Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial.

BACKGROUND: Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches. METHODS: In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386. FINDINGS: Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045). INTERPRETATION: Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules. FUNDING: French Ministry of Health.

Cognitive efficacy of quetiapine in early-onset first-episode psychosis: a 12-week open label trial.

Twenty-three adolescents with psychotic disorders, aged from 13 to 18 years, participated in a 12-week open label trial (17 adolescents completed the study) in order to examine the impact of quetiapine on clinical status and cognitive functions (encompassing processing speed, attention, short-term memory, long-term memory and executive function). An improvement in Clinical Global Impression and Positive and Negative Symptom Scale (P's ≤ 0.001) was observed. In addition, after controlling for amelioration of symptoms, a significant improvement was observed on one executive function (P = 0.044; Trail Making Part B). The remaining cognitive abilities showed stability. In addition, we observed an interaction between quetiapine doses (>300 mg/day or <300 mg/day) and time, where lower doses showed more improvement in verbal short-term memory (P = 0.048), inhibition abilities (P = 0.038) and positive symptoms (P = 0.020). The neuropsychological functioning of adolescents with psychotic disorders remained mainly stable after 12 weeks of treatment with quetiapine. However, lower doses seemed to have a better impact on two components of cognition (inhibition abilities and verbal short-term memory) and on positive symptoms.

Overuse of upper gastrointestinal endoscopy in a country with open-access endoscopy: a prospective study in primary care.

BACKGROUND: This prospective observational study was aimed at evaluating the appropriateness of use of upper gastrointestinal endoscopy (UGE) in primary care in a country with open access to and high availability of the procedure. METHODS: Outpatients were consecutively included in two clinical settings: Setting A (20 primary care physicians during 4 weeks) and B (university-based outpatient clinic during 3 weeks). In patients undergoing UGE, appropriateness of referral was judged by explicit Swiss criteria developed by the RAND/UCLA panel method. RESULTS: Patient visits (8135) were assessed. Six hundred eleven patients complained of upper gastrointestinal symptoms. Physicians decided to perform UGE in 63 of these patients. Twenty-five (40%) of the endoscopies were rated appropriate, 7 (11%) equivocal, and 31 (49%) inappropriate. Overuse of UGE occurred in 5.1% (setting A: 4.7%; setting B:6.5%; p = 0.39) of the patients who presented with upper gastrointestinal symptoms. The decision to perform UGE in previously untreated dyspeptic patients was the most common clinical situation resulting in overuse. CONCLUSIONS: Inappropriate use of UGE is high in Switzerland. However, to better reflect primary care decision making, overuse should be related not only to patients referred for a medical test, but also to the number of patients who complain of the symptoms that would be investigated by the procedure.

Open to closed system transition traced through the TDIC isotopic signature at the aquifer recharge stage, implications for groundwater 14C dating

14C dating models are limited when considering recent groundwater for which the carbon isotopic signature of the total dissolved inorganic carbon (TDIC) is mainly acquired in the unsaturated zone. Reducing the uncertainties of dating thus implies a better identification of the processes controlling the carbon isotopic composition of the TDIC during groundwater recharge. Geochemical interactions between gas, water and carbonates in the unsaturated zone were investigated for two aquifers (the carbonate-free Fontainebleau sands and carbonate-bearing Astian sands, France) in order to identify the respective roles of CO2 and carbonates on the carbon isotopic signatures of the TDIC; this analysis is usually approached using open or closed system terms. Under fully open system conditions, the seasonality of the 13C values in the soil CO2 can lead to important uncertainties regarding the so-called "initial 14C activity" used in 14C correction models. In a carbonate-bearing unsaturated zone such as in the Astian aquifer, we show that an approach based on fully open or closed system conditions is not appropriate. Although the chemical saturation between water and calcite occurs rapidly within the first metre of the unsaturated zone, the carbon isotopic contents (δ13C) of the CO2 and the TDIC evolve downward, impacted by the dissolution-precipitation of the carbonates. In this study, we propose a numerical approach to describe this evolution. The δ13C and the A 14C (radiocarbon activity) of the TDIC at the base of the carbonate-hearing unsaturated zone depends on (i) the δ13C and the A 14C of the TDIC in the soil determined by the soil CO2, (ii) the water's residence time in the unsaturated zone and (iii) the carbonate precipitation-dissolution fluxes. In this type of situation, the carbonate δ13C-A 14C evolutions indicate the presence of secondary calcite and permit the calculation of its accretion flux, equal to ~ 4.5 ± 0.5 x 10-9 mol grock-1 yr-1. More generally, for other sites under temperate climate and with similar properties to the Astian sands site, this approach allows for a reliable determination of the carbon isotopic composition at the base of the unsaturated zone as the indispensable "input function" data of the carbon cycle into the aquifer.

Open elbow arthrolysis for posttraumatic elbow stiffness

Résumé Introduction et objectif : l'articulation du coude est vulnérable à l'enraidissement, en particulier après un traumatisme. Le but de cette étude est d'évaluer les résultats du traitement chirurgical des raideurs post-traumatiques du coude. Type d'étude : étude rétrospective de cohorte. Les patients : dix-huit patients ont été évalués cliniquement par un observateur indépendant dans un intervalle moyen de 16 mois (6 à 43) après avoir subi une arthrolyse ouverte du coude, avec comme indication opératoire une raideur post traumatique du coude. Les traumatismes subis étaient : 11 fractures isolées, 1 luxation isolée, 6 fracture-luxations complexes. Les prises en charge initiales étaient : non-chirurgicales pour 3 patients, résection de la tête radiale pour 1 patient, réduction ouverte et ostéosynthèse pour 14 patients. Les patients ont présenté des types de raideurs mixtes pour la plupart d'entre eux. Type d'intervention : arthrolyse ouverte du coude. Evaluation : la fonction du coude et la satisfaction des patients furent les principales données récoltées. Lacs de l'évaluation, les scores de SECEC (Société Européenne de Chirurgie d'Epaule et du Coude) ont été calculés. Une analyse radiologique a aussi été effectuée. Résultats : trois patients ont présenté des complications postopératoires mineures : 1 déhiscence de plaie, 1 infection sous-cutanée, 1 sérome. Aucune de ces complications n'a eu de répercussion sur le résultat final. Le gain d'amplitude articulaire moyen était de 40°, avec un gain moyen en flexion du coude de 14° (0°-45°), et de 26° en extension (5°-67°) Aucun patient n'a présenté d'instabilité du coude. Il n'y a pas eu de signe de progression d'arthrose sur les clichés radiographiques à la revue. Nous n'avons pas mis en évidence de rapport entre le type de raideur et la voie d'abord sur les résultats. Les patients ayant présentés les raideurs les plus importantes ont bénéficiés des meilleurs résultats en terme de mobilité (p<0.001). Les meilleurs résultats ont été obtenus pour les patients opérés dans la première année aptes le traumatisme initial (p=0.008). Le score SECEC moyen était de 88 points pour les coudes opérés (52-100), et de 96 points pour les coudes sains (88-100). Conclusion : l'arthrolyse ouverte confère de bons résultats pour les patients présentant une raideur post traumatique du coude. Les meilleurs résultats sont obtenus pour les patients présentant une raideur sévère, prise en charge dans l'année qui suit le traumatisme initial.

Comparative genomics of epidemic versus sporadic Staphylococcus aureus strains does not reveal molecular markers for epidemicity.

Staphylococcus aureus, especially when it is methicillin resistant, has been recognised as a major cause of nosocomial and community-acquired infections. It has also been shown that certain strains were able to cause clonal epidemics whereas others showed a more incidental occurrence. On the basis of this behavioural distinction, a genetic feature underlying this difference in epidemicity can be assumed. Understanding the difference will not only contribute to the development of markers for the identification of epidemic strains but will also shed light on the evolution of clones. Genomes of strains from two independent collections (n=18 and n=10 strains) were analysed. Both collections were composed of carefully selected, genetically diverse strains with clinically well-defined epidemic and sporadic behaviour. Comparative genome hybridisation (CGH) was performed using an Agilent array for one collection (up to 11 probes per open reading frame - ORF), and an Affymetrix array for the other (up to 30 probes per ORF). Presence and absence information of probe homologues and ORFs was taken for analysis of molecular variance (AMOVA) at the strain and behaviour levels. Not a single probe showed 100% concordant differences between epidemic and sporadic strains. Moreover, probe differences between groups were always smaller than those within groups. This was also true, when the analysis was focussed on presence versus absence of ORF's or when probe information was transformed into allelic profiles. These findings present strong evidence against the presence or absence of a single common specific genetic factor differentiating epidemic from sporadic S. aureus clones.

