Factores preditivos da formação de aderências pleurais e sucesso da pleurodese nos doentes com derrame pleural

RESUMO: As aderências pleurais podem complicar a realização da pleurodese por toracoscopia. Os autores decidiram realizar este estudo para determinar os factores preditivos da formação e extensão das aderências pleurais e do sucesso da pleurodese em doentes submetidos a toracoscopia e talcagem.Os doentes submetidos a toracoscopia no Georgetown University Medical Center entre Agosto de 1995 e Março de 2002 foram estudados retrospectivamente. Os autores registaram o n.° de toracenteses, a duração do derrame, a malignidade, a origem doença subjacente, a existência de irradiação torácica, a presença e extensão das aderências pleurais e o sucesso da pleurodese. Foram estudados 89 doentes que tinham todos estes dados registados.Numa análise global, só os derrames pleurais que tinham uma duração superior a 5 meses têm um valor preditivo na formação das aderências (p=0,037) e extensão das mesmas (p=0,038). No grupo dos derrames pleurais malignos com uma duração superior a 5 meses este aspecto também tem um valor preditivo na formação (p=0,020) e extensão (p=0,037) das aderências. No grupo particular dos derrames pleurais secundários ao cancro da mama, a duração superior a 5 meses também tem um valor preditivo na formação (p=0,008) e extensão (p=0,011) das aderências pleurais.A regressão estatística determinou que a duração dos derrames superior a 5 meses é neste estudo o único factor preditivo na formação das aderências pleurais e que não existem factores preditivos do sucesso da pleurodese. A duração do derrame pleural, independentemente da sua etiologia, está associada à formação de espessas aderências pleurais, particularmente naqueles que tem uma duração superior a 5 meses. COMENTÁRIO: Nos EUA, 1,5 a 2 milhões de doentes por ano tem um derrame pleural. Cerca de 1/3 são secundários a insuficiência cardíaca e 20% estão relacionados com pneumonias bacterianas. Quinze a 40% são derrames pleurais malignos e, destes, cerca de 30% a 40% são secundários ao cancro do pulmão e 25% ao cancro da mama.A rentabilidade da citologia do líquido pleural (50% a70%) e das biópsias pleurais (39% a 75%) não é satisfatória. Estes factos levam a considerar a toracoscopia o exame indicado nos derrames pleurais sem diagnóstico, pois permite a visualização directa das superfícies pleurais e a realização das biópsias directamente. A toracoscopia permite também realizar a insuflação de talco e a pleurodese.A presença de aderências pleurais dificulta a realização da toracoscopia. A efectividade da pleurodese é diminuída porque as aderências cobrem parcialmente a pleura visceral e a pleura parietal, dificultando a sua aderência.A referência na literatura que a produção de citocinas inflamatórias, a subsequente formação de fibrina e a eventual formação de aderências pleurais, estão relacionadas com o número de toracenteses realizadas previamente à toracoscopia e que poderão afectar o êxito da pleurodese, é um dos aspectos que levou os autores a realizarem este estudo.Os resultados contrariaram em parte estes conceitos. Os autores constataram que a formação das aderências e a sua extensão estavam em parte relacionadas com a gravidade da doença subjacente e com a duração do derrame pleural. Não conseguiram estabelecer relação entre número de toracenteses e a formação de aderências assim como com o êxito ou não da pleurodese.Estatiscamente, só conseguiram estabelecer como factor preditivo da formação e da extensão de aderências a duração do derrame pleural quando superior a 5meses. Em relação aos factores preditivos do sucesso da pleurodese, neste estudo os autores não conseguiram estabelecer; contudo, não foram analisados os valores do pH do líquido pleural que é considerado em algumas séries como factor preditivo (pH <7,20 é um sinal de insucesso da pleurodese).A existência de aderências pleurais não é um factor directo de insucesso da pleurodese, mas como dificulta a realização da toracoscopia e da eventual talcagem é sempre um aspecto a considerar no êxito da toracoscopia/talcagem. Palavras-chave: Derrame pleural, aderências pleurais, toracoscopia, talcage

Social contact networks and mixing among students in K-12 schools in Pittsburgh, PA

Students attending schools play an important role in the transmission of influenza. In this study, we present a social network analysis of contacts among 1,828 students in eight different schools in urban and suburban areas in and near Pittsburgh, Pennsylvania, United States of America, including elementary, elementary-middle, middle, and high schools. We collected social contact information of students who wore wireless sensor devices that regularly recorded other devices if they are within a distance of 3 meters. We analyzed these networks to identify patterns of proximal student interactions in different classes and grades, to describe community structure within the schools, and to assess the impact of the physical environment of schools on proximal contacts. In the elementary and middle schools, we observed a high number of intra-grade and intra-classroom contacts and a relatively low number of inter-grade contacts. However, in high schools, contact networks were well connected and mixed across grades. High modularity of lower grades suggests that assumptions of homogeneous mixing in epidemic models may be inappropriate; whereas lower modularity in high schools suggests that homogenous mixing assumptions may be more acceptable in these settings. The results suggest that interventions targeting subsets of classrooms may work better in elementary schools than high schools. Our work presents quantitative measures of age-specific, school-based contacts that can be used as the basis for constructing models of the transmission of infections in schools

Bayesian Fit of Exclusive b→sℓˉℓb \to s \bar\ell\ell Decays: The Standard Model Operator Basis

We perform a model-independent fit of the short-distance couplings $C_{7,9,10}$ within the Standard Model set of $b\to s\gamma$ and $b\to s\bar\ell\ell$ operators. Our analysis of $B \to K^* \gamma$, $B \to K^{(*)} \bar\ell\ell$ and $B_s \to \bar\mu\mu$ decays is the first to harness the full power of the Bayesian approach: all major sources of theory uncertainty explicitly enter as nuisance parameters. Exploiting the latest measurements, the fit reveals a flipped-sign solution in addition to a Standard-Model-like solution for the couplings $C_i$. Each solution contains about half of the posterior probability, and both have nearly equal goodness of fit. The Standard Model prediction is close to the best-fit point. No New Physics contributions are necessary to describe the current data. Benefitting from the improved posterior knowledge of the nuisance parameters, we predict ranges for currently unmeasured, optimized observables in the angular distributions of $B\to K^*(\to K\pi)\,\bar\ell\ell$.Comment: 42 pages, 8 figures; v2: Using new lattice input for f_Bs, considering Bs-mixing effects in BR[B_s->ll]. Main results and conclusion unchanged, matches journal versio

Overview of the CCP4 suite and current developments.

The CCP4 (Collaborative Computational Project, Number 4) software suite is a collection of programs and associated data and software libraries which can be used for macromolecular structure determination by X-ray crystallography. The suite is designed to be flexible, allowing users a number of methods of achieving their aims. The programs are from a wide variety of sources but are connected by a common infrastructure provided by standard file formats, data objects and graphical interfaces. Structure solution by macromolecular crystallography is becoming increasingly automated and the CCP4 suite includes several automation pipelines. After giving a brief description of the evolution of CCP4 over the last 30 years, an overview of the current suite is given. While detailed descriptions are given in the accompanying articles, here it is shown how the individual programs contribute to a complete software package

Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: Results from the scleroderma lung study

Objective To assess the impact of cyclophosphamide (CYC) on the health-related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment. Methods One hundred fifty-eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference-based measure, the SF-6D. The differences in the HRQOL between the 2 groups at 12 months were calculated using a linear mixed model. Responsiveness was evaluated using the effect size. The proportion of subjects in each treatment group whose scores improved at least as much as or more than the minimum clinically important difference (MCID) in HRQOL measures was assessed. Results After adjustment for baseline scores, differences in the HAQ DI, SF-36 role physical, general health, vitality, role emotional, mental health scales, and SF-36 mental component summary (MCS) score were statistically significant for CYC versus placebo ( P < 0.05). Effect sizes were negligible (<0.20) for all of the scales of the SF-36, HAQ DI, and SF-6D at 12 months. In contrast, a higher proportion of patients who received CYC achieved the MCID compared with placebo in the HAQ DI score (30.9% versus 14.8%), transitional dyspnea index score (46.4% versus 12.7%), SF-36 MCS score (33.3% versus 18.5%), and SF-6D score (21.3% versus 3.8%). Conclusion One year of treatment with CYC leads to an improvement in HRQOL in patients with scleroderma lung disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56039/1/22580_ftp.pd

