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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.
Programmatic surveillance of intestinal schistosomiasis during control can typically use four diagnostic tests, either singularly or in combination, but these have yet to be cross-compared directly. Our study assembled a complete diagnostic dataset, inclusive of infection intensities, from 258 children from five Ugandan primary schools. The schools were purposely selected as typical of the endemic landscape near Lake Albert and reflective of high- and low-transmission settings. Overall prevalence was: 44.1% (95% CI 38.0–50.2) by microscopy of duplicate Kato-Katz smears from two consecutive stools, 56.9% (95% CI 50.8–63.0) by urine-circulating cathodic antigen (CCA) dipstick, 67.4% (95% CI 61.6–73.1) by DNA-TaqMan® and 75.1% (95% CI 69.8–80.4) by soluble egg antigen enzyme-linked immunosorbent assay (SEA-ELISA). A cross-comparison of diagnostic sensitivities, specificities, positive and negative predictive values was undertaken, inclusive of a latent class analysis (LCA) with a LCA-model estimate of prevalence by each school. The latter ranged from 9.6% to 100.0%, and prevalence by school for each diagnostic test followed a static ascending order or monotonic series of Kato-Katz, urine-CCA dipstick, DNA-TaqMan® and SEA-ELISA. We confirm that Kato-Katz remains a satisfactory diagnostic standalone in high-transmission settings but in low-transmission settings should be augmented or replaced by urine-CCA dipsticks. DNA-TaqMan® appears suitable in both endemic settings though is only implementable if resources permit. In low-transmission settings, SEA-ELISA remains the method of choice to evidence an absence infection. We discuss the pros and cons of each method concluding that future surveillance of intestinal schistosomiasis would benefit from a flexible, context-specific approach both in choice and application of each diagnostic method, rather than a single one-size fits all approach.
Conjugated linoleic acid (cis-9, trans-11-C18:2; CLA) in milk arises as a result of microbial biohydrogenation of dietary linoleic and linolenic acids in the rumen (Kepler and Tove, 1967). Milk fat CLA concentrations were significantly (P<0.05) higher when cows were fed silage supplemented with pulp’n brew (a mixture of brewers grains, a by-product of the brewing industry, and sugar beet pulp in dry matter proportions of 0.65:0.35), compared with silage alone (Trial 1). Intake of spring grass resulted in a 2.1–fold increase in milk fat CLA concentrations over cows receiving autumn grass. Throughout lactation in Trial 2, spring calving cows produced higher milk fat CLA concentrations (from 0.5-2.7 g/100 g fatty acid methyl esters (FAME)) than autumn calving cows (0.3-1.7 g/100 g FAME); the former having spent 80% and the latter 50% of lactation on pasture. The CLA content was higher in late lactation milk compared with early lactation milk in both herds. There were no significant differences in milk yields or milk constituent yields between the herds. Manufacturing milk obtained between March and September was analyzed for milk fatty acid composition and the data correlated with grass growth throughout the season. Significant positive correlations were obtained between grass growth rates and concentrations of CLA and linolenic acid in milk fat. The data indicate that seasonal variation in milk fat CLA concentrations may be attributed to variation in pasture growth rates.
Research into the gut microbiota of human infants is necessary in order to better understand how inter-species interactions and ecological succession shape the diversity of the gut microbiota, and in turn, how the specific composition of the gut microbiota impacts on host health both during infancy and in later years. Blastocystis is a ubiquitous intestinal protist that has been linked to a number of intestinal and extra-intestinal diseases. However, emerging data show that asymptomatic carriage is common and that Blastocystis is prevalent in the healthy adult gut microbiota. Nonetheless, little is known about the prevalence and diversity of this microorganism in the healthy infant gut, including when and how individuals become colonized by Blastocystis. Here, we surveyed the prevalence and diversity of Blastocystis in an infant population (n = 59) from an industrialized country (Ireland) using Blastocystis-specific primers at three or more time-points up to 24 months old. Only three infants were positive for Blastocystis (prevalence = 5%) and this was only noted for samples collected at month 24. This rate is comparatively low relative to previously reported prevalence rates in the contemporaneous adult population. These data suggest that infants in Westernized countries that are successfully colonized by Blastocystis most likely acquire this microorganism via horizontal transfer.
n-3 PUFA are lipids that play crucial roles in immune-regulation, cardio-protection and neurodevelopment. However, little is known about the role that these essential dietary fats play in modulating caecal microbiota composition and the subsequent production of functional metabolites. To investigate this, female C57BL/6 mice were assigned to one of three diets (control (CON), n-3 supplemented (n3+) or n-3 deficient (n3−)) during gestation, following which their male offspring were continued on the same diets for 12 weeks. Caecal content of mothers and offspring were collected for 16S sequencing and metabolic phenotyping. n3− male offspring displayed significantly less % fat mass than n3+ and CON. n-3 Status also induced a number of changes to gut microbiota composition such that n3− offspring had greater abundance of Tenericutes, Anaeroplasma and Coriobacteriaceae. Metabolomics analysis revealed an increase in caecal metabolites involved in energy metabolism in n3+ including α-ketoglutaric acid, malic acid and fumaric acid. n3− animals displayed significantly reduced acetate, butyrate and total caecal SCFA production. These results demonstrate that dietary n-3 PUFA regulate gut microbiota homoeostasis whereby n-3 deficiency may induce a state of disturbance. Further studies are warranted to examine whether these microbial and metabolic disturbances are causally related to changes in metabolic health outcomes.
Within the World Health Organization 2012–2020 roadmap for control and elimination of schistosomiasis, the scale-up of mass drug administration with praziquantel is set to change the epidemiological landscape across Africa and Arabia. Central in measuring progress is renewed emphasis upon diagnostics which operate at individual, community and environmental levels by assessing reductions in disease, infections and parasite transmission. However, a fundamental tension is revealed between levels for present diagnostic tools, and methods applied in control settings are not necessarily adequate for application in elimination scenarios. Indeed navigating the transition from control to elimination needs careful consideration and planning. In the present context of control, we review current options for diagnosis of schistosomiasis at different levels, highlighting several strengths and weaknesses therein. Future challenges in elimination are raised and we propose that more cost-effective diagnostics and clinical staging algorithms are needed. Using the Kingdom of Saudi Arabia as a contemporary example, embedding new diagnostic methods within the primary care health system is discussed with reference to both urogenital and intestinal schistosomiasis.
The fetal and early postnatal environment can have a long-term influence on offspring growth. Using a pig model, we investigated the effects of maternal body condition (thin or fat) and maternal gestation feeding level (restricted, control or high) on maternal stress, milk composition, litter size, piglet birth weight and pre-weaning growth. A total of sixty-eight thin (backfat depth about 8 mm) and seventy-two fat (backfat depth about 12 mm) gilts were selected at about 22 weeks. This backfat difference was then accentuated nutritionally up to service at about 32 weeks. During gestation, individual gilts from within each group were randomly allocated to a gestation diet at the following feed allowances: 1·8 kg/d (restricted); 2·5 kg/d (control) and 3·5 kg/d (high) until day 90 of gestation. During gestation restricted gilts had higher levels of cortisol than high and control fed animals. Piglets born to fat gilts had higher average daily gain during the lactation period and higher weaning weights at day 28 than piglets born to thin gilts. Gilts on a high feed level had heavier piglets than those provided with restricted and control allocations. Fat gilts had less saturated fat in their milk at day 21 of lactation and higher unsaturated fat levels. No differences were found in the n-6:n-3 PUFA ratio in the milk between thin and fat gilts. In conclusion, maternal body condition influenced the daily weight gain of offspring up to weaning (day 28) and milk fat composition. Furthermore, maternal feed level during gestation alters maternal cortisol levels and milk fat composition.
In this paper we present results on solid state reactions between Ti and Si1−xGex alloys selectively deposited onto Si (100) substrates using rapid thermal annealing (RTA) for contact applications in novel device structures. Germanium concentrations of 0%, 30%, 50%, and 100% within the reacting Si1−xGex alloy are investigated. The Si1−xGex alloys (approximately 2500 ° thick) are deposited using rapid thermal chemical vapor deposition (RTCVD). Titanium is then deposited by evaporation. Sheet resistance measurements as a function of RTA temperature (10 second anneals) provide indications of various phases that occur during the reactions through the formation of constant sheet resistance plateaus. The RTA temperature required for the formation of a minimum resistivity phase is observed to increase for increasing Ge concentrations within the reacting Si1−xGex alloy. Using x-ray diffraction we have determined that for the reactions of Ti with Si the C49 TiSi2 metastable phase forms prior to the minimum resistivity C54 TiSi2 phase. For the reactions between Ti and Ge a minimum resistivity TiGe2 phase also with the C54 structure forms, however, this phase is preceeded not by a C49 TiGe2 structure, but by a Ti6Ge5 phase. The minimum resistivity phases for Ti reactions with 30% and 50% Ge Si1−xGex, alloy reactions also have a C54 structure with unit cell dimensions varying from that of TiSi2) to TiGe2 as the Ge concentration is increased. The grain structures for the reactions are investigated by cross-sectional transmission electron microscopy (XTEM). As the Ge concentration within the reacting alloy decreases the lateral grain size for the C54 structures increases. A self-aligned germanosilicide process is identified and used to fabricate raised, ultrashallow junctions with Ti(SiGe)2 (germanosilicide) contacts. Forward and reverse bias characterization of the junctions indicate that leakage current induced during silicidation can be eliminated using raised junctions with germanosilicide contacts.
Conjugated linoleic acid (CLA) reduces mammary milk fat synthesis in a dose-dependent manner. Our objective was to determine the effects of lipid-encapsulated CLA (LE-CLA) supplementation on milk production, reproductive performance and metabolic responses in lactating dairy cows fed a grass silage-based diet. Seventy-two Holstein-Friesian cows (32 primiparous and 40 multiparous) were used in a completely randomized block design. Cows received either 80 g of LE-CLA daily or 60 g of calcium salts of palm fatty acids daily (control) from parturition until 60 days in milk. LE-CLA contained a 50:50 mix of cis-9,trans-11 CLA and trans-10,cis-12 CLA, resulting in a daily intake of 6 g of each isomer. Milk production and dry matter intake were recorded daily, and blood samples were collected 3-times a week. Blood samples were analysed for circulating concentrations of glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), insulin and insulin-like growth factor-I (IGF-I). Progesterone was measured in blood samples collected after the first post-partum insemination. Ovarian ultrasound examinations commenced at 8–10 d post partum and were carried out 3-times a week until first ovulation. LE-CLA treatment resulted in decreased milk fat concentration, with consequent improvements in energy balance and body condition score (BCS). The peak concentration of NEFA in blood was reduced by LE-CLA, but circulating concentrations of insulin, glucose, IGF-I, BHBA and progesterone were not affected. There was no effect of LE-CLA supplementation on the post-partum interval to first ovulation. Services per conception tended to be reduced. The reduction in milk energy output and improvement in energy status and BCS in LE-CLA-supplemented cows provides a strong rationale for further studies with greater cow numbers to test effects on reproductive performance.
Recent observation of efficient luminescence in porous silicon has stimulated interest in the electronic and optical properties of Si quantum wires [1,2,3]. If silicon becomes a material suitable for optical applications, techniques for fabricating silicon wires reliably and uniformly will be needed. Once this is achieved, there will be interest not only in optical properties of silicon wires but also transport properties. For instance, to determine the properties of a hypothetical Si LED, one needs to know about both transport and optical properties.
In this paper, we present theoretical studies of electronic, optical and transpon properties of silicon quantum wires ranging in size from 7.7Ä to 31Ä. The electronic and optical properties are treated in an empirical tight-binding approach with excitonic effects included in the effective mass approximation. Carrier transport is treated in a Boltzmann transport framework with nonpolar deformation potential acoustic phonon scattering being the dominant scattering mechanism.
Infrared absorption spectroscopy has been used to measure atomic chlorine concentrations over a range of plasma conditions in both Cl2 and CF3Cl discharges.These measurements were made utilizing the spin-orbit transitions in the ground state of atomic chlorine near 882 cm−1.The concentration studies were performed by passing light from a diode laser through a multi-pass (White) cell set in two opposed windows of a parallel plate plasma etching reactor.The plasma work was preceded by a laboratory measurement of the infrared absorption line strengths of the 2P1/2 ← 2P3/2 transition.This measurement was done in a known concentration of atomic chlorine produced in a low pressure discharge flow system by the reaction of Cl2 or HCl with excess fluorine atoms.These measurements resulted in an integrated line strength of 4.14 (±0.89) × 10−21 cm2-molecule−1-cm−1 for the strongest hyperfine component of the transition at 882.3626 cm−1.
Measured atomic chlorine concentrations in Cl2 discharges varied between 0.2 and 8.0 × 1014 atoms/cm3, representing atomic chlorine fractions on the order of a few percent.The measured atomic chlorine concentrations increased approximately linearly with increasing power and pressure, and increased with increasing frequency above approximately 1 MHz.Below 1 MHz, the atomic chlorine concentration was relatively independent of frequency.
In this paper, we report electrical characterization of raised source/drain MOS transistors fabricated using selectively deposited, in-situ boron doped SixGe1-x as a solid diffusion source to form the source/drain junctions. The alloy can be deposited with an enhanced selectivity at temperatures as low as 600°C resulting in an abrupt doping profile at the SixGe1-x/Si interface. After deposition, junctions are formed by diffusion of boron from the deposited layer into the silicon substrate. The selectively deposited alloy can serve as a sacrificial layer for self-aligned silicide formation elimintaing the problem of silicon consumption in the substrate. In this work, selective depositions were performed in a typical cold-walled, lamp heated rapid thermal chemical vapor deposition (RTCVD) system at ∼ 610 °C using SiH2C12, GeH4 and B2H6 as the reactive gases. Using this process, MOS transistors with effective channel lengths down to 0.45 gtm were successfully fabricated.
Two processes of great importance in the semiconductor industry are vapor deposition and plasma etching. This paper presents a review of laser techniques for spectroscopic characterization of the gas phase species involved in these processes. Band strength and other spectroscopic data for selected molecules are used to give estimates of the detection sensitivity in vibrational and electronic bands. Preliminary results are given from work presently in progress in our laboratory on the detection of such species. The discussion includes examples of the application of these techniques to a number of laboratory deposition and etching devices.
It was hypothesized that differences in starch degradability account for observed differences in rumen vaccenic acid (t11-18:1) and milk rumenic acid (RA) concentrations. To test this hypothesis, starch degradability was varied through grain source and by processing. Eight Holstein cows in mid-lactation were assigned to two 4 × 4 Latin squares with four 21-day periods and four diets: dry rolled barley, ground barley, dry rolled corn and ground corn. Diets contained similar starch content and were supplemented with whole sunflower seed to provide similar total polyunsaturated fatty acid (PUFA) (18:2n-6 + 18:3n-3) contents. Forage/concentrate ratios of all diets were 42 : 58. Rumen, plasma and milk samples were collected in the third week of each period. In situ degradation rates (%/h) for rolled corn, ground corn, rolled barley and ground barley were 5.4, 8.9, 17.0 and 19.4, respectively, for dry matter (DM) and 6.3, 10.8, 25.3 and 43.8, respectively, for starch. DM intakes were greater for corn-based diets (CBD) than for barley-based diets (BBD) with no difference between rolled and ground diets. Daily minimum rumen pH was less (5.2 v. 5.5) and pH duration <5.8 (h/d) was greater (7.4 v. 4.3) for BBD than for CBD. Milk fat content and yield were less for BBD than for CBD with greater values observed for rolling compared with grinding. Variability in milk fat yield was strongly related (R2 = 0.55; P < 0.01) to total starch intake (45%) and milk c9t11-CLA (10%) and none of the t-18:1 isomers or CLA isomers that are typically associated with milk fat depression entered the model. The concentrations (%) of t10-18:1 and t11-18:1 were greater for BBD than for CBD in rumen contents (t10-18:1, 3.5 v. 1.3; t11-18:1, 3.2 v. 1.9), plasma (t10-18:1, 1.2 v. 0.2; t11-18:1, 0.97 v. 0.58) and milk (t10-18:1, 3.8 v. 1.0; t11-18:1, 2.6 v. 1.7) despite greater total PUFA intakes for CBD. Milk RA concentration was greater for BBD than for CBD (1.46 v. 0.89) but was not influenced by the method of grain processing. This study clearly demonstrated that the milk content and profile of t-18:1 and CLA isomers were more strongly influenced by the source of grain starch (barley > corn) than by the method of grain processing indicating that factors inherent in the source of starch were responsible for the observed differences and these factors could not be modified by the processing methods used in this study.