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Medical interventions should ideally only be offered if we know that they help the patient in improving outcome by reducing morbidity and mortality. At present, there is consensus that their effectiveness should be evaluated before incorporation into guidelines.
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.
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.
Defects in crystalline solids control the properties of engineered and natural materials, and their characterization focuses our strategies to optimize performance. Electron microscopy has served as the backbone of our understanding of defect structure and their interactions, owing to beneficial spatial resolution and contrast mechanisms that enable direct imaging of defects. These defects reside in complex microstructures and chemical environments, demanding a combination of experimental approaches for full defect characterization. In this article, we describe recent progress and trends in methods for examining defects using scanning electron microscopy platforms. Several emerging approaches offer attractive benefits, for instance, in correlative microscopy across length scales and in in situ studies of defect dynamics.
Analysis and understanding of the role of hydrogen in metals is a significant challenge for the future of materials science, and this is a clear objective of recent work in the atom probe tomography (APT) community. Isotopic marking by deuteration has often been proposed as the preferred route to enable quantification of hydrogen by APT. Zircaloy-4 was charged electrochemically with hydrogen and deuterium under the same conditions to form large hydrides and deuterides. Our results from a Zr hydride and a Zr deuteride highlight the challenges associated with accurate quantification of hydrogen and deuterium, in particular associated with the overlap of peaks at a low mass-to-charge ratio and of hydrogen/deuterium containing molecular ions. We discuss possible ways to ensure that appropriate information is extracted from APT analysis of hydrogen in zirconium alloy systems that are important for nuclear power applications.
Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.
Lithium-ion capacitors (LICs) and Hybrid LICs (H-LICs) were assembled as three-layered pouch cells in an asymmetric configuration employing Faradaic pre-lithiated hard carbon anodes and non-Faradaic ion adsorption-desorption activated carbon (AC) cathodes for LICs and lithium iron phosphate (LiFePO4-LFP)/AC composite cathodes for H-LICs. The room temperature rate performance was evaluated after the initial LIC and H-LIC cell formation as a function of the electrolyte additives. The capacity retention was measured after charging at high temperature conditions, while the design factor explored was electrolyte additive formulation, with a focus on their stability. The high temperature potential holds simulate electrochemical energy materials under extreme environments and act to accelerate the failure mechanisms associated with cell degradation to determine robust electrolyte/additive combinations.
The trait of extraversion is one of the longest-standing domains that captures the social dimension of personality and can potentially explain the covariation of a wide variety of behaviors. To date, there is a growing recognition that human behavior should be specified not only through the psychological mechanisms underlying each trait but also through their underlying neurobehavioral systems. While imaging studies have revealed important initial insights into the structural and functional neural correlates of extraversion, current knowledge about the relationships between extraversion and brain structures is still rather limited, especially with regard to the relationship between extraversion and white matter (WM). In this study, we aimed to investigate WM microstructure in extraversion in greater depth. Thirty-five healthy volunteers (21 women; mean age 35) underwent magnetic resonance imaging, as a part of a larger project aimed at investigating the longitudinal effect of motor training. WM integrity was assessed using the diffusion tensor imaging technique combining multiple diffusion tensor measures. Extraversion was assessed by the Eysenck Personality Questionnaire-Revised. Voxelwise correlation analyses between fractional anisotropy, axial diffusivities, and radial diffusivities maps and extraversion score showed decreased connectivity in the right inferior fronto-occipital fasciculus and forceps major among individuals who had high extraversion ratings. In conclusion, individual differences in extraversion may reflect differential organization of the WM tracts connecting frontal cortex, temporal, and occipital areas, which are related to socioemotional and control functions.
In tokamak plasmas, sheared flows perpendicular to the driving temperature gradients can strongly stabilise linear modes. While the system is linearly stable, regimes with persistent nonlinear turbulence may develop, i.e. the system is subcritical. A perturbation with small but finite amplitude may be sufficient to push the plasma into a regime where nonlinear effects are dominant and thus allow sustained turbulence. The minimum threshold for nonlinear instability to be triggered provides a criterion for assessing whether a tokamak is likely to stay in the quiescent (laminar) regime. At the critical amplitude, instead of transitioning to the turbulent regime or decaying to a laminar state, the trajectory will map out the edge of chaos. Surprisingly, a quasi-travelling-wave solution is found as an attractor on this edge manifold. This simple advecting solution is qualitatively similar to, but simpler than, the avalanche-like bursts seen in earlier turbulent simulations and provides an insight into how turbulence is sustained in subcritical plasma systems. For large flow shearing rate, the system is only convectively unstable, and given a localised initial perturbation, will eventually return to a laminar state at a fixed spatial location.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
Natural disasters are increasing in frequency and severity. They cause widespread hardship and are associated with detrimental effects on mental health.
Our aim is to provide the best estimate of the effects of natural disasters on mental health through a systematic review and meta-analysis of the rates of psychological distress and psychiatric disorder after natural disasters.
This systematic review and meta-analysis is limited to studies that met predetermined quality criteria. We required included studies to make comparisons with pre-disaster or non-disaster exposed controls, and sample representative populations. Key studies were identified through a comprehensive search of PubMed, EMBASE and PsycINFO from 1980 to 3 March 2017. Random effects meta-analyses were performed for studies that reported key outcomes with appropriate statistics.
Forty-one studies were identified by the literature search, of which 27 contributed to the meta-analyses. Continuous measures of psychological distress were increased after natural disasters (combined standardised mean difference 0.63, 95% CI 0.27–0.98, P = 0.005). Psychiatric disorders were also increased (combined odds ratio 1.84, 95% CI 1.43–2.38, P < 0.001). Rates of post-traumatic stress disorder and depression were significantly increased after disasters. Findings for anxiety and alcohol misuse/dependence were not significant. High rates of heterogeneity suggest that disaster-specific factors and, to a lesser degree, methodological factors contribute to the variance between studies.
Increased rates of psychological distress and psychiatric disorders follow natural disasters. High levels of heterogeneity between studies suggest that disaster variables and post-disaster response have the potential to mitigate adverse effects.
In pikeperch, Sander lucioperca, aquaculture hormonal treatment is usually applied to synchronize ovulation. However, the effect of dopamine (DA) receptor antagonists, in particular those blocking the D1 DA receptors, remains unknown. Thus, the aim of the present study was to investigate and compare the effects of D1 and D2 DA receptor antagonists on the sex-steroid production and reproductive performance of the species. Two experiments were performed during which mature pikeperch females were injected with different molecules: NaCl 0.9% (negative control) or human chorionic gonadotropin 500 IU/kg (positive control) in both experiments, metoclopramide (a D2 receptor antagonist; 4 mg/kg or 20 mg/kg) or SCH23390 (a D1 receptor antagonist; 0.8 mg/kg or 4 mg/kg) alone (experiment 1) or in combination with a salmon gonadotropin-releasing hormone analogue (sGnRHa at 25 µg/kg; experiment 2). In experiment 2, fish were also injected with sGnRHa (25 µg/kg) as positive control. Samplings of oocytes and blood were performed on the day of injection and after 24 h (both experiments), after 48 h (experiment 2) and at the time of ovulation (both experiments). In non-ovulating fish, samplings were performed 7 days (experiment 1) or 14 days (experiment 2) after injection. In experiment 2, various zootechnical parameters of fertilized eggs were recorded (survival, hatching and malformation rates). The two antagonists alone were ineffective in inducing the final stages and regulating sex-steroid (testosterone, 11 ketotestosterone, 17β estradiol and 17,20β-dihydroxy-4-pregnen-3-one) production. When administered with sGnRHa, both SCH23390 and metoclopramide induced the final stages. However, only SCH23390 stimulated testosterone (4 mg/kg) and 17β estradiol (0.8 mg/kg) production compared with sGnRHa alone. None of the treatments affected the survival, hatching or malformation rates. This is the first report suggesting that in pikeperch the D1, but not the D2, DA receptor antagonist would be involved in the testosterone and 17β estradiol production as a potentiator of the sGnRHa effect.
Boyer & Petersen (B&P) argue that folk-economic beliefs are widespread – shaped by evolved cognitive systems – and they offer exemplar beliefs to illustrate their thesis. In this commentary, we highlight evidence of substantial variation in one of these exemplars: beliefs about immigration. Contra claims by B&P, we argue that the balance of this evidence suggests the “folk” may actually hold positive beliefs about the economic impact of immigration.
Moving mesh methods provide an efficient way of solving partial differential equations for which large, localised variations in the solution necessitate locally dense spatial meshes. In one-dimension, meshes are typically specified using the arclength mesh density function. This choice is well-justified for piecewise polynomial interpolants, but it is only justified for spectral methods when model solutions include localised steep gradients. In this paper, one-dimensional mesh density functions are presented which are based on a spatially localised measure of the bandwidth of the approximated model solution. In considering bandwidth, these mesh density functions are well-justified for spectral methods, but are not strictly tied to the error properties of any particular spatial interpolant, and are hence widely applicable. The bandwidth mesh density functions are illustrated in two ways. First, by applying them to Chebyshev polynomial approximation of two test functions, and second, through use in periodic spectral and finite-difference moving mesh methods applied to a number of model problems in acoustics. These problems include a heterogeneous advection equation, the viscous Burgers’ equation, and the Korteweg-de Vries equation. Simulation results demonstrate solution convergence rates that are up to an order of magnitude faster using the bandwidth mesh density functions than uniform meshes, and around three times faster than those using the arclength mesh density function.