Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

Background: The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods: In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a postbronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio of ≤70% and FEV1 <80% of the predicted value. The primary endpoint was trough FEV1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George"s Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation. Results: At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies. Conclusion: Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration: ClinicalTrials.gov: NCT00363896 ACCLAIM/COPD I) and NCT00358436 (ACCLAIM/COPD II).

Diversity of the Quality Criteria in Qualitative Research in the Health Sciences: Lessons from a Lexicometric Analysis Composed of 133 Guidelines

A review of health sciences literature shows a substantial increase in qualitative publications. This work incorporates a certain number of research quality guidelines. We present the results of the Alceste® lexicometric analysis, which includes 133 quality grids for qualitative research covering five disciplinary fields of the health sciences: medicine and epidemiology, public health and health education, nursing, health sociology and anthropology, psychiatry and psychology. This analysis helped to cross-check the disciplinary fields with the various objectives assigned to the different criteria in the grids examined. The results obtained with Alceste® show the variability of the objectives sought by the authors of the guidelines. These discrepancies are not directly associated to disciplinary fields, and appear to be more closely linked to different qualitative research conceptualizations within the disciplines, and with essential qualitative research validation criteria. These conceptualizations must be clarified to help users better understand the objectives targeted by the grids, and promote more appreciation for qualitative research in the health sciences.

Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis

Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value#0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value$0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

GdBaCo2O5+x layered perovskite as an intermediate temperature solid oxide fuel cell cathode

GdBaCo2O5+x (GBCO) was evaluated as a cathode for intermediate-temperature solid oxide fuel cells. A porous layer of GBCO was deposited on an anode-supported fuel cell consisting of a 15m thick electrolyte of yttria-stabilized zirconia (YSZ) prepared by dense screen-printing anda Ni–YSZ cermet as an anode (Ni–YSZ/YSZ/GBCO). Values of power density of 150 mW cm−2 at 700◦C and ca. 250 mW cm−2 at 800◦C are reported for this standard configuration using 5% of H2 in nitrogen as fuel. An intermediate porous layer of YSZ was introduced between the electrolyte and the cathode improving the performance of the cell. Values for power density of 300 mW cm−2 at 700◦C and ca. 500 mW cm−2 at 800◦C in this configuration were achieved.

Quality of Qualitative Research in the Health Sciences : Analysis of the Common Criteria Present in 58 Assessment Guidelines by Expert Users

The number of qualitative research methods has grown substantially over the last twenty years, both in social sciences and, more recently, in the health sciences. This growth came with questions on the quality criteria needed to evaluate this work, and numerous guidelines were published. The latters include many discrepancies though, both in their vocabulary and construction. Many expert evaluators decry the absence of consensual and reliable evaluation tools. The authors present the results of an evaluation of 58 existing guidelines in 4 major health science fields (medicine and epidemiology; nursing and health education; social sciences and public health; psychology / psychiatry, research methods and organization) by expert users (article reviewers, experts allocating funds, editors, etc.). The results propose a toolbox containing 12 consensual criteria with the definitions given by expert users. They also indicate in which disciplinary field each type of criteria is known to be more or less essential. Nevertheless, the authors highlight the limitations of the criteria comparability, as soon as one focuses on their specific definitions. They conclude that each criterion in the toolbox must be explained to come to broader consensus and identify definitions that are consensual to all the fields examined and easily operational.

Complexity of the Paradigms Present in Quality Criteria of Qualitative Research Grids

With qualitative methods being increasingly used in health science fields, numerous grids proposing criteria to evaluate the quality of this type of research have been produced. Expert evaluators deem that there is a lack of consensual tools to evaluate qualitative research. Based on the review of 133 quality criteria grids for qualitative research in health sciences, the authors present the results of a computerized lexicometric analysis, which confirms the variety of intra- and inter-grid constructions, including within the same field. This variety is linked to the authors' paradigmatic references underlying the criteria proposed. These references seem to be built intuitively, reflecting internal representations of qualitative research, thus making the grids and their criteria hard to compare. Consequently, the consensus on the definitions and the number of criteria becomes problematic. The paradigmatic and theoretical references of the grids should be specified so that users could better assess their contributions and limitations.

Comission 49: Interplanetary plasma and heliosphere. TRIENNIAL REPORT 2006 - 2009

Commission 49 covers research on the solar wind, shocks and particle acceleration, both transient and steady-state, e.g., corotating, structures within the heliosphere, and the termination shock and boundary of the heliosphere. The present triennal report is particularly rich in important results and events. The crossing of the solar wind termination shock by Voyager 2 in 2007 is a highlight and a milestone that will certainly have important consequences for astrophysical processes in general (Section 7). The fiftieth anniversary of the International Geophysical Year (19571958), which is also the fiftieth anniversary of the birth of the Space Age, was marked not only by celebrations and a strong Education and Public Outreach Program, but also by efforts in coordinating present observations and in starting new scientific programs, particularly implying developing countries (Section 8). Studies of solar energetic particles (Section 3) and the related radio bursts (Section 4) benefited from new data from a number of spacecraft. The STEREO mission was launched in October 2006 and has obtained new results on 3-D aspects of the inner heliosphere. Meanwhile, solar cycle 24 is expected to become active soon, following what is already the deepest solar minimum of the space age...

Visual SLAM for underwater vehicles using video velocity log and natural landmarks

A visual SLAM system has been implemented and optimised for real-time deployment on an AUV equipped with calibrated stereo cameras. The system incorporates a novel approach to landmark description in which landmarks are local sub maps that consist of a cloud of 3D points and their associated SIFT/SURF descriptors. Landmarks are also sparsely distributed which simplifies and accelerates data association and map updates. In addition to landmark-based localisation the system utilises visual odometry to estimate the pose of the vehicle in 6 degrees of freedom by identifying temporal matches between consecutive local sub maps and computing the motion. Both the extended Kalman filter and unscented Kalman filter have been considered for filtering the observations. The output of the filter is also smoothed using the Rauch-Tung-Striebel (RTS) method to obtain a better alignment of the sequence of local sub maps and to deliver a large-scale 3D acquisition of the surveyed area. Synthetic experiments have been performed using a simulation environment in which ray tracing is used to generate synthetic images for the stereo system

L'Univers en una cadira de rodes

Superació. immobilitat. Grandesa intel·lectual. Infinitud finita. Personatge mediàtic. Excepcionalitat. Icona de la ciència. Ateu diuen que una mica divinitzat. Humà, en definitiva. La llista de qualificatius que es podrien utilitzar per definir Stephen Hawking seria, sens dubte, immensa, i segur que no reflectiria tots els aspectes de la seva personalitat. No és fàcil fer una descripció del tot. També és immens l'Univers on vivim, un espai aparentment inhòspit, com una freda cadira de rodes absolutament mecanitzada; però tanmateix ple d'una bellesa captivadora, que hostatja planetes com el nostre, capaços de generar intel·lectes i personalitats tan pròspers, influents i al mateix temps paradoxals com els de Hawking. Una bellesa, la de l'Univers, que no només és visual i cromàtica, sinó també conceptual, física i matemàtica, curulla de relacions aparentment impossibles. Tanmateix, el treball i la vida de Hawking ens l'han fet una mica menys desconegut, una mica més proper; ens han acostat a la teoria del tot.

Gestió de les dades de recerca i biblioteques: relacions, activitats, motors i influències

La gestió de les dades de recerca és un gran repte per a les organitzacions de recerca. Grans quantitats de dades nascudes en entorns digitals estant essent produïdes en una vasta quantitat de formats a un ritme molt accelerat en l’àmbit universitari. Aquest document analitza la contribució de les biblioteques universitàries a la gestió de dades de recerca (RDM) en el context institucional més ampli. En particular: s’examinen els rols i les relacions implicades en la RDM, s’identifiquen els principals components d’un programa de RDM, s’avaluen els principals motors per a les activitats de la RDM i s’analitzen els factors clau que influeixen en la forma que adopten els desenvolupaments que es porten a terme en la RDM. L’estudi està escrit des de la perspectiva de professionals de les biblioteques, tot analitzant dades provinents de 26 entrevistes semiestructurades a personal bibliotecari de diferents institucions del Regne Unit. És una primera contribució qualitativa al tema que complementa altres enfocaments quantitatius i estudis de casos. Els resultats mostren que encara que les biblioteques estan jugant un rol significatiu en la RDM, hi ha incertesa i variacions en les relacions amb altres actors com els serveis de tecnologia de la informació i les oficines de suport a la recerca. L’èmfasi actual en els programes de RDM està en el desenvolupament de polítiques i directrius, amb algun incipient treball sobre infraestructures tecnològiques i serveis de suport. Els motors per al desenvolupament inclouen l’emmagatzematge, la seguretat, la qualitat, el compliment, la preservació i el compartiment, amb les biblioteques associades més estretament als tres darrers. L’article també destaca un motor “jurisdiccional” en el qual les biblioteques reclamen un rol en aquest espai. Un ampli ventall de factors, incloent el govern, la dotació de recursos i les habilitats, són identificats com influents en els desenvolupaments en curs. A partir de l’anàlisi, es construeix un model dissenyat per capturar els aspectes principals d’un programa institucional de RDM. Aquest model ajuda a esclarir els diferents temes implicats en la RDM, tot identificant capes d’activitat, múltiples actors i motors i un gran nombre de factors que influeixen en la implementació de qualsevol iniciativa. A les institucions els pot ser útil comparar les seves activitats amb les dades i el model de cara a informar sobre les activitats de RDM en curs.