Search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓

A search for the lepton-flavor-violating decays Bs0→e±μ∓ and B0→e±μ∓ is performed with a data sample, corresponding to an integrated luminosity of 1.0  fb-1 of pp collisions at √s=7  TeV, collected by the LHCb experiment. The observed number of Bs0→e±μ∓ and B0→e±μ∓ candidates is consistent with background expectations. Upper limits on the branching fractions of both decays are determined to be B(Bs0→e±μ∓)101  TeV/c2 and MLQ(B0→e±μ∓)>126  TeV/c2 at 95% C.L., and are a factor of 2 higher than the previous bounds

The Efficacy of Sodium Channel Blockers to Prevent Phencyclidine-Induced Cognitive Dysfunction in the Rat: Potential for Novel Treatments for Schizophrenia □ S

ABSTRACT Sodium channel inhibition is a well precedented mechanism used to treat epilepsy and other hyperexcitability disorders. The established sodium channel blocker and broad-spectrum anticonvulsant lamotrigine is also effective in the treatment of bipolar disorder and has been evaluated in patients with schizophrenia. Double-blind placebo-controlled clinical trials found that the drug has potential to reduce cognitive symptoms of the disorder. However, because of compound-related side-effects and the need for dose titration, a conclusive evaluation of the drug&apos;s efficacy in patients with schizophrenia has not been possible. In this series of studies in the rat, we compared the efficacy of the two new molecules to prevent a cognitive deficit induced by the N-methyl-D-aspartic acid receptor antagonist phencyclidine (PCP) in the reversal-learning paradigm in the rat. We also explored the effects of the drugs to prevent brain activation and neurochemical effects of PCP. We found that, like lamotrigine, both GSK2 and GSK3 were able to prevent the deficit in reversal learning produced by PCP, thus confirming their potential in the treatment of cognitive symptoms of schizophrenia. However, higher doses than those required for anticonvulsant efficacy of the drugs were needed for activity in the reversal-learning model, suggesting a lower therapeutic window relative to mechanism-dependent central side effects for this indication

Genomic Signatures of Strain Selection and Enhancement in Bacillus atrophaeus var. globigii, a Historical Biowarfare Simulant

(BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the “military” isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of “military” isolates on lactate-containing media, and showed that the “military” strains exhibited a hypersporulating phenotype.Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation

A high spatial resolution X-ray and H-alpha study of hot gas in the halos of star-forming disk galaxies. II. Quantifying supernova feedback

We investigate how the empirical properties of hot X-ray-emitting gas in a sample of seven starburst and three normal edge-on spiral galaxies (a sample which covers the full range of star-formation intensity found in disk galaxies) correlate with the size, mass, star formation rate and star formation intensity in the host galaxies. Intriguingly, the diffuse X-ray properties of the normal spirals (both in their disks and halos) fall where extrapolation of the trends from the starburst galaxies with superwinds would predict. We demonstrate that the luminosity of diffuse X-ray emission in both disk and halo is directly proportional to the rate of mechanical energy feedback from massive stars. Nevertheless, with only three non-starburst normal spiral galaxies it is hard to exclude an accretion-based origin for extra-planar diffuse X-ray emission around normal star-forming galaxies. Larger galaxies have more extended X-ray-emitting halos, but galaxy mass appears to play no role in determining the properties of the disk or extra-planar X-ray emitting plasma. The combination of these luminosity and size correlations leads to a correlation between the surface brightness of the diffuse X-ray emission and the mean star formation rate per unit area in the disk (L_FIR/D_25^2). We argue that the crucial spatial region around a galaxy that controls whether gas in starburst-driven superwinds will escape into the IGM is not the outer halo ~100 kpc from the host galaxy, but the inner few halo scale heights, within ~20 kpc of the galaxy plane. Given the properties of the gaseous halos we observe, superwind outflows from disk galaxies of mass M ~ 10^10 -- 10^11 Msun should still eject some fraction of their material into the IGM. (abstract abridged)Comment: To appear in 2004 May 10 edition of ApJ. For slightly higher resolution version, see http://proteus.pha.jhu.edu/~dks/dks_published.htm

Plasmid-Cured Chlamydia caviae Activates TLR2-Dependent Signaling and Retains Virulence in the Guinea Pig Model of Genital Tract Infection

Loss of the conserved “cryptic” plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains