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Refractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.
To estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627).
We undertook a cost-effectiveness analysis alongside a randomised trial evaluating RO DBT plus TAU versus TAU alone for refractory depression in three UK secondary care centres. Our economic evaluation, 12 months after randomisation, adopted the perspective of the UK National Health Service (NHS) and personal social services. It evaluated cost-effectiveness by comparing the net cost of RO DBT with the net gain in quality-adjusted life-years (QALYs), estimated using the EQ-5D-3L measure of health-related quality of life.
The additional cost of RO DBT plus TAU compared with TAU alone was £7048 and was associated with a difference of 0.032 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of £220 250 per QALY. This ICER was well above the National Institute for Health and Care Excellence (NICE) upper threshold of £30 000 per QALY. A cost-effectiveness acceptability curve indicated that RO DBT had a zero probability of being cost-effective compared with TAU at the NICE £30 000 threshold.
In its current resource-intensive form, RO DBT is not a cost-effective use of resources in the UK NHS.
Declaration of interest
R.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from the National Institute for Health Research (NIHR). T.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd, and a grant outside the submitted work from the Medical Research Council. He was co-director of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two directors of Radically Open Ltd. H.O'M. reports personal fees outside the submitted work from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.R. provides RO DBT supervision through her company S C Rushbrook Ltd. I.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M. Stanton reports personal fees outside the submitted work from British Isles DBT Training, Stanton Psychological Services Ltd and Taylor & Francis. M. Swales reports personal fees outside the submitted work from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis. B.W. was co-director of Radically Open Ltd between November 2014 and February 2015.
Jaswal & Akhtar provide several quotes ostensibly from people with autism but obtained via the discredited techniques of Facilitated Communication and the Rapid Prompting Method, and they do not acknowledge the use of these techniques. As a result, their argument is substantially less convincing than they assert, and the article lacks transparency.
Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.
To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).
RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.
After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.
The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.
Declaration of interest
Six of the 16 authors have received royalties or fees for RO DBT. R.J.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from NIHR. T.R.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd and a grant outside the submitted work from the Medical Research Council. He was codirector of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two current directors of Radically Open Ltd. H.O’M. reports personal fees from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.C.R. provides RO DBT supervision through S C Rushbrook Ltd. I.T.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M.St. reports personal fees from British Isles DBT Training, Stanton Psychological Services Ltd, and Taylor & Francis Ltd. M.Sw. reports personal fees from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis Ltd. B.W. was codirector of Radically Open Ltd between November 2014 and February 2015.
Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.
Invasive alien species (IASs) on islands have broad impacts across biodiversity, agriculture, economy, health and culture, which tend to be stronger than on continents. Across small-island developing states (SIDSs), although only a small number of IASs are widely distributed, many more, including those with greatest impact, are found on only a small number of islands. Patterns of island invasion are not consistent across SIDS geographic regions, with differences attributable to correlated patterns in island biogeography and human development. We identify 15 of the most globally prevalent IASs on islands. IAS impacts on islands are exacerbated through interactions with a number of other global change threats, including over-exploitation, agricultural intensification, urban development and climate change. Biosecurity is critical in preventing IAS invasion of islands. Eradication of IASs on islands is possible at early stages of invasion, but otherwise is largely restricted to invasive mammals, or otherwise control is the only option. Future directions in IAS management and research on islands must consider IASs within a broader portfolio of threats to species, ecosystems and people's livelihoods on islands. We advocate for stronger collaborations among island countries and territories faced with the same IASs in similar socio-ecological environments.
We have undertaken an adaptive optics imaging survey of extra-solar planetary systems and stars showing interesting radial velocity trends from high precision radial velocity searches. Adaptive Optics increases the resolution and dynamic range of an image, substantially improving the detectability of faint close companions. This survey is sensitive to objects less luminous than the bottom of the main sequence at separations as close as 1″. We have detected stellar companions to the planet bearing stars HD 114762 and Tau Boo. We have also detected a companion to the non-planet bearing star 16 Cyg A.
