Census politics in deeply divided societies

Population censuses in societies that are deeply divided along ethnic, religious or linguistic lines can be sensitive affairs – particularly where political settlements seek to maintain peace through the proportional sharing of power between groups. This brief sets out some key findings from a research project investigating the relationship between census politics and the design of political institutions in Bosnia and Herzegovina, Kenya, Lebanon and Northern Ireland

Willingness to participate in future HIV prevention studies among gay and bisexual men in Scotland, UK: a challenge for intervention trials

This article examines willingness to participate in future HIV prevention research among gay and bisexual men in Scotland, UK. Anonymous, self-complete questionnaires and Orasure Gäó oral fluid samples were collected in commercial gay venues. 1,320 men were eligible for inclusion. 78.2% reported willingness to participate in future HIV prevention research; 64.6% for an HIV vaccine, 57.4% for a behaviour change study, and 53.0% for a rectal microbicide. In multivariate analysis, for HIV vaccine research, greater age, minority ethnicity, and not providing an oral fluid sample were associated with lower willingness; heterosexual orientation and not providing an oral fluid sample were for microbicides; higher education and greater HIV treatment optimism were for behaviour change. STI testing remained associated with being more willing to participate in microbicide research and frequent gay scene use remained associated with being more willing to participate in behaviour change research. Having an STI in the past 12 months remained significantly associated with being willing to participate in all three study types. There were no associations between sexual risk behaviour and willingness. Although most men expressed willingness to participate in future research, recruitment of high-risk men, who have the potential to benefit most, is likely to be more challenging

Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

The structure of an NDR/LATS kinase – mob complex reveals a novel kinase-coactivator system and substrate docking mechanism.

Eukaryotic cells commonly use protein kinases in signaling systems that relay information and control a wide range of processes. These enzymes have a fundamentally similar structure, but achieve functional diversity through variable regions that determine how the catalytic core is activated and recruited to phosphorylation targets. "Hippo" pathways are ancient protein kinase signaling systems that control cell proliferation and morphogenesis; the NDR/LATS family protein kinases, which associate with "Mob" coactivator proteins, are central but incompletely understood components of these pathways. Here we describe the crystal structure of budding yeast Cbk1-Mob2, to our knowledge the first of an NDR/LATS kinase-Mob complex. It shows a novel coactivator-organized activation region that may be unique to NDR/LATS kinases, in which a key regulatory motif apparently shifts from an inactive binding mode to an active one upon phosphorylation. We also provide a structural basis for a substrate docking mechanism previously unknown in AGC family kinases, and show that docking interaction provides robustness to Cbk1's regulation of its two known in vivo substrates. Co-evolution of docking motifs and phosphorylation consensus sites strongly indicates that a protein is an in vivo regulatory target of this hippo pathway, and predicts a new group of high-confidence Cbk1 substrates that function at sites of cytokinesis and cell growth. Moreover, docking peptides arise in unstructured regions of proteins that are probably already kinase substrates, suggesting a broad sequential model for adaptive acquisition of kinase docking in rapidly evolving intrinsically disordered polypeptides

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis

1427 E 60TH ST, CHICAGO, USA, IL, 60637-295

Use of prasugrel vs clopidogrel and outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention in contemporary clinical practice: Results from the PROMETHEUS study

Background and objectivesWe sought to determine the frequency of use and association between prasugrel and outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) in clinical practice

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Marginalization of end-use technologies in energy innovation for climate protection

Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV