Effect of number of probes and their orientation on the calculation of several compressor face distortion descriptors

A study was performed to determine the effects of the number and position of total pressure probes on the calculation of five compressor face distortion descriptors. This study used three sets of 320 steady state total pressure measurements that were obtained with a special rotating rake apparatus in wind tunnel tests of a mixed-compression inlet. The inlet was a one third scale model of the inlet on a YF-12 airplane, and it was tested in the wind tunnel at representative flight conditions at Mach numbers above 2.0. The study shows that large errors resulted in the calculation of the distortion descriptors even with a number of probes that were considered adequate in the past. There were errors as large as 30 and -50 percent in several distortion descriptors for a configuration consisting of eight rakes with five equal-area-weighted probes on each rake

The ultracool dwarf DENIS-P J104814.7-395606. Chromospheres and coronae at the low-mass end of the main-sequence

We have obtained an XMM-Newton observation and a broad-band spectrum from the ultraviolet to the near infrared with X-Shooter for one of the nearest M9 dwarfs, DENIS-P J1048-3956 (4pc). We integrate these data by a compilation of activity parameters for ultracool dwarfs from the literature with the aim to advance our understanding of these objects by comparing them to early-M type dwarf stars and the Sun. Our deep XMM-Newton observation has led to the first X-ray detection of DENIS-P J1048-3956 (log Lx = 25.1) as well as the first measurement of its V band brightness (V = 17.35mag). Flux-flux relations between X-ray and chromospheric activity indicators are here for the first time extended into the regime of the ultracool dwarfs. The approximate agreement of DENIS-P J1048-3956 and other ultracool dwarfs with flux-flux relations for early-M dwarfs suggests that the same heating mechanisms work in the atmospheres of ultracool dwarfs, albeit weaker as judged from their lower fluxes. The observed Balmer decrements of DENIS-P J1048-3956 are compatible with optically thick plasma in LTE at low, nearly photospheric temperature or optically thin LTE plasma at 20000K. Describing the decrements with CaseB recombination requires different emitting regions for Halpha and the higher Balmer lines. The high observed Halpha/Hbeta flux ratio is also poorly fitted by the optically thin models. We derive a similarly high value for the Halpha/Hbeta ratio of vB10 and LHS2065 and conclude that this may be a characteristic of ultracool dwarfs. We add DENIS-P J1048-3956 to the list of ultracool dwarfs detected in both the radio and the X-ray band. The Benz-Guedel relation between radio and X-ray luminosity of late-type stars is well-known to be violated by ultracool dwarfs. We speculate on the presence of two types of ultracool dwarfs with distinct radio and X-ray behavior.Comment: accepted for publication in Astronomy & Astrophysic

Calcifediol mensal versus calcifediol quinzenal no tratamento de pacientes com osteoporose.

GOALS: To evaluate the serum concentrations of 25-hydroxyvitamin D, 25(OH)D, in osteoporotic patients treated for one year with calcifediol. METHODS: We studied 156 patients with osteoporosis (23 men and 133 women) aged 71.9 ± 9.6 years who had been treated with calcifediol for at least one year. Ninety-two of them received 0.266 mg calcifediol every 15 days and he remaining 64 received the same dose once a month. Serum levels of 25(OH)D, intact PTH (iPTH), amino-terminal procollagen type I propeptide (PINP) and carboxy-terminal collagen type I telopeptide (CTX) were determined before and one year after the start of treatment . RESULTS: With both treatment regimens, a significant increase in 25(OH)D concentration was observed (p<0.001). The percentage of patients achieving 25(OH)D levels greater than 20 and 30 ng/ml was similar with both regimens, whereas that of patients exceeding 60 ng/ml was higher with the biweekly dose (p < 0.01 ) . The iPTH concentration significantly decreased after administration of calcifediol, although on this occasion there were no differences between the two forms of treatment. Both markers, PINP and CTX, similarly decreased in patients treated with antiresorptives (p < 0.0001), without these changes being related to the calcifediol regimen. CONCLUSIONS: A monthly administration of 0.266 mg calcifediol is adequate to achieve effective levels of vitamin D, and is also safe enough to avoid potentially harmful levels of vitamin D, so it would be preferable to the biweekly regimen in standard clinical practice.METAS: Avaliar as concentrações séricas de 25-hidroxivitamina D, 25 (OH) D, em pacientes osteoporóticos tratados por um ano com calcifediol. MÉTODOS: Foram estudados 156 pacientes com osteoporose (23 homens e 133 mulheres) com idade de 71,9 ± 9,6 anos que haviam recebido tratamento com calcifediol por pelo menos um ano. Noventa e dois deles receberam 0,266 mg de calcifediol a cada 15 dias e os 64 restantes receberam a mesma dose uma vez por mês. Os níveis séricos de 25 (OH) D, PTH intacto (iPTH), propeptídeo amino-terminal do procolágeno tipo I (PINP) e telopeptídeo carboxi-terminal do colágeno tipo I (CTX) foram determinados antes e um ano após o início do tratamento. RESULTADOS: Com ambos os regimes de tratamento, um aumento significativo na concentração de 25 (OH) D foi observado (p <0,001). A porcentagem de pacientes que atingiram níveis de 25 (OH) D maiores que 20 e 30 ng / ml foi semelhante com ambos os regimes, enquanto a de pacientes que ultrapassaram 60 ng / ml foi maior com a dose quinzenal (p <0,01) . A concentração de iPTH diminuiu significativamente após a administração de calcifediol, embora nesta ocasião não houvesse diferenças entre as duas formas de tratamento. Ambos os marcadores, PINP e CTX, diminuíram de forma semelhante em pacientes tratados com antirreabsortivos (p <0,0001), sem que essas alterações estivessem relacionadas ao regime de calcifediol. CONCLUSÕES: A administração mensal de 0,266 mg de calcifediol é adequada para atingir níveis eficazes de vitamina D, e também é segura o suficiente para evitar atingir níveis potencialmente prejudiciais desta, por isso seria preferível ao regime quinzenal na prática clínica habitual

Interleukin-2 therapy in patients with HIV infection

BACKGROUND Used in combination with antiretroviral therapy, subcutaneous recombinant interleukin-2 raises CD4+ cell counts more than does antiretroviral therapy alone. The clinical implication of these increases is not known. METHODS We conducted two trials: the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). In each, patients infected with the human immunodeficiency virus (HIV) who had CD4+ cell counts of either 50 to 299 per cubic millimeter (SILCAAT) or 300 or more per cubic millimeter (ESPRIT) were randomly assigned to receive interleukin-2 plus antiretroviral therapy or antiretroviral therapy alone. The interleukin-2 regimen consisted of cycles of 5 consecutive days each, administered at 8-week intervals. The SILCAAT study involved six cycles and a dose of 4.5 million IU of interleukin-2 twice daily; ESPRIT involved three cycles and a dose of 7.5 million IU twice daily. Additional cycles were recommended to maintain the CD4+ cell count above predefined target levels. The primary end point of both studies was opportunistic disease or death from any cause. RESULTS In the SILCAAT study, 1695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4111 patients (2071 receiving interleukin-2 plus antiretroviral therapy and 2040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone--by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P=0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P=0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P=0.73) and 1.10 (P=0.35), respectively, in the SILCAAT study and 0.90 (P=0.42) and 1.23 (P=0.003), respectively, in ESPRIT. CONCLUSIONS Despite a substantial and sustained increase in the CD4+ cell count, as compared with antiretroviral therapy alone, interleukin-2 plus antiretroviral therapy yielded no clinical benefit in either study. (ClinicalTrials.gov numbers, NCT00004978 [ESPRIT] and NCT00013611 [SILCAAT study].

Pulmonary long-term consequences of COVID-19 infections after hospital discharge

Objectives: COVID-19 survivors are reporting residual abnormalities after discharge from the hospital. Limited information is available about this stage of recovery or the lingering effects of the virus on pulmonary function and inflammation. The aim of this study was to describe lung function and to identify biomarkers in serum and induced sputum samples from patients recovering from COVID-19 hospitalisation. Methods: Patients admitted to Spanish hospitals with laboratory-confirmed COVID-19 infection by a real-time PCR (RT-PCR) assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited for this study. Each hospital screened their lists of discharged patients at least 45 days after symptom onset. SARS-CoV-2-infected patients were divided into mild/moderate and severe disease groups according to the severity of their symptoms during hospitalisation. Patients’ epidemiological and medical histories, comorbidities, chronic treatments, and laboratory parameters were evaluated. Pulmonary function tests, the standardised 6-minute walk test (6 MWT) and chest computed tomography (CT) were also performed. The levels of proteases, their inhibitors, and shed receptors were measured in serum and induced sputum samples. Results: A total of 100 patients with respiratory function tests were included in this study. The median number of days after the onset of symptoms was 104 (IQR 89.25, 126.75). COVID-19 was severe in 47% (47/100) of patients. CT was normal in 48% (48/100) of patients. Lung function was normal (FEV1 ≥80%, FVC ≥80%, FEV1/FVC ≥0.7, and diffusing capacity for carbon monoxide [DLCO] ≥80%) in 92% (92/100), 94% (94/100), 100% (100/100) and 48% (48/100) of patients, respectively. Multivariate analysis showed that a DLCO <80% (OR 5.92; 95%CI 2.28-15.37; p <0.0001) and a lower serum LDH level (OR 0.98; 95%CI 0.97-0.99) were associated with the severe disease group of SARS-CoV-2 during hospital stay. Conclusions: A diffusion deficit (DLCO <80%) was still present after hospital discharge and was associated with the most severe SARS-CoV-2 cases

