Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

Body composition: overview of methods and future directions of research.

A short overview is given on the most important analytical body composition methods. Principles of the methods and advantages and limitations of the methods are discussed also in relation to other fields of research such as energy metabolism. Attention is given to some new developments in body composition research such as chemical multiple-compartment models, computerized tomography or nuclear magnetic resonance imaging (tissue level), and multifrequency bioelectrical impedance. Possible future directions of body composition research in the light of these new developments are discussed.

Tackling self-selection into treatment and self-selection into the sample biases in VAA research

Self‐selection into treatment and self‐selection into the sample are major concerns of VAA research and need to be controlled for if the aim is to deduce causal effects from VAA use in observational data. This paper focuses on the methodological aspects of VAA research and outlines omnipresent endogeneity issues, partly imposed through unobserved factors that affect both whether individuals chose to use VAAs and their electoral behavior. We promote using Heckman selection models and apply various versions of the model to data from the Swiss electorate and smartvote users in order to see to what extent selection biases interfere with the estimated effects of interest.

What process research tells us about brief intervention efficacy.

ISSUE: This article explores mechanisms of the efficacy of brief intervention (BI). APPROACH: We conducted a BI trial at the emergency department of the Lausanne University Hospital, of whom 987 at-risk drinkers were randomised into BI and control groups. The overall results demonstrated a general decrease in alcohol use with no differences across groups. The intention to change was explored among 367 patients who completed BI. Analyses of 97 consecutive tape-recorded sessions explored patient and counsellor talks during BI, and their relationship to alcohol use outcome. KEY FINDINGS: Evaluation of the articulation between counsellor behaviours and patient language revealed a robust relationship between counsellor motivational interviewing (MI) skills and patient change talk during the intervention. Further exploration suggested that communication characteristics of patients during BI predicted changes in alcohol consumption 12 months later. Moreover, despite systematic training, important differences in counsellor performance were highlighted. Counsellors who had superior MI skills achieved better outcomes overall, and maintained efficacy across all levels of patient ability to change, whereas counsellors with inferior MI skills were effective mostly with patients who had higher levels of ability to change. Finally, the descriptions of change talk trajectories within BI and their association with drinking 12 months later showed that final states differed from initial states, suggesting an impact resulting from the progression of change talk during the course of the intervention. IMPLICATION: These findings suggest that BI should focus on the general MI attitude of counsellors who are capable of eliciting beneficial change talk from patients. [Daeppen J-B, Bertholet N, Gaume J. What process research tells us about brief intervention efficacy.

Administració pública electronica i immigracio: una nova oportunitat per una societat xarxa catalana inclusiva

Aquest projecte explora dues dinàmiques socials interrelacionades: a) L'increment de la diversitat cultural al territori català i la necessitat d'implementar polítiques públiques per millorar la convivència i la cohesió social. b) El desenvolupament de la societat xarxa catalana mitjançant la disseminació de les noves tecnologies de la informació i la comunicació en I'espai de I'administració pública. Mes en concret, el projecte aborda la qüestió de la participació de les persones immigrades en la societat xarxa catalana mitjançant una metodologia que combina la investigació online i offline. Es posa un especial èmfasi en I'estudi de I ‘accés i ús dels serveis oferts per I'administració pública electrònica de les persones immigrades a Catalunya. Els nous usuaris i usuàries dels serveis públics presenten condicionants i necessitats particulars que depenen del seu origen cultural i de la seva situació administrativa. Aquest projecte estudia el grau d'adequació de la e-Administració a les demandes i necessitats especifiques d'aquest grup de població. En aquest sentit, I'estudi explora les possibilitats per a poder promoure la cohesió social mitjançant el desenvolupament d'una administració pública electronica mes inclusiva i interactiva a Catalunya. L’anàlisi de I'adaptació i adopció de I'administració electrònica catalana en el context de la població immigrada s'ha fet des d'un doble camí metodològic. D' una banda, s'ha realitzat una incursió en com I'administració pública catalana, tant local com autonòmica, s'ha adaptat a la diversitat dels seus usuaris mitjançant I'observació de webs i entrevistes a responsables tècnics i polítics. D'altra banda, s'han fet entrevistes amb persones immigrades amb perfils socio-culturals diversos. podem apuntar que I'administració pública electrònica a Catalunya es una realitat per a moltes persones immigrades que ja han provat de fer-la servir per a usos socialment importants. Existeixen, però, impediments tant des de la pròpia dinàmica de I'administració, que no ha posat aquesta qüestió en un lloc prioritari, com des de les persones que desconfien dels seus propis coneixements i no sempre troben allò que busquen. Amb tot, ens trobem amb un espai que obre expectatives de futur molt amplies. Un espai molt idoni per a repensar les formes que exigeixen els reptes de la nova ciutadania

Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Retrospective research: What are the ethical and legal requirements?

Retrospective research is conducted on already available data and/or biologic material. Whether such research requires that patients specifically consent to the use of "their" data continues to stir controversy. From a legal and ethical point of view, it depends on several factors. The main criteria to be considered are whether the data or the sample is anonymous, whether the researcher is the one who collected it and whether the patient was told of the possible research use. In Switzerland, several laws delineate the procedure to be followed. The definition of "anonymous" is open to some interpretation. In addition, it is debatable whether consent waivers that are legally admissible for data extend to research involving human biological samples. In a few years, a new Swiss federal law on human research could clarify the regulatory landscape. Meanwhile, hospital-internal guidelines may impose stricter conditions than required by federal or cantonal law. Conversely, Swiss and European ethical texts may suggest greater flexibility and call for a looser interpretation of existing laws. The present article provides an overview of the issues for physicians, scientists, ethics committee members and policy makers involved in retrospective research in Switzerland. It aims at provoking more open discussions of the regulatory problems and possible future legal and ethical solutions.

The Swiss regulatory framework for pædiatric health research

Medical research on minors entails both risks and benefits. Under Swiss law, clinical trials on children, including nontherapeutic drug trials, are permissible. However, ethics committees must systematically verify that all clinical studies have a favorable risk-benefit profile. Additional safeguards are designed to ensure that children are not unnecessarily involved in research and that proper consent is always obtained. Federal Swiss law is undergoing revision to extend these protections beyond clinical trials to a broad array of health research. The Swiss drug agency also seeks to improve the incentives for pharmaceutical firms to develop new paediatric drugs and relevant paediatric drug labels.

Bridging the Gap: establishing the necessary infrastructure and knowledge for teaching and research in neuroscience in Africa.

Advances in neuroscience research over the last few decades have increased our understanding of how individual neurons acquire their specific properties and assemble into complex circuits, and how these circuits are affected in disease. One of the important motives driving neuroscience research is the development of new scientific techniques and interdisciplinary cooperation. Compared to developed countries, many countries on the African continent are confronted with poor facilities, lack of funding or career development programs for neuroscientists, all of which deter young scientists from taking up neuroscience as a career choice. This article highlights some steps that are being taken to promote neuroscience education and research in Africa.

Domestic and International Research Joint Ventures: The Effect of Collusion

We analyze the effect of research joint ventures (RJVs) on consumer welfare in an international context when collusion can occur. The main novelty of our analysis is to study the differentiated effect of domestic and international RJVs. The recent literature shows that RJVs with collusion harm consumers. However, our results introduce a qualifi cation to this statement: international RJVs with collusion might be bene ficial for consumers when internationalization costs are high. The EU and US competition policy advises against RJVs that facilitate collusion on the grounds of their expected negative effects. Our results suggest that antitrust authorities should distinguish between domestic and international RJVs and, in certain cases, be more benevolent with international RJVs. Keywords: collusion; domestic research joint venture; international research joint venture JEL Classi fication Numbers: K21, L24, L44, O32

Annual Report of Highway Division Highway Research and Development in Iowa, 2004

Annual report for Iowa Department of Transportation