The number of pediatric antimicrobial stewardship programs (ASPs) is increasing and program evaluation is a key component to improve efficiency and enhance stewardship strategies.
To determine the antimicrobials and diagnoses most strongly associated with a recommendation provided by a well-established pediatric ASP.
DESIGN AND SETTING
Retrospective cohort study from March 3, 2008, to March 2, 2013, of all ASP reviews performed at a free-standing pediatric hospital.
ASP recommendations were classified as follows: stop therapy, modify therapy, optimize therapy, or consult infectious diseases. A multinomial distribution model to determine the probability of each ASP recommendation category was performed on the basis of the specific antimicrobial agent or disease category. A logistic model was used to determine the odds of recommendation disagreement by the prescribing clinician.
The ASP made 2,317 recommendations: stop therapy (45%), modify therapy (26%), optimize therapy (19%), or consult infectious diseases (10%). Third-generation cephalosporins (0.20) were the antimicrobials with the highest predictive probability of an ASP recommendation whereas linezolid (0.05) had the lowest probability. Community-acquired pneumonia (0.26) was the diagnosis with the highest predictive probability of an ASP recommendation whereas fever/neutropenia (0.04) had the lowest probability. Disagreement with ASP recommendations by the prescribing clinician occurred 22% of the time, most commonly involving community-acquired pneumonia and ear/nose/throat infections.
Evaluation of our pediatric ASP identified specific clinical diagnoses and antimicrobials associated with an increased likelihood of an ASP recommendation. Focused interventions targeting these high-yield areas may result in increased program efficiency and efficacy.
We hypothesised that hypothalamic feeding-related neuropeptides are differentially expressed in obese-prone and lean-prone rats and trigger overeating-induced obesity. To test this hypothesis, in the present study, we measured energy balance and hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA expressions in male JCR:LA-cp rats. We compared, in independent cohorts, free-feeding obese-prone (Obese-FF) and lean-prone (Lean-FF) rats at pre-weaning (10 d old), weaning (21–25 d old) and early adulthood (8–12 weeks). A group of Obese-pair-feeding (PF) rats pair-fed to the Lean-FF rats was included in the adult cohort. The body weights of 10-d-old Obese-FF and Lean-FF pups were not significantly different. However, when the pups were shifted from dams' milk to solid food (weaning), the obese-prone rats exhibited more energy intake over the days than the lean-prone rats and higher body and fat pad weights and fasting plasma glucose, leptin, insulin and lipid levels. These differences were consistent with higher energy consumption and lower energy expenditure. In the young adult cohort, the differences between the Obese-FF and Lean-FF rats became more pronounced, yielding significant age effects on most of the parameters of the metabolic syndrome, which were reduced in the Obese-PF rats. The obese-prone rats displayed higher NPY expression than the lean-prone rats at pre-weaning and weaning, and the expression levels did not differ by age. In contrast, POMC expression exhibited significant age-by-genotype differences. At pre-weaning, there was no genotype difference in POMC expression, but in the weanling cohort, obese-prone pups exhibited lower POMC expression than the lean-prone rats. This genotype difference became more pronounced at adulthood. Overall, the development of hyperphagia-induced obesity in obese-prone JCR rats is related to POMC expression down-regulation in the presence of established NPY overexpression.
The traditional CdCl2 passivation of CdTe is expanded by adding other chlorides such as MgCl2, NaCl, and MnCl2 into the process through a two-step passivation procedure that combines closed space sublimation step with a vapor process. This allows the possibility of forming a highly doped field at the back of the device that could act as an electron reflector that could boost device performance by directing electrons back into the absorber layer and increasing the voltage while limiting recombination at the back of the device. The effects the two-step passivation process on device performance are characterized by current-voltage measurements, and by electroluminescence and laser-beam induced current images to show the degree of device uniformity. Additionally, capacitance voltage measurements are used to study doping density, depletion width, and possible formation of a field at the back of the device.
Heat generated by radioactive decay of spent fuel represents a potentially important barrier to water accumulation on commercial spent nuclear fuel in breached waste packages. In the absence of water, fuel degradation and radionuclide release will be negligible. Thermal models for the proposed Yucca Mountain Repository suggest that, after a period of approximately 1000-4000 years (depending on loadingand ventilation conditions), the repository drift walls may decline to sub-boiling temperatures, thus allowing humidity in the drift to increase. The question thus arises, is the thermal gradient between the fuel and the drift sufficient to prevent water accumulation in a humid drift environment throughout the regulatory period? The answer depends on the balance between processes that oppose water condensation ontothe fuel (decay heat) and those that promote condensation such as the deliquescence of hygroscopic phaseswithin the fuel.
Our experimental results indicate that deliquescence could lead to the condensation of water onto spent fuel despite the thermal “self-drying”effect if the following criteria are met: (1) the fission product salt CsI is present in the fuel or in the fuel-cladding gap, (2) the relative humidity in the driftexceeds 80% while temperatures in the waste package are around 90oC. Previous work suggests that these criteria may be met for some fuel pins within the proposed Yucca Mountain Repository. However,experiments that account for the role of U(VI) alteration phases suggest that deliquescence may be a self-limiting process in the sense that deliquescent components (e.g. Cs, Ba, Sr) may be incorporatedinto nondeliquescent U(VI) phases that form from the corrosion of spent fuel.
Semicrystalline polyimide, Regulus™ NEW-TPI, is a thermoplastic polyimide
produced by mitsui Toatsu. This aromatic polyimide possesses outstanding
heat resistance, high tensile strength, excellent electrical properties, and
strong solvent resistance. It has become the subject of recent study in our
group [1–6] and others [7–13]. The flexible ether and meta linkages in the
monomer unit lower its glass transition temperature (Tg) to 250°C in
quenched amorphous material.
Nanoporous templates made from diblock copolymer films are used for electrochemical fabrication of hexagonal arrays of vertical cobalt magnetic nanowires at terabit/in2 density. The nanowire diameter and areal density are determined by the copolymer molecular weight, whereas the nanowire length and internal crystal morphology are controlled through the dc electrodeposition growth process. The array magnetic properties can be modified substantially by electrodeposition pH conditions while keeping wire size and interwire distance constant. Optimum pH control results in preferential growth of c-axis oriented crystallites with large perpendicular coercivity. The appearance of exchange bias behavior, exhibited at low temperatures, is also investigated.
There is increasing interest in the potential chronic beneficial effects of dietary n-3 PUFA on the metabolic syndrome (MetS) and associated cardiovascular complications. We have recently established that increased dietary n-3 PUFA has a profound acute benefit on fasting lipids and the postprandial pro-inflammatory response in the JCR:LA-cp rat, a model of the MetS. However, it is unclear to what extent chronic dietary n-3 PUFA intervention can modulate the progression of end-stage metabolic and vascular complications. The present study aimed to determine the chronic effects of dietary n-3 PUFA supplementation on fasting and non-fasting dyslipidaemia, insulin resistance and vascular complications in the JCR:LA-cp rodent model. JCR:LA-cp rats were fed an isoenergetic lipid-balanced diet supplemented with 5 % n-3 PUFA (w/w) of the total fat (fish oil-derived EPA/DHA) for 16 weeks. Fasting and non-fasting (postprandial) plasma lipid profile was assessed. Hepatic and adipose tissue was probed for the expression of lipogenic proteins (acyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element-binding protein-1 (SREBP-1)), while the activity of Jun N-terminal kinase (JNK) was assessed via Western blot to target phosphorylated JNK protein in primary enterocytes. The frequency of myocardial lesions was assessed by haematoxylin and eosin staining. Increased dietary n-3 PUFA improved both the fasting and postprandial lipid profiles (TAG, cholesterol and apoB48) in the JCR:LA-cp rat, potentially via the down-regulation of the hepatic or adipose tissue expression of lipogenic enzymes (ACC, FAS and SREBP-1). Rats fed the 5 % n-3 PUFA diet had lower (58·2 %; P < 0·01) enterocytic phosphorylated JNK protein and secreted less cholesterol (30 %; P < 0·05) into mesenteric lymph compared with the control. The chronic metabolic benefits of dietary n-3 PUFA may underlie the potential to reduce vascular complications during the MetS, including the observed reduction in the frequency (approximately 80 %) of late-stage 3 myocardial lesions.
Relationships between the X-ray and radio behavior of black hole X-ray binaries during outbursts have established a fundamental coupling between the accretion disks and radio jets in these systems. I begin by reviewing the prevailing paradigm for this disk-jet coupling, also highlighting what we know about similarities and differences with neutron star and white dwarf binaries. Until recently, this paradigm had not been directly tested with dedicated high-angular resolution radio imaging over entire outbursts. Moreover, such high-resolution monitoring campaigns had not previously targetted outbursts in which the compact object was either a neutron star or a white dwarf. To address this issue, we have embarked on the Jet Acceleration and Collimation Probe Of Transient X-Ray Binaries (JACPOT XRB) project, which aims to use high angular resolution observations to compare disk-jet coupling across the stellar mass scale, with the goal of probing the importance of the depth of the gravitational potential well, the stellar surface and the stellar magnetic field, on jet formation. Our team has recently concluded its first monitoring series, including (E)VLA, VLBA, X-ray, optical, and near-infrared observations of entire outbursts of the black hole candidate H 1743-322, the neutron star system Aquila X-1, and the white dwarf system SS Cyg. Here I present preliminary results from this work, largely confirming the current paradigm, but highlighting some intriguing new behavior, and suggesting a possible difference in the jet formation process between neutron star and black hole systems.
The aim of this study was to determine the effect of acute plasma volume expansion on arterial blood-gas status during 6.5 min strenuous cycling exercise comparing six athletes with and six athletes without exercise-induced arterial hypoxaemia (EIAH). We hypothesized that plasma volume expansion could improve arterial oxygen pressure in a homogeneous sample of athletes - those with EIAH. In this paper we have extended the analysis and results of our recently published surprising findings that lengthening cardiopulmonary transit time did not improve arterial blood-gas status in a heterogeneous sample of endurance cyclists. One 500 ml bag of 10 % Pentastarch (infusion condition) or 60 ml 0.9 % saline (placebo) was infused prior to exercise in a randomized, double-blind fashion on two different days. Power output, cardiac output, oxygen consumption and arterial blood gases were measured during strenuous exercise. Cardiac output and oxygen consumption were not affected by acute hypervolaemia. There were group × condition interaction effects for arterial oxygen pressure and alveolar-arterial oxygen pressure difference, suggesting that those with hypoxaemia experienced improved arterial oxygen pressure (+4 mmHg) and lower alveolar-arterial oxygen pressure difference (-2 mmHg) with infusion. In conclusion, acute hypervolaemia improves blood-gas status in athletes with EIAH. The impairment of gas exchange occurs within the first minute of exercise, and is not impaired further throughout the remaining duration of exercise. This suggests that arterial oxygen pressure is only minimally mediated by cardiac output. Experimental Physiology (2003) 88.4, 555-564.
We have extended by five the number of deep-level traps known to create dark current in charge-coupled device (CCD) image sensors. These include Mn, Pt, and three much weaker traps that are as yet unidentified. Using dark current spectroscopy (DCS) we show that the generation rates at 55°C range from 6400 electrons/s for Mn to only 2 electrons/s for the weakest trap, which lies 0.27 eV off mid-gap. These weak traps determine the bandwidths and resolution of the trap peaks seen in the dark current spectra.