An ongoing case-control study to evaluate the NHS Bowel Cancer Screening Programme

© 2014 Massat et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

3-Methyl-1-butanol production in Escherichia coli: random mutagenesis and two-phase fermentation

Interest in producing biofuels from renewable sources has escalated due to energy and environmental concerns. Recently, the production of higher chain alcohols from 2-keto acid pathways has shown significant progress. In this paper, we demonstrate a mutagenesis approach in developing a strain of Escherichia coli for the production of 3-methyl-1-butanol by leveraging selective pressure toward l-leucine biosynthesis and screening for increased alcohol production. Random mutagenesis and selection with 4-aza-d,l-leucine, a structural analogue to l-leucine, resulted in the development of a new strain of E. coli able to produce 4.4 g/L of 3-methyl-1-butanol. Investigation of the host’s sensitivity to 3-methyl-1-butanol directed development of a two-phase fermentation process in which titers reached 9.5 g/L of 3-methyl-1-butanol with a yield of 0.11 g/g glucose after 60 h

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

Healthy Firms: Constraints to Growth among Private Health Sector Facilities in Ghana and Kenya

Background: Health outcomes in developing countries continue to lag the developed world, and many countries are not on target to meet the Millennium Development Goals. The private health sector provides much of the care in many developing countries (e.g., approximately 50 percent in Sub-Saharan Africa), but private providers are often poorly integrated into the health system. Efforts to improve health systems performance will need to include the private sector and increase its contributions to national health goals. However, the literature on constraints private health care providers face is limited. Methodology/Principal Findings: We analyze data from a survey of private health facilities in Kenya and Ghana to evaluate growth constraints facing private providers. A significant portion of facilities (Ghana: 62 percent; Kenya: 40 percent) report limited access to finance as the most significant barrier they face; only a small minority of facilities report using formal credit institutions to finance day to day operations (Ghana: 6 percent; Kenya: 11 percent). Other important barriers include corruption, crime, limited demand for goods and services, and poor public infrastructure. Most facilities have paper-based rather than electronic systems for patient records (Ghana: 30 percent; Kenya: 22 percent), accounting (Ghana: 45 percent; Kenya: 27 percent), and inventory control (Ghana: 41 percent; Kenya: 24 percent). A majority of clinics in both countries report undertaking activities to improve provider skills and to monitor the level and quality of care they provide. However, only a minority of pharmacies report undertaking such activities

Soft X‐ray and ENA Imaging of the Earth’s Dayside Magnetosphere

The LEXI and SMILE missions will provide soft X‐ray images of the Earth's magnetosheath and cusps after their anticipated launch in 2023 and 2024, respectively. The IBEX mission showed the potential of an Energetic Neutral Atom (ENA) instrument to image dayside magnetosheath and cusps, albeit over the long hours required to raster an image with a single pixel imager. Thus, it is timely to discuss the two imaging techniques and relevant science topics. We simulate soft X‐ray and low‐ENA images that might be observed by a virtual spacecraft during two interesting solar wind scenarios: a southward turning of the interplanetary magnetic field and a sudden enhancement of the solar wind dynamic pressure. We employ the OpenGGCM global magnetohydrodynamics model and a simple exospheric neutral density model for these calculations. Both the magnetosheath and the cusps generate strong soft X‐rays and ENA signals that can be used to extract the locations and motions of the bow shock and magnetopause. Magnetopause erosion corresponds closely to the enhancement of dayside reconnection rate obtained from the OpenGGCM model, indicating that images can be used to understand global‐scale magnetopause reconnection. When dayside imagers are installed with high‐ENA inner‐magnetosphere and FUV/UV aurora imagers, we can trace the solar wind energy flow from the bow shock to the magnetosphere and then to the ionosphere in a self‐standing manner without relying upon other observatories. Soft X‐ray and/or ENA imagers can also unveil the dayside exosphere density structure and its response to space weather

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Investor heterogeneity and the cross-section of U.K. investment trust performance

We use the upper and lower bounds derived by Ferson and Lin (2010) to examine the impact of investor heterogeneity on the performance of U.K. investment trusts relative to alternative linear factor models. We find using the upper bounds that investor heterogeneity has an important impact for nearly all investment trusts. The upper bounds are large in economic terms and significantly different from zero. We find no evidence of any trusts where all investors agree on the sign of performance beyond what we expect by chance. Using the lower bound, we find that trusts with a larger disagreement about trust performance have a weaker relation between the trust premium and past Net Asset Value (NAV) performance

Rhabdovirus Matrix Protein Structures Reveal a Novel Mode of Self-Association

The matrix (M) proteins of rhabdoviruses are multifunctional proteins essential for virus maturation and budding that also regulate the expression of viral and host proteins. We have solved the structures of M from the vesicular stomatitis virus serotype New Jersey (genus: Vesiculovirus) and from Lagos bat virus (genus: Lyssavirus), revealing that both share a common fold despite sharing no identifiable sequence homology. Strikingly, in both structures a stretch of residues from the otherwise-disordered N terminus of a crystallographically adjacent molecule is observed binding to a hydrophobic cavity on the surface of the protein, thereby forming non-covalent linear polymers of M in the crystals. While the overall topology of the interaction is conserved between the two structures, the molecular details of the interactions are completely different. The observed interactions provide a compelling model for the flexible self-assembly of the matrix protein during virion morphogenesis and may also modulate interactions with host proteins

Vesicular Stomatitis Virus Infection Promotes Immune Evasion by Preventing NKG2D-Ligand Surface Expression

Vesicular stomatitis virus (VSV) has recently gained attention for its oncolytic ability in cancer treatment. Initially, we hypothesized that VSV infection could increase immune recognition of cancer cells through induction of the immune stimulatory NKG2D-ligands. Here we show that VSV infection leads to a robust induction of MICA mRNA expression, however the subsequent surface expression is potently hindered. Thus, VSV lines up with human cytomegalovirus (HCMV) and adenovirus, which actively subvert the immune system by negatively affecting NKG2D-ligand surface expression. VSV infection caused an active suppression of NKG2D-ligand surface expression, affecting both endogenous and histone deacetylase (HDAC)-inhibitor induced MICA, MICB and ULBP-2 expression. The classical immune escape mechanism of VSV (i.e., the M protein blockade of nucleocytoplasmic mRNA transport) was not involved, as the VSV mutant strain, VSVΔM51, which possess a defective M protein, prevented MICA surface expression similarly to wild-type VSV. The VSV mediated down modulation of NKG2D-ligand expression did not involve apoptosis. Constitutive expression of MICA bypassed the escape mechanism, suggesting that VSV affect NKG2D-ligand expression at an early post-transcriptional level. Our results show that VSV possess an escape mechanism, which could affect the immune recognition of VSV infected cancer cells. This may also have implications for immune recognition of cancer cells after combined treatment with VSV and chemotherapeutic drugs

Inferring Ecological Processes from Taxonomic, Phylogenetic and Functional Trait β-Diversity

Understanding the influences of dispersal limitation and environmental filtering on the structure of ecological communities is a major challenge in ecology. Insight may be gained by combining phylogenetic, functional and taxonomic data to characterize spatial turnover in community structure (β-diversity). We develop a framework that allows rigorous inference of the strengths of dispersal limitation and environmental filtering by combining these three types of β-diversity. Our framework provides model-generated expectations for patterns of taxonomic, phylogenetic and functional β-diversity across biologically relevant combinations of dispersal limitation and environmental filtering. After developing the framework we compared the model-generated expectations to the commonly used “intuitive” expectation that the variance explained by the environment or by space will, respectively, increase monotonically with the strength of environmental filtering or dispersal limitation. The model-generated expectations strongly departed from these intuitive expectations: the variance explained by the environment or by space was often a unimodal function of the strength of environmental filtering or dispersal limitation, respectively. Therefore, although it is commonly done in the literature, one cannot assume that the strength of an underlying process is a monotonic function of explained variance. To infer the strength of underlying processes, one must instead compare explained variances to model-generated expectations. Our framework provides these expectations. We show that by combining the three types of β-diversity with model-generated expectations our framework is able to provide rigorous inferences of the relative and absolute strengths of dispersal limitation and environmental filtering. Phylogenetic, functional and taxonomic β-diversity can therefore be used simultaneously to infer processes by comparing their empirical patterns to the expectations generated by frameworks similar to the one developed here