nuclei (AGN), which are known to be variable but have never been observed to turn on or off. Tidal disruption of stars by dormant massive black holes has been inferred indirectly but the on- set of a tidal disruption event has never been observed. Here we report the first discovery of the onset of a relativistic accretion-powered jet in the new extragalactic transient, Swift J164449.3+573451. The behaviour of this new source differs from both theoretical models of tidal disruption events and observations of the jet-dominated AGN known as blazars. These differences may stem from transient effects associated with the onset of a powerful jet. Such an event in the massive black hole at the centre of our Milky Way galaxy could strongly ionize the upper atmosphere of the Earth, if beamed towards us.Comment: Submitted to Nature. 4 pages, 3 figures (main paper). 26 pages, 13 figures (supplementary information

Solid-state synthesis and characterization of σ-Alkane complexes, [Rh(L2)(η2,η2-C7H12)][BArF4] (L2 = bidentate chelating phosphine)

The use of solid/gas and single-crystal to single-crystal synthetic routes is reported for the synthesis and characterization of a number of σ-alkane complexes: [Rh(R2P(CH2)nPR2)(η2,η2-C7H12)][BArF4]; R = Cy, n = 2; R = iPr, n = 2,3; Ar = 3,5-C6H3(CF3)2. These norbornane adducts are formed by simple hydrogenation of the corresponding norbornadiene precursor in the solid state. For R = Cy (n = 2), the resulting complex is remarkably stable (months at 298 K), allowing for full characterization using single-crystal X-ray diffraction. The solid-state structure shows no disorder, and the structural metrics can be accurately determined, while the 1H chemical shifts of the Rh···H–C motif can be determined using solid-state NMR spectroscopy. DFT calculations show that the bonding between the metal fragment and the alkane can be best characterized as a three-center, two-electron interaction, of which σCH → Rh donation is the major component. The other alkane complexes exhibit solid-state 31P NMR data consistent with their formation, but they are now much less persistent at 298 K and ultimately give the corresponding zwitterions in which [BArF4]− coordinates and NBA is lost. The solid-state structures, as determined by X-ray crystallography, for all these [BArF4]− adducts are reported. DFT calculations suggest that the molecular zwitterions within these structures are all significantly more stable than their corresponding σ-alkane cations, suggesting that the solid-state motif has a strong influence on their observed relative stabilities

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2

The influence of postgraduate qualifications on educational identity formation of healthcare professionals

Demand for postgraduate qualifications in medical education can be judged by the increase in providers worldwide over the last two decades. However, research into the impact of such courses on identity formation of healthcare professionals is limited. This study investigates the influence of such programmes on graduates’ educational identities, practices and career progression. Informed by constructivist grounded theory (CGT), semi-structured interviews were conducted with 27 graduates (2008–2012) from one postgraduate programme, who were at different stages in their careers worldwide. The audio data were transcribed and analysed using a CGT approach. Participants enrolled in award-bearing medical education courses for various intrinsic and extrinsic reasons. The findings from this study highlight their development as educators, and educational researchers, leaders and learners, as their self-efficacy in educational practices and engagement in scholarly activities increased. Graduates attributed career progression to the qualification, with many being promoted into senior positions. They also described substantial performance attainments in the workplace. The findings contribute to understanding the complexity and nuances of educational identity formation of healthcare professionals. A qualification in medical education encouraged transformational changes and epistemological development as an educator. Awareness of these findings will inform both those considering enrolment and those supporting them of potential benefits of these programmes