Deletion of the viral anti-apoptotic gene F1L in the HIV/AIDS vaccine candidate MVA-C enhances immune responses against HIV-1 antigens.

Vaccinia virus (VACV) encodes an anti-apoptotic Bcl-2-like protein F1 that acts as an inhibitor of caspase-9 and of the Bak/Bax checkpoint but the role of this gene in immune responses is not known. Because dendritic cells that have phagocytosed apoptotic infected cells cross-present viral antigens to cytotoxic T cells inducing an antigen-specific immunity, we hypothesized that deletion of the viral anti-apoptotic F1L gene might have a profound effect on the capacity of poxvirus vectors to activate specific immune responses to virus-expressed recombinant antigens. This has been tested in a mouse model with an F1L deletion mutant of the HIV/AIDS vaccine candidate MVA-C that expresses Env and Gag-Pol-Nef antigens (MVA-C-ΔF1L). The viral gene F1L is not required for virus replication in cultured cells and its deletion in MVA-C induces extensive apoptosis and expression of immunomodulatory genes in infected cells. Analysis of the immune responses induced in BALB/c mice after DNA prime/MVA boost revealed that, in comparison with parental MVA-C, the mutant MVA-C-ΔF1L improves the magnitude of the HIV-1-specific CD8 T cell adaptive immune responses and impacts on the CD8 T cell memory phase by enhancing the magnitude of the response, reducing the contraction phase and changing the memory differentiation pattern. These findings reveal the immunomodulatory role of F1L and that the loss of this gene is a valid strategy for the optimization of MVA as vaccine vector.

¿Por qué no ha fructificado la propuesta del profesor como investigador? Y algunas propuestas para resistir a un presente nostálgico

En aquest article es revisa el marc que ha permès situar algunes de les propostes de John Elliot en l'educació espanyola. En especial, es para atenció al desafiament que va suposar el plantejament de la investigació en l'acció i la noció del professor com a investigador. Alhora que s'analitza la seva acollida favorable inicial entre una part de la comunitat acadèmica i el professorat innovador, es revisen algunes de les possibles causes de per què no va fructificar en el marc d'una reforma com la de 1990. Tot això serveix de pont per destacar la vigència de les idees i aportacions de John Elliott, amb motiu de la seva investidura com a doctor honoris causa per la Universitat Autònoma de Barcelona, en el moment històric que viu el nostre sistema educatiu a partir de l'aprovació de la LOCE. Tenir en compte les idees i propostes de John Elliott pot suggerir-nos algunes formes de resistència en un moment que molts educadors innovadors i compromesos en el seu treball viuen com a profundament regressiu.

Evaluation des campagnes de prévention contre le SIDA en Suisse : Kantonale Strategien der AIDS-Prävention und -Bekämpfung : Schlussbericht 1988

Der vorliegende Bericht versucht, zusammenfassend den Fortgang der Präventionsarbeit in ausgewählten Kantonen bis November 1988 nachzuvollziehen und nach bestimmten Kriterien analytisch zu beurteilen. Die Studie lehnt sich an die von 1987, "Kantonale Aktivitäten der AIDS-Prävention", an. Es wird bei dieser Untersuchung aber nicht darum gehen, einen Katalog der Massnahmen, welche in den ausgewählten Kantonen getrooffen wurden, zu erstellen. Vielmehr wird der Prozess, der sich auf kantonaler Ebene im Bereich der Aidsprophylaxe abspielt, im Mittelpunkt der Aufmerksamkeit stehen. Im Verlaufe der Etablierung und Institutionalisierung der AIDS-Prävention werden auf Konzepte und Strategien entwickelt, die aufeinander abgestimmt werden müssen. Dem Zusammenspiel zwischen den verschiedenen, an der AIDS-Prävention und -Bekämpfung beteiligten Akteuren und der Koordination ihrer je einzelnen Konzepte und Strategien wird deshalb besondere Aufmerksamkeit geschenkt. Die Prozess der Institutionalisierung der AIDS-Prävention auf kantonaler Ebene, eventuelle Formen der Planifikation der Gesundheitsvorsorge, bilden einen weiteren Teil des Untersuchungsinteresses.

HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies.

OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively for 104 921 person-years. We used Poisson regression models to identify factors independently associated with deaths from ADM and nADM. Analyses of factors associated with mortality due to nADM were repeated after excluding nADM known to be associated with a specific risk factor. RESULTS: Three hundred five patients died due to a malignancy, 298 prior to the cutoff for this analysis (ADM: n = 110; nADM: n = 188). The mortality rate due to ADM decreased from 20.1/1000 person-years of follow-up [95% confidence interval (CI) 14.4, 25.9] when the most recent CD4 cell count was <50 cells/microl to 0.1 (0.03, 0.3)/1000 person-years of follow-up when the CD4 cell count was more than 500 cells/microl; the mortality rate from nADM decreased from 6.0 (95% CI 3.3, 10.1) to 0.6 (0.4, 0.8) per 1000 person-years of follow-up between these two CD4 cell count strata. In multivariable regression analyses, a two-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality included lower CD4 cell count, older age, current/ex-smoking status, longer cumulative exposure to combination antiretroviral therapy, active hepatitis B infection and earlier calendar year. CONCLUSION: The severity of immunosuppression is predictive of death from both ADM and nADM in HIV-infected populations.

¿Hi ha diferències emocionals entre els TGD?

Aquest treball final de grau s'ha plantejat amb el principal objectiu de realitzar una recerca bibliogràfica, el més actualitzada possible, on es recullin les característiques fonamentals dels trastorns generalitzats del desenvolupament (avaluació, diagnòstic, tractament, etc.).

Prévention du sida chez les toxicomanes en Suisse: une évolution encourageante. [Prevention of AIDS in drug addicts in Switzerland: an encouraging development].

Switzerland has adopted a prevention strategy including the promotion of non-sharing injection material and use of condoms. The access to sterile equipment has been made easier, but regional differences still exist. Studies conducted between 1989 and 1992 among drug users in different Swiss regions are reviewed in order to examine if progress in prevention occurred. Syringe sharing diminished everywhere, but rather high sharing rates persist where sterile material is less accessible. Condom use increased, but the situation is still unsatisfactory considering the high HIV prevalence among i.v. drug users. Where several surveys have been conducted consecutively, a stabilization of HIV prevalence was observed. This suggests a slowing down of the progression of the epidemic among drug users. These results, obtained in few years, are encouraging in the light of the pessimism which prevailed at the beginning of the epidemic about the ability of drug users to adopt preventive behaviour.

The study club program : suggestions relating to courses of study and aids furnished by the Traveling Library, 1909

This leaflet includes information on programs for Women's Clubs. Some possible subjects for the club's discussions are literature, history and fine arts. Several methods of study are covered. Groups are encouraged to use public libraries and the Iowa Traveling Library to obtain reference materials for their topics.

Com ha de ser una activitat científica efectiva basada en l'experimentació i l'estudi de l'entorn proper? Estudi de casos i proposta de criteris a tenir en compte en el disseny d’activitats científiques escolars en l’entorn

Actualment moltes fonts d'informació ens descriuen i argumenten com han de ser les activitats científiques a l'escola per garantir l'aprenentatge significatiu de l'alumnat, i d'altres estudis ens mostren com han de ser les activitats escolars en l'entorn; però no hi ha estudis que ens descriguin i argumentin com han de ser les activitats científiques escolars basades en l'experimentació i l'estudi de l'entorn proper. Així doncs, aquesta investigació s'endinsa per solucionar un problema actual que és: com ha de ser una bona activitat científica escolar basada en l'experimentació i l'estudi de l'entorn proper? En resposta a això, aquest treball es basa en una investigació avaluativa que analitza diversos projectes de ciències basats en l'entorn a partir de l'observació d'uns criteris específics elaborats, per una banda a partir de les idees d'experts sobre com ha de ser una bona activitat científica i com ha de ser una activitat escolar d'entorn efectiva; i per altra banda a partir de les idees extretes de les entrevistes fetes a mestres promotores de projectes científics escolars innovadors centrats i duts a terme en l'entorn proper.

