General, PDB-based collective variables for protein folding

New, automated forms of data-analysis are required in order to understand the high-dimensional trajectories that are obtained from molecular dynamics simulations on proteins. Dimensionality reduction algorithms are particularly appealing in this regard as they allow one to construct unbiased, low-dimensional representations of the trajectory using only the information encoded in the trajectory. The downside of this approach is that different sets of coordinates are required for each different chemical systems under study precisely because the coordinates are constructed using information from the trajectory. In this paper we show how one can resolve this problem by using the sketch-map algorithm that we recently proposed to construct a low-dimensional representation of the structures contained in the protein data bank (PDB). We show that the resulting coordinates are as useful for analysing trajectory data as coordinates constructed using landmark configurations taken from the trajectory and that these coordinates can thus be used for understanding protein folding across a range of systems.

Debating Darwin at the Cape

This paper focuses attention on the fortunes of Darwin's theory among the English-speaking community in Cape Colony during the latter part of the nineteenth century. The paper begins with a review of early encounters with Darwin dwelling particularly on the response of figures like Roderick Noble - professor and editor of the Cape Monthly Magazine, the geologist John Shaw, and Sir Henry Barkly, governor of the colony. Besides these more theoretical responses, Darwin's ideas were also mobilised in a range of scientific inquiries on such subjects as birds and butterflies. But most conspicuous was the use of evolutionary thought-forms in the work of the eminent philologist Wilhelm Bleek, cousin of Darwin's leading German apologist, Ernst Haeckel. The prevailing sense is of a liberal intelligentsia calmly interacting with a novel theory with all due deference. During the 1870s, an address by Langham Dale at the South African Public Library injected new energy into the Darwin discussion. Dale expressed disquiet over some of the anthropological implications of evolution as well as its apparent reductionism, and this stimulated a range of reactions. Several anonymous commentators responded but the most sustained evaluation of Dale's position emanated from the Queenstown physician and later politician, Sir William Bisset Berry. Then, in 1874, copious extracts from John Tyndall's infamous 'Belfast Address' were printed in the Cape Monthly and this added yet further impetus to the debate. Tyndall's seeming materialism bothered a number of readers, not least Hon William Porter, former attorney-general of Cape Colony. To figures like these the materialist extrapolations of radical Darwinians such as Haeckel were deeply disturbing, not just for religious reasons, but because they seemed to destabilise the moral and pedagogic progressivism that lay at the heart of their civilising credo. While reservations about Darwin's proposals were certainly audible, taken in the round Darwinian conversations among the English-speaking literati at the Cape were conducted with liberal sentiments, not least when evolutionary science approached questions of race. For Darwin's writings were seen to confirm a monogenetic account of the origin and unity of the human race, and could readily be called upon to justify the paternalistic ideology that governed colonial affairs.

Six-year follow-up of the SPHERE RCT: secondary prevention of heart disease in general practice.

Objective: To determine the long-term effectiveness of a complex intervention in primary care aimed at improving outcomes for patients with coronary heart disease.

Design: A 6-year follow-up of a cluster randomised controlled trial, which found after 18 months that both total and cardiovascular hospital admissions were significantly reduced in intervention practices (8% absolute reduction).

Setting: 48 general practices in the Republic of Ireland and Northern Ireland.

Participants: 903 patients with established coronary heart disease at baseline in the original trial.

Intervention: The original intervention consisted of tailored practice and patient plans; training sessions for practitioners in medication prescribing and behavioural change; and regular patient recall system. Control practices provided usual care. Following the intervention period, all supports from the research team to intervention practices ceased.

Outcome measures: Primary outcome: hospital admissions, all cause and cardiovascular; secondary outcomes: mortality; blood pressure and cholesterol control.

Results: At 6-year follow-up, data were collected from practice records of 696 patients (77%). For those who had died, we censored their data at the point of death and cause of death was established. There were no significant differences between the intervention and control practices in either total (OR 0.83 (95% CI 0.54 to 1.28)) or cardiovascular hospital admissions (OR 0.91 (95% CI 0.49 to 1.65)). We confirmed mortality status of 886 of the original 903 patients (98%). There were no significant differences in mortality (15% in intervention and 16% in control) or in the proportions of patients above target control for systolic blood pressure or total cholesterol.

Conclusions: Initial significant differences in the numbers of total and cardiovascular hospital admissions were not maintained at 6 years and no differences were found in mortality or blood pressure and cholesterol control. Policymakers need to continue to assess the effectiveness of previously efficacious programmes.

Trial registration number: Current Controlled Trials ISRCTN24081411.

