Study protocol: Delayed intervention randomised controlled trial within the Medical Research Council (MRC) Framework to assess the effectiveness of a new palliative care service

Background: Palliative care has been proposed to help meet the needs of patients who suffer progressive non-cancer conditions but there have been few evaluations of service development initiatives. We report here a novel protocol for the evaluation of a new palliative care service in this context. Methods/Design: Using the MRC Framework for the Evaluation of Complex Interventions we modelled a new palliative care and neurology service for patients severely affected by Multiple Sclerosis (MS). We conducted qualitative interviews with patients, families and staff, plus a literature review to model and pilot the service. Then we designed a delayed intervention randomised controlled trial to test its effectiveness as part of phase II of the MRC framework. Inclusion criteria for the trial were patients identified by referring clinicians as having unresolved symptoms or psychological concerns. Referrers were advised to use a score of greater than 8 on the Expanded Disability Scale was a benchmark. Consenting patients newly referred to the new service were randomised to either receive the palliative care service immediately (fast-track) or after a 12-week wait (standard best practice). Face to face interviews were conducted at baseline (before intervention), and at 4–6, 10–12 (before intervention for the standard-practice group), 16– 18 and 22–24 weeks with patients and their carers using standard questionnaires to assess symptoms, palliative care outcomes, function, service use and open comments. Ethics committee approval was granted separately for the qualitative phase and then for the trial. Discussion: We publish the protocol trial here, to allow methods to be reviewed in advance of publication of the results. The MRC Framework for the Evaluation of Complex Interventions was helpful in both the design of the service, methods for evaluation in convincing staff and the ethics committee to accept the trial. The research will provide valuable information on the effects of palliative care among non-cancer patients and a method to evaluate palliative care in this context

Enhancing graduate employability in product design: a case study exploring approaches taken on a BSc Product Design course

Purpose – This paper presents a case study to discuss approaches taken within a traditional undergraduate degree course to embed employability skills, encourage student uptake of sandwich placement and increase graduate prospects. A number of new initiatives are presented, including working with live industrial clients, formally preparing students for placement applications and the introduction of an externally facing student run design consortium. Alongside these new initiatives, details of the existing sandwich year provision are also considered and their effectiveness. Design/methodology/approach – A case study based action research approach presents changes to a specific undergraduate course, measuring the effectiveness over a 4-year period using externally collected national DLHE data and internal student feedback to assess the long-term effects on employability. Findings – The paper considers improvements in the graduate employability over the 4 year period covered, in particular, an increase in the graduate employability from 81%-100% and graduate prospects from 62.5% to 95.2% for sandwich students. Data presented also considers additional student feedback correlating with an increase in their preparedness for employment. Practical implications – The implications of undertaking the changes highlighted within this paper have been relatively straightforward, due to the small incremental nature of the changes and the opportunities available through the agencies within the university, and should be replicable at least in part at other HE institutions. Originality/value – This paper considers the impact of employability initiatives undertaken on a single undergraduate course and how these have affected the employability of graduates over a 4-year period, supported by student feedback both internally and externally through national feedback mechanisms. It is anticipated that this research would be beneficial for informing and guiding the development of employability on other undergraduate programmes

Florivory as an opportunity benefit of aposematism

A.D.H. was supported by the European Research Council (Advanced Grant 250209 to A. Houston) and fellowships from the Wissenschaftskolleg zu Berlin and the Natural Environment Research Council (NE/L011921/1).Inconspicuous prey pay a cost of reduced feeding opportunities. Flowers are highly nutritious but are positioned where prey would be apparent to predators and often contain toxins to reduce consumption. However, many herbivores are specialized to subvert these defenses by retaining toxins for their own use. Here, we present a model of the growth and life history of a small herbivore that can feed on leaves or flowers during its development and can change its primary defense against visual predators between crypsis and warning coloration. When herbivores can retain plant toxins, their fitness is greatly increased when they are aposematic and can consume flowers. Thus, toxin sequestration leading to aposematism may enable a significant opportunity benefit for florivory. Florivory by cryptic herbivores is predicted when toxins are very potent but are at high concentration only in flowers and not in leaves. Herbivores should usually switch to eating flowers only when large and in most conditions should switch simultaneously from crypsis to aposematism. Our results suggest that florivory should be widespread in later instars of small aposematic herbivores and should be associated with ontogenic color change. Florivory is likely to play an underappreciated role in herbivorous insect life histories and host plant reproductive success.Publisher PDFPeer reviewe

Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Diminishing returns drive altruists to help extended family

Altruism between close relatives can be easily explained. However, paradoxes arise when organisms divert altruism towards more distantly related recipients. In some social insects, workers drift extensively between colonies and help raise less related foreign brood, seemingly reducing inclusive fitness. Since being highlighted by W. D. Hamilton, three hypotheses (bet hedging, indirect reciprocity and diminishing returns to cooperation) have been proposed for this surprising behaviour. Here, using inclusive fitness theory, we show that bet hedging and indirect reciprocity could only drive cooperative drifting under improbable conditions. However, diminishing returns to cooperation create a simple context in which sharing workers is adaptive. Using a longitudinal dataset comprising over a quarter of a million nest cell observations, we quantify cooperative payoffs in the Neotropical wasp Polistes canadensis, for which drifting occurs at high levels. As the worker-to-brood ratio rises in a worker’s home colony, the predicted marginal benefit of a worker for expected colony productivity diminishes. Helping related colonies can allow effort to be focused on related brood that are more in need of care. Finally, we use simulations to show that cooperative drifting evolves under diminishing returns when dispersal is local, allowing altruists to focus their efforts on related recipients. Our results indicate the power of nonlinear fitness effects to shape social organization, and suggest that models of eusocial evolution should be extended to include neglected social interactions within colony networks

The tilt of mean sea level along the east coast of North America

The tilt of mean sea level along the North American east coast has been a subject of debate for many decades. Improvements in geoid and ocean circulation models, and GPS positioning of tide gauge benchmarks, provide an opportunity to produce new tilt estimates. Tilts estimated using tide gauge measurements referenced to high-resolution geoid models (the geodetic approach) and ocean circulation models (the ocean approach) are compared. The geodetic estimates are broadly similar, with tilts downward to the north through the Florida Straits and at Cape Hatteras. Estimates from the ocean approach show good agreement with the geodetic estimates, indicating a convergence of the two approaches and resolving the long standing debate as to the sign of the tilt. These tilts differ from those used by Yin and Goddard (2013) to support a link between changing ocean circulation and coastal sea level rise

Randomised controlled trial of a new palliative care service: Compliance, recruitment and completeness of follow-up

<p>Abstract</p> <p>Background</p> <p>Palliative care has been proposed for progressive non-cancer conditions but there have been few evaluations of service developments. We analysed recruitment, compliance and follow-up data of a fast track (or wait list control) randomised controlled trial of a new palliative care service – a design not previously used to assess palliative care.</p> <p>Methods/Design</p> <p>An innovative palliative care service (comprising a consultant in palliative medicine, a clinical nurse specialist, an administrator and a psychosocial worker) was delivered to people severely affected by multiple sclerosis (MS), and their carers, in southeast London. Our design followed the MRC Framework for the Evaluation of Complex Interventions. In phase II we conducted randomised controlled trial, of immediate referral to the service (fast-track) versus a 12-week wait (standard best practice). Main outcome measures were: compliance (the extent the trial protocol was adhered to), recruitment (target 50 patients), attrition and missing data rates; trial outcomes were Palliative Care Outcome Scale and MS Impact Scale.</p> <p>Results</p> <p>69 patients were referred, 52 entered the trial (26 randomised to each arm), 5 refused consent and 12 were excluded from the trial for other reasons, usually illness or urgent needs, achieving our target numbers. 25/26 fast track and 21/26 standard best practice patients completed the trial, resulting in 217/225 (96%) of possible interviews completed, 87% of which took place in the patient's home. Main reasons for failure to interview and/or attrition were death or illness. There were three deaths in the standard best practice group and one in the fast-track group during the trial. At baseline there were no differences between groups. Missing data for individual questionnaire items were small (median 0, mean 1–5 items out of 56+ items per interview), not associated with any patient or carer characteristics or with individual questionnaires, but were associated with interviewer.</p> <p>Conclusion</p> <p>This is the first time a fast track (or wait list) randomised trial has been reported in palliative care. We found it achieved good recruitment and is a feasible method to evaluate palliative care services when patients are expected to live longer than 3–6 months. Home interviews are needed for a trial of this kind; interviewers need careful recruitment, training and supervision; and there should be careful separation from the clinical service of the control patients to prevent accidental contamination.</p> <p>Trial Registration</p> <p>Clinical Trials.Gov NCT00364963</p

Direct observations of a complex coronal web driving highly structured slow solar wind

The solar wind consists of continuous streams of charged particles that escape into the heliosphere from the Sun, and is split into fast and slow components, with the fast wind emerging from the interiors of coronal holes. Near the ecliptic plane, the fast wind from low-latitude coronal holes is interspersed with a highly structured slow solar wind, the source regions and drivers of which are poorly understood. Here we report extreme-ultraviolet observations that reveal a spatially complex web of magnetized plasma structures that persistently interact and reconnect in the middle corona. Coronagraphic white-light images show concurrent emergence of slow wind streams over these coronal web structures. With advanced global MHD coronal models, we demonstrate that the observed coronal web is a direct imprint of the magnetic separatrix web (S-web). By revealing a highly dynamic portion of the S-web, our observations open a window into important middle-coronal processes that appear to play a key role in driving the structured slow solar wind.Comment: This version of the article has been accepted for publication, after peer review but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1038/s41550-022-01834-

Diminishing returns drive altruists to help extended family

This is the author accepted manuscript. The final version is available from nature Research via the DOI in this recordData availability: The transitions data for P. canadensis are available in the Supplementary Information.Code availability: The statistical code and individual-based simulation code are available in the Supplementary Information.Altruism between close relatives can be easily explained. However, paradoxes arise when organisms divert altruism towards more distantly related recipients. In some social insects, workers drift extensively between colonies and help raise less related foreign brood, seemingly reducing inclusive fitness. Since being highlighted by W. D. Hamilton, three hypotheses (bet hedging, indirect reciprocity and diminishing returns to cooperation) have been proposed for this surprising behaviour. Here, using inclusive fitness theory, we show that bet hedging and indirect reciprocity could only drive cooperative drifting under improbable conditions. However, diminishing returns to cooperation create a simple context in which sharing workers is adaptive. Using a longitudinal dataset comprising over a quarter of a million nest cell observations, we quantify cooperative payoffs in the Neotropical wasp Polistes canadensis, for which drifting occurs at high levels. As the worker-to-brood ratio rises in a worker’s home colony, the predicted marginal benefit of a worker for expected colony productivity diminishes. Helping related colonies can allow effort to be focused on related brood that are more in need of care. Finally, we use simulations to show that cooperative drifting evolves under diminishing returns when dispersal is local, allowing altruists to focus their efforts on related recipients. Our results indicate the power of nonlinear fitness effects to shape social organization, and suggest that models of eusocial evolution should be extended to include neglected social interactions within colony networks.Smithsonian Tropical Research Institute (STRI)National Geographic SocietyNatural Environment Research Council (NERC)European Research Council (ERC