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We assessed the prevalence of antibiotic prescriptions among ambulatory patients tested for coronavirus disease 2019 (COVID-19) in a large public US healthcare system and found a low overall rate of antibiotic prescriptions (6.7%). Only 3.8% of positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) tests were associated with an antibiotic prescription within 7 days.
Numerous theories posit different core features to borderline personality disorder (BPD). Recent advances in network analysis provide a method of examining the relative centrality of BPD symptoms, as well as examine the replicability of findings across samples. Additionally, despite the increase in research supporting the validity of BPD in adolescents, clinicians are reluctant to diagnose BPD in adolescents. Establishing the replicability of the syndrome across adolescents and adults informs clinical practice and research. This study examined the stability of BPD symptom networks and centrality of symptoms across samples varying in age and clinical characteristics.
Cross-sectional analyses of BPD symptoms from semi-structured diagnostic interviews from the Collaborative Longitudinal Study of Personality Disorders (CLPS), the Methods to Improve Diagnostic Assessment and Service (MIDAS) study, and an adolescent clinical sample. Network attributes, including edge (partial association) strength and node (symptom) expected influence, were compared.
The three networks were largely similar and strongly correlated. Affective instability and identity disturbance emerged as relatively central symptoms across the three samples, and relationship difficulties across adult networks. Differences in network attributes were more evident between networks varying both in age and in BPD symptom severity level.
Findings highlight the relative importance of affective, identity, and relationship symptoms, consistent with several leading theories of BPD. The network structure of BPD symptoms appears generally replicable across multiple large samples including adolescents and adults, providing further support for the validity of the diagnosis across these developmental phases.
Transforming towards global sustainability requires a dramatic acceleration of social change. Hence, there is growing interest in finding ‘positive tipping points’ at which small interventions can trigger self-reinforcing feedbacks that accelerate systemic change. Examples have recently been seen in power generation and personal transport, but how can we identify positive tipping points that have yet to occur? We synthesise theory and examples to provide initial guidelines for creating enabling conditions, sensing when a system can be positively tipped, who can trigger it, and how they can trigger it. All of us can play a part in triggering positive tipping points.
Recent work on positive tipping points towards sustainability has focused on social-technological systems and the agency of policymakers to tip change, whilst earlier work identified social-ecological positive feedbacks triggered by diverse actors. We bring these together to consider positive tipping points across social-technological-ecological systems and the potential for multiple actors and interventions to trigger them. Established theory and examples provide several generic mechanisms for triggering tipping points. From these we identify specific enabling conditions, reinforcing feedbacks, actors and interventions that can contribute to triggering positive tipping points in the adoption of sustainable behaviours and technologies. Actions that can create enabling conditions for positive tipping include targeting smaller populations, altering social network structure, providing relevant information, reducing price, improving performance, desirability and accessibility, and coordinating complementary technologies. Actions that can trigger positive tipping include social, technological and ecological innovations, policy interventions, public investment, private investment, broadcasting public information, and behavioural nudges. Positive tipping points can help counter widespread feelings of disempowerment in the face of global challenges and help unlock ‘paralysis by complexity’. A key research agenda is to consider how different agents and interventions can most effectively work together to create system-wide positive tipping points whilst ensuring a just transformation.
Social media summary
We identify key actors and actions that can enable and trigger positive tipping points towards global sustainability.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care.
We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive and anxiety disorder symptoms and diagnoses, in primary care depression RCTs (the Revised Clinical Interview Schedule: CIS-R). Two-stage random-effects meta-analyses were conducted.
Twelve (n = 6024) of thirteen eligible studies (n = 6175) provided individual patient data. There was a 31% (95%CI: 25 to 37) difference in depressive symptoms at 3–4 months per standard deviation increase in baseline depressive symptoms. Four additional factors: the duration of anxiety; duration of depression; comorbid panic disorder; and a history of antidepressant treatment were also independently associated with poorer prognosis. There was evidence that the difference in prognosis when these factors were combined could be of clinical importance. Adding these variables improved the amount of variance explained in 3–4 month depressive symptoms from 16% using depressive symptom severity alone to 27%. Risk of bias (assessed with QUIPS) was low in all studies and quality (assessed with GRADE) was high. Sensitivity analyses did not alter our conclusions.
When adults seek treatment for depression clinicians should routinely assess for the duration of anxiety, duration of depression, comorbid panic disorder, and a history of antidepressant treatment alongside depressive symptom severity. This could provide clinicians and patients with useful and desired information to elucidate prognosis and aid the clinical management of depression.
Overweight and obesity are universal health challenges. Recent evidence emphasises the potential benefits of addressing psychological factors associated with obesity in dietary programmes. This pilot study investigated the efficacy and acceptability of a combined online and face-to-face dietary intervention that used self-compassion, goal-setting and self-monitoring to improve dietary behaviour, as well as psychological factors associated with dietary behaviour.
