Three principal granite provinces are defined across SE Asia, as follows. (1) The Western Thailand-Myanmar/Burma province consists of hornblende-biotite I-type granodiorite-granites and felsic ...biotite-K-feldspar (± garnet ± tourmaline) granites associated with abundant tin mineralization in greisen-type veins. New ion microprobe U-Pb dating results from Phuket Island show zircon core ages of 212 ± 2 and 214 ± 2 Ma and a thermal overprint with rims of 81.2 ± 1.2 and 85-75 Ma. (2) The North Thailand-West Malaya Main Range province has mainly S-type biotite granites and abundant tin mineralization resulting from crustal thickening following collision of the Sibumasu plate with Indochina during the Mid-Triassic. Biotite granites around Kuala Lumpur contain extremely U-rich zircons (up to 38000 ppm) that yield ages of 215 ± 7 and 210 ± 7 Ma. (3) The East Malaya province consists of dominantly Permian-Triassic I-type hornblende-biotite granites but with subordinate S-type plutons and A-type syenite-gabbros. Biotite-K-feldspar granites from Tioman Island off the east coast of Malaysia also yield a zircon age of 80 ± 1 Ma, showing Cretaceous magmatism in common with province 1. Geological and U-Pb geochronological data suggest that two east-dipping (in present-day coordinates) subduction zones are required during the Triassic, one along the Bentong-Raub Palaeo-Tethyan suture, and the other west of the Phuket-Burma province 1 belt. SUPPLEMENTARY MATERIAL: A full description of U-Pb analytical methods used and data tables are available at www.geolsoc.org.uk/SUP18523.
The UK Department of Health Enhanced Recovery Partnership Programme collected data on 24 513 surgical patients in the UK from 2009–2012. Enhanced Recovery is an approach to major elective surgery ...aimed at minimizing perioperative stress for the patient. Previous studies have shown Enhanced Recovery to be associated with reduced hospital length of stay and perioperative morbidity.
In this national clinical audit, National Health Service hospitals in the UK were invited to submit patient-level data. The data regarding length of stay and compliance with each element of Enhanced Recovery protocols for colorectal, orthopaedic, urological and gynaecological surgery patients were analysed. The relationship between Enhanced Recovery protocol compliance and length of stay was measured.
From 16 267 patients from 61 hospital trusts, three out of four surgical specialties showed Enhanced Recovery, compliance being weakly associated with shorter length of stay (correlation coefficients −0.18, −0.14, −0.25 in colorectal, orthopaedics and gynaecology respectively). At a cut-off of 80% compliance, good compliance was associated with two, one and three day reductions in median length of stay respectively in colorectal, orthopaedic and urological surgeries, with no saving in gynaecology.
This study is the largest assessment of the relationship between Enhanced Recovery protocol compliance and outcome in four surgical specialties. The data suggest that higher compliance with an Enhanced Recovery protocol has a weak association with shorter length of stay. This suggests that changes in process, resulting from highly protocolised pathways, may be as important in reducing perioperative length of stay as any individual element of Enhanced Recovery protocols in isolation.
Emergency laparotomies are performed commonly throughout the world, but one in six patients die within a month of surgery. Current international initiatives to reduce the considerable associated ...morbidity and mortality are founded upon delivering individualised perioperative care. However, while the identification of high-risk patients requires the routine assessment of individual risk, no method of doing so has been demonstrated to be practical and reliable across the commonly encountered spectrum of presentations, co-morbidities and operative procedures. A systematic review of Embase and Medline identified 20 validation studies assessing 25 risk assessment tools in patients undergoing emergency laparotomy. The most frequently studied general tools were APACHE II, ASA-PS and P-POSSUM. Comparative, quantitative analysis of tool performance was not feasible due to the heterogeneity of study design, poor reporting and infrequent within-study statistical comparison of tool performance. Reporting of calibration was notably absent in many prognostic tool validation studies. APACHE II demonstrated the most consistent discrimination of individual outcome across a variety of patient groups undergoing emergency laparotomy when used either preoperatively or postoperatively (area under the curve 0.76–0.98). While APACHE systems were designed for use in critical care, the ability of APACHE II to generate individual risk estimates from objective, exclusively preoperative data items may lead to better-informed shared decisions, triage and perioperative management of patients undergoing emergency laparotomy. Future endeavours should include the recalibration of APACHE II and P-POSSUM in contemporary cohorts, modifications to enable prediction of morbidity and assessment of the impact of adoption of these tools on clinical practice and patient outcomes.
