Schizotypy : do not worry, it is not all worrisome

A long-standing tradition in personality research in psychology, and nowadays increasingly in psychiatry, is that psychotic and psychotic-like thoughts are considered common experiences in the general population. Given their widespread occurrence, such experiences cannot merely reflect pathological functioning. Moreover, reflecting the multi-dimensionality of schizotypy, some dimensions might be informative for healthy functioning while others less so. Here, we explored these possibilities by reviewing research that links schizotypy to favourable functioning such as subjective wellbeing, cognitive functioning (major focus on creativity) and personality correlates. This research highlights the existence of healthy people with psychotic-like traits who mainly experience positive schizotypy (but also affective features mapping onto bipolar disorder). These individuals seem to benefit from a healthy way to organise their thoughts and experiences, i.e. they employ an adaptive cognitive framework to explain and integrate their unusual experiences. We conclude that, instead of focussing only on the pathological, future studies should explore the behavioural, genetic, imaging and psychopharmacological correlates that define the healthy expression of psychotic-like traits. Such studies would inform on protective or compensatory mechanisms of psychosis-risk and could usefully inform us on the evolutionary advantages of the psychosis dimension.

15-hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer.

PURPOSE: We have investigated the expression and regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in gastric cancer. EXPERIMENTAL DESIGN: Clinical gastric adenocarcinoma samples were analyzed by immunohistochemistry and quantitative real-time PCR for protein and mRNA expression of 15-PGDH and for methylation status of 15-PGDH promoter. The effects of interleukin-1beta (IL-1beta) and epigenetic mechanisms on 15-PGDH regulation were assessed in gastric cancer cell lines. RESULTS: In a gastric cancer cell line with a very low 15-PGDH expression (TMK-1), the 15-PGDH promoter was methylated and treatment with a demethylating agent 5-aza-2'-deoxycytidine restored 15-PGDH expression. In a cell line with a relatively high basal level of 15-PGDH (MKN-28), IL-1beta repressed expression of 15-PGDH mRNA and protein. This effect of IL-1beta was at least in part attributed to inhibition of 15-PGDH promoter activity. SiRNA-mediated knockdown of 15-PGDH resulted in strong increase of prostaglandin E(2) production in MKN-28 cells and increased cell growth of these cells by 31% in anchorage-independent conditions. In clinical gastric adenocarcinoma specimens, 15-PGDH mRNA levels were 5-fold lower in gastric cancer samples when compared with paired nonneoplastic tissues (n = 26) and 15-PGDH protein was lost in 65% of gastric adenocarcinomas (n = 210). CONCLUSIONS: 15-PGDH is down-regulated in gastric cancer, which could potentially lead to accelerated tumor progression. Importantly, our data indicate that a proinflammatory cytokine linked to gastric carcinogenesis, IL-1beta, suppresses 15-PGDH expression at least partially by inhibiting promoter activity of the 15-PGDH gene.

Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.

From MuSIASEM theory to practice: report and reflections from field research in Kampot province, Cambodia

This document contains a report and summary of the field research activities in a rural community of rice farmers in Kampot province, Cambodia in 2011, which I conducted within the context of my PhD research at ICTA-UAB (Institute of Environmental Science and Technology, Autonomous University of Barcelona, Spain). The purpose of the field research was to gather data for a MuSIASEM analysis (Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism) at the village and household level, in order to analyze the multidimensional challenges that small farmers may face nowadays within the context of global rural change and declining access to land. While the literature on MuSIASEM offers a great variety of theoretical explanations and practical applications, there is little information available for students regarding the practical steps required for doing a MuSIASEM analysis at the local level. Within this context, this report offers not only a documentation of the field research design and data collection methods, but further provides a general overview on some organizational and preparative aspects, including some personal reflections, that one may face when preparing and conducting field research for MuSIASEM analysis. In summary, this document thus serves three objectives: (i) to assure methodological transparency for the future work, based on the collected data during field research, (ii) to share my personal experience on the preparative and practical steps required for field research and data collection for a MuSIASEM analysis at the local level, and (iii) to make available for the further interested reader some more detailed background information on the case study village.

CD44 attenuates activation of the hippo signaling pathway and is a prime therapeutic target for glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor that, by virtue of its resistance to chemotherapy and radiotherapy, is currently incurable. Identification of molecules whose targeting may eliminate GBM cells and/or sensitize glioblastoma cells to cytotoxic drugs is therefore urgently needed. CD44 is a major cell surface hyaluronan receptor and cancer stem cell marker that has been implicated in the progression of a variety of cancer types. However, the major downstream signaling pathways that mediate its protumor effects and the role of CD44 in the progression and chemoresponse of GBM have not been established. Here we show that CD44 is upregulated in GBM and that its depletion blocks GBM growth and sensitizes GBM cells to cytotoxic drugs in vivo. Consistent with this observation, CD44 antagonists potently inhibit glioma growth in preclinical mouse models. We provide the first evidence that CD44 functions upstream of the mammalian Hippo signaling pathway and that CD44 promotes tumor cell resistance to reactive oxygen species-induced and cytotoxic agent-induced stress by attenuating activation of the Hippo signaling pathway. Together, our results identify CD44 as a prime therapeutic target for GBM, establish potent antiglioma efficacy of CD44 antagonists, uncover a novel CD44 signaling pathway, and provide a first mechanistic explanation as to how upregulation of CD44 may constitute a key event in leading to cancer cell resistance to stresses of different origins. Finally, our results provide a rational explanation for the observation that functional inhibition of CD44 augments the efficacy of chemotherapy and radiation therapy.

Immigració, cohesió social i convivéncia al espai públic

L'assentament de població immigrada ha repercutit en el paisatge social de les ciutats que s'ha diversificat i s’ha tornat més complex, la qual cosa ha originat profunds canvis demogràfics i socioeconòmics. L'objectiu principal de aquesta investigació és analitzar la convivència a l'espai públic entre població autòctona i migrant, i elaborar possibles propostes d'actuació. L'espai públic és un espai fonamental per la socialització i la convivència entre diferents grups de població, però també és un espai de conflicte. Per analitzar aquesta relació entre convivència i espai públic s'ha estudiat la quotidianitat de la població immigrada als espais públics i la interacció a l'espai físic entre població autòctona i immigrada a través del treball de camp a tres barris de tres municipis de la província de Barcelona. La metodologia de la recerca s'ha concretat a través de l'estudi de casos, utilitzant en cadascun d'ells diferents tècniques que pertanyen a metodologies qualitatives i quantitatives. A través del treball de camp s'ha determinat que els usos que fa la població immigrant de l'espai públic són molt variats: socialització, feina, cura, oci, pràctica d'esports, celebracions i, en alguns casos, dormir, entre d’altres. També s'ha pogut establir una relació entre la intensitat i el tipus d'ús que es fa de l'espai públic i diferents variables com gènere, origen o tipus de projecte migratori. El projecte ha permès identificar elements que poden millorar la convivència en l'espai públic i a partir d'aquí s'han generat algunes línies d'actuació.

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.

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.

Exploring chromium (VI) dioxodihalides chemistry: is density functional theory the most suitable tool?

A comparative systematic study of the CrO2F2 compound has been performed using different conventional ab initio methodologies and density functional procedures. Two points have been analyzed: first, the accuracy of results yielded by each method under study, and second, the computational cost required to reach such results. Weighing up both aspects, density functional theory has been found to be more appropriate than the Hartree-Fock (HF) and the analyzed post-HF methods. Hence, the structural characterization and spectroscopic elucidation of the full CrO2X2 series (X=F,Cl,Br,I) has been done at this level of theory. Emphasis has been given to the unknown CrO2I2 species, and specially to the UV/visible spectra of all four compounds. Furthermore, a topological analysis in terms of charge density distributions has revealed why the valence shell electron pair repulsion model fails in predicting the molecular shape of such CrO2X2 complexes

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

The mif gene is transcriptionally regulated by glucose in insulin-secreting cells.

Macrophage migration inhibitory factor (MIF) is an important regulator of glucose homeostasis. In pancreatic beta-cells, MIF expression is regulated by glucose and its secretion potentiates the glucose-induced insulin secretion. The molecular mechanisms by which glucose mediates its effect on MIF expression are not elucidated. Herein, we report that incubating the differentiated insulin-secreting cell line INS-1 in high glucose concentration increases MIF transcriptional activity as well as the reporter gene activity driven by the -1033 to +63 bp fragment of the MIF promoter. A minimal region located between -187 and -98 bp of this promoter sequence contributes both to basal activity and glucose-responsiveness of the gene. Within this promoter region, two cis-binding sequences were identified by mobility shift assays and footprinting experiments. Both cis-elements interact with nuclear proteins expressed specifically in insulin-secreting cells. In conclusion, we identified a minimal region of the MIF promoter which contributes to the glucose stimulation of the mif gene in insulin-secreting cells.