Role of Mitochondrial Complex IV in Age-Dependent Obesity

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion

Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial

This article has been accepted for publication in Clinical Infectious Diseases ©2014 The Authors .Published by Oxford University Press on Clinical Infectious Disease 60.5. DOI: 10.1093/cid/ciu898Background. It is unclear whether metabolic or body composition effects may differ between protease inhibitor-based regimens recommended for initial treatment of HIV infection. Methods. ATADAR is a phase IV, open-label, multicenter randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Pre-defined end-points were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. Results. At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95%CI -0.6 to 21.6); and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95%CI -0.5 to 17.6). Seven vs. five patients discontinued atazanavir/ritonavir or darunavir/ritonavir due to adverse effects. Total and HDL cholesterol similarly increased in both arms, but triglycerides increased more in atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95%CI 726.7 to 4997.7; P=0.0090), limb fat (estimated difference 1403.3 gr; 95%CI 388.4 to 2418.2; P=0.0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm2; 95%CI 1.9 to 55.0; P=0.0362) increased more in atazanavir/ritonavir than in darunavir/ritonavir arm. Body fat changes in atazanavir/ritonavir arm were associated with higher insulin resistance. Conclusions. We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically-relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and total and subcutaneous fat than darunavir/ritonavir and fat gains with atazanavir/ritonavir were associated with insulin resistanceThis is an Investigator Sponsored Research study. It was supported in part by research grants from Bristol‐Myers Squibb and Janssen‐Cilag; Instituto de Salud Carlos III (PI12/01217) and Red Temática Cooperativa de Investigación en SIDA G03/173 (RIS‐EST11), Ministerio de Ciencia e Innovación, Spain. (Registration number: NCT01274780; registry name: ATADAR; EUDRACT; 2010‐021002‐38)

Network meta‐analysis of post‐exposure prophylaxis randomized clinical trials

Objectives: We performed a network meta‐analysis of PEP randomized clinical trials to evaluate the best regimen. / Methods: After MEDLINE/Pubmed search, studies were included if: (1) were randomized, (2) comparing at least 2 PEP three‐drug regimens and, (3) reported completion rates or discontinuation at 28 days. Five studies with 1105 PEP initiations were included and compared ritonavir‐boosted lopinavir (LPV/r) vs. atazanavir (ATV) (one study), cobicistat‐boosted elvitegravir (EVG/c) (one study), raltegravir (RAL) (one study) or maraviroc (MVC) (two studies). We estimated the probability of each treatment of being the best based on the evaluation of five outcomes: PEP non‐completion at day 28, PEP discontinuation due to adverse events, PEP switching due to any cause, lost to follow‐up and adverse events. / Results: Participants were mostly men who have sex with men (n = 832, 75%) with non‐occupational exposure to HIV (89.86%). Four‐hundred fifty‐four (41%) participants failed to complete their PEP course for any reason. The Odds Ratio (OR) for PEP non‐completion at day 28 in each antiretroviral compared to LPV/r was: ATV 0.95 (95% CI 0.58–1.56; EVG/c: OR 0.65 95% CI 0.30–1.37; RAL: OR 0.68 95% CI 0.41–1.13; and MVC: OR 0.69 95% CI 0.47–1.01. In addition, the rankogram showed that EVG/c had the highest probability of being the best treatment for the lowest rates in PEP non‐completion at day 28, switching, lost to follow‐up or adverse events and MVC for PEP discontinuations due to adverse events. / Conclusions: Our study shows the advantages of integrase inhibitors when used as PEP, particularly EVG as a Single‐Tablet Regimen

Gene expression in a paleopolyploid: a transcriptome resource for the ciliate Paramecium tetraurelia

International audienceBACKGROUND: The genome of Paramecium tetraurelia, a unicellular model that belongs to the ciliate phylum, has been shaped by at least 3 successive whole genome duplications (WGD). These dramatic events, which have also been documented in plants, animals and fungi, are resolved over evolutionary time by the loss of one duplicate for the majority of genes. Thanks to a low rate of large scale genome rearrangement in Paramecium, an unprecedented large number of gene duplicates of different ages have been identified, making this organism an outstanding model to investigate the evolutionary consequences of polyploidization. The most recent WGD, with 51% of pre-duplication genes still in 2 copies, provides a snapshot of a phase of rapid gene loss that is not accessible in more ancient polyploids such as yeast. RESULTS: We designed a custom oligonucleotide microarray platform for P. tetraurelia genome-wide expression profiling and used the platform to measure gene expression during 1) the sexual cycle of autogamy, 2) growth of new cilia in response to deciliation and 3) biogenesis of secretory granules after massive exocytosis. Genes that are differentially expressed during these time course experiments have expression patterns consistent with a very low rate of subfunctionalization (partition of ancestral functions between duplicated genes) in particular since the most recent polyploidization event. CONCLUSIONS: A public transcriptome resource is now available for Paramecium tetraurelia. The resource has been integrated into the ParameciumDB model organism database, providing searchable access to the data. The microarray platform, freely available through NimbleGen Systems, provides a robust, cost-effective approach for genome-wide expression profiling in P. tetraurelia. The expression data support previous studies showing that at short evolutionary times after a whole genome duplication, gene dosage balance constraints and not functional change are the major determinants of gene retention

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study

Background. We analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients. Methods. From July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study. Results. The prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered ?high risk? for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid?related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection. Conclusions. The routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid?related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients