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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.
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.
The majority of studies examining botulinum toxin A (BTX-A) in the management of upper limb muscle overactivity and pain focus on the distal arm and hand. Research has begun to look at BTX-A efficacy in more proximal upper limb muscles, with literature showing equivocal findings. This scoping review identified 15 studies meeting inclusion criteria whose data were examined against three outcome variables: muscle overactivity, range of movement and pain. Overall, while the majority of injected participants improved on these variables, between-study methodological variability such as research design potentially underpowered studies and arbitrary decision making gave a high likelihood of influencing the interpretation of their results. Future research is warranted, with a robust focus on functional anatomy, a critical appraisal of how BTX-A may help the individual being studied and utilising individualised rather than protocol-driven research paradigms.
This article argues for a cross-culturally pluralistic conception of spiritual exemplarity. Three main modes of exemplarity are identified, distinguished by their underlying aspirations, which I label ‘allegiance’, ‘enlightened insight’, and ‘emulation’. After challenging some attempts to privilege the modes of exemplarity characteristic of theistic religions, I argue that perhaps the fullest example of the aspiration to emulation is the form of Daoism presented in The Book of Zhuāngzǐ. I conclude that what one finds across different cultures and traditions is a plurality of modes of spiritual exemplarity that should be acknowledge and explored, rather than given more reductive analyses that narrow our sense of the variety of ways of living a spiritual life.
Exposure to stressful life events is an established risk factor for the development of adolescent mental disorder. Growing evidence also suggests that neighbourhood social environments, including strong social cohesion, could have a protective effect on mental health. However, little is known about how neighbourhood social cohesion may buffer against the effects of stressful life events on adolescent mental health. Our aim was to assess whether neighbourhood social cohesion modifies the association between stressful life events and adolescent mental health outcomes.
Data were drawn from a nationally-representative prospective sample of Canadian adolescents, including 5183 adolescents aged 12/13 years at T1 and 14/15 years at T2. Caregivers reported neighbourhood social cohesion at T1, and exposure to stressful life events between T1 and T2. Symptoms of mental health and behaviour problems were self-reported by adolescents at T1 and T2. Multivariable logistic regression was used to determine whether the relationship between stressful life events and outcomes was modified by neighbourhood social cohesion.
Associations between stressful life events and adolescent outcomes were statistically significantly lower in neighbourhoods with greater social cohesion for: depression/anxiety (high cohesion OR = 0.98 v. low cohesion OR = 3.11), suicidal ideation (ORhigh = 1.30 v. ORlow = 5.25), aggression/conduct disorder (ORhigh = 1.09 v. ORlow = 4.27), and property offence (ORhigh = 1.21 v. ORlow = 4.21).
Greater neighbourhood social cohesion appeared to buffer the effects of stressful life events on several domains of adolescent mental health. This potentially presents a target for public health intervention to improve adolescent mental health and behavioural outcomes.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Many ancient traditions recognise certain people as exemplars of virtue, the models for the good or flourishing human life. Certain traditions, however, incorporate a cosmic mode of emulation, where the virtues are manifestations, in human form, of qualities or aspects of the ground or source of the world. I defend this claim using the sustained case study of the forms of Daoist exemplarity found in the Book of Zhuangzi, then consider the charge that the aspiration to cosmic emulation is inhumane. It emerges that there are forms of emulation where the ultimate model for the good or flourishing life as manifested by the exemplar is nothing human.
The expression of suicidal ideation is considered to be an important warning sign for suicide. However, the predictive properties of suicidal ideation as a test of later suicide are unclear.
To assess the strength of the association between suicidal ideation and later suicide measured by odds ratio (OR), sensitivity, specificity and positive predictive value (PPV).
We located English-language studies indexed in PubMed that reported the expression or non-expression of suicidal ideation among people who later died by suicide or did not. A random effects meta-analysis was used to assess the pooled OR, sensitivity, specificity and PPV of suicidal ideation for later suicide among groups of people from psychiatric and non-psychiatric settings.
There was a moderately strong but highly heterogeneous association between suicidal ideation and later suicide (n = 71, OR = 3.41, 95% CI 2.59–4.49, 95% prediction interval 0.42–28.1, I2 = 89.4, Q-value = 661, d.f.(Q) = 70, P ≤0.001). Studies conducted in primary care and other non-psychiatric settings had similar pooled odds to studies of current and former psychiatric patients (OR = 3.86 v. OR = 3.23, P = 0.7). The pooled sensitivity of suicidal ideation for later suicide was 41% (95% CI 35–48) and the pooled specificity was 86% (95% CI 76–92), with high between-study heterogeneity. Studies of suicidal ideation expressed by current and former psychiatric patients had a significantly higher pooled sensitivity (46% v. 22%) and lower pooled specificity (81% v. 96%) than studies conducted in non-psychiatric settings. The PPV among non-psychiatric cohorts (0.3%, 95% CI 0.1%–0.5%) was significantly lower (Q-value = 35.6, P < 0.001) than among psychiatric samples (3.9%, 95% CI 2.2–6.6).
Estimates of the extent of the association between suicidal ideation and later suicide are limited by unexplained between-study heterogeneity. The utility of suicidal ideation as a test for later suicide is limited by a modest sensitivity and low PPV.
M.M.L. and C.J.R. have provided expert evidence in civil, criminal and coronial matters. I.B.H. has been a Commissioner in Australia's National Mental Health Commission since 2012. He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to Headspace. I.B.H. has previously led community-based and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca) projects focused on the identification and better management of anxiety and depression. He is a Board Member of Psychosis Australia Trust and a member of Veterans Mental Health Clinical Reference group. He was a member of the Medical Advisory Panel for Medibank Private until October 2017. He is the Chief Scientific Advisor to, and an equity shareholder in, InnoWell. InnoWell has been formed by the University of Sydney and PricewaterhouseCoopers to administer the $30 M Australian Government Funded Project Synergy. Project Synergy is a 3-year programme for the transformation of mental health services through the use of innovative technologies.
Objectives: This study examined the effects of anodal transcranial direct current stimulation (a-tDCS) on sentence and word comprehension in healthy adults. Methods: Healthy adult participants, aged between 19 and 30 years, received either a-tDCS over the left inferior frontal gyrus (n=18) or sham stimulation (n=18). Participants completed sentence comprehension and word comprehension tasks before and during stimulation. Accuracy and reaction times (RTs) were recorded as participants completed both tasks. Results: a-tDCS was found to significantly decrease RT on the sentence comprehension task compared to baseline. There was no change in RT following sham stimulation. a-tDCS was not found to have a significant effect on accuracy. Also, a-tDCS did not affect accuracy or RTs on the word comprehension task. Conclusions: The study provides evidence that non-invasive anodal electrical stimulation can modulate sentence comprehension in healthy adults, at least compared to their baseline performance. (JINS, 2019, 25, 331–335)
Lake Untersee is a perennially ice-covered Antarctic lake that consists of two basins. The deepest basin, next to the Anuchin Glacier is aerobic to its maximum depth of 160 m. The shallower basin has a maximum depth of 100 m, is anoxic below 80 m, and is shielded from convective currents. The thermal profile in the anoxic basin is unusual in that the water temperature below 50 m is constant at 4°C but rises to 5°C between 70 m and 80 m depth, then drops to 3.7°C at the bottom. Field measurements were used to conduct a thermal and stability analysis of the anoxic basin. The shape of the thermal maximum implies two discrete locations of energy input, one of 0.11 W m-2 at 71 m depth and one of 0.06 W m-2 at 80 m depth. Heat from microbial activity cannot account for the required amount of energy at either depth. Instead, absorption of solar radiation due to an increase in water opacity at these depths can account for the required energy input. Hence, while microbial metabolism is not an important source of heat, biomass increases opacity in the water column resulting in greater absorption of sunlight.
Ill persons suffer from a variety of epistemically-inflected harms and wrongs. Many of these are interpretable as specific forms of what we dub pathocentric epistemic injustices, these being ones that target and track ill persons. We sketch the general forms of pathocentric testimonial and hermeneutical injustice, each of which are pervasive within the experiences of ill persons during their encounters in healthcare contexts and the social world. What's epistemically unjust might not be only agents, communities and institutions, but the theoretical conceptions of health that structure our responses to illness. Thus, we suggest that although such pathocentric epistemic injustices have a variety of interpersonal and structural causes, they are also sustained by a deeper naturalistic conception of the nature of illness.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Ongoing, rapid innovations in fields ranging from microelectronics, aerospace, and automotive to defense, energy, and health demand new advanced materials at even greater rates and lower costs. Traditional materials R&D methods offer few paths to achieve both outcomes simultaneously. Materials informatics, while a nascent field, offers such a promise through screening, growing databases of materials for new applications, learning new relationships from existing data resources, and building fast predictive models. We highlight key materials informatics successes from the atomic-scale modeling community, and discuss the ecosystem of open data, software, services, and infrastructure that have led to broad adoption of materials informatics approaches. We then examine emerging opportunities for informatics in materials science and describe an ideal data ecosystem capable of supporting similar widespread adoption of materials informatics, which we believe will enable the faster design of materials.