Cost-Effectiveness of a Chemoprophylactic Intervention with Single Dose Rifampicin in Contacts of New Leprosy Patients

In 2008, 249,007 new leprosy patients were detected in the world. It therefore remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy. The study is based on a large trial including 21,711 contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to contacts and followed them up for four years. The main outcome measure was the development of clinical leprosy. The cost effectiveness was expressed in US dollars per prevented leprosy case. Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total $6,009 was invested and 38 leprosy cases were prevented after 2 years, costing$158 per prevented leprosy case. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Validation of a method to estimate direct normal irradiance of UVA and PAR bands from global horizontal measurements for cloudless sky conditions in Valencia, Spain, by a measurement campaign

A method is proposed to provide measurement of direct normal solar irradiance of bands with wavelength ranges (315-400 nm, 400-700 nm) from measurements of global horizontal band irradiance for cloudless sky conditions in Valencia. Global and normal direct irradiance data for every air mass were obtained by applying the SMART2 model to the atmosphere of Valencia. The direct normal to global irradiance ratio was parameterized versus the relative optical air mass. A measurement campaign of global horizontal and diffuse irradiance of UVA and PAR bands was carried out in Valencia, after which, the inferred direct normal irradiance was compared with those provided by the method. The result of the comparison shows that the method is acceptably accurate. The proposed model tends to underestimate the direct normal irradiance of the UVA band by 6%, although for values below 25 W/m2 the model overestimates the direct irradiance by 6%, while for values above 25 W/m2 the model underestimates it by 10%. The other two error estimators used ranging from 11% to 15% are similar in the defined interval measurements in relation to the whole UVA band. Regarding the PAR band, the model overestimates the direct normal irradiance of the PAR band by only 2.2%. With this, the results of the PAR band are more conclusive, as it has been found that for direct normal irradiance values higher than 280 W/m2 the MBE error is almost zero and the other two estimator errors are small, about 5%. © 2010 Springer-Verlag.This work was supported by the Spanish Government through MEC grant MAT2009-14625-C03-03, and is a part of the activities of the Grup d'Optoelectronica i Semiconductors of the Polytechnic University of Valencia. The translation of this paper was funded by the Universidad Politecnica de Valencia, Spain.Serrano Jareño, MA.; Boscá Berga, JV. (2011). Validation of a method to estimate direct normal irradiance of UVA and PAR bands from global horizontal measurements for cloudless sky conditions in Valencia, Spain, by a measurement campaign. Theoretical and Applied Climatology. 103(1):95-101. https://doi.org/10.1007/s00704-010-0284-9S951011031Barth J, Cadet J, Césarini JP, Fitzpatrick TB, McKinlay A, Mutzhas M, Pathak M, Peak M, Sliney D, Urbach F (1999) TC 6-26 report: Standardization of the terms UV-A1, UV-A2 and UV-B, CIE 134-1999 ISBN 3-900-734-94-1Batlles FJ, Olmo FJ, Alados-Arboledas L (1995) On shadowband correction methods for diffuse irradiance measurements. Solar Energy 54(5):105–114Drummond AJ (1956) On the measurement of sky radiation. Arch 602 Meteor Geophys Bioklim B 7:413–436Gueymard C (1995) SMARTS2: a simple model of the atmospheric radiative transfer of sunshine: algorithms and performance assessment. FSEC-PF-270-95, Florida Solar Energy CenterGueymard C (2003) SMARTS2 code, versión 2.9.2. User’s Manual, Solar Consulting Services Bailey CO. Available from http://rredc.nrel.gov/solar/models/SMARTS/smarts_index.htmlGueymard C (2004) The sun’s total and spectral irradiance for solar energy applications and solar radiation models. Solar Energy 76:423–453Häder DP, Lebert M, Marangoni R, Colombetti G (1999) ELDONET-European light dosimeter network hardware and software. J Photochem Photobiol B: Biol 52:51–58Häder DP, Lebert M, Colombetti G, Figueroa F (2001) European light dosimeter network (ELDONET). Helgol Mar Res 55:35–44Iqbal M (1983) An introduction to solar radiation. Academic, TorontoKudish AI, Evseev EG (2008) The assessment of four different correction models applied to the diffuse radiation measured with a shadow ring using global and normal beam radiation measurements for Beer Sheva, Israel. Solar Energy 82(2):144–156LeBaron BA, Michalsky JJ, Perez R (1990) A simple procedure for correcting shadowband data for all sky conditions. Solar Energy 44:249–256Marín Fernández MJ (2007) Estudio de la irradiancia solar ultravioleta y eritemática en la Comunidad Valenciana. Doctoral Thesis University of Valencia (Spain)Perez R, Ineichen P, Seals R, Michalsky JJ, Stewart R (1990) Modelling daylight availability and irradiance components from direct and global irradiance. Sol Energy 44:271–289Pinazo JM, Cañada J, Bosca JV (1995) A new method to determine Ångström's turbidity coefficient: its application for Valencia. Solar Energy 54:219–226Serrano MA, Boscá JV, Cañada J (2008) The determination of a band factor to express irradiance of UV and PAR wavelength ranges in a clean and dry atmosphere at Valencia (Spain). Int J Ambient Energy 29(4):171–180Utrillas MP, Boscà JV, Martinez-Lozano JA, Cañada J, Tena F, Pinazo JM (1998) A comparative study of Spectral2, and Smarts2 parameterised models based on spectral irradiance measurements at Valencia, Spain. Solar Energy 63:161–171Utrillas MP, Marín MJ, Esteve AR, Tena F, Cañada J, Estellés V, Martínez Lozano JA (2007) Diffuse UV erythemal radiation experimental values. J Geophy Res 112:387–39

