To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
The giant carnivorous phorusrhacid bird Phorusrhacos longissimus (Aves, Cariamiformes) was first described in 1887 by Florentino Ameghino on the basis of a jaw fragment. The majority of a skull of the species still encased in crumbling rock was preserved only long enough for illustrations to be made by Carlos Ameghino in the field and for a brief description to be written. Skull remains of this species have remained scarce, and few postcranial remains have been figured. Here, we reassess the cranial anatomy of this outstanding ‘terror bird’ species taking into account data from a newly discovered skull. An additional specimen of a well-preserved dorsal vertebra referable to Phorusrhacinae is also described from a separate locality within the Miocene Santa Cruz Formation (late early Miocene) from Santa Cruz Province in Argentina. The skull includes most of the rostrum, skull roof, and mandible and is compared with material from other members of the Phorusrhacinae. The new data from the skull and vertebra provide morphological features of this clade that benefit future taxonomic and phylogenetic analyses of this iconic group of birds.
The diurnal feeding patterns of dairy cows affects the 24 h robot utilisation of pasture-based automatic milking systems (AMS). A decline in robot utilisation between 2400 and 0600 h currently occurs in pasture-based AMS, as cow feeding activity is greatly reduced during this time. Here, we investigate the effect of a temporal variation in feed quality and quantity on cow feeding behaviour between 2400 and 0600 h as a potential tool to increase voluntary cow trafficking in an AMS at night. The day was allocated into four equal feeding periods (0600 to 1200, 1200 to 1800, 1800 to 2400 and 2400 to 0600 h). Lucerne hay cubes (CP = 19.1%, water soluble carbohydrate = 3.8%) and oat, ryegrass and clover hay cubes with 20% molasses (CP = 11.8%, water soluble carbohydrate = 10.7%) were offered as the ‘standard’ and ‘preferred’ (preference determined previously) feed types, respectively. The four treatments were (1) standard feed offered ad libitum (AL) throughout 24 h; (2) as per AL, with preferred feed replacing standard feed between 2400 and 0600 h (AL + P); (3) standard feed offered at a restricted rate, with quantity varying between each feeding period (20:10:30:60%, respectively) as a proportion of the (previously) measured daily ad libitum intake (VA); (4) as per VA, with preferred feed replacing standard feed between 2400 and 0600 h (VA + P). Eight non-lactating dairy cows were used in a 4 × 4 Latin square design. During each experimental period, treatment cows were fed for 7 days, including 3 days habituation and 4 days data collection. Total daily intake was approximately 8% greater (P < 0.001) for the AL and AL + P treatments (23.1 and 22.9 kg DM/cow) as compared with the VA and VA + P treatments (21.6 and 20.9 kg DM/cow). The AL + P and VA treatments had 21% and 90% greater (P < 0.001) dry matter intake (DMI) between 2400 and 0600 h, respectively, compared with the AL treatment. In contrast, the VA + P treatment had similar DMI to the VA treatment. Our experiment shows ability to increase cow feeding activity at night by varying feed type and quantity, though it is possible that a penalty to total DMI may occur using VA. Further research is required to determine if the implementation of variable feed allocation on pasture-based AMS farms is likely to improve milking robot utilisation by increasing cow feeding activity at night.
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.
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.
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.
A new sample support film for small spot XRF analysis has been developed that improves detection limits by a factor of 10 over traditional polymer supports. The surface characteristics of this new film are excellent for retaining drops of sample solution in one place and allowing the solution to dry into a single spot A dimpling technique was developed to further aid in concentrating the evaporated samples to the prescribed spot size and position. The film showed good resistance to chemical attacfc from the solution, even some strong acids and bases. The detection limits achieved using micro sample XRF with the ultra thin sample support were sufficient to be a comparable alternative to ICP-MS and GFAAS for elemental analysis.
We present the results of a preliminary study of the use of polychromatic synchrotron radiation in energy-dispersive mode for the rapid characterization of thin film and multilayer materials. This technique takes advantage of the high intensity and excellent collimation properties of white beam synchrotron radiation. The glancing angle diffraction geometry allows structural depth probing as well as enhanced signal-to-noise by suppressing substrate contributions. The technique was successfully applied to metallic films a few hundred Angstroms thick, and to W-C multilayers.
High-temperature X-ray diffractometer measurements by the Bureau showed that alpha-alumina expands anisotropically with expansion parallel to the c axis approximately 10% greater than that parallel to the a axis. Thermal-expansion characteristics of four different alumina samples were determined up to 1200°C; the results are presented in both tabular and graphical form. The combined random and systematic errors in the measurements are considered less than 3% above 500°C and approximately 2% at 1000°C. No differences in expansion were observed between the samples or between the heating and cooling cycles.
Critical evaluation of the literature showed that published values for thermal-expansion coefficients of single crystals vary over a range of 40% (relative values) and disagreement concerning whether expansion of alpha-alumina is isotropic or anisotropic. Systematic and experimental errors were found to be the principal factor for the variation in results, rather than differences in measuring techniques or in samples.
Published values for polycrystalline aggregates also varied. Two laboratories reported values 20–30% lower than those of the Bureau of Mines, but two other laboratories agree with the Bureau within 3–5% above 500°C.
This paper summarizes developments in the field of high-temperature X-ray diffractometers through 1959, evaluates various furnace designs, and describes briefly the X-ray diffraction facilities of the Federal Bureau of Mines.
X-ray optics, for those furnaces that have precision sample movements, are equivalent in resolution and line profile to conventional X-ray techniques. There is a 10-25% loss of intensity due to absorption of X-rays in the furnace windows, magnitude of which depends on wavelength and type of window used, and a reduction (5–40° 2θ) of useful angular range from limiting X-ray windows, radiation shielding, or the viewport for an optical pyrometer. In oxidizing atmospheres, temperatures up to 1500°C were obtained with furnaces wound with platinum—20% rhodium wire. Under nonoxidizing conditions temperatures of 1800 to 2000°C were obtained with both tantalum-foil and tungsten-wire heaters.
Accurate temperature measurement over the area and depth of samples being studied is the most difficult problem in high-temperature X-ray diffractometry. Below 500°C, there are several furnace designs which are reported to reduce thermal differentials to less than 1°C across the sample. However, at temperatures around 1000°C, there are thermal gradients of 20-30°C/cm across the sample and 100–600°C/cm through the sample holder, making thermocouple location critical. Secondary standards have been used extensively to calibrate the furnaces; however, there is disagreement concerning which are the most reliable data to use. For these reasons, plus others discussed in this report, there is a probable error in the temperature determination of ±10 to 20°C at 1000°C, with the error increasing with temperature.
Widespread interest in light element analysis using XRF has stimulated the development of thin x-ray tube windows. Thinner windows enhance the soft x-ray output of the tube, which more efficiently excite the light elements in the sample. A computer program that calculates the effect of window thickness on light element sample fluorescence has been developed. The code uses an NIST algorithm to calculate the x-ray tube spectrum given various tube parameters such as beryllium window thickness, operating voyage, anode composition, and take-off angle. The interaction of the tube radiation with the sample matrix is modelled to provide the primary and secondary fluorescence from the sample. For x-rays in the energy region 30 - 1000 eV the mass attenuation coefficients were interpolated from the photo absorption data compilation of Henke, et al. The code also calculates the x-ray background due to coherent and incoherent scatter from the sample, as well as the contribution of such scatter to the sample fluorescence. Given the sample fluorescence and background the effect of tube window thickness on detection limits for light elements can be predicted.
Minimizing the negative ecological impacts of exotic plant invasions is one goal of land management. Using selective herbicides is one strategy to achieve this goal; however, the unintended consequences of this strategy are not always fully understood. The recently introduced herbicide indaziflam has a mode of action not previously used in non-crop weed management. Thus, there is limited information about the impacts of this active ingredient when applied alone or in combination with other non-crop herbicides. The objective of this research was to evaluate native species tolerance to indaziflam and imazapic applied alone and with other broadleaf herbicides. Replicated field plots were established at two locations in Colorado with a diverse mix of native forbs and grasses. Species richness and abundance were compared between the nontreated control plots and plots where indaziflam and imazapic were applied alone and in combination with picloram and aminocyclopyrachlor. Species richness and abundance did not decrease when indaziflam or imazapic were applied alone; however, species abundance was reduced by treatments containing picloram and aminocyclopyrachlor. Species richness was only impacted at one site 1 yr after treatment (YAT) by these broadleaf herbicides. Decreases in abundance were mainly due to reductions in forbs that resulted in a corresponding increase in grass cover. Our data suggest that indaziflam will control downy brome (Bromus tectorum L.) for multiple years without reduction in perennial species richness or abundance. If B. tectorum is present with perennial broadleaf weeds requiring the addition of herbicides like picloram or aminocyclopyrachlor, forb abundance could be reduced, and in some cases there could be a temporary reduction in perennial species richness.
The orthorhombic mineral moolooite, CuC2O4. nH2O, described by Clarke and Williams (1986) using Debye-Scherrer photographic data, has a fully-disordered stacking fault (FDSF) structure. Related monoclinic models have been reported for various synthesised samples based on Schmittler (1968). In the present study, synchrotron radiation diffraction data for moolooite and synthesised specimens have been examined with particular reference to crystallographic disorder. The moolooite data correspond to space group Pnnm, with a = 5.3064(2), b = 5.6804(2), c = 2.5630(1) Å; Vc = 77.26(1) Å3; and Z = 1; and the FDSF structure along the b-direction has been confirmed. The synthetic specimen data from the study indicate partial ordering, with space group P21/n; and the cell parameters for one specimen being a = 5.957(7), b = 5.611(5), c = 5.133(7) Å; β = 115.16(2)°; Vc = 155.27 Å3 and Z = 2. The level of zeolitic water in the materials has been considered using the approach of Schmittler based on thermogravimetry and pycnometry. The new data for natural topotype material correspond to CuC2O4.1.0H2O. It is postulated that the level of water for natural and synthetic specimens may be attributed to the conditions under which the material forms.
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.
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.