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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.
Overweight and obesity may increase risk of disease progression in men with prostate cancer, but there have been few studies of weight loss interventions in this patient group. Based on existing literature and patient preferences we designed a self-help diet and physical activity intervention with telephone-based dietitian support. Men treated for prostate cancer who were overweight or obese were randomised to intervention or wait-list mini-intervention groups. The intervention group had an initial group meeting, a supporting letter from their urological consultant, three telephone dietitian consultations at 4-week intervals, a pedometer and access to web-based diet and physical activity resources. At 12 weeks, men in both groups were given digital scales for providing follow-up weight measurements, and the wait-list group received a mini-intervention of the supporting letter, a pedometer and access to the web-based resources. Sixty-two men were randomised; fifty-four completed baseline and 12-week measurements, and fifty-one and twenty-seven provided measurements at 6 and 12 months, respectively. In a repeated measures model, mean (95 % CI) difference in weight change between groups (wait-list mini-intervention minus intervention) at 12 weeks was −2·13 (−3·44, −0·82) kg (P = 0·002). At 12 months the corresponding value was −2·43 (−4·50, −0·37) kg (P = 0·022). Mean (95 % CI) difference in global QoL score change between groups at 12 weeks was 12·3 (4·93, 19·7) (P = 0·002); at 12 months there were no significant differences between groups. Results suggest the potential of self-help diet and physical activity intervention with trained support for modest but sustained weight loss in this patient group.
Observation of the ion source generated background has been an area of focus during our routine analytical work. It is noted that the results of very-low-ratio samples are dependent upon the particular procedures for measurement using the present-day Cs+ sputter ion sources. When measured without excessive Cs+ fluxes and without interleafing with other higher-ratio samples and references, the accelerator mass spectrometry (AMS) sensitivity can be somewhat improved. In some cases, it appears possible to assess old radiocarbon (14C) samples to beyond the long-standing 60 kyr limit. A number of observational studies are made for the sole purpose of minimizing the final contamination to the rare isotopes that is generated within the ion source.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
High resolution Bragg-case X-ray double and triple axis diffractometry and Laue-case white beam synchrotron X-ray topography experiments have been performed on undoped  oriented float-zone GaAs crystals have been grown under microgravity conditions in space on the D2 mission. Near the seed, excellent anomalous transmission was achieved and a clear cellular structure of dislocations observed. The double and triple axis rocking curves were comparable with those from semi-insulating terrestrial material. Following a heater failure, the molten zone height dropped and reciprocal space maps revealed a long ridge of scatter transverse to the diffraction vector direction. This corresponds to the presence of a distribution of sub-grains containing little internal strain. Continued growth resulted in twin formation.
Quantitative analysis of six clay minerals commonly found in drilling mud solids is studied by x-ray diffraction using the method of internal standards. Standard clay samples are used with three internal standards to derive calibration curves from which four synthetic mud solids are analyzed. If careful sample preparation and handling are employed, reasonably accurate and reproducible results are obtained.
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)
Choices regarding the disposition of wealth at retirement can have substantial implications for retirement income security. We analyze the factors determining annuity payout option choices within the context of a public sector defined pension plan with no default annuity option. Using combined administrative records and survey data, we explore the role of individual and household characteristics as well as risk preferences, time preferences, and financial literacy. We also document retiree well-being and satisfaction with retirement decision making. The evidence is consistent with predictions over which households might benefit most from each annuity option. Comparing retirees who chose different types of annuities, we find that these groups of retirees report very different levels of well-being in retirement. All retirees report lower levels of retirement income security over time, with strong differences among those who chose different types of annuities.
Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated.
We used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods.
Bacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%–14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change.
Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.
Multi-sire mating of a mob of ewes is commonly used in commercial sheep production systems. However, ram mating success (defined as the number of lambs sired by an individual) can vary between rams in the mating group. If this trait was repeatable and heritable, selection of rams capable of siring larger numbers of lambs could reduce the number of rams required for mating and ultimately lead to increased genetic gain. However, genetic correlations with other productive traits, such as growth and female fertility, could influence the potential for ram mating success to be used as a selection trait. In order to investigate this trait, parentage records (including accuracy of sire assignment) from 15 commercial ram breeding flocks of various breeds were utilised to examine the repeatability and heritability of ram mating success in multi-sire mating groups. In addition, genetic and phenotypic correlations with growth and female fertility traits were estimated using ASReml. The final model used for the ram mating success traits included age of the ram and mating group as fixed effects. Older rams (3+years old) had 15% to 20% greater mating success than younger rams (1 or 2 years of age). Increasing the stringency of the criteria for inclusion of both an individual lamb, based on accuracy of sire assignment, or a whole mating group, based on how many lambs had an assigned sire, increased repeatability and heritability estimates of the ram mating success traits examined. With the most stringent criteria employed, where assignment of sire accuracy was >0.95 and the total number of lambs in the progeny group that failed to have a sire assigned was<0.05, repeatability and heritability for loge(number of lambs) was 0.40±0.09 and 0.26±0.12, respectively. For proportion of lambs sired, repeatability and heritability were both 0.30±0.09. The two ram mating traits (loge(nlamb) and proportion) were highly correlated, both phenotypically and genetically (0.88±0.01 and 0.94±0.06, respectively). Both phenotypic and genetic correlations between ram mating success and growth and other female fertility traits were low and non-significant. In conclusion, there is scope to select rams capable of producing high numbers of progeny and thus increase selection pressure on rams to increase genetic gain.
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.
Current policy emphasises the importance of ‘living well’ with dementia, but there has been no comprehensive synthesis of the factors related to quality of life (QoL), subjective well-being or life satisfaction in people with dementia. We examined the available evidence in a systematic review and meta-analysis. We searched electronic databases until 7 January 2016 for observational studies investigating factors associated with QoL, well-being and life satisfaction in people with dementia. Articles had to provide quantitative data and include ⩾75% people with dementia of any type or severity. We included 198 QoL studies taken from 272 articles in the meta-analysis. The analysis focused on 43 factors with sufficient data, relating to 37639 people with dementia. Generally, these factors were significantly associated with QoL, but effect sizes were often small (0.1–0.29) or negligible (<0.09). Factors reflecting relationships, social engagement and functional ability were associated with better QoL. Factors indicative of poorer physical and mental health (including depression and other neuropsychiatric symptoms) and poorer carer well-being were associated with poorer QoL. Longitudinal evidence about predictors of QoL was limited. There was a considerable between-study heterogeneity. The pattern of numerous predominantly small associations with QoL suggests a need to reconsider approaches to understanding and assessing living well with dementia.
Breast milk is the only source of the essential amino acid tryptophan (TRP) in breast-fed infants. Low levels of TRP could have implications for infant neurodevelopment. The objectives of the present study were to compare the relationship of TRP and its neuroactive pathway metabolites kynurenine (Kyn) and kynurenic acid (KynA) in preterm and term expressed breast milk (EBM) in the first 14 d following birth, and the relationship of TRP metabolism to maternal stress and immune status. A total of twenty-four mothers were recruited from Cork University Maternity Hospital: twelve term (>38 weeks) and twelve preterm (<35 weeks). EBM samples were collected on days 7 and 14. Free TRP, Kyn and KynA were measured using HPLC, total TRP using MS, cytokines using the Meso Scale Discovery (MSD) assay system, and cortisol using a cortisol ELISA kit. Although total TRP was higher in preterm EBM in comparison with term EBM (P < 0·05), free TRP levels were lower (P < 0·05). Kyn, KynA and the Kyn:TRP ratio increased significantly in term EBM from day 7 to day 14 (P < 0·05), but not in preterm EBM. TNF-α, IL-6 and IL-8 were higher in day 7 preterm and term EBM in comparison with day 14. There were no significant differences between term and preterm EBM cortisol levels. Increased availability of total TRP, lower levels of free TRP and alterations in the temporal dynamics of TRP metabolism in preterm compared with term EBM, coupled with higher EBM inflammatory markers on day 7, may have implications for the neurological development of exclusively breast-fed preterm infants.
Accurate and reproducible patient positioning is a critical step in radiotherapy for breast cancer. This has seen the use of permanent skin markings becoming standard practice in many centres. Permanent skin markings may have a negative impact on long-term cosmetic outcome, which may in turn, have psychological implications in terms of body image. The aim of this study was to investigate the feasibility of using a semi-permanent tattooing device for the administration of skin marks for breast radiotherapy set-up.
Materials and methods
This was designed as a phase II double-blinded randomised-controlled study comparing our standard permanent tattoos with the Precision Plus Micropigmentation (PPMS) device method. Patients referred for radical breast radiotherapy were eligible for the study. Each study participant had three marks applied using a randomised combination of the standard permanent and PPMS methods and was blinded to the type of each mark. Follow up was at routine appointments until 24 months post radiotherapy. Participants and a blind assessor were invited to score the visibility of each tattoo at each follow-up using a Visual Analogue Scale. Tattoo scores at each time point and change in tattoo scores at 24 months were analysed by a general linear model using the patient as a fixed effect and the type of tattoo (standard or research) as covariate. A simple questionnaire was used to assess radiographer feedback on using the PPMS.
In total, 60 patients were recruited to the study, of which 55 were available for follow-up at 24 months. Semi-permanent tattoos were more visible at 24 months than the permanent tattoos. Semi-permanent tattoos demonstrated a greater degree of fade than the permanent tattoos at 24 months (final time point) post completion of radiotherapy. This was not statistically significant, although it was more apparent for the patient scores (p=0·071) than the blind assessor scores (p=0·27). No semi-permanent tattoos required re-marking before the end of radiotherapy and no adverse skin reactions were observed.
The PPMS presents a safe and feasible alternative to our permanent tattooing method. An extended period of follow-up is required to fully assess the extent of semi-permanent tattoo fade.