A Tentative Detection of a Starspot During Consecutive Transits of an Extrasolar Planet from the Ground: No Evidence of a Double Transiting Planet System Around TrES-1

There have been numerous reports of anomalies during transits of the planet TrES-1b. Recently, Rabus and coworkers' analysis of HST observations lead them to claim brightening anomalies during transit might be caused by either a second transiting planet or a cool starspot. Observations of two consecutive transits are presented here from the University of Arizona's 61-inch Kuiper Telescope on May 12 and May 15, 2008 UT. A 5.4 +/- 1.7 mmag (0.54 +/- 0.17%) brightening anomaly was detected during the first half of the transit on May 12 and again in the second half of the transit on May 15th. We conclude that this is a tentative detection of a r greater than or equal to 6 earth radii starspot rotating on the surface of the star. We suggest that all evidence to date suggest TrES-1 has a spotty surface and there is no need to introduce a second transiting planet in this system to explain these anomalies. We are only able to constrain the rotational period of the star to 40.2 +22.9 -14.6 days, due to previous errors in measuring the alignment of the stellar spin axis with the planetary orbital axis. This is consistent with the previously observed P_obs = 33.2 +22.3 -14.3 day period. We note that this technique could be applied to other transiting systems for which starspots exist on the star in the transit path of the planet in order to constrain the rotation rate of the star. (abridged)Comment: 21 pages, 3 tables, 6 figures, Accepted to Ap

Evaluating the benefit of early patient and public involvement for product development and testing with small companies

Introduction: There is a growing understanding of the benefits of patient and public involvement (PPI), and its evaluation, in research. An online version of the CUBE PPI evaluation framework has been developed. We sought to use the CUBE to evaluate the value of early PPI with two small healthcare companies during product development. Methods: Contributors were recruited online and had lived experience of either type 1 diabetes or obesity. Two1-hsessions were run with a company developing a smartphone application to manage diabetes (DEE-EM): one with young people (YP; n = 5) and one with parents (n = 7). Two 1-hsessions were run with a company developing a weight-loss product, both with adults (n = 7 in each session). Sessions were facilitated by an independent University researcher and attended by company representatives, who presented their product. One facilitator led the evaluation of the session by giving a demonstration of the CUBE and asking simple questions in the YP session. Results: A high proportion of contributors completed the CUBE (80.5% DEE-EM; 93% Oxford Medical Products). Responses were positive to all four CUBE dimensions (in italics). Contributors felt there were diverse ways to contribute to the sessions, and that they had a strong voice to add to the discussion. Balance was achieved regarding whose concerns (public or company) led the agenda, and contributors felt that both companies would make changes based on the discussion. The supportive attitude of both companies resulted in most contributors feeling comfortable participating in PPI sessions with the industry, while recognising the profit-making aspect of their work. Conclusions: PPI with small healthcare companies is both feasible and worthwhile. The CUBE framework facilitated the evaluation of the interaction between experts in different knowledge spaces. We provide recommendations for future projects, including considerations of who should participate and the level of implicit endorsement of the product that participation implies. Patient or Public Contribution: People with lived experience of type 1 diabetes or obesity were invited to contribute to one of four PPI sessions, which they then evaluated. One contributor agreed to contribute to the analysis of the evaluation data and interpretation and preparation of the manuscript

A Delphi study of rescue and clinical subject matter experts on the extrication of patients following a motor vehicle collision

Background Approximately 1.3 million people die each year globally as a direct result of motor vehicle collisions (MVCs). Following an MVC some patients will remain trapped in their vehicle; these patients have worse outcomes and may require extrication. Following new evidence, updated multidisciplinary guidance for extrication is needed. Methods This Delphi study has been developed, conducted and reported to CREDES standards. A literature review identified areas of expertise and appropriate individuals were recruited to a Steering Group. The Steering Group formulated initial statements for consideration. Stakeholder organisations were invited to identify subject matter experts (SMEs) from a rescue and clinical background (total 60). SMEs participated over three rounds via an online platform. Consensus for agreement / disagreement was set at 70%. At each stage SMEs could offer feedback on, or modification to the statements considered which was reviewed and incorporated into new statements or new supporting information for the following rounds. Stakeholders agreed a set of principles based on the consensus statements on which future guidance should be based. Results Sixty SMEs completed Round 1, 53 Round 2 (88%) and 49 Round 3 (82%). Consensus was reached on 91 statements (89 agree, 2 disagree) covering a broad range of domains related to: extrication terminology, extrication goals and approach, self-extrication, disentanglement, clinical care, immobilisation, patient-focused extrication, emergency services call and triage, and audit and research standards. Thirty-three statements did not reach consensus. Conclusion This study has demonstrated consensus across a large panel of multidisciplinary SMEs on many key areas of extrication and related practice that will provide a key foundation in the development of evidence-based guidance for this subject area

I’m deleting as fast as I can: Negotiating learning practices in cyberspace

Learning in and through work is one of the many spaces in which pedagogy may unfold. Web technologies amplify this fluidity and online learning now encompasses a plethora of practices. In this paper I focus on the delete button and deleting practices of self-employed workers engaged in informal work-related learning in online communities. How the relational and material aspects of online pedagogical practices are being negotiated is explored. While deleting appears to be an everyday practice, understanding the delete button as a fluid object in fluid space begins to illuminate its complexity and multiple enactments. Deleting practices which work to stem the tide of information pushing itself onto screens, as well as those practices that attempt to delete traces left behind on screens and ‘in the cloud’, are examined. Actor Network Theory provides the theoretical and conceptual tools for this exploration. I conclude with observations on the politics of the delete button and implications for more sophisticated digital fluency in everyday pedagogy

PARC:a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults

Background: The survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role in the pathophysiology of a number of pediatric cancers. We report the first in child study of a recombinant human arginase, BCT-100, in children with relapsed/refractory hematological, solid or CNS cancers.Procedure: PARC was a single arm, Phase I/II, international, open label study. BCT-100 was given intravenously over one hour at weekly intervals. The Phase I section utilized a modified 3 + 3 design where escalation/de-escalation was based on both the safety profile and the complete depletion of arginine (defined as adequate arginine depletion; AAD <8μM arginine in the blood after 4 doses of BCT-100). The Phase II section was designed to further evaluate the clinical activity of BCT-100 at the pediatric RP2D determined in the Phase I section, by recruitment of patients with pediatric cancers into 4 individual groups. A primary evaluation of response was conducted at eight weeks with patients continuing to receive treatment until disease progression or unacceptable toxicity.Results: 49 children were recruited globally. The Phase I cohort of the trial established the Recommended Phase II Dose of 1600U/kg iv weekly in children, matching that of adults. BCT-100 was very well tolerated. No responses defined as a CR, CRi or PR were seen in any cohort within the defined 8 week primary evaluation period. However a number of these relapsed/refractory patients experienced prolonged radiological SD.Conclusion: Arginine depletion is a clinically safe and achievable strategy in children with cancer. The RP2D of BCT-100 in children with relapsed/refractory cancers is established at 1600U/kg intravenously weekly and can lead to sustained disease stability in this hard to treat population.Clinical trial registration: EudraCT, 2017-002762-44; ISRCTN, 21727048; and ClinicalTrials.gov, NCT03455140

Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)

Background Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts. Methods A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis. Results Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid. Conclusions Cryotherapy is more costly and no more effective than salicylic acid

CHAMP: Cognitive behaviour therapy for health anxiety in medical patients, a randomised controlled trial

BACKGROUND: Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT) in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. METHOD/DESIGN: The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out) to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. DISCUSSION: This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also whether the cost of treatment is offset by savings from reduced use of other health services in comparison to the control group.Cognitive behaviour therapy for Health Anxiety in Medical Patients (CHAMP) TRIAL REGISTRATION: Current Controlled Trials ISRCTN14565822

A Research Agenda for Helminth Diseases of Humans: Towards Control and Elimination

Human helminthiases are of considerable public health importance in sub-Saharan Africa, Asia, and Latin America. The acknowledgement of the disease burden due to helminth infections, the availability of donated or affordable drugs that are mostly safe and moderately efficacious, and the implementation of viable mass drug administration (MDA) interventions have prompted the establishment of various large-scale control and elimination programmes. These programmes have benefited from improved epidemiological mapping of the infections, better understanding of the scope and limitations of currently available diagnostics and of the relationship between infection and morbidity, feasibility of community-directed or school-based interventions, and advances in the design of monitoring and evaluation (M&E) protocols. Considerable success has been achieved in reducing morbidity or suppressing transmission in a number of settings, whilst challenges remain in many others. Some of the obstacles include the lack of diagnostic tools appropriate to the changing requirements of ongoing interventions and elimination settings; the reliance on a handful of drugs about which not enough is known regarding modes of action, modes of resistance, and optimal dosage singly or in combination; the difficulties in sustaining adequate coverage and compliance in prolonged and/or integrated programmes; an incomplete understanding of the social, behavioural, and environmental determinants of infection; and last, but not least, very little investment in research and development (R&D). The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to undertake a comprehensive review of recent advances in helminthiases research, identify research gaps, and rank priorities for an R&D agenda for the control and elimination of these infections. This review presents the processes undertaken to identify and rank ten top research priorities; discusses the implications of realising these priorities in terms of their potential for improving global health and achieving the Millennium Development Goals (MDGs); outlines salient research funding needs; and introduces the series of reviews that follow in this PLoS Neglected Tropical Diseases collection, “A Research Agenda for Helminth Diseases of Humans.

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care