We report a method of growing a diamond layer via chemical vapour deposition (CVD) utilizing a mixture of microdiamond and nanodiamond seeding to give a low effective thermal boundary resistance ...(TBReff) for heat-spreading applications in high-frequency, high-power electronic devices. CVD diamond was deposited onto thin layers of both GaN and AlN on Si substrates, comparing conventional nanodiamond seeding with a two-step process involving sequential seeding with microdiamond then nanodiamond. Thermal properties were determined using transient thermoreflectance (TTR), and the samples were also analysed with SEM and X-ray tomography. While diamond growth directly onto GaN proved to be unsuccessful due to poor adhesion, films grown on AlN were adherent and robust. The two-step mixed-seeding method gave TBReff values < 6 m2 K GW−1 that were 30 times smaller than for films grown under identical conditions but using nanodiamond seeding alone. Such remarkably low thermal barriers obtained with the mixed-seeding process offer a promising route for fabrication of high-power GaN HEMTs using diamond as a heat spreader with an AlN interlayer.
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Recent advances combining two-photon calcium imaging and two-photon optogenetics with computer-generated holography now allow us to read and write the activity of large populations of neurons in vivo ...at cellular resolution and with high temporal resolution. Such 'all-optical' techniques enable experimenters to probe the effects of functionally defined neurons on neural circuit function and behavioral output with new levels of precision. This greatly increases flexibility, resolution, targeting specificity and throughput compared with alternative approaches based on electrophysiology and/or one-photon optogenetics and can interrogate larger and more densely labeled populations of neurons than current voltage imaging-based implementations. This protocol describes the experimental workflow for all-optical interrogation experiments in awake, behaving head-fixed mice. We describe modular procedures for the setup and calibration of an all-optical system (~3 h), the preparation of an indicator and opsin-expressing and task-performing animal (~3-6 weeks), the characterization of functional and photostimulation responses (~2 h per field of view) and the design and implementation of an all-optical experiment (achievable within the timescale of a normal behavioral experiment; ~3-5 h per field of view). We discuss optimizations for efficiently selecting and targeting neuronal ensembles for photostimulation sequences, as well as generating photostimulation response maps from the imaging data that can be used to examine the impact of photostimulation on the local circuit. We demonstrate the utility of this strategy in three brain areas by using different experimental setups. This approach can in principle be adapted to any brain area to probe functional connectivity in neural circuits and investigate the relationship between neural circuit activity and behavior.
Many theories of brain function propose that activity in sparse subsets of neurons underlies perception and action. To place a lower bound on the amount of neural activity that can be perceived, we ...used an all-optical approach to drive behaviour with targeted two-photon optogenetic activation of small ensembles of L2/3 pyramidal neurons in mouse barrel cortex while simultaneously recording local network activity with two-photon calcium imaging. By precisely titrating the number of neurons stimulated, we demonstrate that the lower bound for perception of cortical activity is ~14 pyramidal neurons. We find a steep sigmoidal relationship between the number of activated neurons and behaviour, saturating at only ~37 neurons, and show this relationship can shift with learning. Furthermore, activation of ensembles is balanced by inhibition of neighbouring neurons. This surprising perceptual sensitivity in the face of potent network suppression supports the sparse coding hypothesis, and suggests that cortical perception balances a trade-off between minimizing the impact of noise while efficiently detecting relevant signals.
Rationale
How striatal dopamine synthesis capacity (DSC) contributes to the pathogenesis of negative symptoms in first-episode schizophrenia (SZ) and delusional disorder (DD) has seldom been ...explored. As negative symptoms during active psychotic episodes can be complicated by secondary influences, such as positive symptoms, longitudinal investigations may help to clarify the relationship between striatal DSC and negative symptoms and differentiate between primary and secondary negative symptoms.
Objective
A longitudinal study was conducted to examine whether baseline striatal DSC would be related to negative symptoms at 3 months in first-episode SZ and DD patients.
Methods
Twenty-three first-episode age- and gender-matched patients (11 DD and 12 SZ) were consecutively recruited through an early intervention service for psychosis in Hong Kong. Among them, 19 (82.6%) patients (9 DD and 10 SZ) were followed up at 3 months. All patients received an
18
F-DOPA PET/MR scan at baseline.
Results
Baseline striatal DSC (
K
occ;30–60
) was inversely associated with negative symptoms at 3 months in first-episode SZ patients (
r
s
= − 0.80,
p
= 0.010). This association remained in SZ patients even when controlling for baseline negative, positive, and depressive symptoms, as well as cumulative antipsychotic dosage (
β
= − 0.69,
p
= 0.012). Such associations were not observed in first-episode DD patients. Meanwhile, the severity of negative symptoms at 3 months was associated with more positive symptoms in DD patients (
r
s
= 0.74,
p
= 0.010) and not in SZ patients.
Conclusions
These findings highlight the role of striatal DSC in negative symptoms upon resolution of active psychotic episodes among first-episode SZ patients. Baseline striatal dopamine activity may inform future symptom expression with important treatment implications.
Chikungunya fever is an acute febrile illness caused by the chikungunya virus (CHIKV), which is transmitted to humans by Aedes mosquitoes. Although chikungunya fever is rarely fatal, patients can ...experience debilitating symptoms that last from months to years. Here we comprehensively assess the global distribution of chikungunya and produce high-resolution maps, using an established modelling framework that combines a comprehensive occurrence database with bespoke environmental correlates, including up-to-date Aedes distribution maps. This enables estimation of the current total population-at-risk of CHIKV transmission and identification of areas where the virus may spread to in the future. We identified 94 countries with good evidence for current CHIKV presence and a set of countries in the New and Old World with potential for future CHIKV establishment, demonstrated by high environmental suitability for transmission and in some cases previous sporadic reports. Aedes aegypti presence was identified as one of the major contributing factors to CHIKV transmission but significant geographical heterogeneity exists. We estimated 1.3 billion people are living in areas at-risk of CHIKV transmission. These maps provide a baseline for identifying areas where prevention and control efforts should be prioritised and can be used to guide estimation of the global burden of CHIKV.
In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10
) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for ...nonsynonymous variation. We identify a signal at GLP2R (p.Asp470Asn) shared among higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes, with β-arrestin signaling as the underlying mechanism. Genetically higher serine levels are shown to reduce the likelihood (by 95%) and predict development of macular telangiectasia type 2, a rare degenerative retinal disease. Integration of genomic and small molecule data across platforms enables the discovery of regulators of human metabolism and translation into clinical insights.
Outcome selection underpins clinical trial interpretation. Inconsistency in outcome selection and reporting hinders comparison of different trials' results, reducing the utility of research findings.
...We conducted an iterative consensus process to develop a set of Core Outcome Measures for Perioperative and Anaesthetic Care (COMPAC), following the established Core Outcome Measures for Effectiveness Trials (COMET) methodology. First, we undertook a systematic review of RCTs in high-impact journals to describe current outcome reporting trends. We then surveyed patients, carers, researchers, and perioperative clinicians about important outcomes after surgery. Finally, a purposive stakeholder sample participated in a modified Delphi process to develop a core outcome set for perioperative and anaesthesia trials.
Our systematic review revealed widespread inconsistency in outcome reporting, with variable or absent definitions, levels of detail, and temporal criteria. In the survey, almost all patients, carers, and clinicians rated clinical outcome measures critically important, but clinicians rated patient-centred outcomes less highly than patients and carers. The final core outcome set was: (i) mortality/survival (postoperative mortality, long-term survival); (ii) perioperative complications (major postoperative complications/adverse events; complications/adverse events causing permanent harm); (iii) resource use (length of hospital stay, unplanned readmission within 30 days); (iv) short-term recovery (discharge destination, level of dependence, or both); and (v) longer-term recovery (overall health-related quality of life).
This core set, incorporating important outcomes for both clinicians and patients, should guide outcome selection in future perioperative medicine or anaesthesia trials. Mapping these alongside standardised endpoint definitions will yield a comprehensive perioperative outcome framework.
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