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

Cascade diagrams for depicting complex interventions in randomised trials

Many medical interventions—particularly non-pharmacological ones—are complex, consisting of multiple interacting components targeted at different organisational levels.1 2 Published descriptions of complex interventions often do not contain enough detail to enable their replication.2-5 Reports of behaviour change interventions should include descriptions of setting, mode, intensity, and duration, and characteristics of the participants.6 Graphical methods, such as that showing the relative timing of assessments and intervention components,7 may improve clarity of reporting. However, these approaches do not reveal the connections between the different “actors” in a complex intervention.8 Different audiences may want different things from a description of an intervention, but visualising relationships between actors can clarify crucial features such as the fidelity with which the intervention is passed down a chain of actors and possible routes of contamination between treatment arms. Here we describe a new graphical approach—the cascade diagram—that highlights these potential problems

Research ethics oversight in Norway : structure, function, and challenges

Background While the development and evaluation of clinical ethics services in Norway has been recognized internationally, the country’s research ethics infrastructure at times may have been less well developed. In 2016, media interest in the controversial nature of some health services research and pilot studies highlighted gaps in the system with certain types of research having no clear mechanisms through which they may be given due independent consideration. It is not clear that new legislation, implemented in 2017, will address this problem. Summary We explore relevant law, committee scope, and the function of the system. We show that 1) Norwegian law provides for ethics assessment for all forms of health research; 2) regional RECs in Norway might not have always enforced this provision, considering some interventional health services research to be outside their remit; and 3) Norwegian law does not explicity provide for local/university RECs, meaning that, in practice, there may be no readily accessible mechanisms for the assessment of research that is excluded by regional RECs. This may include health services research, pilot studies, and undergraduate research. New 2017 legislation has no effect on this specifically but focuses on institutions regulating researcher activity. This may place researchers in the difficult situation of on one hand, needing to hold to recognized ethical standards, while on the other, not readily having access to independent committee scrutiny to facilitate consistent operation with these standards. Conclusion To support researchers in Norway and to protect the public, it may be necessary either to widen the regional RECs’ remit or to make legislative alterations that permit and do not discourage the existence of local RECs

The work of return to work. Challenges of returning to work when you have chronic pain : a meta-ethnography

Aims To understand obstacles to returning to work, as perceived by people with chronic non-malignant pain and as perceived by employers, and to develop a conceptual model. Design Synthesis of qualitative research using meta-ethnography. Data sources Eleven bibliographic databases from inception to April 2017 supplemented by citation tracking. Review methods We used the methods of meta-ethnography. We identified concepts and conceptual categories, and developed a conceptual model and line of argument. Results We included 41 studies. We identified three core categories in the conceptual model: managing pain, managing work relationships and making workplace adjustments. All were influenced by societal expectations in relation to work, self (self-belief, self-efficacy, legitimacy, autonomy and the meaning of work for the individual), health/illness/pain representations, prereturn to work support and rehabilitation, and system factors (healthcare, workplace and social security). A mismatch of expectations between the individual with pain and the workplace contributed to a feeling of being judged and difficulties asking for help. The ability to navigate obstacles and negotiate change underpinned mastering return to work despite the pain. Where this ability was not apparent, there could be a downward spiral resulting in not working. Conclusions For people with chronic pain, and for their employers, navigating obstacles to return to work entails balancing the needs of (1) the person with chronic pain, (2) work colleagues and (3) the employing organisation. Managing pain, managing work relationships and making workplace adjustments appear to be central, but not straightforward, and require substantial effort to culminate in a successful return to work

Obstacles to returning to work with chronic pain : in-depth interviews with people who are off work due to chronic pain and employers

Background: The global burden of chronic pain is growing with implications for both an ageing workforce and employers. Many obstacles are faced by people with chronic pain in finding employment and returning to work after a period of absence. Few studies have explored obstacles to return-to-work (RTW) from workers’ and employers’ perspectives. Here we explore views of both people in pain and employers about challenges to returning to work of people who are off work with chronic pain. Methods: We did individual semi-structured interviews with people who were off work (unemployed or off sick) with chronic pain recruited from National Health Service (NHS) pain services and employment services, and employers from small, medium, and large public or private sector organisations. We analysed data using the Framework method. Results: We interviewed 15 people off work with chronic pain and 10 employers. Obstacles to RTW for people with chronic pain spanned psychological, pain related, financial and economic, educational, and work-related domains. Employers were concerned about potential attitudinal obstacles, absence, ability of people with chronic pain to fulfil the job requirements, and the implications for workplace relationships. Views on disclosure of the pain condition were conflicting with more than half employers wanting early full disclosure and two-thirds of people with chronic pain declaring they would not disclose for fear of not getting a job or losing a job. Both employers and people with chronic pain thought that lack of confidence was an important obstacle. Changes to the job or work conditions (e.g. making reasonable adjustments, phased return, working from home or redeployment) were seen by both groups as facilitators. People with chronic pain wanted help in preparing to RTW, education for managers about pain and supportive working relationships. Conclusions: People with chronic pain and employers may think differently in terms of perceptions of obstacles to RTW. Views appeared disparate in relation to disclosure of pain and when this needs to occur. They appeared to have more in common regarding opinions about how to facilitate successful RTW. Increased understanding of both perspectives may be used to inform the development of improved RTW interventions

Opportunity lost: Mystification, elite politics and financial reform in the UK

The first phase of the crisis in Britain – from the 2007 failure of Northern Rock to the post Lehman systemic crisis of autumn 2008 – was a demystifying moment, when finance sector alibis, technocratic expertise and the assumptions of the political classes were tested and found wanting under pressure of unanticipated events. The banking rescue of 2007-8 amounted to the socialization of banking losses at a cost to the UK taxpayer of up to £1,000 billion or more (if we include contingent liabilities and exclude quantitative easing). British taxpayers got very little in return. The challenge of a brief democratic moment was met by the restatement of old pre-crisis narratives about the importance of ‘flexible’, market responsive regulation, and about the social value of finance. The result so far is marginalisation of left and radical forces (or no change on the past twenty-five years). Against this background, this essay has two interlinked aims. First, it presents an analysis of political obstacles to democratic control and reform of the finance sector that caused the financial crisis of 2007-8; a crisis that, after extreme intervention to save banks and support markets, has by 2010-11 become a fiscal crisis for individual states and a sovereign debt crisis for the eurozone. Second, it addresses (in this context) the role of ‘ideology’ within the socio-political process by examining how discourses format the world through what is now called ‘performativity’. And it shows how this new kind of discursive description can be developed and integrated with more established kinds of institutional analysis so as to generate new insights into the political obstacles to reform. The argument below is illustrated with UK evidence and our aim is to provide an analysis of national peculiarities, but the issues raised are relevant to other jurisdictions (national and supra national). We hope to raise broad questions about the mechanisms of elite power in present day capitalism where the importance of narrative has intensified since Reagan and Thatcher. We also aim to encourage reflection on how narrative power could be challenged so as to deliver a more democratic reform of finance

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

Shareholder protection, income inequality and social health:a proposed research agenda

This paper develops a proposed research agenda in order to highlight how corporate governance, accounting and company law are relevant to the consideration of income inequality and wider social health. To illustrate this proposed research agenda, this paper draws on corporate governance research in the law and finance tradition, as well as macro-level studies in accounting concerned with the wider corporate governance context, in order to consider the association between shareholder protection, income inequality and child mortality. Under 5 child mortality is an objective indication of a country’s ability to nurture its children. In an influential body of work, La Porta et al. (1997a, 1997b, 1998, 2008) concluded that a common law legal system which protected the interests of shareholders gave rise to better economic and social outcomes. However, drawing on corporate governance and accounting literature we contend that such a conclusion is flawed. The findings of this paper suggest that common law countries (i.e. those with the greater legal protection for investors) have worse social outcomes in terms of under-5 child mortality.PostprintPeer reviewe

Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes