Molecular theory of hydrophobic mismatch between lipids and peptides

Effects of the mismatch between the hydrophobic length, d, of transmembrane alpha helices of integral proteins and the hydrophobic thickness, D_h, of the membranes they span are studied theoretically utilizing a microscopic model of lipids. In particular, we examine the dependence of the period of a lamellar phase on the hydrophobic length and volume fraction of a rigid, integral, peptide. We find that the period decreases when a short peptide, such that d<D_h, is inserted. More surprising, we find that the period increases when a long peptide, such that d>D_h, is inserted. The effect is due to the replacement of extensible lipid tails by rigid peptide. As the peptide length is increased, the lamellar period continues to increase, but at a slower rate, and can eventually decrease. The amount of peptide which fails to incorporate and span the membrane increases with the magnitude of the hydrophobic mismatch |d-D_h|. We explicate these behaviors which are all in accord with experiment. Predictions are made for the dependence of the tilt of a single trans-membrane alpha helix on hydrophobic mismatch and helix density.Comment: 14 pages, 5 figure

Racionalidad y valores éticos en las ciencias y la tecnología

Not available.En este artículo se critica la concepción según la cual la tecnología está libre de valores y que en sí misma no plantea problemas éticos. Frente a ella, se defiende la concepción de acuerdo con la cual las personas y los fines que ellas persiguen intencionalmente forman parte de los sistemas técnicos mismos, al igual que los conocimientos y creencias que se ponen en juego al operar esos sistemas; y, por tanto, la tecnología ya no puede concebirse como indiferente al bien y al mal. Se analiza, además, el problema que afrontaron los científicos Mario Molina y Sherwood Rowland —Premios Nobel de Química 1995— en sus estudios sobre el agujero de la capa de ozono en la atmósfera terrestre, para ilustrar, por un lado, que es factible actuar de manera responsable en una situación en la que un sistema técnico está produciendo daños, aun cuando no exista evidencia contundente para aceptar una relación causal entre la operación del sistema y los daños en cuestión; y, por otro lado, que hay situaciones en las que los científicos y los tecnólogos tienen responsabilidades morales qua científicos y tecnólogos. El artículo concluye con una revisión de los deberes para los científicos y tecnólogos, para el Estado y las instituciones de educación e investigación, así como para los ciudadanos en general, con respecto a ciertos problemas éticos que plantea la tecnología

Restoration of Hypoglycemia Awareness After Islet Transplantation

OBJECTIVE—To determine the impact of islet transplantation (ITx) on hypoglycemia awareness in patients with unstable type 1 diabetes and its relation to islet function

Constituting monetary conservatives via the 'savings habit': New Labour and the British housing market bubble

The ongoing world credit crunch might well kill off the most recent bubble dynamics in the British housing market by driving prices systematically downwards from their 2007 peak. Nonetheless, the experience of that bubble still warrants analytical attention. The Labour Government might not have been responsible for consciously creating it, but it has certainly grasped the opportunities the bubble has provided in an attempt to enforce a process of agential change at the heart of the British economy. The key issue in this respect is the way in which the Government has challenged the legitimacy of passive welfare receipts in favour of establishing a welfare system based on incorporating the individual into an active asset-holding society. The housing market has taken on new political significance as a means for individuals first to acquire assets and then to accumulate wealth on the back of asset ownership. The ensuing integration of the housing market into an increasingly reconfigured welfare system has permeated into the politics of everyday life. It has been consistent with individuals remaking their political subjectivities in line with preferences for the type of conservative monetary policies that typically keep house price bubbles inflated

A Core Outcome Set for Preventive Intervention Trials in Chronic and Episodic Migraine (COSMIG):an international, consensus-derived and multistakeholder initiative

Objective Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG). Design A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners. Results There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed. Conclusion International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire

Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG): an international, consensus-derived and multistakeholder initiative

OBJECTIVE: Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG). DESIGN: A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners. RESULTS: There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed. CONCLUSION: International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire

Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study

Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’ Handbook, and the process was repeated. Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies