Estimate of Effectiveness of Palivizumab in the Prevention of Respiratory Syncytial Virus-Related Hospitalizations in a Cohort of Premature Children

As recomendações da Secção de Neonatologia da Sociedade Portuguesa de Pediatria (SNN-SPP) prevêem a profilaxia medicamentosa da infecção por vírus sincicial respiratório (VSR) com palivizumab em idades gestacionais (IG)inferiores a 30 semanas. Alguns Hospitais de Apoio Perinatal Diferenciado seguem práticas mais restritas, limitando o seu uso à extrema prematuridade e/ou a prematuros com doença pulmonar crónica da prematuridade. Objectivos. Estimar a relação custo-eficácia da profilaxia com palivizumab segundo as recomendações da SNN-SPP, através da aplicação de um modelo teórico a uma coorte real de prematuros. Metodologia. Estudo prospectivo histórico. Coorte de crianças nascidas num Hospital de Apoio Perinatal Diferenciado entre 1/10/2002 e 30/04/2005 com IG ² 35 semanas. Considerou- se caso o internamento no mesmo hospital por bronquiolite por VSR nas épocas 2003/04 e 2004/05. Baseando-nos nas recomendações SNN-SPP e no Number Needed to Treat dos estudos IMpact e IRIS, estimámos a redução prevista nas taxas de hospitalização caso a profilaxia fosse efectuada, comparando os seus custos com a redução de custos de hospitalização. Resultados. Dos 356 recém-nascidos elegíveis, nove foram excluídos por óbito e dois por administração de palivizumab. A taxa de hospitalização por bronquiolite por VSR nas 345 crianças incluídas foi 9,3%. No subgrupo com indicação para profilaxia (26 crianças) a taxa de hospitalização foi 15,4%, com uma estimativa de custo médio de hospitalização de Û 6.542,35. Não ocorreu nenhuma morte por infecção por VSR. A redução estimável no número de hospitalizações sob profilaxia seria de 1,5 (IMpact) ou 2,4 (IRIS). O custo necessário para prevenir um internamento seria de Û 26.263,11 na melhor estimativa e Û 57.716,26 na pior estimativa. Conclusão. Com o modelo desenvolvido, não conseguimos demonstrar nesta coorte uma estimativa de relação custo-eficácia favorável à administração de Palivizumab segundo recomendações da SNN-SPP

Kerr-CFT From Black-Hole Thermodynamics

We analyze the near-horizon limit of a general black hole with two commuting killing vector fields in the limit of zero temperature. We use black hole thermodynamics methods to relate asymptotic charges of the complete spacetime to those obtained in the near-horizon limit. We then show that some diffeomorphisms do alter asymptotic charges of the full spacetime, even though they are defined in the near horizon limit and, therefore, count black hole states. We show that these conditions are essentially the same as considered in the Kerr/CFT corresponcence. From the algebra constructed from these diffeomorphisms, one can extract its central charge and then obtain the black hole entropy by use of Cardy's formula.Comment: 19 pages, JHEP3, no figures. V2: References added, small typos fixe

Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

Contrasting changes in the abundance and diversity of North American bird assemblages from 1971 to 2010

This article is based upon work from COST Action ES1101 "Harmonising Global Biodiversity Modelling" (Harmbio), supported by COST (European Cooperation in Science and Technology).Although it is generally recognized that global biodiversity is declining, few studies have examined long-term changes in multiple biodiversity dimensions simultaneously. In this study we quantified and compared temporal changes in the abundance, taxonomic diversity, functional diversity and phylogenetic diversity of bird assemblages, using roadside monitoring data of the North American Breeding Bird Survey from 1971 to 2010. We calculated 12 abundance and diversity metrics based on five year average abundances of 519 species for each of 768 monitoring routes. We did this for all bird species together as well as for four sub-groups based on breeding habitat affinity (grassland, woodland, wetland and shrubland breeders). The majority of the biodiversity metrics increased or remained constant over the study period, whereas the overall abundance of birds showed a pronounced decrease, primarily driven by declines of the most abundant species. These results highlight how stable or even increasing metrics of taxonomic, functional or phylogenetic diversity may occur in parallel with substantial losses of individuals. We further found that patterns of change differed among the species sub-groups, with both abundance and diversity increasing for woodland birds and decreasing for grassland breeders. The contrasting changes between abundance and diversity and among the breeding habitat groups underscore the relevance of a multi-faceted approach to measuring biodiversity change. Our findings further stress the importance of monitoring the overall abundance of individuals in addition to metrics of taxonomic, functional or phylogenetic diversity, thus confirming the importance of population abundance as an essential biodiversity variable.Publisher PDFPeer reviewe

Extreme Food-Plant Specialisation in Megabombus Bumblebees as a Product of Long Tongues Combined with Short Nesting Seasons

© 2015 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/4.0/ The attached file is the published version of the article

Convergence of marine megafauna movement patterns in coastal and open oceans

The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals’ movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content

Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells

BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naive cells. We also observed these findings in clinical melanoma specimens. Moreover, the increased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was instead correlated with the noncanonical Hh pathway, involving TGF beta/SMAD (transforming growth factor-beta/Sma- and Mad-related family) signaling. Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with both growth arrest and senescence. Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of the melanoma cells in a three-dimensional skin reconstruct model and was associated with a decrease in metalloproteinase (MMP2/MMP9) expression and microphthalmia transcription factor upregulation. Gant61 monotherapy did not alter the drug sensitivity of naive cells, but could reverse the resistance of melanoma cells chronically treated with vemurafenib. We further noted that alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, suggesting that this could be a potential therapeutic strategy for the prevention of therapeutic escape. Our results suggest that targeting the Hh pathway in BRAFi-resistant melanoma may represent a viable therapeutic strategy to restore vemurafenib sensitivity, reducing or even inhibiting the acquired chemoresistance in melanoma patients.Fapesp-grant number 2012/04194-1, 2013/05172-4, 2014/24400-0 and 2015/10821-7, CNPq-grant number 150447/2013-2 and 471512/2013-3 and PRODOC-grant no 3193-32/2010. Work in the lab of KS Smalley was supported by the National Institutes of Health grants R01 CA161107, R21 CA198550, and Skin SPORE grant P50 CA168536info:eu-repo/semantics/publishedVersio

Reprogramming energy metabolism and inducing angiogenesis : co-expression of monocarboxylate transporters with VEGF family members in cervical adenocarcinomas

Background: Deregulation of cellular energetic metabolism was recently pointed out as a hallmark of cancer cells. This deregulation involves a metabolic reprogramming that leads to a high production of lactate. Lactate efflux, besides contributing for the glycolytic flux, also acts in the extracellular matrix, contributing for cancer malignancy, by, among other effects, induction of angiogenesis. However, studies on the interplay between cancer metabolism and angiogenesis are scarce. Therefore, the aim of the present study was to evaluate the metabolic and vascular molecular profiles of cervical adenocarcinomas, their co-expression, and their relation to the clinical and pathological behavior. Methods: The immunohistochemical expression of metabolism-related proteins (MCT1, MCT4, CD147, GLUT1 and CAIX) as well as VEGF family members (VEGF-A, VEGF-C, VEGF-D, VEGFR-1, VEGFR-2 and VEGFR-3) was assessed in a series of 232 cervical adenocarcinomas. The co-expression among proteins was assessed and the expression profiles were associated with patients’ clinicopathological parameters. Results: Among the metabolism-related proteins, MCT4 and CAIX were the most frequently expressed in cervical adenocarcinomas while CD147 was the less frequently expressed protein. Overall, VEGF family members showed a strong and extended expression with VEGF-C and VEGFR-2 as the most frequently expressed and VEGFR-1 as the less expressed member. Co-expression of MCT isoforms with VEGF family members was demonstrated. Finally, MCT4 was associated with parametrial invasion and HPV18 infection, CD147 and GLUT1 with distant metastasis, CAIX with tumor size and HPV18 infection, and VEGFR-1 with local and lymphnode metastasis. Conclusions: The results herein presented provide additional evidence for a crosstalk between deregulating cellular energetics and inducing angiogenesis. Also, the metabolic remodeling and angiogenic switch are relevant to cancer progression and aggressiveness in adenocarcinomas.CP received a post-doctoral fellowship (SFRH/BPD/69479/2010) and FM-S received a doctoral fellowship (SFRH/BD/87139/2012) from FCT (Portuguese Foundation for Science and Technology). This work was supported by the FCT grant ref. PTDC/SAU-FCF/104347/2008, under the scope of "Programa Operacional Tematico Factores de Competitividade" (COMPETE) of "Quadro Comunitario de Apoio III" and co-financed by Fundo Comunitario Europeu FEDER, and also by FAPESP 2008/03232-1

Sterile neutrino portal to Dark Matter II: exact dark symmetry

We analyze a simple extension of the standard model (SM) with a dark sector composed of a scalar and a fermion, both singlets under the SM gauge group but charged under a dark sector symmetry group. Sterile neutrinos, which are singlets under both groups, mediate the interactions between the dark sector and the SM particles, and generate masses for the active neutrinos via the seesaw mechanism. We explore the parameter space region where the observed Dark Matter relic abundance is determined by the annihilation into sterile neutrinos, both for fermion and scalar Dark Matter particles. The scalar Dark Matter case provides an interesting alternative to the usual Higgs portal scenario. We also study the constraints from direct Dark Matter searches and the prospects for indirect detection via sterile neutrino decays to leptons, which may be able to rule out Dark Matter masses below and around 100 GeV

A historical overview of the classification, evolution, and dispersion of Leishmania parasites and sandflies

Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites