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In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of
was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
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.
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.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Reflection high-energy electron diffraction (RHEED) is one of the most robust and widespread techniques used for in-situ monitoring during molecular beam epitaxy (MBE) growth. Thus, all MBE systems have an electron gun allowing additional electron-beam stimulated in-situ characterizations. At WVU we are developing two such techniques, spectral analysis of cathodoluminescence (CL) in wide bandgap semiconductors and reflection high-energy electron diffraction-total reflection angle x-ray spectroscopy (RHEED-TRAXS) for in-situ composition monitoring and control.A pressing issue remaining for epitaxial growth is real-time compositional control to a high level of accuracy. For many materials, such as multi-element nitrides and oxides with unity sticking coefficients, it would be extremely beneficial to monitor the composition to a fraction of a monolayer. This technique needs to be both element-specific and surface-sensitive. RHEED-TRAXS is a leading contender as such a technique. The electron beam from a RHEED gun impinges on the sample at a small angle of incidence approximately equal to the critical angle for x-ray reflection. This geometry ensures that the measurement is extremely surface sensitive. This technique can be used to obtain both structural information, via RHEED, and chemical information, via x-ray detection. We are currently developing a compact RHEED-TRAXS using a state-of-the-art Si P-intrinsic-N (PIN) photodiode technology. We have used this system to investigate Ga and In coverage during the growth of GaN, and have observed Ga bi-layer evolution during growth, Mg destabilization of the Ga wetting layer, and significant In surface segregation. We are also investigating the in-situ, real-time composition measurements in complex oxide systems such as YMnO3 with promising initial results.In-situ cathodoluminescence (CL) occurring during RHEED is a strong candidate to determine the growth temperature and alloy composition for wide bandgap semiconductors. CL is easily detected up to and beyond typical growth temperatures for GaN and InGaN, accurately and reproducibly determining sample temperature during growth. Room CL measurement at room temperature can also be used as a means to check the quality of the substrate by comparing intensities of the GaN band edge energy peak and defect peaks. We have performed a detailed study of the factors influencing high temperature CL, and find the reproducibility of CL data and ability for fast CL scanning provide strong advantages for use in the growth of GaN films. CL could also be observed during growth using a ccd camera. This could be used to see temperature inhomogenaities, and potentially to map alloy composition fluctuations. Using tunable narrow bandpass optical filters, we can obtain a spatial/spectral map of sample CL. We will present CL images of samples at differing temperatures.This work was supported by the AFOSR MURI F49620-03-1-0330 and by ONR Grant N00014-02-1-0974.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
We evaluated the impact of an electronic health record based 72-hour antimicrobial time-out (ATO) on antimicrobial utilization. We observed that 6 hours after the ATO, 21% of empiric antimicrobials were discontinued or de-escalated. There was a significant reduction in the duration of antimicrobial therapy but no impact on overall antimicrobial usage metrics.
Despite the lack of another Flagship-class mission such as Cassini–Huygens, prospects for the future exploration of Saturn are nevertheless encouraging. Both NASA and the European Space Agency (ESA) are exploring the possibilities of focused interplanetary missions (1) to drop one or more in situ atmospheric entry probes into Saturn and (2) to explore the satellites Titan and Enceladus, which would provide opportunities for both in situ investigations of Saturn’s magnetosphere and detailed remote-sensing observations of Saturn’s atmosphere. Additionally, a new generation of powerful Earth-based and near-Earth telescopes with advanced instrumentation spanning the ultraviolet to the far-infrared promise to provide systematic observations of Saturn’s seasonally changing composition and thermal structure, cloud structures and wind fields. Finally, new advances in amateur telescopic observations brought on largely by the availability of low-cost, powerful computers, low-noise, large-format cameras, and attendant sophisticated software promise to provide regular, longterm observations of Saturn in remarkable detail.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
Hyperbolic polariton modes are highly appealing for a broad range of applications in nanophotonics, including surfaced enhanced sensing, sub-diffractional imaging, and reconfigurable metasurfaces. Here we show that attenuated total reflectance (ATR) micro-spectroscopy using standard spectroscopic tools can launch hyperbolic polaritons in a Kretschmann–Raether configuration. We measure multiple hyperbolic and dielectric modes within the naturally hyperbolic material hexagonal boron nitride as a function of different isotopic enrichments and flake thickness. This overcomes the technical challenges of measurement approaches based on nanostructuring, or scattering scanning near-field optical microscopy. Ultimately, our ATR approach allows us to compare the optical properties of small-scale materials prepared by different techniques systematically.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
High-intensity femtosecond laser–plasma interaction experiments were performed to investigate laser–plasma wakefield acceleration in the “bubble” regime. Using a 15 TW laser pulse, the emission of side-scattered radiation was spectrally and spatially resolved and was consequently used to diagnose the evolution of the laser pulse during the acceleration process. Side-scattered emission was observed immediately before wavebreaking at a frequency of ωL + 1.7ωp (where ωL is the laser frequency and ωp is the background plasma frequency). This emission may result from scattering of laser light by large amplitude plasma oscillations generated in the shell of the wakefield “bubble” and which occurs immediately prior to the wavebreaking/injection process. The observed variation of the frequency of scattered light with electron density agrees with theoretical estimates.
Lateral memristors consisting of planar Ag electrodes (with sub-micrometer separation) supported on thin films of amorphous zinc-tin-oxide have been characterized. After an initial filament-forming process, each device exhibited volatile, resistive switching. In the low resistance state, the transport mechanism and conductance depended on prior activity and on the imposed current limit, mimicking biologic synaptic plasticity. Microscopic observations performed on each device revealed nanoscale filaments between the electrodes. These filaments were subject to Rayleigh instability and exhibited relaxation times determined by their effective radii. The relaxation times and on:off resistance ratios suggest suitability for threshold switching selector devices.
In 785 mother–child (50% male) pairs from a longitudinal epidemiological birth cohort, we investigated associations between inflammation-related epigenetic polygenic risk scores (i-ePGS), environmental exposures, cognitive function, and child and adolescent internalizing and externalizing problems. We examined prenatal and postnatal effects. For externalizing problems, one prenatal effect was found: i-ePGS at birth associated with higher externalizing problems (ages 7–15) indirectly through lower cognitive function (age 7). For internalizing problems, we identified two effects. For a prenatal effect, i-ePGS at birth associated with higher internalizing symptoms via continuity in i-ePGS at age 7. For a postnatal effect, higher postnatal adversity exposure (birth through age 7) associated with higher internalizing problems (ages 7–15) via higher i-ePGS (age 7). Hence, externalizing problems were related mainly to prenatal effects involving lower cognitive function, whereas internalizing problems appeared related to both prenatal and postnatal effects. The present study supports a link between i-ePGS and child and adolescent mental health.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.
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.
We present a multi-frequency study of the intermediate spiral SAB(r)bc type galaxy NGC 6744, using available data from the Chandra X-Ray telescope, radio continuum data from the Australia Telescope Compact Array and Murchison Widefield Array, and Wide-field Infrared Survey Explorer infrared observations. We identify 117 X-ray sources and 280 radio sources. Of these, we find nine sources in common between the X-ray and radio catalogues, one of which is a faint central black hole with a bolometric radio luminosity similar to the Milky Way’s central black hole. We classify 5 objects as supernova remnant (SNR) candidates, 2 objects as likely SNRs, 17 as H ii regions, 1 source as an AGN; the remaining 255 radio sources are categorised as background objects and one X-ray source is classified as a foreground star. We find the star-formation rate (SFR) of NGC 6744 to be in the range 2.8–4.7 M⊙~yr − 1 signifying the galaxy is still actively forming stars. The specific SFR of NGC 6744 is greater than that of late-type spirals such as the Milky Way, but considerably less that that of a typical starburst galaxy.