Towards rational catalyst design: a general optimization framework

Rational catalyst design is one of the most fundamental goals in heterogeneous catalysis. Herein, we briefly review our previous design work, and then introduce a general optimization framework, which converts catalyst design into an optimization problem. Furthermore, an example is given using the gradient ascent method to show how this framework can be used for rational catalyst design. This framework may be applied to other design schemes.

Perceptions of high involvement work practices, person-organization fit and burnout: a time lagged study of health care employees

Previous research demonstrates that high-involvement work practices (HIWPs) may be associated with burnout (emotional exhaustion and depersonalization); however, to date, the process through which HIWPs influence burnout is not clear. This article examined the impact of HIWPs on long-term burnout (emotional exhaustion and depersonalization) by considering the mediating role of person-organization fit (P-O fit) in this relationship. The study used a time-lagged design and was conducted in a Canadian general hospital among health care personnel. Findings from structural equation modeling (N = 185) revealed that perceived HIWPs were positively associated with P-O fit. There was no direct effect of HIWPs on burnout; rather, P-O fit fully mediated the relationship between employee perceptions of HIWPs and burnout. This study fills a void in the HR and burnout literature by demonstrating the role that P-O fit has in explaining how HIWPs alleviate emotional exhaustion and depersonalization. © 2016 Wiley Periodicals, Inc.

Systematic review of interventions to improve the psychological well-being of general practitioners

BACKGROUND: The health of doctors who work in primary care is threatened by workforce and workload issues. There is a need to find and appraise ways in which to protect their mental health, including how to achieve the broader, positive outcome of well-being. Our primary outcome was to evaluate systematically the research evidence regarding the effectiveness of interventions designed to improve General Practitioner (GP) well-being across two continua; psychopathology (mental ill-health focus) and 'languishing to flourishing' (positive mental health focus). In addition we explored the extent to which developments in well-being research may be integrated within existing approaches to design an intervention that will promote mental health and prevent mental illness among these doctors.

METHODS: Medline, Embase, Cinahl, PsychINFO, Cochrane Register of Trials and Web of Science were searched from inception to January 2015 for studies where General Practitioners and synonyms were the primary participants. Eligible interventions included mental ill-health prevention strategies (e.g. promotion of early help-seeking) and mental health promotion programmes (e.g. targeting the development of protective factors at individual and organizational levels). A control group was the minimum design requirement for study inclusion and primary outcomes had to be assessed by validated measures of well-being or mental ill-health. Titles and abstracts were assessed independently by two reviewers with 99 % agreement and full papers were appraised critically using validated tools.

RESULTS: Only four studies (with a total of 997 GPs) from 5392 titles met inclusion criteria. The studies reported statistically significant improvement in self-reported mental ill-health. Two interventions used cognitive-behavioural techniques, one was mindfulness-based and one fed-back GHQ scores and self-help information.

CONCLUSION: There is an urgent need for high quality, controlled studies in GP well-being. Research on improving GP well-being is limited by focusing mainly on stressors and not giving systematic attention to the development of positive mental health.

Patterns and predictors of help-seeking contacts with health services and general practitioner detection of suicidality prior to suicide: a cohort analysis of suicides occurring over a two-year period

Background: Contact with primary care and psychiatric services prior to suicide may be considerable, presenting
opportunities for intervention. However, there is scant knowledge on the frequency, nature and determinants of
contact.
Method: Retrospective cohort study-an analysis of deaths recorded as suicide by the Northern Ireland Coroner’s
Office linked with data from General Practice patient records over a 2 year period
Results: Eighty-seven per cent of suicides were in contact with General Practice services in the 12 months before
suicide. The frequency of contact with services was considerable, particularly among patients with a common
mental disorder or substance misuse problems. A diagnosis of psychiatric problems was absent in 40 % of suicides.
Excluding suicide attempts, the main predictors of a noted general practitioner concern for patient suicidality are
male gender, frequency of consultations, diagnosis of mental illness and substance misuse.
Conclusions: Despite widespread and frequent contact, a substantial proportion of suicidal people were
undiagnosed and untreated for mental health problems. General Practitioner alertness to suicidality may be too
narrowly focused.

On the Musical Reception of the 'Badisches Wiegenlied' in the German Folk Movement

This is a single-authored extended essay on the history of reception (musical and textual) of the Badisches Wiegenlied in the German folk song movement in both East and West Germany. As such it expands on the co-written short essay on the song Badisches Wiegenlied also published in the Liederlexikon. This is part of the AHRC and DFG funded project 'The History of Reception of the Songs of the 1848 Revolution' (2009-2013).

Near Vienna in the German Land

This is an essay including annotated critical editions documenting the history of reception of this song since 1848. Published in the Liederlexikon for the AHRC and DFG funded project 'The History of Reception of the Songs of the 1848 Revolution' (2009-2013).