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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.
A number of clinical trials have examined the effect of L-arginine on lipid profile in recent years; however, the results remain equivocal. Therefore, the present study aims to summarize and quantitatively examine the available evidence on the effectiveness L-arginine supplementation on lipid parameters by employing a systematic review and meta-analytic approach. Online databases including PubMed, Scopus, ISI Web of Science, Cochrane library, and Google Scholar were searched up to April 2019 for randomized controlled trials that examined the effect of L-arginine supplementation on lipid profile in adults. Treatment effects were expressed as weighted mean difference (WMD) and the corresponding standard error (SE) in concentrations of serum lipids. To estimate the overall effect of L-arginine supplementation, we employed the random-effects model. In total, 12 studies were included in the systematic review. The meta-analysis revealed that L-arginine supplementation did not significantly change the concentrations of total cholesterol (WMD: -5.03 mg/dl; 95% CI: -10.78 to 0.73, P= 0.08, I2=39.0%), low-density lipoprotein (WMD: -0.47 mg/dl; 95% CI: -3.61 to 2.66, P=0.76, I2=0.0%), or high-density lipoprotein (WMD: 0.57 mg/dl; 95% CI: -1.28 to 2.43, P=0.54, I2=68.4%). A significant reduction was observed only in serum triglyceride (TG) levels (WMD: -7.04 mg/dl; 95% CI: -11.42 to -2.67, P<0.001, I2=0.0%). This meta-analysis concludes that L-arginine supplementation can significantly reduce blood TG levels, however, there is insufficient evidence to support its hypocholesterolaemic effects. To draw straightforward conclusions regarding generalized recommendations for L-arginine supplementation for improving lipid profile, there is a need for more well-controlled trials targeting exclusively patients with dyslipidaemia.
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.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Declining sea ice is expected to change the Arctic's physical and biological systems in ways that are difficult to predict. This study used stable isotope compositions (δ13C and δ15N) of archaeological, historic, and modern Pacific walrus (Odobenus rosmarus divergens) bone collagen to investigate the impacts of changing sea ice conditions on walrus diet during the last ~4000 yr. An index of past sea ice conditions was generated using dinocyst-based reconstructions from three locations in the northeastern Chukchi Sea. Archaeological walrus samples were assigned to intervals of high and low sea ice, and δ13C and δ15N were compared across ice states. Mean δ13C and δ15N values were similar for archaeological walruses from intervals of high and low sea ice; however, variability among walruses was greater during low-ice intervals, possibly indicating decreased availability of preferred prey. Overall, sea ice conditions were not a primary driver of changes in walrus diet. The diet of modern walruses was not consistent with archaeological low sea ice intervals. Rather, the low average trophic position of modern walruses (primarily driven by males), with little variability among individuals, suggests that trophic changes to this Arctic ecosystem are still underway or are unprecedented in the last ~4000 yr.
Whitehouse's article posits several plausible hypotheses, but suffers from an unwarranted reliance on the importance of distinct social groups in the causation of self-sacrificing behavior. A focus on relationships between individual kin is better able to account for both the evolution of self-sacrifice and present forms of self-sacrifice. The practical importance of this point is discussed.
The Infectious Disease Society of America (IDSA) publishes guidelines regularly for the management of skin and soft tissue infections; however, the extent to which practice patterns follow these guidelines and if this can affect treatment failure rates is unknown. We observed the treatment failure rates from a multicentre retrospective ambulatory cohort of adult emergency department patients treated for a non-purulent skin infection. We used multivariable logistic regression to examine the role of IDSA classification and whether adherence to IDSA guidelines reduced treatment failure. A total of 759 ambulatory patients were included in the cohort with 17.4% failing treatment. Among all patients, 56.0% had received treatments matched to the IDSA guidelines with 29.1% over-treated, and 14.9% under-treated based on the guidelines. After adjustment for age, gender, infection location and medical comorbidities, patients with a moderate infection type had three times increased risk of treatment failure (adjusted risk ratio (aRR) 2.98; 95% confidence interval (CI) 1.15–7.74) and two times increased risk with a severe infection type (aRR 2.27; 95% CI 1.25–4.13) compared with mild infection types. Patients who were under-treated based on IDSA guidelines were over two times more likely to fail treatment (aRR 2.65; 95% CI 1.16–6.05) while over-treatment was not associated with treatment failure. Patients ⩾70 years of age had a 56% increased risk of treatment failure (aRR 1.56; 95% CI 1.04–2.33) compared with those <70 years. Following the IDSA guidelines for non-purulent SSTIs may reduce the treatment failure rates; however, older adults still carry an increased risk of treatment failure.
In (3) Tutte showed that the order of a regular graph of degree d and even girth g > 4 is greater than or equal to
Here the girth of a graph is the length of the shortest circuit. It was shown in (2) that this lower bound cannot be attained for regular graphs of degree > 2 for g ≠ 6, 8, or 12. When this lower bound is attained, the graph is called minimal. In a group-theoretic setting a similar situation arose and it was noticed by Gleason that minimal regular graphs of girth 12 could be constructed from certain groups. Here we construct these graphs making only incidental use of group theory. Also we give what is believed to be an easier construction of minimal regular graphs of girth 8 than is given in (2). These results are contained in the following two theorems.
Chronic suppurative otitis media is a massive public health problem in numerous low- and middle-income countries. Unfortunately, few low- and middle-income countries can offer surgical therapy.
A six-month long programme in Cambodia focused on training local surgeons in type I tympanoplasty was instigated. Qualitative educational and quantitative surgical outcomes were evaluated in the 12 months following programme completion. A four-month long training programme in mastoidectomy and homograft ossiculoplasty was subsequently implemented, and the preliminary surgical and educational outcomes were reported.
A total of 124 patients underwent tympanoplasty by the locally trained surgeons. Tympanic membrane closure at six weeks post-operation was 88.5 per cent. Pure tone audiometry at three months showed that 80.9 per cent of patients had improved hearing, with a mean gain of 17.1 dB. The trained surgeons reported high confidence in performing tympanoplasty. Early outcomes suggest the local surgeons can perform mastoidectomy and ossiculoplasty as safely as overseas-trained surgeons, with reported surgeon confidence reflecting these positive outcomes.
The training programme has demonstrated success, as measured by surgeon confidence and operative outcomes. This approach can be emulated in other settings to help combat the global burden of chronic suppurative otitis media.
The supplementing of sow diets with lipids during pregnancy and lactation has been shown to reduce sow condition loss and improve piglet performance. The aim of this study was to determine the effects of supplemental palm oil (PO) on sow performance, plasma metabolites and hormones, milk profiles and pre-weaning piglet development. A commercial sow ration (C) or an experimental diet supplemented with 10% extra energy in the form of PO, were provided from day 90 of gestation until weaning (24 to 28 days postpartum) in two groups of eight multiparous sows. Gestation length of PO sows increased by 1 day (P<0.05). Maternal BW changes were similar throughout the trial, but loss of backfat during lactation was reduced in PO animals (C: −3.6±0.8 mm; PO: −0.1±0.8 mm; P<0.01). Milk fat was increased by PO supplementation (C day 3: 8.0±0.3% fat; PO day 3: 9.1±0.3% fat; C day 7: 7.8±0.5% fat; PO day 7: 9.9±0.5% fat; P<0.05) and hence milk energy yield of PO sows was also elevated (P<0.05). The proportion of saturated fatty acids was greater in colostrum from PO sows (C: 29.19±0.31 g/100 g of fat; PO: 30.77±0.36 g/100 g of fat; P<0.01). Blood samples taken on 105 days of gestation, within 24 h of farrowing, day 7 of lactation and at weaning (28±3 days post-farrowing) showed there were no differences in plasma concentrations of triacylglycerol, non-esterified fatty acids, insulin or IGF-1 throughout the trial. However, circulating plasma concentrations of both glucose and leptin were elevated during lactation in PO sows (P<0.05 and P<0.005, respectively) and thyroxine was greater at weaning in PO sows (P<0.05). Piglet weight and body composition were similar at birth, as were piglet growth rates throughout the pre-weaning period. A period of 7 days after birth, C piglets contained more body fat, as indicated by their lower fat-free mass per kg (C: 66.4±0.8 arbitrary units/kg; PO: 69.7±0.8 arbitrary unit/kg; P<0.01), but by day 14 of life this situation was reversed (C: 65.8±0.6 arbitrary units/kg; PO: 63.6±0.6 arbitrary units/kg; P<0.05). Following weaning, PO sows exhibited an increased ratio of male to female offspring at their subsequent farrowing (C: 1.0±0.3; PO: 2.2±0.2; P<0.05). We conclude that supplementation of sow diets with PO during late gestation and lactation appears to increase sow milk fat content and hence energy supply to piglets. Furthermore, elevated glucose concentrations in the sow during lactation may be suggestive of impaired glucose homoeostasis.
Comprising Holostei and Teleostei, the ~32,000 species of neopterygian fishes are anatomically disparate and represent the dominant group of aquatic vertebrates today. However, the pattern by which teleosts rose to represent almost all of this diversity, while their holostean sister-group dwindled to eight extant species and two broad morphologies, is poorly constrained. A geometric morphometric approach was taken to generate a morphospace from more than 400 fossil taxa, representing almost all articulated neopterygian taxa known from the first 150 million years—roughly 60%—of their history (Triassic‒Early Cretaceous). Patterns of morphospace occupancy and disparity are examined to: (1) assess evidence for a phenotypically “dominant” holostean phase; (2) evaluate whether expansions in teleost phenotypic variety are predominantly abrupt or gradual, including assessment of whether early apomorphy-defined teleosts are as morphologically conservative as typically assumed; and (3) compare diversification in crown and stem teleosts. The systematic affinities of dapediiforms and pycnodontiforms, two extinct neopterygian clades of uncertain phylogenetic placement, significantly impact patterns of morphological diversification. For instance, alternative placements dictate whether or not holosteans possessed statistically higher disparity than teleosts in the Late Triassic and Jurassic. Despite this ambiguity, all scenarios agree that holosteans do not exhibit a decline in disparity during the Early Triassic‒Early Cretaceous interval, but instead maintain their Toarcian‒Callovian variety until the end of the Early Cretaceous without substantial further expansions. After a conservative Induan‒Carnian phase, teleosts colonize (and persistently occupy) novel regions of morphospace in a predominantly gradual manner until the Hauterivian, after which expansions are rare. Furthermore, apomorphy-defined teleosts possess greater phenotypic variety than typically assumed. Comparison of crown and stem teleost partial disparity indicates that, despite a statistically significant increase in crown teleost disparity between the Late Jurassic and earliest Cretaceous, stem teleosts remained important long-term contributors to overall teleost disparity during this time.