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Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.
In this paper we report an independent determination of the Location of the break (change in spectral index) in the spectrum of the diffuse X-ray background by applying a simple analysis technique to data already in the literature.
We previously reported an association between 5HTTLPR genotype and
outcome following cognitive–behavioural therapy (CBT) in child anxiety
(Cohort 1). Children homozygous for the low-expression short-allele
showed more positive outcomes. Other similar studies have produced mixed
results, with most reporting no association between genotype and CBT
To replicate the association between 5HTTLPR and CBT outcome in child
anxiety from the Genes for Treatment study (GxT Cohort 2,
n = 829).
Logistic and linear mixed effects models were used to examine the
relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both
cohorts were performed.
There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2.
Mega-analyses identified a significant association between 5HTTLPR and
remission from all anxiety disorders at follow-up (odds ratio 0.45,
P = 0.014), but not primary anxiety disorder
The association between 5HTTLPR genotype and CBT outcome did not
replicate. Short-allele homozygotes showed more positive treatment
outcomes, but with small, non-significant effects. Future studies would
benefit from utilising whole genome approaches and large, homogenous
Ideal magnetohydrodynamics (IMHD) is strongly constrained by an infinite number of microscopic constraints expressing mass, entropy and magnetic flux conservation in each infinitesimal fluid element, the latter preventing magnetic reconnection. By contrast, in the Taylor relaxation model for formation of macroscopically self-organized plasma equilibrium states, all these constraints are relaxed save for the global magnetic fluxes and helicity. A Lagrangian variational principle is presented that leads to a new, fully dynamical, relaxed magnetohydrodynamics (RxMHD), such that all static solutions are Taylor states but also allows state with flow. By postulating that some long-lived macroscopic current sheets can act as barriers to relaxation, separating the plasma into multiple relaxation regions, a further generalization, multi-region relaxed magnetohydrodynamics (MRxMHD) is developed.
On June 13, 2012, a group of key stakeholders, leaders, and national experts on tuberculosis (TB), occupational health, and laboratory science met in Atlanta, Georgia, to focus national discussion on the higher than expected positive results occurring among low-risk, unexposed healthcare workers undergoing serial testing with interferon-γ release assays (IGRAs). The objectives of the meeting were to present the latest clinical and operational research findings on the topic, to discuss evaluation and treatment algorithms that are emerging in the absence of national guidance, and to develop a consensus on the action steps needed to assist programs and physicians in the interpretation of serial testing IGRA results. This report summarizes its proceedings.
Aqueous corrosion of zirconium alloys has become the major factor limiting prolonged fuel campaigns in nuclear plant. Studies using SEM, TEM and electrochemical impedance measurements have been interpreted as showing a dense inner-most oxide layer, and an increased thickness of the layer has been correlated to a better corrosion resistance. Many authors have reported that an ‘intermediate layer’ at the metal oxide interface has a complex structure or/and stochiometry different to that of both the bulk oxide and bulk metal, sometimes claimed to be a suboxide phase. Diffraction evidence has suggested the presence of both cubic ZrO and rhombohedral Zr3O phases, and compositional analysis has revealed similar variations in local oxygen stoichiometry.
We have carried out a systematic investigation of the structure and chemistry of the metal/oxide interface in samples of commercial ZIRLO corroded for times up to 180 days. We have developed new experimental techniques for the study of these interfaces both by Electron Energy Loss Spectroscopy (EELS) analysis in the Transmission Electron Microscope (TEM) and by Atom Probe Tomography (APT), and exactly the same samples have been investigated by both techniques. Our results show the development of a clearly defined suboxide layer of stoichiometry close to ZrO, and the subsequent disappearance of this layer at the first of the characteristic ‘breakaway’ transitions in the oxidation kinetics. We can correlate this behaviour with changes in the structure of the oxide layer, and particularly the development of interconnected porosity that links the corroding interface with the aqueous environment. Using high resolution SIMS analysis of isotopically spiked samples we demonstrate the penetration of the oxidising species through these porous outer oxide layers.
The new Core-XAS (X-ray absorption spectroscopy) beamline (B18) at Diamond aims to provide a reliable spectrometer for a broad scientific community. With this in mind, B18 has been built as a general-purpose beamline and offers to users a variety of sample environments and detection methods. Here we will present the first commissioning results and some of the capabilities of this versatile instrument.
Two approaches to defining almost-invariant surfaces for magnetic fields with imperfect magnetic surfaces are compared. Both methods are based on treating magnetic field-line flow as a 1½-dimensional Hamiltonian (or Lagrangian) dynamical system. In the quadratic-flux minimizing surface approach, the integral of the square of the action gradient over the toroidal and poloidal angles is minimized, while in the ghost surface approach a gradient flow between a minimax and an action-minimizing orbit is used. In both cases the almost-invariant surface is constructed as a family of periodic pseudo-orbits, and consequently it has a rational rotational transform. The construction of quadratic-flux minimizing surfaces is simple, and easily implemented using a new magnetic field-line tracing method. The construction of ghost surfaces requires the representation of a pseudo field line as an (in principle) infinite-dimensional vector and also is inherently slow for systems near integrability. As a test problem the magnetic field-line Hamiltonian is constructed analytically for a topologically toroidal, non-integrable ABC-flow model, and both types of almost-invariant surface are constructed numerically.
We develop a multiple interface variational model, comprising multiple Taylor-relaxed plasma regions separated by ideal magnetohydrodynamic (MHD) barriers. A principal motivation is the development of a mathematically rigorous ideal MHD model to describe intrinsically three-dimensional equilibria, with non-zero internal pressure. A second application is the description of transport barriers as constrained minimum energy states. As a first example, we calculate the plasma solution in a periodic cylinder, generalizing the analysis of the treatment of Kaiser and Uecker (2004 Q. J. Mech. Appl. Math.57, 1–17), who treated the single interface in cylindrical geometry. Expressions for the equilibrium field are generated, and equilibrium states computed. Unlike other Taylor relaxed equilibria, for the equilibria investigated here, only the plasma core necessarily has reverse magnetic shear. We show the existence of tokamak-like equilibria, with increasing safety factor and stepped-pressure profiles.
We report the synthesis of photoreactive and light-emitting liquid crystals which can be patterned photolithographically to form polymer networks for use in organic light-emitting diodes. The resolution capability of the photopatterning is investigated using a phase mask of period one micron to spatially modulate the irradiance of ultraviolet light incident to the monomer thin film. A surface relief grating of the same period and depth 85 nm is formed on exposure and washing. An OLED incorporating a novel green light-emitting liquid-crystal has a luminous efficiency of 4.3 lm W-1 at 100 cd m-2 and gives a luminance of 990 cd m-2 at an operating voltage of 10 V.
The SMAC cluster sample (Hudson et al. 1999), with a depth of ˜ 12000km s-1, has a bulk velocity of ˜ 600 km s-1, with respect to the Cosmic Microwave Background (CMB) frame. Other surveys (Willick 1999, hereafter LP10k; Lauer & Postman 1994, hereafter ACIF) have also yielded large bulk motions on similarly large scales. Taken at face value, these results appear to be in conflict with bulk flows expected from favoured cosmological models. However, at the same time, other surveys (notably Dale et al. 1999, hereafter SC) have found rather small bulk motions on large scales. We have measured bulk flows from the above mentioned surveys plus SNIa (Riess et al. 1995) in a consistent way. The results are given in Table 1. The measurement errors are due to peculiar velocity errors. Note that these are the errors typically quoted. Based on these errors alone, there appears to be conflict between some of the surveys (e.g. SC vs SMAC).
Rabbit haemorrhagic disease virus (RHDV) has killed many millions of wild rabbits in Europe and Australia, but has had little impact in the United Kingdom, despite outbreaks having occurred since 1994. High seroprevalence detected in the absence of associated mortality had suggested the presence of an endemic non-pathogenic strain which may be ‘protecting’ UK populations. Following the first detailed field study of RHDV epidemiology in the United Kingdom, using mark–recapture with serum sampling, we report that RHDV caused highly prevalent persistent infection in seropositive rabbits in the absence of associated mortality. Furthermore the virus strains responsible could not be distinguished phylogenetically from known pathogenic isolates, and were clearly very different from the only previously identified non-pathogenic strain of RHDV. These findings suggest that many – perhaps most – strains of RHDV may be propagated through both ‘pathogenic’ and ‘non-pathogenic’ modes of behaviour. Transmission occurred predominantly during and just after the breeding season.
Motivated by, but independent of, some recent work in quantum stochastic calculus, a theory of differential and integral calculus is developed which is intrinsic to the universal enveloping algebra of a Lie algebra whose Lie bracket is obtained by taking commutators in an associative algebra. The differential map satisfies a generalisation of Leibniz' formula called the Leibniz–Itô formula, which involves the associative multiplication. There is an analogue of the Taylor–Maclaurin expansion. Through passing to formal power series, a theory of product integrals is developed; such integrals are characterised by a group-like property with respect to the coproduct.