P104 White coat hypertension is associated with increased small vessel disease in the brain

Objective: Small vessel disease, measured by brain white matter hyperintensity (WMH), is associated with increased stroke risk and cognitive impairment. This study aimed to explore the relationship between WMH on computerised tomography (CT) and white coat hypertension (WCH) in patients with recent transient ischaemic attack (TIA) or lacunar stroke (LS). Methods: Ninety-six patients recruited for the ASIST trial (Arterial Stiffness in Lacunar Stroke and TIA) underwent measurement of clinic blood pressure (BP) and ambulatory BP monitoring (APBM) within two weeks of TIA or LS. Patients were grouped by BP phenotypes. Twenty-three patients had normotension (clinic BP 140/90 mmHg and day-time ABPM <135/85 mmHg). CT brain images were scored for WMH using the four-point Fazekas visual rating scale. Patients were grouped into no-mild WMH (scores 0–1) or moderate-severe (scores 2–3) groups. The relationship between BP and WMH was explored with chi-square and logistic regression accounting for known cardiovascular risk factors (age, gender, smoking, diabetes and hyperlipidaemia). Results: 44% of WCH patients had moderate-severe WMH compared to 17% of normotensives (p = 0.047). Logistical regression incorporating WCH as the independent factor and cardiovascular risk factors as independent variables showed WCH to be the only independent significant factor contributing to WMH (p = 0.024). Conclusion: Patients with WCH were more likely to have moderate-severe WMH on CT brain than normotensives. WCH was associated with increased WMH, independent of other cardiovascular risk factors. This study suggests that WCH is associated with increased small vessel disease in the brain and may benefit from treatment

Black hole uniqueness theorems and new thermodynamic identities in eleven dimensional supergravity

We consider stationary, non-extremal black holes in 11-dimensional supergravity having isometry group $\mathbb{R} \times U(1)^8$. We prove that such a black hole is uniquely specified by its angular momenta, its electric charges associated with the various 7-cycles in the manifold, together with certain moduli and vector valued winding numbers characterizing the topological nature of the spacetime and group action. We furthermore establish interesting, non-trivial, relations between the thermodynamic quantities associated with the black hole. These relations are shown to be a consequence of the hidden $E_{8(+8)}$ symmetry in this sector of the solution space, and are distinct from the usual "Smarr-type" formulas that can be derived from the first law of black hole mechanics. We also derive the "physical process" version of this first law applicable to a general stationary black hole spacetime without any symmetry assumptions other than stationarity, allowing in particular arbitrary horizon topologies. The work terms in the first law exhibit the topology of the horizon via the intersection numbers between cycles of various dimensions.Comment: 50pp, 3 figures, v2: references added, correction in appendix B, conclusions added, v3: reference section edited, typos removed, minor changes in appendix

Uniqueness Theorem for Static Black Hole Solutions of sigma-models in Higher Dimensions

We prove the uniqueness theorem for self-gravitating non-linear sigma-models in higher dimensional spacetime. Applying the positive mass theorem we show that Schwarzschild-Tagherlini spacetime is the only maximally extended, static asymptotically flat solution with non-rotating regular event horizon with a constant mapping.Comment: 5 peges, Revtex, to be published in Class.Quantum Gra

Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

Uniqueness Theorem of Static Degenerate and Non-degenerate Charged Black Holes in Higher Dimensions

We prove the uniqueness theorem for static higher dimensional charged black holes spacetime containing an asymptotically flat spacelike hypersurface with compact interior and with both degenerate and non-degenerate components of the event horizon.Comment: 9 pages, RevTex, to be published in Phys.Rev.D1

Extrema of Mass, First Law of Black Hole Mechanics and Staticity Theorem in Einstein-Maxwell-axion-dilaton Gravity

Using the ADM formulation of the Einstein-Maxwell axion-dilaton gravity we derived the formulas for the variation of mass and other asymptotic conserved quantities in the theory under consideration. Generalizing this kind of reasoning to the initial dota for the manifold with an interior boundary we got the generalized first law of black hole mechanics. We consider an asymptotically flat solution to the Einstein-Maxwell axion-dilaton gravity describing a black hole with a Killing vector field timelike at infinity, the horizon of which comprises a bifurcate Killing horizon with a bifurcate surface. Supposing that the Killing vector field is asymptotically orthogonal to the static hypersurface with boundary S and compact interior, we find that the solution is static in the exterior world, when the timelike vector field is normal to the horizon and has vanishing electric and axion- electric fields on static slices.Comment: 17 pages, Revtex, a few comments (introduction) and references adde

New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90

Act1 is an essential adaptor molecule in IL-17-mediated signaling and is recruited to the IL-17 receptor upon IL-17 stimulation. Here, we report that Act1 is a client protein of the molecular chaperone, Hsp90. The Act1 variant (D10N) linked to psoriasis susceptibility is defective in its interaction with Hsp90, resulting in a global loss of Act1 function. Act1-/- mice modeled the mechanistic link between Act1 loss of function and psoriasis susceptibility. Although Act1 is necessary for IL-17-mediated inflammation, Act1-/- mice exhibited a hyper TH17 response and developed spontaneous IL-22-dependent skin inflammation. In the absence of IL-17-signaling, IL-22 is the main contributor to skin inflammation, providing a molecular mechanism for the association of Act1 (D10N) with psoriasis susceptibility

Uniqueness and non-uniqueness of static vacuum black holes in higher dimensions

We prove the uniqueness theorem for asymptotically flat static vacuum black hole solutions in higher dimensional space-times. We also construct infinitely many non-asymptotically flat regular static black holes on the same spacetime manifold with the same spherical topology.Comment: to appear in Progress of Theoretical Physics Supplement No. 14

To what extent is behaviour a problem in English schools?:Exploring the scale and prevalence of deficits in classroom climate

The working atmosphere in the classroom is an important variable in the process of education in schools, with several studies suggesting that classroom climate is an important influence on pupil attainment. There are wide differences in the extent to which classroom climate is considered to be a problem in English schools. Some ‘official’ reports suggest that behaviour in schools is ‘satisfactory or better’ in the vast majority of schools; other sources have pointed to behaviour being a serious and widespread problem. The paper details four studies conducted over the past decade which aimed to explore these disparities. The aim of the research was to gain a more accurate insight into the extent to which deficits in classroom climate limit educational attainment and equality of educational opportunity in English schools. The findings question the suggestion that behaviour is satisfactory or better in 99.7% of English schools and the concluding section suggests ways in which deficits in classroom climate might be addressed. Although the study is limited to classrooms in England, OECD studies suggest that deficits in the working atmosphere in classrooms occur in many countries. The study therefore has potential relevance for education systems in other countries