Influence of Ebola on tuberculosis case finding and treatment outcomes in Liberia.

Setting: National Leprosy and Tuberculosis (TB) Control Programme, Liberia. Objectives: To assess TB case finding, including human immunodeficiency virus (HIV) associated interventions and treatment outcomes, before (January 2013-March 2014), during (April 2014-June 2015) and after (July-December 2015) the Ebola virus disease outbreak. Design: A cross-sectional study and retrospective cohort analysis of outcomes. Results: The mean quarterly numbers of individuals with presumptive TB and the proportion diagnosed as smear-positive were: pre-Ebola (n = 7032, 12%), Ebola (n = 6147, 10%) and post-Ebola (n = 6795, 8%). For all forms of TB, stratified by category and age group, there was a non-significant decrease in the number of cases from the pre-Ebola to the Ebola and post-Ebola periods. There were significant decreases in numbers of cases with smear-positive pulmonary TB (PTB) from the pre-Ebola period (n = 855), to the Ebola (n = 640, P < 0.001) and post-Ebola (n = 568, P < 0.001) periods. The proportions of patients tested for HIV, found to be HIV-positive and started on antiretroviral therapy decreased as follows: pre-Ebola (respectively 72%, 15% and 34%), Ebola (69%, 14% and 30%) and post-Ebola (68%, 12% and 26%). Treatment success rates among TB patients were: 80% pre-Ebola, 69% Ebola (P < 0.001) and 73% post-Ebola (P < 0.001). Loss to follow-up was the main contributing adverse outcome. Conclusion: The principal negative effects of Ebola were the significant decreases in diagnoses of smear-positive PTB, the declines in HIV testing and antiretroviral therapy uptake and poor treatment success. Ways to prevent these adverse effects from recurring in the event of another Ebola outbreak need to be found

Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies

Background: The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention. Methods and Findings: To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, p < 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both p < 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both p < 0.001), high-density lipoprotein (correlation coefficient 0.16 and ?0.14, respectively; both p < 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both p < 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, p = 0.001) and lipoprotein(a) (correlation coefficient ?0.11, p < 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect. Conclusions: In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of APOE genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE

Effect of spirometry on intra-thoracic pressures

Due to the high intra-thoracic pressures associated with forced vital capacity manoeuvres, spirometry is contraindicated for vulnerable patients. However, the typical pressure response to spirometry has not been reported. Eight healthy, recreationally-active men performed spirometry while oesophageal pressure was recorded using a latex balloon-tipped catheter. Peak oesophageal pressure during inspiration was - 47 ± 9 cmH O (37 ± 10% of maximal inspiratory pressure), while peak oesophageal pressure during forced expiration was 102 ± 34 cmH O (75 ± 17% of maximal expiratory pressure). The deleterious consequences of spirometry might be associated with intra-thoracic pressures that approach maximal values during forced expiration

You turn me cold: evidence for temperature contagion

Introduction During social interactions, our own physiological responses influence those of others. Synchronization of physiological (and behavioural) responses can facilitate emotional understanding and group coherence through inter-subjectivity. Here we investigate if observing cues indicating a change in another's body temperature results in a corresponding temperature change in the observer. Methods Thirty-six healthy participants (age; 22.9±3.1 yrs) each observed, then rated, eight purpose-made videos (3 min duration) that depicted actors with either their right or left hand in visibly warm (warm videos) or cold water (cold videos). Four control videos with the actors' hand in front of the water were also shown. Temperature of participant observers' right and left hands was concurrently measured using a thermistor within a Wheatstone bridge with a theoretical temperature sensitivity of <0.0001°C. Temperature data were analysed in a repeated measures ANOVA (temperature × actor's hand × observer's hand). Results Participants rated the videos showing hands immersed in cold water as being significantly cooler than hands immersed in warm water, F(1,34) = 256.67, p0.1). There was however no evidence of left-right mirroring of these temperature effects p>0.1). Sensitivity to temperature contagion was also predicted by inter-individual differences in self-report empathy. Conclusions We illustrate physiological contagion of temperature in healthy individuals, suggesting that empathetic understanding for primary low-level physiological challenges (as well as more complex emotions) are grounded in somatic simulation

Thermoelastic properties of magnesiowustite, (Mg1-xFex)O: determination of the Anderson-Gruneisen parameter by time-of-flight neutron powder diffraction at simultaneous high pressures and temperatures

The ability to perform neutron diffraction studies at simultaneous high pressures and high temperatures is a relatively recent development. The suitability of this technique for determining P-V-T equations of state has been investigated by measuring the lattice parameters of Mg1-xFexO ( x = 0.2, 0.3, 0.4), in the range P < 10.3 GPa and 300 < T < 986 K, by time-of-flight neutron powder diffraction. Pressures were determined using metallic Fe as a marker and temperatures were measured by neutron absorption resonance radiography. Within the resolution of the experiment, no evidence was found for any change in the temperature derivative of the isothermal incompressibility, partial derivative K-T/partial derivative T, with composition. By assuming that the equation-of-state parameters either varied linearly or were invariant with composition, the 60 measured state points were fitted simultaneously to a P-V-T-x equation of state, leading to values of partial derivative K-T/partial derivative T = -0.024 (9) GPa K-1 and of the isothermal Anderson-Gruneisen parameter delta(T) = 4.0 (16) at 300 K. Two designs of simultaneous high-P/T cell were employed during this study. It appears that, by virtue of its extended pressure range, a design using toroidal gaskets is more suitable for equation-of-state studies than is the system described by Le Godec, Dove, Francis, Kohn, Marshall, Pawley, Price, Redfern, Rhodes, Ross, Schofield, Schooneveld, Syfosse, Tucker & Welch [Mineral. Mag. (2001), 65, 737-748]. (c) 2008 International Union of Crystallography Printed in Singapore - all rights reserved

‘One Thing Better’ And ‘Redesigning Design Education’- A Collaboration Between Industry And Academia.

The Design industries are in positive flux and academia is trying to follow the pace as best it can; however some of the structures within academic frameworks restrict flexibility to mimic an industrial scenario. This disconnect can be compounded by educational alignment issues where different academic levels i.e. school to university can have large gaps between academic, industry and student expectations. This paper frames the collaboration, design and explorative stages between the authors, through prototyping a new final year module called Service and System Design. The research project intends to start with some tangible experiences for the authors and students alike and ultimately is anticipated to have wider impact within the author’s institution and beyond. For the first of the two theme based projects, the students are tasked to focus on designing ‘One thing better’ in the context of the module. This project is intended to generate evidence for the industry partner to understand the level of students’ abilities so that the support mechanisms can be tailored for an improved outcome on the second larger project, ‘Redesigning Design Education’. This project takes a deeper dive approach with the intention of students following the project theme and reflecting on their own ‘design learning’ experiences, using those as a catalyst guided by both industry and academic. The research evidenced in this paper has been carried out with a pre –process focus, with the intention of provoking dialogue within the design disciplines academic and industrial communities so that further developments can be integrated into multi-disciplinary projects as the next stage of the research activity

Trace as an alternative decategorification functor

Categorification is a process of lifting structures to a higher categorical level. The original structure can then be recovered by means of the so-called "decategorification" functor. Algebras are typically categorified to additive categories with additional structure and decategorification is usually given by the (split) Grothendieck group. In this expository article we study an alternative decategorification functor given by the trace or the zeroth Hochschild--Mitchell homology. We show that this form of decategorification endows any 2-representation of the categorified quantum sl(n) with an action of the current algebra U(sl(n)[t]) on its center.Comment: 47 pages with tikz figures. arXiv admin note: text overlap with arXiv:1405.5920 by other author

Electrostatically gated membrane permeability in inorganic protocells

Although several strategies are now available to produce functional microcompartments analogous to primitive cell-like structures, little progress has been made in generating protocell constructs with self-controlled membrane permeability. Here we describe the preparation of water-dispersible colloidosomes based on silica nanoparticles and delineated by a continuous semipermeable inorganic membrane capable of self-activated, electrostatically gated permeability. We use crosslinking and covalent grafting of a pH-responsive copolymer to generate an ultrathin elastic membrane that exhibits selective release and uptake of small molecules. This behaviour, which depends on the charge of the copolymer coronal layer, serves to trigger enzymatic dephosphorylation reactions specifically within the protocell aqueous interior. This system represents a step towards the design and construction of alternative types of artificial chemical cells and protocell models based on spontaneous processes of inorganic self-organization

<i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration

AIMS: To evaluate the associations of emergent genome-wide-association study-derived coronary heart disease (CHD)-associated single nucleotide polymorphisms (SNPs) with established and emerging risk factors, and the association of genome-wide-association study-derived lipid-associated SNPs with other risk factors and CHD events. METHODS AND RESULTS: Using two case–control studies, three cross-sectional, and seven prospective studies with up to 25 000 individuals and 5794 CHD events we evaluated associations of 34 genome-wide-association study-identified SNPs with CHD risk and 16 CHD-associated risk factors or biomarkers. The Ch9p21 SNPs rs1333049 (OR 1.17; 95% confidence limits 1.11–1.24) and rs10757274 (OR 1.17; 1.09–1.26), MIA3 rs17465637 (OR 1.10; 1.04–1.15), Ch2q36 rs2943634 (OR 1.08; 1.03–1.14), APC rs383830 (OR 1.10; 1.02, 1.18), MTHFD1L rs6922269 (OR 1.10; 1.03, 1.16), CXCL12 rs501120 (OR 1.12; 1.04, 1.20), and SMAD3 rs17228212 (OR 1.11; 1.05, 1.17) were all associated with CHD risk, but not with the CHD biomarkers and risk factors measured. Among the 20 blood lipid-related SNPs, LPL rs17411031 was associated with a lower risk of CHD (OR 0.91; 0.84–0.97), an increase in Apolipoprotein AI and HDL-cholesterol, and reduced triglycerides. SORT1 rs599839 was associated with CHD risk (OR 1.20; 1.15–1.26) as well as total- and LDL-cholesterol, and apolipoprotein B. ANGPTL3 rs12042319 was associated with CHD risk (OR 1.11; 1.03, 1.19), total- and LDL-cholesterol, triglycerides, and interleukin-6. CONCLUSION: Several SNPs predicting CHD events appear to involve pathways not currently indexed by the established or emerging risk factors; others involved changes in blood lipids including triglycerides or HDL-cholesterol as well as LDL-cholesterol. The overlapping association of SNPs with multiple risk factors and biomarkers supports the existence of shared points of regulation for these phenotypes