Contacts of underserved tuberculosis patients have higher odds of TB disease in North West England: a cohort study

OBJECTIVE: To investigate the association between patients' social risk factors and the risk of tuberculous infection and TB disease among their contacts in England. DESIGN: This was a cohort study of all TB cases from North West England diagnosed between 27 March 2012 and 28 June 2016. The social risk factors of TB cases were evaluated to estimate their need for enhanced case management (ECM), from 0 (standard of care) to 3 (intensive social support). RESULTS: A total of 2139 cases and their 10 019 contacts met the eligibility criteria. Being a contact of a patient with smear-positive TB with high ECM or being of Black Caribbean ethnicity was independently associated with greater odds of active TB disease (smear-positive vs. smear-negative, OR 5.3, 95%CI 3.2–8.7; ECM-3 vs. ECM-0, OR 2.2, 95%CI 1.01–5.0; Black Caribbean vs. White, OR 7.4, 95%CI 2.1–25). Being a contact of a patient with smear-positive TB or of Black Caribbean ethnicity was also independently associated with greater odds of tuberculous infection (smear-positive vs. smear-negative, OR 5.3, 95%CI 3.8–7.3; and Black Caribbean vs. White, OR 6.7, 95%CI 2.0–25). CONCLUSIONS: The social complexity and ethnicity of patients were associated with tuberculous infection and TB disease in their contacts

Legionella and risk management in hospitals - A bibliographic research methodology for people responsible for built environments and facility management

An ongoing research project investigates the roles and duties of persons responsible for the built environment with respect to risk management of water systems and Legionella prevention from a facility management’s perspective. Our literature review provides an approach for selecting and analysing abstracts of initially 177 journal articles, subjected to certain topic-specific inclusion and exclusion criteria. Different decision strategies of either logic ‘yes/no’, Boolean operators ‘OR’ or ‘AND’ and decisions for single counts or cumulative counts of the identified three principal keywords ‘Legionella’, ‘hospital’ and ‘water’, were completed. A final list of ten principal reference articles from 29 journals was compiled. It suggests that the interconnected perspective of water systems, Legionella and hospitals seems to be underrepresented in the field of the built environment and facility management. The term ‘stakeholder’, which would refer to decision-makers, was not found more than once. Our result is a useful summary of established sources of information on environmental Legionella research. The results can be helpful for those new to the topic

A Pan-African Convection-Permitting Regional Climate Simulation with the Met Office Unified Model: CP4-Africa

This is the final version. Available on open access from the American Meteorological Society via the DOI in this recordA convection-permitting multiyear regional climate simulation using the Met Office Unified Model has been run for the first time on an Africa-wide domain. The model has been run as part of the Future Climate for Africa (FCFA) Improving Model Processes for African Climate (IMPALA) project, and its configuration, domain, and forcing data are described here in detail. The model [Pan-African Convection-Permitting Regional Climate Simulation with the Met Office UM (CP4-Africa)] uses a 4.5-km horizontal grid spacing at the equator and is run without a convection parameterization, nested within a global atmospheric model driven by observations at the sea surface, which does include a convection scheme. An additional regional simulation, with identical resolution and physical parameterizations to the global model, but with the domain, land surface, and aerosol climatologies of CP4-Africa, has been run to aid in the understanding of the differences between the CP4-Africa and global model, in particular to isolate the impact of the convection parameterization and resolution. The effect of enforcing moisture conservation in CP4-Africa is described and its impact on reducing extreme precipitation values is assessed. Preliminary results from the first five years of the CP4-Africa simulation show substantial improvements in JJA average rainfall compared to the parameterized convection models, with most notably a reduction in the persistent dry bias in West Africa, giving an indication of the benefits to be gained from running a convection-permitting simulation over the whole African continent.Natural Environment Research Council (NERC

Learning from a Rapid Health Impact Assessment of a proposed maternity service reconfiguration in the English NHS

<p>Abstract</p> <p>Background</p> <p>Within many parts of the country, the NHS is undertaking reconfiguration of services. Such proposals can prove a tipping point and provoke public protest, often with significant involvement of local and national politicians. We undertook a rapid Health Impact Assessment (HIA) of a proposed reconfiguration of maternity services in Huddersfield and Halifax in England. The aim of the HIA was to help the PCT Boards to assess the reconfiguration's possible consequences on access to maternity services, and maternal and infant health outcomes across different socio-economic groups in Kirklees. We report on the findings of the HIA and the usefulness of the process to decision making.</p> <p>Methods</p> <p>This HIA used routine maternity data for 2004–2005 in Huddersfield, in addition to published evidence. Standard HIA techniques were used.</p> <p>Results</p> <p>We re-highlighted the socio economic differences in smoking status at booking and quitting during pregnancy. We focused on the key concerns of the public, that of adverse obstetric events on a Midwife Led Unit (MLU) with distant obstetric cover. We estimate that twenty percent of women giving birth in a MLU may require urgent transfer to obstetric care during labour. There were no significant socio economic differences. Much of the risk can be mitigated though robust risk management policies. Additional travelling distances and costs could affect lower socio-economic groups the greatest because of lower car ownership and geographical location in relation to the units. There is potential that with improved community antenatal and post natal care, population outcomes could improve significantly, the available evidence supports this view.</p> <p>Conclusion</p> <p>Available evidence suggests that maternity reconfiguration towards enhanced community care could have many potential benefits but carries risk. Investment is needed to realise the former and mitigate the latter.</p> <p>The usefulness of this Health Impact Assessment may have been impeded by its timing, and the politically charged environment of the proposals. Nonetheless, the methods used are readily applicable to assess the impact of other service reconfigurations. The analysis was simple, not time intensive and used routinely available data. Careful consideration should be given to both the timing and the political context in which an analysis is undertaken.</p

Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels

Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K+ channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the “helix-bundle crossing”. However, in the inwardly rectifying (Kir) potassium channel family, the role of this “hinge” residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper “hinge” residues are in close contact with the base of the pore α-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the “lower” gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue

The Cosmology of Composite Inelastic Dark Matter

Composite dark matter is a natural setting for implementing inelastic dark matter - the O(100 keV) mass splitting arises from spin-spin interactions of constituent fermions. In models where the constituents are charged under an axial U(1) gauge symmetry that also couples to the Standard Model quarks, dark matter scatters inelastically off Standard Model nuclei and can explain the DAMA/LIBRA annual modulation signal. This article describes the early Universe cosmology of a minimal implementation of a composite inelastic dark matter model where the dark matter is a meson composed of a light and a heavy quark. The synthesis of the constituent quarks into dark mesons and baryons results in several qualitatively different configurations of the resulting dark matter hadrons depending on the relative mass scales in the system.Comment: 31 pages, 4 figures; references added, typos correcte

Multiway modeling and analysis in stem cell systems biology

<p>Abstract</p> <p>Background</p> <p>Systems biology refers to multidisciplinary approaches designed to uncover emergent properties of biological systems. Stem cells are an attractive target for this analysis, due to their broad therapeutic potential. A central theme of systems biology is the use of computational modeling to reconstruct complex systems from a wealth of reductionist, molecular data (e.g., gene/protein expression, signal transduction activity, metabolic activity, etc.). A number of deterministic, probabilistic, and statistical learning models are used to understand sophisticated cellular behaviors such as protein expression during cellular differentiation and the activity of signaling networks. However, many of these models are bimodal i.e., they only consider row-column relationships. In contrast, multiway modeling techniques (also known as tensor models) can analyze multimodal data, which capture much more information about complex behaviors such as cell differentiation. In particular, tensors can be very powerful tools for modeling the dynamic activity of biological networks over time. Here, we review the application of systems biology to stem cells and illustrate application of tensor analysis to model collagen-induced osteogenic differentiation of human mesenchymal stem cells.</p> <p>Results</p> <p>We applied Tucker1, Tucker3, and Parallel Factor Analysis (PARAFAC) models to identify protein/gene expression patterns during extracellular matrix-induced osteogenic differentiation of human mesenchymal stem cells. In one case, we organized our data into a tensor of type protein/gene locus link × gene ontology category × osteogenic stimulant, and found that our cells expressed two distinct, stimulus-dependent sets of functionally related genes as they underwent osteogenic differentiation. In a second case, we organized DNA microarray data in a three-way tensor of gene IDs × osteogenic stimulus × replicates, and found that application of tensile strain to a collagen I substrate accelerated the osteogenic differentiation induced by a static collagen I substrate.</p> <p>Conclusion</p> <p>Our results suggest gene- and protein-level models whereby stem cells undergo transdifferentiation to osteoblasts, and lay the foundation for mechanistic, hypothesis-driven studies. Our analysis methods are applicable to a wide range of stem cell differentiation models.</p

Impact of Splenectomy on Thrombocytopenia, Chemotherapy, and Survival in Patients with Unresectable Pancreatic Cancer

Patients with unresectable pancreatic cancer (PDAC) or endocrine tumors (PET) often develop splenic vein thrombosis, hypersplenism, and thrombocytopenia which limits the administration of chemotherapy. From 2001 to 2009, 15 patients with recurrent or unresectable PDAC or PET underwent splenectomy for hypersplenism and thrombocytopenia. The clinical variables of this group of patients were analyzed. The overall survival of patients with PDAC was compared to historical controls. Of the 15 total patients, 13 (87%) had PDAC and 2 (13%) had PET. All tumors were either locally advanced (n = 6, 40%) or metastatic (n = 9, 60%). The platelet counts significantly increased after splenectomy (p &lt; 0.01). All patients were able to resume chemotherapy within a median of 11.5 days (range 6–27). The patients with PDAC had a median survival of 20 months (range 4–67) from the time of diagnosis and 10.6 months (range 0.6–39.8) from the time of splenectomy. Splenectomy for patients with unresectable PDAC or PET who developed hypersplenism and thrombocytopenia that limited the administration of chemotherapy, significantly increased platelet counts, and led to resumption of treatment in all patients. Patients with PDAC had better disease-specific survival as compared to historical controls

Environmental and diagenetic controls on the morphology and calcification of the Ediacaran metazoan Cloudina

Abstract Cloudina is a globally distributed Ediacaran metazoan, with a tubular, funnel-in-funnel form built of thin laminae (ca. 1–10 μm). To what degree local environmental controlled morphology, and whether early diagenesis controlled the degree of calcification of Cloudina, is debated. Here we test these hypotheses by considering assemblages from four, coeval localities from the Upper Omkyk Member, Nama Group, Namibia, from inner ramp to mid-ramp reef across the Zaris Subbasin. We show that sinuosity of the Cloudina tube is variable between sites, as is the relative thickness of the tube wall, suggesting these features were environmentally controlled. Walls are thickest in high-energy reef settings, and thinnest in the low-energy, inner ramp. While local diagenesis controls preservation, all diagenetic expressions are consistent with the presence of weakly calcified, organic-rich laminae, and lamina thicknesses are broadly constant. Finally, internal ‘cements’ within Cloudina are found in all sites, and pre-date skeletal breakage, transport, as well as syn-sedimentary botryoidal cement precipitation. Best preservation shows these to be formed by fine, pseudomorphed aragonitic acicular crystals. Sr concentrations and Mg/Ca show no statistically significant differences between internal Cloudina cements and botryoidal cements, but we infer all internal cements to have precipitated when Cloudina was still in-situ and added considerable mechanical strength, but may have formed post-mortem or in abandoned parts of the skeleton