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Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The ACA shifted U.S. health policy from centering on principles of actuarial fairness toward social solidarity. Yet four legal fixtures of the health care system have prevented the achievement of social solidarity: federalism, fiscal pluralism, privatization, and individualism. Future reforms must confront these fixtures to realize social solidarity in health care, American-style.
This commentary describes limitations of mental health parity requirements in ensuring access to insurance coverage for mental health treatment and surveys regulatory options employed by states in Medicaid managed care programs as supplements to parity that can further reduce the risk of inappropriate denials of coverage.
Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
Introduction: In 2018, Canadian postgraduate specialist Emergency Medicine (EM) programs began implementing a competency-based medical education (CBME) assessment system. To support improvement of this assessment program, we sought to evaluate its short-term educational outcomes nationally and within individual programs. Methods: Program-level data from the 2018 resident cohort were amalgamated and analyzed. The number of Entrustable Professional Activity (EPA) assessments (overall and for each EPA) and the timing of resident promotion through program stages was compared between programs and to the guidelines provided by the national EM specialty committee. Total EPA observations from each program were correlated with the number of EM and pediatric EM rotations. Results: Data from 15 of 17 (88.2%) EM programs containing 9,842 EPA observations from 68 of the 77 (88.3%) Canadian EM specialist residents in the 2018 cohort were analyzed. The average number of EPAs observed per resident in each program varied from 92.5 to 229.6 and correlated strongly with the number of blocks spent on EM and pediatric EM (r = 0.83, p < 0.001). Relative to the guidelines outlined by the specialty committee, residents were promoted later than expected and with fewer EPA observations than suggested. Conclusion: We present a new approach to the amalgamation of national and program-level assessment data. There was demonstrable variation in both EPA-based assessment numbers and promotion timelines between programs and with national guidelines. This evaluation data will inform the revision of local programs and national guidelines and serve as a starting point for further reaching outcome evaluation. This process could be replicated by other national assessment programs.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
Negative symptoms have been previously reported during the psychosis prodrome, however our understanding of their relationship with treatment-phase negative symptoms remains unclear.
Objectives:
We report the prevalence of psychosis prodrome onset negative symptoms (PONS) and ascertain whether these predict negative symptoms at first presentation for treatment.
Methods:
Presence of expressivity or experiential negative symptom domains was established at first presentation for treatment using the Scale for Assessment of Negative Symptoms (SANS) in 373 individuals with a first episode psychosis. PONS were established using the Beiser Scale. The relationship between PONS and negative symptoms at first presentation was ascertained and regression analyses determined the relationship independent of confounding.
Results:
PONS prevalence was 50.3% in the schizophrenia spectrum group (n = 155) and 31.2% in the non-schizophrenia spectrum group (n = 218). In the schizophrenia spectrum group, PONS had a significant unadjusted (χ2 = 10.41, P < 0.001) and adjusted (OR = 2.40, 95% CI = 1.11–5.22, P = 0.027) association with first presentation experiential symptoms, however this relationship was not evident in the non-schizophrenia spectrum group. PONS did not predict expressivity symptoms in either diagnostic group.
Conclusion:
PONS are common in schizophrenia spectrum diagnoses, and predict experiential symptoms at first presentation. Further prospective research is needed to examine whether negative symptoms commence during the psychosis prodrome.
The concept of indicated prevention has proliferated in psychiatry. Accumulating evidence suggests that it may indeed be possible to prevent or delay the onset of a First Episode of Psychosis (FEP) though adequate interventions in individuals deemed at Clinical High Risk (CHR) for such an event. However, a challenge undermining these efforts is the relatively poor predictive accuracy of clinical assessments used in practice for CHR individuals. to improve prediction by combining different types of assessments.
Objectives
To improve prediction of clinical course of disease by combining biological and clinical types of assessment.
Aims
To present a probabilistic prediction model containing clinical and biological data for the transition to first episode psychosis.
Methods
Using data from published studies, and employing predictive models based on the odds ratio form of Bayes’ rule, we simulated scenarios where clinical interview, neurocognitive testing, structural magnetic resonance imaging (MRI) and electrophysiology are part of the initial assessment process of a CHR individual (Extended Diagnostic Approach).
Results
Our findings indicate that for most at-risk patients, at least three types of assessments are necessary to arrive at a clinically meaningful differentiation into high- intermediate-, and low-risk groups. In particular, patients with equivocal results in the initial assessments require additional diagnostic testing to produce an accurate risk profile forming part of the comprehensive initial assessment.
Conclusions
The findings may inform future research into reliable identification and personalized therapeutic targeting of CHR patients, to prevent transition to full-blown psychosis and to inform decision in intervention.
Predicting transition from clinical high risk (CHR) to first episode psychosis has proven difficult. Assessment of oxidative stress biomarkers and the niacin skin flush response (NSFR) may improve prediction accuracy.
Objectives
To predict transition to psychosis based on combined clinical and blood biomarker.
Aims
To analyse data from patients in placebo group of a 12-week trial of omega-3 fatty acid supplementation in CHR. Transition likelihood ratios (LRs) for baseline historical risks, clinical assessments (PANSS subscales and total, GAF), NSFR and blood markers (nervonic acid, superoxide dismutase, glutathione) were calculated. Variables with the highest positive and lowest negative LRs were included in an odds ratio form of Bayes’ rule transition prediction models. Model accuracy was calculated by area under the receiver operating curves (AUROC) of each model.
Results
1-year transition to psychosis was 28% (n=40). Historical data showed no predictability (sensitivity 30%, specificity 100% (AUROC)=0.688, p=0.085). Clinical assessments alone produced a sensitivity of 30% at a specificity of 95% (AUROC=0.83, p<0.0001). The biomarker panel alone predicted transition with 40% sensitivity and 100% specificity (AUROC=0.73, p=0.03). Combining history and clinical assessment provided no improvement above clinical data alone (sensitivity = 30%, specificity = 100%, AUROC=0.85, p< 0.0001). The combination of history, clinical assessment and biomarkers identified transition with a sensitivity of 60% and specificity of 100% (AUROC=0.87, p< 0.0001).
Conclusions
Probabilistic models combining biomarkers and clinical data are able to target high-risk subgroups within CHR and may help to personalise treatment.
The comparative effectiveness of antidepressant medication and cognitive-behaviour therapy for the acute treatment of depression is contentious.
Objective:
To compare the acute outcomes of antidepressant medication, cognitive-behaviour therapy (CBT), and the combination of the two, in adult, depressed patients.
Methods:
Sixteen electronic databases together with reference lists were searched for randomised and other clinical trials that compared CBT, antidepressants, or their combination.
Results:
In the comparison between CBT and antidepressants, 8 studies met inclusion criteria. Five studies met the inclusion criteria for the second comparison between single therapy and combination therapy. In the antidepressant and CBT comparison, effect sizes favoured CBT over antidepressants with a significant advantage for CBT on some outcome measures. Combined treatment appeared more effective than antidepressants. However, combined treatment did not emerge more effective than CBT.
Conclusions:
Antidepressants may not be considered more efficacious than CBT for the acute treatment of depressed patients nor can combination therapy be regarded as more effective than CBT alone.
The purpose of this paper was to examine national differences in the desire to participate in decision-making of people with severe mental illness in six European countries.
Methods
The data was taken from a European longitudinal observational study (CEDAR; ISRCTN75841675). A sample of 514 patients with severe mental illness from the study centers in Ulm, Germany, London, England, Naples, Italy, Debrecen, Hungary, Aalborg, Denmark and Zurich, Switzerland were assessed as to desire to participate in medical decision-making. Associations between desire for participation in decision-making and center location were analyzed with generalized estimating equations.
Results
We found large cross-national differences in patients’ desire to participate in decision-making, with the center explaining 47.2% of total variance in the desire for participation (P < 0.001). Averaged over time and independent of patient characteristics, London (mean = 2.27), Ulm (mean = 2.13) and Zurich (mean = 2.14) showed significantly higher scores in desire for participation, followed by Aalborg (mean = 1.97), where scores were in turn significantly higher than in Debrecen (mean = 1.56). The lowest scores were reported in Naples (mean = 1.14). Over time, the desire for participation in decision-making increased significantly in Zurich (b = 0.23) and decreased in Naples (b = −0.14). In all other centers, values remained stable.
Conclusions
This study demonstrates that patients’ desire for participation in decision-making varies by location. We suggest that more research attention be focused on identifying specific cultural and social factors in each country to further explain observed differences across Europe.
Correlation of Rodinian and Gondwanan crustal domains relies on a thorough knowledge of those vestiges preserved today. The Bunger Hills hold a critical place in East Antarctica, recording the Mesoproterozoic assembly of Australo-Antarctica in Rodinia and the Neoproterozoic–Cambrian amalgamation of Indo- and Australo-Antarctica in Gondwana. It is situated in a region of disputed overlap between the different components of Rodinia and Gondwana, where there is little consensus on the location of sutures in this region and thus often speculative geological interpretations. The Bunger Hills therefore provide an opportunity to better understand the tectonic setting and palaeogeography during the assembly of these supercontinents. Recent work has confirmed that the Bunger Hills are one of few rare outcrops in Wilkes Land, East Antarctica that can be directly correlated with the broader Musgrave–Albany–Fraser–Wilkes Orogen (MAFWO). Whilst other constituent terranes of the MAFWO have been intensely studied, our geological knowledge of the Bunger Hills was comparatively limited until recently. In light of recent geological and geophysical developments, this contribution serves as an updated and concise standalone reference for the present state of knowledge of the Neoarchean–Cambrian evolution of the Bunger Hills region.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
Methods
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
Results
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
Conclusions
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Emerging cybertechnologies, such as social digibots, bend epistemological conventions of life and culture already complicated by human and animal relationships. Virtually-augmented niches of machines and organic life promise new free-energy-governed selection of intelligent digital life. These provocative eco-evolutionary contexts demand a theory of (natural and artificial) minds to characterize and validate the immersive social phenomena universally-shaping cultural affordances.
A developing application of laser-driven currents is the generation of magnetic fields of picosecond–nanosecond duration with magnitudes exceeding $B=10~\text{T}$. Single-loop and helical coil targets can direct laser-driven discharge currents along wires to generate spatially uniform, quasi-static magnetic fields on the millimetre scale. Here, we present proton deflectometry across two axes of a single-loop coil ranging from 1 to 2 mm in diameter. Comparison with proton tracking simulations shows that measured magnetic fields are the result of kiloampere currents in the coil and electric charges distributed around the coil target. Using this dual-axis platform for proton deflectometry, robust measurements can be made of the evolution of magnetic fields in a capacitor coil target.
Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.
Additional crystallographic data are given for the recently reported mineral middlebackite, which has been described for discoveries at Iron Knob in South Australia and Passo di San Lugano near Trento, Italy. The material examined in the present study was from a third finding of the mineral, viz. from a quartz outcrop at Mooloo Downs Station in Western Australia within which it was co-located with the chemically- and structurally-related mineral moolooite, CuIIC2O4·nH2O, reported by Clarke and Williams (1986). In this study, the crystal structure was elucidated independently of the other studies using a combination of the a priori charge flipping and simulated annealing methods with synchrotron radiation diffraction (SRD) powder data. The principal crystal data for the Mooloo Downs material are: space group P21/c with lattice parameters a = 7.2659(18) Å, b = 5.7460(11) Å, c = 5.6806(11) Å, β = 104.588(3)°; Vc = 229.46(18) Å3; empirical formula CuII2C2O4(OH)2 with 2 formula units per unit cell; and calculated density = 3.605 g cm−3. The lattice parameters agree approximately with values given for the other studies, but not within the reported error estimates. The atom coordinates, interatomic distances, and angles for the Mooloo Downs material are compared with those from the other studies using single crystal data, with the values from all three studies agreeing approximately, but again not within the reported uncertainties. The crystal chemistry found for middlebackite received strong confirmation through the synthesis for the first time of di-copper oxalate di-hydroxide. Laboratory X-ray diffraction powder data for the synthetic form of the mineral from this study agree closely with the SRD data for the natural mineral.