“¿Cómo ha ido la Feria?” Estimación del impacto económico de acontecimientos turístos: tres estudios de caso

Los acontecimientos pueden contribuir al desarrollo turístico de una ciudad y beneficiar a sus habitantes y empresas. Sin embargo, para poder diseñar los acontecimientos correctamente, es necesario comprender qué características determinan su impacto económico. Esta investigación pretende contribuir a tal entendimiento mediante la estimación y comparación del impacto económico de tres acontecimientos. Para estimar el impacto económico adoptamos un modelo básico de tres factores: (1) número de visitantes por (2) gasto medio por turista por (3) multiplicador. Primero estimamos el número de visitantes particulares y profesionales mediante diversos sistemas de conteo, encuestas personales e información suministrada por el organizador de los eventos. En segundo lugar, obtuvimos los importes y componentes del gasto de los visitantes por medio de una encuesta; también contamos los gastos de organización de los eventos a partir de sus respectivos presupuestos. Y, tercero, utilizamos multiplicadores de tablas input-output para analizar el impacto de los gastos directos sobre la producción, el valor añadido y el empleo y su distribución entre sectores económicos. Además, calculamos y comparamos ratios de rentabilidad de los tres eventos y dimos recomendaciones para aumentar su impacto económico.

Projecte de reg per degoteig en una parcel•la de 8,5 ha de vinya del celler Lavinyeta situat a Mollet de Peralada

Aquest projecte pretén satisfer la demanda del Celler Lavinyeta, que vol instaurar unsistema de reg per degoteig en una parcel•la de 8,5 ha. Es vol millorar la producció deraïm per a la vinificació però principalment es vol aconseguir obtenir una producció elmés estable possible en el temps.El celler Lavinyeta es troba al terme municipal de Mollet de Peralada, a la comarca del’Alt Empordà. De totes maneres, algunes parcel•les de la finca pertanyen al municipide Sant Climent de Sescebes

Training Aids to Reduce Potential County Liability, HR-289, Draft, 1987

Iowans who travel secondary roads regard these roads as a very important part of their lives. These highways provide a means of transporting products to market and children to school. They are also links to nearby cities and towns. Nearly 3.8 billion vehicle miles of travel occur each year on Iowa's nearly 90,000 mile secondary road system. Accidents do happen. However, improvements in highways, in vehicles, in driver education, in legislation, and in enforcement have combined to make driving in Iowa very safe. If our highways are to remain safe, these efforts need to be continued. This presentation was developed to help county highway department personnel in their effort to maintain and improve highway safety. The presentation is not a standard, specification or regulation.

Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

BACKGROUND: Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. PARTICIPANTS AND METHODS: Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. RESULTS: Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P<5×10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. CONCLUSION: No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.

Constitution, Diversification and Normalisation of a Health Problem: Organising the Fight against AIDS in Switzerland (1984-2005)

The article traces the formation, diversification and normalization of the AIDS cause in Switzerland. Particular emphasis is placed on interactions between the medical field, public authorities and associative space, the latter being understood as the place where individual and collective actors compete to define the cause. The authors argue that the major phases in the structuring of the struggle, the pace of state intervention and the creation of a multi-organizational field, can only be understood if one adopts a 'configurational perspective' attentive to the manner in which, in a given context and under the effect of particular constraints, key actors strategically interact and contribute to transforming their environment and their chances of reaching their goals. This approach takes into account the changing socio-biological characteristics of those who have committed themselves to the cause. In turn, internal movement divisions about how to respond to the epidemic as well as the changing perceptions of the disease have modified the opportunities for commitment, encouraging certain individual kinds of people and excluding others.

Using STD occurence to monitor AIDS prevention : final report of the Working Group on STD Surveillance.

The overall aim of the project has been to assess the extent to which data on the frequency of occurence of STDs [Sexually transmitted diseases] might be useful in the monitoring and evaluation of AIDS prevention programmes. The objectives have been to answer the following questions: (a) Can measures of STD occurence be used as an outcome measure of AIDS/HIV preventive efforts ? In particular: -> which diseases might be useful ? -> in what ways could they be used ? (b) If measures of STD occurence can be used in this way, is existing surveillance data in Western Europe adequate for the purpose ? If not why not ? (c) What do data from existing STD surveillance systems tell us about the success or failure of AIDS prevention to date ? (d) What needs to be done in order taht STD surveillance data in the countries of Western Europe could be used for this purpose ? [Authors, p. 4]