Intangible Capital: four years of growth as an open-access scientific publication

Con este nuevo número, la revista Intangible Capital, inicia el cuarto volumen avanzando hacia el quinto año de publicación. Como ya es tradición en la revista, iniciamos este nuevo volumen evaluando el anterior y presentando las nuevas direcciones. Como principales aportaciones del 2007, se destacan hechos relevantes como la renovación de convenios para la indexación científica de la revista, el cambio de plataforma a OJS, la inclusión de un nuevo editor, la nueva composición del editorial board, el equipo de revisores, el cambio a un modelo bilingüe de revista, la nueva financiación obtenida y el trabajo que estamos realizando gran número de editores científicos de acceso abierto en España para el reconocimiento por parte de la Comisión Nacional Evaluadora de la Actividad Investigadora.This issue opens the fourth volume of the Intangible Capital journal, which makes its way towards the fifth year of publication. As usually, we start this volume by evaluating the previous one and tracing new directions. Among the main contributions during the year 2007, we consider important to highlight the following aspects: the renewal of the scientific indexation agreements, the platform change to OJS, the appointment of a new editor, new members included in the editorial board, the board of reviewers, the change towards a bilingual model, the new financing obtained and, the last but not the least, the work undertaken together with many scientific editors of open access Spanish journals for obtaining the positive evaluation of the CNEAI (National Commission for the Evaluation of the Research Activity) and thus, being a proof of scientific excellence

Impact of bedside open lung biopsies on the management of mechanically ventilated immunocompromised patients with acute respiratory distress syndrome of unknown etiology.

BACKGROUND: Open lung biopsy (OLB) is helpful in the management of patients with acute respiratory distress syndrome (ARDS) of unknown etiology. We determine the impact of surgical lung biopsies performed at the bedside on the management of patients with ARDS. METHODS: We reviewed all consecutive cases of patients with ARDS who underwent a surgical OLB at the bedside in a medical intensive care unit between 1993 and 2005. RESULTS: Biopsies were performed in 19 patients mechanically ventilated for ARDS of unknown etiology despite extensive diagnostic process and empirical therapeutic trials. Among them, 17 (89%) were immunocompromised and 10 patients experienced hematological malignancies. Surgical biopsies were obtained after a median (25%-75%) mechanical ventilation of 5 (2-11) days; mean (+/-SD) Pao(2)/Fio(2) ratio was 119.3 (+/-34.2) mm Hg. Histologic diagnoses were obtained in all cases and were specific in 13 patients (68%), including 9 (47%) not previously suspected. Immediate complications (26%) were local (pneumothorax, minimal bleeding) without general or respiratory consequences. The biopsy resulted in major changes in management in 17 patients (89%). It contributed to a decision to limit care in 12 of 17 patients who died. CONCLUSION: Our data confirm that surgical OLB may have an important impact on the management of patients with ARDS of unknown etiology after extensive diagnostic process. The procedure can be performed at the bedside, is safe, and has a high diagnostic yield leading to major changes in management, including withdrawal of vital support, in the majority of patients.

An analysis of the currently available calibrations inStromgren photometry by using open clusters

In recent years, several authors have revised the calibrations used to compute physical parameters (tex2html_wrap_inline498, tex2html_wrap_inline500, log g, [Fe/H]) from intrinsic colours in the tex2html_wrap_inline504 photometric system. For reddened stars, these intrinsic colours can be computed through the standard relations among colour indices for each of the regions defined by Strömgren (1966) on the HR diagram. We present a discussion of the coherence of these calibrations for main-sequence stars. Stars from open clusters are used to carry out this analysis. Assuming that individual reddening values and distances should be similar for all the members of a given open cluster, systematic differences among the calibrations used in each of the photometric regions might arise when comparing mean reddening values and distances for the members of each region. To classify the stars into Strömgren's regions we extended the algorithm presented by Figueras et al. (1991) to a wider range of spectral types and luminosity classes. The observational ZAMS are compared with the theoretical ZAMS from stellar evolutionary models, in the range tex2html_wrap_inline506 K. The discrepancies are also discussed.

Aproximació al moviment "open access"

[eng] The article describes the background and current state of the open access (OA) movement. Its objectives --with roots in scientists' traditional desire to disseminate their works, in librarians' concerns about the serials crisis, and in technological advances-- were formally articulated in the Budapest Open Access Initiative (BOAI) declaration of 2002. This statement established two strategies for providing access to scientific information without any economic, technical, or legal obstacles: 1) publication of articles in OA journals or 2) deposit by authors of their works in stable institutional or subject-based repositories. The article suggests that this second "route" appears to offer greater possibilities of attaining open access in the short term. However, there still is a lot of work to be done in disseminating the concepts of OA and in training authors regarding procedures for depositing their works: in other words what is needed is a series of promotional activities for overcoming one of today's greatest challenges: author inertia.

The situation of open access institutional repositories in Spain: 2009 report

Introduction. The DRIVER I project drew up a detailed report of European repositories based on data gathered in a survey in which Spain's participation was very low. This created a highly distorted image of the implementation of repositories in Spain. This study aims to analyse the current state of Spanish open-access institutional repositories and to describe their characteristics. Method. The data were gathered through a Web survey. The questionnaire was based on that used by DRIVER I: coverage; technical infrastructure and technical issues; institutional policies; services created; and stimulators and inhibitors for establishing, filling and maintaining their digital institutional repositories. Analysis. Data were tabulated and analysed systematically according responses obtained from the questionnaire and grouped by coverage. Results. Responses were obtained from 38 of the 104 institutions contacted, which had 29 institutional repositories. This represents 78.3% of the Spanish repositories according to the BuscaRepositorios directory. Spanish repositories contained mainly full-text materials (journal articles and doctoral theses) together with metadata. The software most used was DSpace, followed by EPrints. The metadata standard most used was Dublin Core. Spanish repositories offered more usage statistics and fewer author-oriented services than the European average. The priorities for the future development of the repositories are the need for clear policies on access to scientific production based on public funding and the need for quality control indicators. Conclusions.This is the first detailed study of Spanish institutional repositories. The key stimulants for establishing, filling and maintaining were, in order of importance, the increase of visibility and citation, the interest of decision-makers, simplicity of use and search services. On the other hand the main inhibitors identified were the absence of policies, the lack of integration with other national and international systems and the lack of awareness efforts among academia.

A virtual exhibition of open source software for libraries

Frequently the choice of a library management program is conditioned by social, economic and/or political factors that result in the selection of a system that is not altogether suitable for the library’s needs, characteristics and functions. Open source software is quickly becoming a preferred solution, owing to the freedom to copy, modify and distribute it and the freedom from contracts, as well as for greater opportunities for interoperability with other applications. These new trends regarding open source software in libraries are also reflected in LIS studies, as evidenced by the different courses addressing automated programs, repositorymanagement, including the Linux/GNU operating system, among others. The combination of the needs of the centres and the new trends for open source software is the focus of a virtual laboratory for the use of open source software for library applications. It was the result of a project, whose aim was to make a useful contribution to the library community, that was carried out by a group of professors of the School of Library and Information Science of the University of Barcelona, together with a group of students, members of a Working Group on Open Source Software for Information Professionals, of the Professional Library Association of Catalonia.

Neuronal activity in the hub of extrasynaptic Schwann cell-axon interactions.

The integrity and function of neurons depend on their continuous interactions with glial cells. In the peripheral nervous system glial functions are exerted by Schwann cells (SCs). SCs sense synaptic and extrasynaptic manifestations of action potential propagation and adapt their physiology to support neuronal activity. We review here existing literature data on extrasynaptic bidirectional axon-SC communication, focusing particularly on neuronal activity implications. To shed light on underlying mechanisms, we conduct a thorough analysis of microarray data from SC-rich mouse sciatic nerve at different developmental stages and in neuropathic models. We identify molecules that are potentially involved in SC detection of neuronal activity signals inducing subsequent glial responses. We further suggest that alterations in the activity-dependent axon-SC crosstalk impact on peripheral neuropathies. Together with previously reported data, these observations open new perspectives for deciphering glial mechanisms of neuronal function support.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. METHODS: In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. FINDINGS: Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8-28·8) in the cilengitide group and 26·3 months (23·9-34·7) in the control group (hazard ratio 1·02, 95% CI 0·81-1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). INTERPRETATION: The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. FUNDING: Merck KGaA, Darmstadt, Germany.