Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control

Anomalous spectral weight in photoemission spectra of the hole doped Haldane chain Y2-xSrxBaNiO5

In this paper, we present photoemission experiments on the hole doped Haldane chain compound $Y_{2-x}Sr_xBaNiO_5$. By using the photon energy dependence of the photoemission cross section, we identified the symmetry of the first ionisation states (d type). Hole doping in this system leads to a significant increase in the spectral weight at the top of the valence band without any change in the vicinity of the Fermi energy. This behavior, not observed in other charge transfer oxides at low doping level, could result from the inhomogeneous character of the doped system and from a Ni 3d-O 2p hybridization enhancement due to the shortening of the relevant Ni-O distance in the localized hole-doped regions.Comment: 5 pages, 4 figure

Study of the Falling Friction Effect on Rolling Contact Parameters

[EN] The existence of a wheel rail friction coefficient that depends on the slip velocity has been associated in the literature with important railway problems like the curving squeal and certain corrugation problems in rails. Rolling contact models that take into account this effect were carried out through the so-called Exact Theories adopting an exact elastic model of the solids in contact, and Simplified Theories which assume simplified elastic models such as Winkler. The former ones, based on Kalker s Variational Theory, give rise to numerical problems; the latter ones need to adopt hypotheses that significantly deviate from actual conditions, leading to unrealistic solutions of the contact problem. In this paper, a methodology based on Kalker s Variational Theory is presented, in which a local slip velocity-dependent friction law is considered. A formulation to get steady-state conditions of rolling contact by means of regularisation of the Coulomb s law is proposed. The model allows establishing relationships in order to estimate the global properties (creepage velocities vs. total longitudinal forces) through local properties (local slip velocity vs. coefficient of friction) or vice versa. The proposed model shows a good agreement with experimental tests while solving the numerical problems previously mentioned.The authors acknowledge the financial contribution of the Spanish Ministry of Economy and Competitiveness through the Project TRA2013-45596-C2-1-R.Giner Navarro, J.; Baeza González, LM.; Vila Tortosa, MP.; Alonso Pazos, A. (2017). Study of the Falling Friction Effect on Rolling Contact Parameters. Tribology Letters. 65(1). https://doi.org/10.1007/s11249-016-0810-8S651Grassie, S.L., Elkins, J.A.: Rail corrugation on North American transit systems. Veh. Syst. Dyn. 28, 5–17 (1998)Hsu, S.S., Huang, Z., Iwnicki, S.D., Thompson, D.J., Jones, C.J.C., Xie, G., Allen, P.D.: Experimental and theoretical investigation of railway wheel squeal. Proc. Inst. Mech. Eng. F J. Rail Rapid Transit 221, 59–73 (2007)Kalker, J.J.: Three-Dimensional Elastic Bodies in Rolling Contact. Kluwer, Dordrecht (1990)Polach, O.: Influence of locomotive tractive effort on the forces between wheel and rail. Veh. Syst. Dyn. 35, 7–22 (2001)Giménez, J.G., Alonso, A., Gómez, E.: Introduction of a friction coefficient dependent on the slip in the FastSim algorithm. Veh. Syst. Dyn. 43, 233–244 (2005)Baeza, L., Vila, P., Roda, A., Fayos, J.: Prediction of corrugation in rails using a non-stationary wheel–rail contact model. Wear 265, 1156–1162 (2008)Vollebregt, E.A.H., Schuttelaars, H.M.: Quasi-static analysis of two-dimensional rolling contact with slip-velocity dependent friction. J. Sound Vib. 331, 2141–2155 (2012)Avlonitis, M., Kalaitzidou, K., Streator, J.: Investigation of friction statics and real contact area by means a modified OFC model. Tribol. Int. 69, 168–175 (2014)Berger, E.J., Mackin, T.J.: On the walking stick–slip problem. Tribol. Int. 75, 51–60 (2014)Alonso, A., Guiral, A., Baeza, B., Iwnicki, S.D.: Wheel–rail contact: experimental study of the creep forces–creepage relationships. Veh. Syst. Dyn. 52(S1), 469–487 (2014)Spiryagin, M., Polach, O., Cole, C.: Creep force modelling for rail traction vehicles based on the Fastsim algorithm. Veh. Syst. Dyn. 51, 1765–1783 (2013)Vollebregt, E.A.H.: Numerical modeling of measured railway creep versus creep-force curves with CONTACT. Wear 314, 87–95 (2014)Kalker, J.J.: On the Rolling Contact of Two Elastic Bodies in the Presence of Dry Friction. PhD Thesis, Technical University of Delft (Holland) (1967)Baeza, L., Fuenmayor, F.J., Carballeira, J., Roda, A.: Influence of the wheel–rail contact instationary process on contact parameters. J. Strain Anal. Eng. 42, 377–387 (2007)Le Rouzic, J., Le Bot, A., Perret-Liaudet, J., Guibert, M., Rusanov, A., Douminge, L., Bretagnol, F., Mazuyer, D.: Friction-induced vibration by Stribeck’s law: application to wiper blade squeal noise. Tribol. Lett. 49, 563–572 (2013)Rabinowicz, E.: The nature of the static and kinetic coefficients of friction. J. Appl. Phys. 22, 1373–1379 (1951)Carter, F.W.: On the action of locomotive driving wheel. Proc. R. Soc. Lon. Ser. A 112, 151–157 (1926)Kalker, J.J.: A fast algorithm for the simplified theory of rolling contact. Veh. Syst. Dyn. 11, 1–13 (1982

Evaluation of two formulations of adjuvanted RTS, S malaria vaccine in children aged 3 to 5 years living in a malaria-endemic region of Mozambique: a Phase I/IIb randomized double-blind bridging trial

BACKGROUND: Previous trials of the RTS, S malaria candidate vaccine have shown that this vaccine is safe, tolerated and immunogenic. The development plan for this vaccine aims at administering it in the first year of life through the Expanded Program on Immunization (EPI). The objective was to evaluate the safety and reactogenicity of RTS, S/AS02D (0.5 ml dose), a pediatric formulation of GlaxoSmithKline Biologicals' current malaria candidate vaccine RTS, S/AS02A (0.25 ml dose). A 0.5 ml dose of AS02D is composed of the same active ingredients in the same quantities as in a 0.25 ml dose of AS02A and has been developed to be easily introduced into routine EPI practices. METHODS: We performed a phase I/IIb randomized double-blind bridging study in a malaria-endemic region of Mozambique, to compare the safety and immunogenicity of both candidate vaccines with the aim of replacing RTS, S/AS02A with RTS, S/AS02D as the candidate pediatric vaccine. 200 Mozambican children aged 3 to 5 years were randomized 1:1 to receive one of the 2 vaccines according to a 0, 1, 2 month schedule. RESULTS: Both vaccines were safe and had similar reactogenicity profiles. All subjects with paired pre and post-vaccination samples showed a vaccine response with respect to anti-circumsporozoite (CS) antibodies irrespective of initial anti-CS serostatus. Geometric mean titers (GMTs) were 191 EU/ml (95% CI 150–242) in recipients of RTS, S/AS02D compared to 180 EU/ml (95% CI 146–221) in recipients of RTS, S/AS02A. For the anti-hepatitis B surface antigen (HBsAg), all subjects were seroprotected at day 90, and the GMTs were 23978 mIU/ml (95% CI 17896–32127) in RTS, S/AS02D recipients and 17410 mIU/ml (95% CI 13322–22752) in RTS, S/AS02A recipients. There was a decrease in anti-CS GMTs between months 3 and 14 in both groups (191 vs 22 EU/mL in RTS, S/AS02D group and 180 vs 29 EU/mL in RTS, S/AS02A group). CONCLUSION: Our data show that the RTS, S/AS02D is safe, well tolerated, and demonstrates non-inferiority (defined as upper limit of the 95% confidence interval of the anti-CS GMT ratio of RTS, S/AS02A to RTS, S/AS02D below 3.0) of the antibody responses to circumsporozoite and HBsAg induced by the RTS, S/AS02D as compared to the RTS, S/AS02A

Exogenous Glucose Administration Impairs Glucose Tolerance and Pancreatic Insulin Secretion during Acute Sepsis in Non-Diabetic Mice

Objectives:The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support.Methods:Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 μL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs.Measurements:And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml).Conclusions:The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia. © 2013 Watanabe et al

Birth weight and the risk of atrial fibrillation in whites and African Americans: The atherosclerosis risk in communities (ARIC) study

Background: Low birth weight (LBW) has been associated with an increased risk of cardiovascular disease (CVD). A previous study, however, found higher risk of atrial fibrillation (AF) in individuals with higher birth weight (BW). To further understand this apparent paradox, we examined the relationship between AF and BW in the Atherosclerosis Risk in Communities (ARIC) cohort. Methods: The analysis included 10,132 individuals free of AF at baseline (1996-1998), who provided BW information, were not born premature, and were not a twin. Self-reported BW was categorized as low (&lt;2.5 kg), medium (2.5-4 kg), and high (&gt;4.0 kg). AF incidence was ascertained from hospital discharge codes and death certificates. We used multivariable Cox proportional hazard models to determine the hazard ratios (HR) and 95% confidence intervals (CI) of AF across BW groups. Results: During an average follow-up of 10.3 years, we identified 882 incident AF cases. LBW was associated with higher risk of AF. Compared to individuals in the medium BW category, the HR (95% CI) of AF was 1.33 (0.99, 1.78) for LBW and 1.00 (0.81, 1.24) for high BW after adjusting for sociodemographic variables (p for trend = 0.29). Additional adjustment for CVD risk factors did not attenuate the associations (HR 1.42, 95% CI 1.06, 1.90 for LBW and HR 0.86, 95% CI 0.69-1.07 for high BW, compared to medium BW, p for trend = 0.01).Conclusion: LBW was associated with a higher risk of AF. This association was independent of known predictors of AF and is consistent with that observed for other cardiovascular diseases. © 2014 Lawani et al.; licensee BioMed Central Ltd

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

A new paradigm in respiratory hygiene: modulating respiratory secretions to contain cough bioaerosol without affecting mucus clearance

<p>Abstract</p> <p>Background</p> <p>Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action.</p> <p>Methods</p> <p>To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an <it>ex-vivo </it>model and then to an <it>in-vivo </it>large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes.</p> <p>Results</p> <p>Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways.</p> <p>Conclusion</p> <p>The <it>ex-vivo </it>frog palate and the <it>in-vivo </it>mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial phase of developing the concept of mucomodulation: Can we modulate the physical characteristics of the respiratory secretions to reduce aerosolization without affecting normal mucociliary clearance function, or even better improving it?</p