Clinical trials in a remote Aboriginal setting: lessons from the BOABS smoking cessation study

Background: There is limited evidence regarding the best approaches to helping Indigenous Australians to stop smoking. The composite analysis of the only two smoking cessation randomised controlled trials (RCTs)investigating this suggests that one-on-one extra support delivered by and provided to Indigenous Australians in a primary health care setting appears to be more effective than usual care in encouraging smoking cessation. This paper describes the lessons learnt from one of these studies, the Be Our Ally Beat Smoking (BOABS) Study, and how to develop and implement an integrated smoking cessation program. Methods: Qualitative study using data collected from multiple documentary sources related to the BOABS Study. As the project neared completion the research team participated in four workshops to review and conduct thematic analyses of these documents. Results: Challenges we encountered during the relatively complex BOABS Study included recruiting sufficient number of participants; managing the project in two distant locations and ensuring high quality work across both sites; providing appropriate training and support to Aboriginal researchers; significant staff absences, staff shortages and high workforce turnover; determining where and how the project fitted in the clinics and consequent siloing of the Aboriginal researchers relating to the requirements of RCTs; resistance to change, and maintaining organisational commitment and priority for the project.The results of this study also demonstrated the importance of local Aboriginal ownership, commitment, participation and control. This included knowledge of local communities, the flexibility to adapt interventions to local settings and circumstances, and taking sufficient time to allow this to occur. Conclusions: The keys to the success of the BOABS Study were local development, ownership and participation, worker professional development and support, and operating within a framework of cultural safety. There were difficulties associated with the BOABS Study being an RCT, and many of these are shared with stand-alone programs. Interventions targeted at particular health problems are best integrated with usual primary health care. Research to investigate complex interventions in Indigenous health should not be limited to randomised clinical trials and funding needs to reflect the additional, but necessary, cost of providing for local control of planning and implementation

Rescaling quality of life values from discrete choice experiments for use as QALYs: a cautionary tale

Background: Researchers are increasingly investigating the potential for ordinal tasks such as ranking and discrete choice experiments to estimate QALY health state values. However, the assumptions of random utility theory, which underpin the statistical models used to provide these estimates, have received insufficient attention. In particular, the assumptions made about the decisions between living states and the death state are not satisfied, at least for some people. Estimated values are likely to be incorrectly anchored with respect to death (zero) in such circumstances. Methods: Data from the Investigating Choice Experiments for the preferences of older people CAPability instrument (ICECAP) valuation exercise were analysed. The values (previously anchored to the worst possible state) were rescaled using an ordinal model proposed previously to estimate QALY-like values. Bootstrapping was conducted to vary artificially the proportion of people who conformed to the conventional random utility model underpinning the analyses. Results: Only 26% of respondents conformed unequivocally to the assumptions of conventional random utility theory. At least 14% of respondents unequivocally violated the assumptions. Varying the relative proportions of conforming respondents in sensitivity analyses led to large changes in the estimated QALY values, particularly for lower-valued states. As a result these values could be either positive (considered to be better than death) or negative (considered to be worse than death). Conclusion: Use of a statistical model such as conditional (multinomial) regression to anchor quality of life values from ordinal data to death is inappropriate in the presence of respondents who do not conform to the assumptions of conventional random utility theory. This is clearest when estimating values for that group of respondents observed in valuation samples who refuse to consider any living state to be worse than death: in such circumstances the model cannot be estimated. Only a valuation task requiring respondents to make choices in which both length and quality of life vary can produce estimates that properly reflect the preferences of all respondents

Dysbindin Promotes the Post-Endocytic Sorting of G Protein-Coupled Receptors to Lysosomes

BackgroundDysbindin, a cytoplasmic protein long known to function in the biogenesis of specialized lysosome-related organelles (LROs), has been reported to reduce surface expression of D2 dopamine receptors in neurons. Dysbindin is broadly expressed, and dopamine receptors are members of the large family of G protein-coupled receptors (GPCRs) that function in diverse cell types. Thus we asked if dysbindin regulates receptor number in non-neural cells, and further investigated the cellular basis of this regulation.Methodology/principal findingsWe used RNA interference to deplete endogenous dysbindin in HEK293 and HeLa cells, then used immunochemical and biochemical methods to assess expression and endocytic trafficking of epitope-tagged GPCRs. Dysbindin knockdown up-regulated surface expression of D2 receptors compared to D1 receptors, as reported previously in neurons. This regulation was not mediated by a change in D2 receptor endocytosis. Instead, dysbindin knockdown specifically reduced the subsequent trafficking of internalized D2 receptors to lysosomes. This distinct post-endocytic sorting function explained the minimal effect of dysbindin depletion on D1 receptors, which recycle efficiently and traverse the lysosomal pathway to only a small degree. Moreover, dysbindin regulated the delta opioid receptor, a more distantly related GPCR that is also sorted to lysosomes after endocytosis. Dysbindin was not required for lysosomal trafficking of all signaling receptors, however, as its depletion did not detectably affect down-regulation of the EGF receptor tyrosine kinase. Dysbindin co-immunoprecipitated with GASP-1 (or GPRASP-1), a cytoplasmic protein shown previously to modulate lysosomal trafficking of D2 dopamine and delta opioid receptors by direct interaction, and with HRS that is a core component of the conserved ESCRT machinery mediating lysosome biogenesis and sorting.Conclusions/significanceThese results identify a distinct, and potentially widespread function of dysbindin in promoting the sorting of specific GPCRs to lysosomes after endocytosis

Using text messages to support recovering substance misusers

YesBackground: The use of digital technology in health and social care is developing rapidly. It is promoted in UK policy and research which suggests varied results surrounding its implementation and outcomes. Introduction: This article aimed to test the implementation and outcomes of a short messaging service sent to a dedicated phone. The target cohort were drug treatment clients in two sites in Northern England. Materials and methods: Through staff focus groups and interviews with a small cohort of clients, the implementation and perceptions of the system were examined. Results: Nineteen participants were recruited to site 1 (15 male, 4 female, average age=37.7 years) and 12 participants were recruited to site 2 (9 male, 3 female, average age=40.3 years). One outcome that was of interest was well-being in treatment which, in this study, was described as an overall sense of feeling better rather than just focusing on the rehabilitation aspect of the programme. Other outcomes included: the successful completion of treatment and any relapse or associated reported drug use. Discussion: The system shows some evidence of its ‘social actor’ role; however, its implementation was hindered by staff citing that it called for increased resources. For future implementation the use of client’s own phones may be considered which may help to embed the system more fully in recovery planning and targeting clients at a different treatment stage. Conclusions: Despite some indications of positive results for clients and a perception that the system may have value as an addition to existing clinical interventions, more evaluation is required to determine whether this system can be implemented in a drug treatment setting

A systematic review of tests of empathy in medicine

Abstract Background Empathy is frequently cited as an important attribute in physicians and some groups have expressed a desire to measure empathy either at selection for medical school or during medical (or postgraduate) training. In order to do this, a reliable and valid test of empathy is required. The purpose of this systematic review is to determine the reliability and validity of existing tests for the assessment of medical empathy. Methods A systematic review of research papers relating to the reliability and validity of tests of empathy in medical students and doctors. Journal databases (Medline, EMBASE, and PsycINFO) were searched for English-language articles relating to the assessment of empathy and related constructs in applicants to medical school, medical students, and doctors. Results From 1147 citations, we identified 50 relevant papers describing 36 different instruments of empathy measurement. As some papers assessed more than one instrument, there were 59 instrument assessments. 20 of these involved only medical students, 30 involved only practising clinicians, and three involved only medical school applicants. Four assessments involved both medical students and practising clinicians, and two studies involved both medical school applicants and students. Eight instruments demonstrated evidence of reliability, internal consistency, and validity. Of these, six were self-rated measures, one was a patient-rated measure, and one was an observer-rated measure. Conclusion A number of empathy measures available have been psychometrically assessed for research use among medical students and practising medical doctors. No empathy measures were found with sufficient evidence of predictive validity for use as selection measures for medical school. However, measures with a sufficient evidential base to support their use as tools for investigating the role of empathy in medical training and clinical care are available.</p

An Evolutionary Upgrade of Cognitive Load Theory: Using the Human Motor System and Collaboration to Support the Learning of Complex Cognitive Tasks

Cognitive load theory is intended to provide instructional strategies derived from experimental, cognitive load effects. Each effect is based on our knowledge of human cognitive architecture, primarily the limited capacity and duration of a human working memory. These limitations are ameliorated by changes in long-term memory associated with learning. Initially, cognitive load theory's view of human cognitive architecture was assumed to apply to all categories of information. Based on Geary's (Educational Psychologist 43, 179-195 2008; 2011) evolutionary account of educational psychology, this interpretation of human cognitive architecture requires amendment. Working memory limitations may be critical only when acquiring novel information based on culturally important knowledge that we have not specifically evolved to acquire. Cultural knowledge is known as biologically secondary information. Working memory limitations may have reduced significance when acquiring novel

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions

Operation and performance of the ATLAS Tile Calorimeter in Run 1

The Tile Calorimeter is the hadron calorimeter covering the central region of the ATLAS experiment at the Large Hadron Collider. Approximately 10,000 photomultipliers collect light from scintillating tiles acting as the active material sandwiched between slabs of steel absorber. This paper gives an overview of the calorimeter’s performance during the years 2008–2012 using cosmic-ray muon events and proton–proton collision data at centre-of-mass energies of 7 and 8TeV with a total integrated luminosity of nearly 30 fb−1. The signal reconstruction methods, calibration systems as well as the detector operation status are presented. The energy and time calibration methods performed excellently, resulting in good stability of the calorimeter response under varying conditions during the LHC Run 1. Finally, the Tile Calorimeter response to isolated muons and hadrons as well as to jets from proton–proton collisions is presented. The results demonstrate excellent performance in accord with specifications mentioned in the Technical Design Report

Performance of missing transverse momentum reconstruction with the ATLAS detector using proton–proton collisions at √s = 13 TeV

The performance of the missing transverse momentum (EmissT) reconstruction with the ATLAS detector is evaluated using data collected in proton–proton collisions at the LHC at a centre-of-mass energy of 13 TeV in 2015. To reconstruct EmissT, fully calibrated electrons, muons, photons, hadronically decaying τ -leptons, and jets reconstructed from calorimeter energy deposits and charged-particle tracks are used. These are combined with the soft hadronic activity measured by reconstructed charged-particle tracks not associated with the hard objects. Possible double counting of contributions from reconstructed charged-particle tracks from the inner detector, energy deposits in the calorimeter, and reconstructed muons from the muon spectrometer is avoided by applying a signal ambiguity resolution procedure which rejects already used signals when combining the various EmissT contributions. The individual terms as well as the overall reconstructed EmissT are evaluated with various performance metrics for scale (linearity), resolution, and sensitivity to the data-taking conditions. The method developed to determine the systematic uncertainties of the EmissT scale and resolution is discussed. Results are shown based on the full 2015 data sample corresponding to an integrated luminosity of 3.2 fb−1