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

Phylogeography of Japanese encephalitis virus:genotype is associated with climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

Simultaneous sleep study and nasoendoscopic investigation in a patient with obstructive sleep apnoea syndrome refractory to continuous positive airway pressure: a case report

<p>Abstract</p> <p>Introduction</p> <p>The standard treatment for obstructive sleep apnoea syndrome is nasal continuous positive airway pressure. In most cases the obstruction is located at the oropharyngeal level, and nasal continuous positive airway pressure is usually effective. In cases of non-response to nasal continuous positive airway pressure other treatments like mandibular advancement devices or upper airway surgery (especially bi-maxillary advancement) may also be considered.</p> <p>Case presentation</p> <p>We report the case of a 38-year-old Caucasian man with severe obstructive sleep apnoea syndrome, initially refractory to nasal continuous positive airway pressure (and subsequently also to a mandibular advancement devices), in which the visualization of the upper airway with sleep endoscopy and the concomitant titration of positive pressure were useful in the investigation and resolution of sleep disordered breathing. In fact, there was a marked reduction in the size of his nasopharynx, and a paresis of his left aryepiglotic fold with hypertrophy of the right aryepiglotic fold. The application of bi-level positive airway pressure and an oral interface successfully managed his obstructive sleep apnoea.</p> <p>Conclusion</p> <p>This is a rare case of obstructive sleep apnoea syndrome refractory to treatment with nocturnal ventilatory support. Visualization of the endoscopic changes, during sleep and under positive pressure, was of great value to understanding the mechanisms of refractoriness. It also oriented the therapeutic option. Refractoriness to obstructive sleep apnoea therapy with continuous positive airway pressure is rare, and each case should be approached individually.</p

Ultracold atomic gases in optical lattices: mimicking condensed matter physics and beyond

We review recent developments in the physics of ultracold atomic and molecular gases in optical lattices. Such systems are nearly perfect realisations of various kinds of Hubbard models, and as such may very well serve to mimic condensed matter phenomena. We show how these systems may be employed as quantum simulators to answer some challenging open questions of condensed matter, and even high energy physics. After a short presentation of the models and the methods of treatment of such systems, we discuss in detail, which challenges of condensed matter physics can be addressed with (i) disordered ultracold lattice gases, (ii) frustrated ultracold gases, (iii) spinor lattice gases, (iv) lattice gases in "artificial" magnetic fields, and, last but not least, (v) quantum information processing in lattice gases. For completeness, also some recent progress related to the above topics with trapped cold gases will be discussed.Comment: Review article. v2: published version, 135 pages, 34 figure

Early and Late Direct Costs in a Southern African Antiretroviral Treatment Programme: A Retrospective Cohort Analysis

Gary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa