Considering the case for an antidepressant drug trial involving temporary deception: a qualitative enquiry of potential participants

<p>Abstract</p> <p>Background</p> <p>Systematic reviews of randomised placebo controlled trials of antidepressant medication show small and decreasing differences between pharmacological and placebo arms. In part this finding may relate to methodological problems with conventional trial designs, including their assumption of additivity between drug and placebo trial arms. Balanced placebo designs, which include elements of deception, may address the additivity question, but pose substantial ethical and pragmatic problems. This study aimed to ascertain views of potential study participants of the ethics and pragmatics of various balanced placebo designs, in order to inform the design of future antidepressant drug trials.</p> <p>Methods</p> <p>A qualitative approach was employed to explore the perspectives of general practitioners, psychiatrists, and patients with experience of depression. The doctors were chosen via purposive sampling, while patients were recruited through participating general practitioners. Three focus groups and 12 in-depth interviews were conducted. A vignette-based topic guide invited views on three deceptive strategies: post hoc, authorised and minimised deception. The focus groups and interviews were tape-recorded and transcribed. Transcripts were analysed thematically using Framework.</p> <p>Results</p> <p>Deception in non-research situations was typically perceived as acceptable within specific parameters. All participants could see the potential utility of introducing deception into trial designs, however views on the acceptability of deception within antidepressant drug trials varied substantially. Authorized deception was the most commonly accepted strategy, though some thought this would reduce the effectiveness of the design because participants would correctly guess the deceptive element. The major issues that affected views about the acceptability of deception studies were the welfare and capacity of patients, practicalities of trial design, and the question of trust.</p> <p>Conclusion</p> <p>There is a trade-off between pragmatic and ethical responses to the question of whether, and under what circumstances, elements of deception could be introduced into antidepressant drug trials. Ensuring adequate ethical safeguards within balanced placebo designs is likely to diminish their ability to address the crucial issue of additivity. The balanced placebo designs considered in this study are unlikely to be feasible in future trials of antidepressant medication. However there remains an urgent need to improve the quality of antidepressant drug trials.</p

The Gluonic Field of a Heavy Quark in Conformal Field Theories at Strong Coupling

We determine the gluonic field configuration sourced by a heavy quark undergoing arbitrary motion in N=4 super-Yang-Mills at strong coupling and large number of colors. More specifically, we compute the expectation value of the operator tr[F^2+...] in the presence of such a quark, by means of the AdS/CFT correspondence. Our results for this observable show that signals propagate without temporal broadening, just as was found for the expectation value of the energy density in recent work by Hatta et al. We attempt to shed some additional light on the origin of this feature, and propose a different interpretation for its physical significance. As an application of our general results, we examine when the quark undergoes oscillatory motion, uniform circular motion, and uniform acceleration. Via the AdS/CFT correspondence, all of our results are pertinent to any conformal field theory in 3+1 dimensions with a dual gravity formulation.Comment: 1+38 pages, 16 eps figures; v2: completed affiliation; v3: corrected typo, version to appear in JHE

Influence of 1α, 25-dihydroxyvitamin D3 [1, 25(OH)2D3] on the expression of Sox 9 and the transient receptor potential vanilloid 5/6 ion channels in equine articular chondrocytes

Background Sox 9 is a major marker of chondrocyte differentiation. When chondrocytes are cultured in vitro they progressively de-differentiate and this is associated with a decline in Sox 9 expression. The active form of vitamin D, 1, 25 (OH)2D3 has been shown to be protective of cartilage in both humans and animals. In this study equine articular chondrocytes were grown in culture and the effects of 1, 25 (OH)2D3 upon Sox 9 expression examined. The expression of the transient receptor potential vanilloid (TRPV) ion channels 5 and 6 in equine chondrocytes in vitro, we have previously shown, is inversely correlated with de-differentiation. The expression of these channels in response to 1, 25 (OH)2D3 administration was therefore also examined. Results The active form of vitamin D (1, 25 (OH)2D3) when administered to cultured equine chondrocytes at two different concentrations significantly increased the expression of Sox 9 at both. In contrast 1, 25 (OH)2D3 had no significant effect upon the expression of either TRPV 5 or 6 at either the protein or the mRNA level. Conclusions The increased expression of Sox 9, in equine articular chondrocytes in vitro, in response to the active form of vitamin D suggests that this compound could be utilized to inhibit the progressive de-differentiation that is normally observed in these cells. It is also supportive of previous studies indicating that 1α, 25-dihydroxyvitamin D3 can have a protective effect upon cartilage in animals in vivo. The previously observed correlation between the degree of differentiation and the expression levels of TRPV 5/6 had suggested that these ion channels may have a direct involvement in, or be modulated by, the differentiation process in vitro. The data in the present study do not support this

Women take care and men take charge’: The case of leadership and gender in the Public and Commercial Services Union

This article presents the findings of a case study that aimed to understand the specific leadership styles that are valued by women and men lay representatives in the Public and Commercial Services (PCS) union and to determine the gendered implications for increasing women’s leadership and representation in trade unions. Survey responses from PCS lay representatives (reps) show the majority of women and men agreed that the leadership style they value, and makes a good union leader, is post-heroic (communal) leadership. This approach is associated with leadership characteristics such as being helpful, sensitive, and kind and are generally practised by women. This contrasts with male union leaders who are associated with a traditional, heroic (agentic) leadership style characterised by confidence, self-reliance, and decisiveness. Although some differences exist that highlight gender issues, both women and men lay reps have positive attitudes towards increasing women’s representation and participation in union leadership

Teaching the history of geography:Current challenges and future directions

Drawing upon the personal reflections of geographical educators in Brazil, Canada, the UK, and the US, this Forum provides a state-of-the-discipline review of teaching in the history of geography; identifies the practical and pedagogical challenges associated with that teaching; and offers suggestions and provocations as to future innovation. The Forum shows how teaching in the history of geography is valued – as a tool of identity making, as a device for cohort building and professionalization, and as a means of interrogating the disciplinary present – but also how it is challenged by neoliberal educational policies, competing priorities in curriculum design, and sub-disciplinary divisions

Population Pharmacokinetics of Telapristone (CDB-4124) and its Active Monodemethylated Metabolite CDB-4453, with a Mixture Model for Total Clearance

Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h−1. Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmetest) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration