Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial.

BACKGROUND: Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. METHODS: In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70-89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0-2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. FINDINGS: 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30.3 months (range 8.6-45.2). Median overall survival was 10.3 months for doublet chemotherapy and 6.2 months for monotherapy (hazard ratio 0.64, 95% CI 0.52-0.78; p<0.0001); 1-year survival was 44.5% (95% CI 37.9-50.9) and 25.4% (19.9-31.3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48.4%] vs 28 [12.4%]; asthenia 23 [10.3%] vs 13 [5.8%]). INTERPRETATION: Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. FUNDING: Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer.

HIV-1 elite controllers: beware of super-infections.

Super- and co-infection with HIV-1 are generally associated with accelerated disease progression. We report on the outcome of super-infection in two HIV-1 infected individuals previously known as elite controllers. Both presented an acute retroviral syndrome following super-infection and showed an immuno-virological progression thereafter. Host genotyping failed to reveal any of the currently recognized protective factors associated with slow disease progression. This report indicates that elite controllers should be informed of the risk of super-infection, and illustrates the complexity of mounting broad anti-HIV immunity.

Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations?

Since 2004, four antiangiogenic drugs have been approved for clinical use in patients with advanced solid cancers, on the basis of their capacity to improve survival in phase III clinical studies. These achievements validated the concept introduced by Judah Folkman that the inhibition of tumor angiogenesis could control tumor growth. It has been suggested that biomarkers of angiogenesis would greatly facilitate the clinical development of antiangiogenic therapies. For these four drugs, the pharmacodynamic effects observed in early clinical studies were important to corroborate activities, but were not essential for the continuation of clinical development and approval. Furthermore, no validated biomarkers of angiogenesis or antiangiogenesis are available for routine clinical use. Thus, the quest for biomarkers of angiogenesis and their successful use in the development of antiangiogenic therapies are challenges in clinical oncology and translational cancer research. We review critical points resulting from the successful clinical trials, review current biomarkers, and discuss their potential impact on improving the clinical use of available antiangiogenic drugs and the development of new ones.

Dominant Role of CD80-CD86 Over CD40 and ICOSL in the Massive Polyclonal B Cell Activation Mediated by LAT(Y136F) CD4(+) T Cells.

Coordinated interactions between T and B cells are crucial for inducing physiological B cell responses. Mutant mice in which tyrosine 136 of linker for activation of T cell (LAT) is replaced by a phenylalanine (Lat(Y136F)) exhibit a strong CD4(+) T cell proliferation in the absence of intended immunization. The resulting effector T cells produce high amounts of T(H)2 cytokines and are extremely efficient at inducing polyclonal B cell activation. As a consequence, these Lat(Y136F) mutant mice showed massive germinal center formations and hypergammaglobulinemia. Here, we analyzed the involvement of different costimulators and their ligands in such T-B interactions both in vitro and in vivo, using blocking antibodies, knockout mice, and adoptive transfer experiments. Surprisingly, we showed in vitro that although B cell activation required contact with T cells, CD40, and inducible T cell costimulator molecule-ligand (ICOSL) signaling were not necessary for this process. These observations were further confirmed in vivo, where none of these molecules were required for the unfolding of the LAT CD4(+) T cell expansion and the subsequent polyclonal B cell activation, although, the absence of CD40 led to a reduction of the follicular B cell response. These results indicate that the crucial functions played by CD40 and ICOSL in germinal center formation and isotype switching in physiological humoral responses are partly overcome in Lat(Y136F) mice. By comparison, the absence of CD80-CD86 was found to almost completely block the in vitro B cell activation mediated by Lat(Y136F) CD4(+) T cells. The role of CD80-CD86 in T-B cooperation in vivo remained elusive due to the upstream implication of these costimulatory molecules in the expansion of Lat(Y136F) CD4(+) T cells. Together, our data suggest that CD80 and CD86 costimulators play a key role in the polyclonal B cell activation mediated by Lat(Y136F) CD4(+) T cells even though additional costimulatory molecules or cytokines are likely to be required in this process.

Deaths rates in public hospitals of eastern cape province of South Africa.

BACKGROUND: South Africa (SA) is experiencing a rapid epidemiologic transition as a consequence of political, economic and social changes. In this study we described, based on hospital data, the mortality patterns of Non communicable Diseases (NCD), Communicable Diseases (CD), the NCD/CD ratios, and the trends of deaths. METHODS: We conducted a cross-sectional survey of all deaths occurring in several public hospitals in the Eastern Cape Province of SA between 2002 and 2006. Causes of deaths were coded according to the ICD 10 Edition. RESULTS: A total of 107380 admissions responded to the inclusion criteria between 2002 and 2006. The crude death rate was 4.3% (n=4566) with a mean age of 46±21 years and a sex ratio of 3.1 men (n=3453): 1 woman (n=1113). Out of all deaths, there were 62.9% NCD (n=2872) vs. 37.1% CD (n=1694) with NCD/CD ratio of 1.7. The ratio NCD/CD deaths in men was 1.3 (n=1951/1502) vs. NCD/CD deaths in women of 1.9 (n=735/378). The peak of deaths was observed in winter season. The majority of NCD deaths were at age of 30-64 years, whereas the highest rate of CD deaths was at age< 30 years. The trend of deaths including the majority of NCD, increased from 2002 to 2006. There was a tendency of increase in tuberculosis deaths, but a tendency of decrease in HIV/AIDS deaths was from 2002 to 2006. CONCLUSION: Non-communicable diseases are the leading causes of deaths in rural Eastern Cape province of SA facing Post-epidemiologic transition stages. We recommend overarching priority actions for the response to the Non-communicable Diseases: policy change, prevention, treatment, international cooperation, research, monitoring, accountability, and re-orientation of health systems.

Prise en charge du cholestérol pour prévenir le risque cardiovasculaire:recommandations américaines 2013.Prise de position du Groupe de travail Suisse Lipides et Athérosclérose (GSLA).

Les dernières recommandations américaines de l'American College of Cardiology et de l'American Heart Association proposent d'abaisser le seuil de prescription de statines pour la prévention cardiovasculaire primaire, et d'abandonner les cibles de LDL-cholestérol pour utiliser le plus souvent des statines de haute intensité. Le Groupe de travail Suisse Lipides et Athérosclérose (GSLA) pense que ces recommandations ne devraient pas être appliquées en Suisse, car elles augmenteraient très fortement le nombre de personnes à bas risque sous statines, chez qui le rapport bénéfice/risque au long cours est incertain, et pourraient diminuer l'importance du style de vie, première priorité dans la prévention cardiovasculaire primaire. En outre, l'abandon des cibles de LDL-cholestérol limite l'individualisation de la prise en charge quant au choix du type et du dosage de la statine, et pourrait diminuer l'adhérence thérapeutique. Pour ces raisons, le GSLA recommande de poursuivre avec les stratégies de prévention bien établies en Suisse et résumées dans les recommandations du GSLA 2012.

Personality and personality disorders in urban and rural Africa: results from a field trial in Burkina Faso

When conducting research in different cultural settings, assessing measurement equivalence is of prime importance to determine if constructs and scores can be compared across groups. Structural equivalence implies that constructs have the same meaning across groups, metric equivalence implies that the metric of the scales remains stable across groups, and full scale or scalar equivalence implies that the origin of the scales is the same across groups. Several studies have observed that the structure underlying both normal personality and personality disorders (PDs) is stable across cultures. Most of this cross-cultural research was conducted in Western and Asian cultures. In Africa, the few studies were conducted with well-educated participants using French or English instruments. No research was conducted in Africa with less privileged or preliterate samples. The aim of this research was to study the structure and expression of normal and abnormal personality in an urban and a rural sample in Burkina Faso. The sample included 1,750 participants, with a sub-sample from the urban area of Ouagadougou (n = 1,249) and another sub-sample from a rural village, Soumiaga (n = 501). Most participants answered an interview consisting of a Mooré language adaptation of the Revised NEO Personality Inventory and of the International Personality Disorders Examination. Mooré is the language of the Mossi ethnic group, and the most frequently spoken local language in Burkina Faso. A sub-sample completed the same self-report instruments in French. Demographic variables only had a small impact on normal and abnormal personality traits mean levels. The structure underlying normal personality was unstable across regions and languages, illustrating that translating a complex psychological inventory into a native African language is a very difficult task. The structure underlying abnormal personality and the metric of PDs scales were stable across regions. As scalar equivalence was not reached, mean differences cannot be interpreted. Nevertheless, these differences could be due to an exaggerated expression of abnormal traits valued in the two cultural settings. Our results suggest that studies using a different methodology should be conducted to understand what is considered, in different cultures, as deviating from the expectations of the individual's culture, and as a significant impairment in self and interpersonal functioning, as defined by the DSM-5.

Les competències genèriques en l’educació superior. Recerca sobre la percepció dels estudiants respecte l’impacte que té la metodologia de Seminari de Blanquerna en l’adquisició de competències genèriques.

L'objectiu de l'article és contribuir a la reflexió actual sobre les competències genèriques en l'educació superior. Es va desenvolupar una investigació sobre l'adquisició de competències genèriques en els programes de ciències socials de llicenciatura (Psicologia) de Blanquerna-Universitat Ramon Llull. Per a aquests estudis s’ha estat desenvolupant una metodologia innovadora anomenada Seminari. El seu propòsit se centra, entre altres qüestions, en el desenvolupament de competències genèriques. En primer lloc, les competències genèriques són avaluades respecte si són o no són percebudes com a importants per part dels estudiants d'últim curs, i respecte quin és el context principal per la seva adquisició. La metodologia de Seminari, que es caracteritza en aquest estudi, correlaciona més estretament amb la percepció de la importància de les competències en el món professional que els altres contextos, fins i tot les assignatures o l’adquisició de competències fora de la universitat. La investigació té com a objectiu el contribuir a aconseguir una millor comprensió dels millors contextos per a l'adquisició de competències genèriques en l'educació superior i de la importància d’aquestes en el món professional. Es desenvolupa implícitament una metodologia per a l'estudi de l'adquisició de competències i per a la caracterització d'un model educatiu centrat en competències.

Metodologies per a la coresponsabilitat en l'aprenentatge universitari

L’Espai Europeu d’Educació Superior ha propiciat un replantejament metodològic basat en el desenvolupament de competències que permet formular noves propostes d’estil docent universitari. En aquest article plantegem un model metodològic proper als principis del constructivisme social i del pensament complex, aplicable a un mòdul dels estudis de grau en Educació Infantil i en Educació Primària, analitzant diferents estratègies didàctiques utilitzades per facilitar l’aprenentatge dels estudiants. Les diverses propostes metodològiques tenen com a denominador comú que totes elles estan centrades en l’alumne, que dinamitzen diferents àmbits competencials i que afavoreixen la coresponsabilitat entre professor i estudiant en el procés d’aprenentatge. Els resultats d’un estudi fet el curs 2008-09 sobre la percepció dels estudiants en relació a metodologies afins a les proposades, ens han resultat d’utilitat a l’hora de ratificar la pertinença de la majoria d’estratègies, per incorporar-les al pla docent del mòdul Societat, família i escola I.

Una Proposta d'avaluació per competències a la universitat en una estructura modular

En aquest treball presentem una proposta d’avaluació per competències en una estructura modular que és fruit de la nostra experiència com a professors universitaris. Volem oferir un instrument d’avaluació conjunta per a tot l’equip de professors de mòdul que sigui vàlid, àgil i operatiu i que permeti donar feedback a cada estudiant del seu procés d’aprenentatge. Després de presentar els trets més singulars de la nostra institució i exposar alguns referents teòrics en relació a l’avaluació de competències, indiquem quines són les competències que hem seleccionat i aprofundim en la metodologia de treball i avaluació de les mateixes. Aquesta metodologia varia segons els espais acadèmics: gran grup, grup mig i seminari. A cadascun d’aquests espais es treballen i s’avaluen unes competències determinades, tot i que d’una forma més genèrica totes es desenvolupen conjuntament ens els tres àmbits. Considerem que és fonamental assenyalar que no es tracta d’avaluar “per assignatures” ni “per activitats”, sinó d’avaluar les competències que es desenvolupen a través de les matèries i de les propostes de treball que s’especifiquen en el pla docent.. L’ instrument d’avaluació que presentem possibilita la participació de tot el professorat implicat en el mateix mòdul i alhora permet que cada professor utilitzi els seus propis indicadors d’avaluació, aconseguint harmonitzar les dinàmiques de treball individuals i de grup.

Educació física en anglès : percepcions dels estudiants entorn d'una experiència metodològica en el marc universitari

L’article presenta una experiència AICLE en el marc universitari, a través de l’execució de dues assignatures de l’àrea d’educació física dels estudis de Magisteri en llengua anglesa. El projecte suposa una primera experiència pilot de la introducció d’assignatures AICLE a la FPCEE Blanquerna (Universitat Ramon Llull), abans de la plena implementació dels nous plans d’estudi. Es mostra una proposta didàctica pel tractament de les assignatures en format AICLE, així com, una anàlisi de les creences dels estudiants participants entorn l’experiència desenvolupada. La metodologia de la recerca, basada en una investigació acció, ha utilitzat dues estratègies de recollida de dades: els grups de discussió i el diari de classe. L’anàlisi qualitativa de les dades s’ha realitzat amb el suport del ATLAS.ti. Els resultats i la discussió permeten introduir nous indicadors d’interès al debat metodològic de les assignatures en format AICLE en el marc universitari.