Clinical surveillance of thrombotic microangiopathies in Scotland, 2003-2005

The prevalence, incidence and outcomes of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopaenic purpura (TTP) are not well established in adults or children from prospective studies. We sought to identify both outcomes and current management strategies using prospective, national surveillance of HUS and TTP, from 2003 to 2005 inclusive. We also investigated the links between these disorders and factors implicated in the aetiology of HUS and TTP including infections, chemotherapy, and immunosuppression. Most cases of HUS were caused by verocytotoxin-producing Escherichia coli (VTEC), of which serotype O157 predominated, although other serotypes were identified. The list of predisposing factors for TTP was more varied although use of immunosuppressive agents and severe sepsis, were the most frequent precipitants. The study demonstrates that while differentiating between HUS and TTP is sometimes difficult, in most cases the two syndromes have quite different predisposing factors and clinical parameters, enabling clinical and epidemiological profiling for these disorders

Violence against female sex workers in Karnataka state, south India: impact on health, and reductions in violence following an intervention program.

ABSTRACT: BACKGROUND: Violence against female sex workers (FSWs) can impede HIV prevention efforts and contravenes their human rights. We developed a multi-layered violence intervention targeting policy makers, secondary stakeholders (police, lawyers, media), and primary stakeholders (FSWs), as part of wider HIV prevention programming involving >60,000 FSWs in Karnataka state. This study examined if violence against FSWs is associated with reduced condom use and increased STI/HIV risk, and if addressing violence against FSWs within a large-scale HIV prevention program can reduce levels of violence against them. METHODS: FSWs were randomly selected to participate in polling booth surveys (PBS 2006-2008; short behavioural questionnaires administered anonymously) and integrated behavioural-biological assessments (IBBAs 2005-2009; administered face-to-face). RESULTS: 3,852 FSWs participated in the IBBAs and 7,638 FSWs participated in the PBS. Overall, 11.0% of FSWs in the IBBAs and 26.4% of FSWs in the PBS reported being beaten or raped in the past year. FSWs who reported violence in the past year were significantly less likely to report condom use with clients (zero unprotected sex acts in previous month, 55.4% vs. 75.5%, adjusted odds ratio (AOR) 0.4, 95% confidence interval (CI) 0.3 to 0.5, p < 0.001); to have accessed the HIV intervention program (ever contacted by peer educator, 84.9% vs. 89.6%, AOR 0.7, 95% CI 0.4 to 1.0, p = 0.04); or to have ever visited the project sexual health clinic (59.0% vs. 68.1%, AOR 0.7, 95% CI 0.6 to 1.0, p = 0.02); and were significantly more likely to be infected with gonorrhea (5.0% vs. 2.6%, AOR 1.9, 95% CI 1.1 to 3.3, p = 0.02). By the follow-up surveys, significant reductions were seen in the proportions of FSWs reporting violence compared with baseline (IBBA 13.0% vs. 9.0%, AOR 0.7, 95% CI 0.5 to 0.9 p = 0.01; PBS 27.3% vs. 18.9%, crude OR 0.5, 95% CI 0.4 to 0.5, p < 0.001). CONCLUSIONS: This program demonstrates that a structural approach to addressing violence can be effectively delivered at scale. Addressing violence against FSWs is important for the success of HIV prevention programs, and for protecting their basic human rights

Sites of Biosynthesis of Outer and Inner Membrane Proteins of Neurospora crassa Mitochondria

Outer and inner membranes of Neurospora crassa mitochondria were separated by the combined swelling, shrinking, sonication procedure. Membranes were characterized by electron microscopy and by marker enzyme activities. A red carotenoid pigment was found to be concentrated in the outer membrane. The inner mitochondrial membrane was resolved into about 20 protein bands on polyacrylamide gel electrophoresis, whereas the outer membrane shows essentially one single protein band. Only negligible incorporation of radioactive amino acids occurs into outer membrane when isolated mitochondria are synthesizing polypeptide chains. In agreement with this observation labeling of outer membrane protein is almost entirely blocked, when whole Neurospora cells are incubated with radioactive amino acids in the presence of cycloheximide, an inhibitor of cytoplasmic protein synthesis. Finally, the essential electrophoretic protein band from outer membrane does not become labeled when mitochondria are incubated with radioactive amino acids either in vitro or in vivo in the presence of cycloheximide. It is concluded that the vast majority, if not all, of the outer membrane protein is synthesized by the cytoplasmic system and that polypeptide chains formed by the mitochondrial ribosomes are integrated into the inner mitochondrial membrane

Science and Film-making

The essay reviews the literature, mostly historical, on the relationship between science and film-making, with a focus on the science documentary. It then discusses the circumstances of the emergence of the wildlife making-of documentary genre. The thesis examined here is that since the early days of cinema, film-making has evolved from being subordinate to science, to being an equal partner in the production of knowledge, controlled by non-scientists

Notes on the Third Law of Thermodynamics.I

We analyze some aspects of the third law of thermodynamics. We first review both the entropic version (N) and the unattainability version (U) and the relation occurring between them. Then, we heuristically interpret (N) as a continuity boundary condition for thermodynamics at the boundary T=0 of the thermodynamic domain. On a rigorous mathematical footing, we discuss the third law both in Carath\'eodory's approach and in Gibbs' one. Carath\'eodory's approach is fundamental in order to understand the nature of the surface T=0. In fact, in this approach, under suitable mathematical conditions, T=0 appears as a leaf of the foliation of the thermodynamic manifold associated with the non-singular integrable Pfaffian form $\delta Q_{rev}$. Being a leaf, it cannot intersect any other leaf $S=$ const. of the foliation. We show that (N) is equivalent to the requirement that T=0 is a leaf. In Gibbs' approach, the peculiar nature of T=0 appears to be less evident because the existence of the entropy is a postulate; nevertheless, it is still possible to conclude that the lowest value of the entropy has to belong to the boundary of the convex set where the function is defined.Comment: 29 pages, 2 figures; RevTex fil

The Importance of Audit Firm Characteristics and the Drivers of Auditor Change in UK Listed Companies

This paper explores the importance of audit firm characteristics and the factors motivating auditor change based on questionnaire responses from 210 listed UK companies (a response rate of 70%). Twenty-nine potentially desirable auditor characteristics are identified from the extant literature and their importance elicited. Exploratory factor analysis reduces these variables to eight uncorrelated underlying dimensions: reputation/quality; acceptability to third parties; value for money; ability to provide non-audit services; small audit firm; specialist industry knowledge; non-Big Six large audit firm; and geographical proximity. Insights into the nature of 'the Big Six factor' emerge. Two thirds of companies had recently considered changing auditors; the main reasons cited being audit fee level, dissatisfaction with audit quality and changes in top management. Of those companies that considered change, 73% did not actually do so, the main reasons cited being fee reduction by the incumbent and avoidance of disruption. Thus audit fee levels are both a key precipitator of change and a key factor in retaining the status quo

Functional and Biogenetical Heterogeneity of the Inner Membrane of Rat-Liver Mitochondria

Rat liver mitochondria were fragmented by a combined technique of swelling, shrinking, and sonication. Fragments of inner membrane were separated by density gradient centrifugation. They differed in several respects: electronmicroscopic appearance, phospholipid and cytochrome contents, electrophoretic behaviour of proteins and enzymatic activities. Three types of inner membrane fractions were isolated. The first type is characterized by a high activity of metal chelatase, low activities of succinate-cytochrome c reductase and of glycerolphosphate dehydrogenase, as well as by a high phospholipid content and low contents of cytochromes aa3 and b. The second type displays maximal activities of glycerolphosphate dehydrogenase and metal chelatase, but contains relatively little cytochromes and has low succinate-cytochrome c reductase activity. The third type exhibits highest succinate-cytochrome c reductase activity, a high metal chelatase activity and highest cytochrome contents. However, this fraction was low in both glycerolphosphate dehydrogenase activity and phospholipid content. This fraction was also richest in the following enzyme activities: cytochrome oxidase, oligomycin-sensitive ATPase, proline oxidase, 3-hydroxybutyrate dehydrogenase and rotenone-sensitive NADH-cytochrome c reductase. Amino acid incorporation in vitro and in vivo in the presence of cycloheximide occurs predominantly into inner membrane fractions from the second type. These data suggest that the inner membrane is composed of differently organized parts, and that polypeptides synthesized by mitochondrial ribosomes are integrated into specific parts of the inner membrane

Observation of the Leggett-Rice effect in a unitary Fermi gas

We observe that the diffusive spin current in a strongly interacting degenerate Fermi gas of $^{40}$K precesses about the local magnetization. As predicted by Leggett and Rice, precession is observed both in the Ramsey phase of a spin-echo sequence, and in the nonlinearity of the magnetization decay. At unitarity, we measure a Leggett-Rice parameter $\gamma = 1.08(9)$ and a bare transverse spin diffusivity $D_0^\perp = 2.3(4)\,\hbar/m$ for a normal-state gas initialized with full polarization and at one fifth of the Fermi temperature, where $m$ is the atomic mass. One might expect $\gamma = 0$ at unitarity, where two-body scattering is purely dissipative. We observe $\gamma \rightarrow 0$ as temperature is increased towards the Fermi temperature, consistent with calculations that show the degenerate Fermi sea restores a non-zero $\gamma$. Tuning the scattering length $a$, we find that a sign change in $\gamma$ occurs in the range $0 < (k_F a)^{-1} \lesssim 1.3$, where $k_F$ is the Fermi momentum. We discuss how $\gamma$ reveals the effective interaction strength of the gas, such that the sign change in $\gamma$ indicates a switching of branch, between a repulsive and an attractive Fermi gas.Comment: 9 pages, 5 figures; Changed to the more conventional kF=(3 pi^2 n)^1/3, instead of the polarized definition we used in v

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults. METHODS: HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay. RESULTS: 47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells. CONCLUSION: H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR201105000289276