Embedded mixed methods including a 4-week before-after trial and a one-on-one interview. Quantitative outcomes of the study were the levels of self-compassion; eating pathology; depression, anxiety and stress; and dietary intake. Qualitative outcomes were participants’ perceptions about the acceptability of the intervention.
UNSW Kensington campus.
Fourteen participants with overweight and obesity aged between 18 and 55 years old.
Results showed that the intervention significantly improved self-compassion and some aspects of dietary intake (e.g. decrease in energy intake) at Week Four compared with Week Zero. Some aspects of eating pathology also significantly decreased (e.g. Eating Concern). However, changes in self-compassion over the 4 weeks did not significantly predict Week Four study outcomes, except for level of stress. Most participants found self-compassion, goal-setting and self-monitoring to be essential for dietary behaviour change. However, participants also indicated that an online programme needed to be efficient, simple and interactive.
In conclusion, the current study provides preliminary but promising findings of an effective and acceptable combined online and face-to-face intervention that used self-compassion, goal-setting and self-monitoring to improve dietary habits. However, the results need to be examined in future long-term randomised controlled trials.
Academic Medical Centers (AMCs) offer patient care and perform research. Increasingly, AMCs advertise to the public in order to garner income that can support these dual missions. In what follows, we raise concerns about the ways that advertising blurs important distinctions between them. Such blurring is detrimental to AMC efforts to fulfill critically important ethical responsibilities pertaining both to science communication and clinical research, because marketing campaigns can employ hype that weakens research integrity and contributes to therapeutic misconception and misestimation, undermining the informed consent process that is essential to the ethical conduct of research. We offer ethical analysis of common advertising practices that justify these concerns. We also suggest the need for a deliberative body convened by the Association of American Medical Colleges and others to develop a set of voluntary guidelines that AMCs can use to avoid in the future, the problems found in many current AMC advertising practices.
Some UK insurers have been using real-world economic scenarios for more than 30 years. Popular approaches have included random walks, time series models, arbitrage-free models with added risk premiums or 1-year Value at Risk distribution fits. Based on interviews with experienced practitioners as well as historical documents and meeting minutes, this paper traces historical model evolution in the United Kingdom and abroad. We examine the possible catalysts for changes in modelling practice with a particular emphasis on regulatory and socio-cultural influences. We apply past lessons to provide some guidance to the direction of capital market modelling in future, which has been key for business and strategy decisions.
Self-screening using an electronic version of the Malnutrition Universal Screening Tool (‘MUST’) has been developed but its implementation requires investigation. A total of 100 outpatients (mean age 50 (sd 16) years; 57 % male) self-screened with an electronic version of ‘MUST’ and were then screened by a healthcare professional (HCP) to assess concurrent validity. Ease of use, time to self-screen and prevalence of malnutrition were also assessed. A further twenty outpatients (mean age 54 (sd 15) years; 55 % male) examined preference between self- screening with paper and electronic versions of ‘MUST’. For the three-category classification of ‘MUST’ (low, medium and high risk), agreement between electronic self-screening and HCP screening was 94 % (κ=0·74, se 0·092; P<0·001). For the two-category classification (low risk; medium+high risk) agreement was 96 % (κ=0·82, se 0·085; P<0·001), comparable with the previously reported paper-based self-screening. In all, 15 % of patients categorised themselves ‘at risk’ of malnutrition (5 % medium, 10 % high). Electronic self-screening took 3 min (sd 1·2 min), 40 % faster than previously reported for the paper-based version. Patients found the tool easy or very easy to understand (99 %) and complete (98 %). Patients that assessed both tools found the electronic tool easier to complete (65 %) and preferred it (55 %) to the paper version. Electronic self-screening using ‘MUST’ in a heterogeneous group of hospital outpatients is acceptable, user-friendly and has ‘substantial to almost-perfect’ agreement with HCP screening. The electronic format appears to be as agreeable and often the preferred format when compared with the validated paper-based ‘MUST’ self-screening tool.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and gastrointestinal discomfort. It is thus pertinent to establish the efficacy of lower n-3 PUFA doses. Eight male adults with asthma and HIB and eight controls without asthma were randomly supplemented with two n-3 PUFA doses (6·2 g/d (3·7 g EPA and 2·5 g DHA) and 3·1 g/d (1·8 g EPA and 1·3 g DHA)) and a placebo, each for 21 d followed by 14 d washout. A eucapnic voluntary hyperpnoea (EVH) challenge was performed before and after treatments. Outcome measures remained unchanged in the control group. In the HIB group, the peak fall in forced expiratory volume in 1 s (FEV1) after EVH at day 0 (−1005 (sd 520) ml, −30 (sd 18) %) was unchanged after placebo. The peak fall in FEV1 was similarly reduced from day 0 to day 21 of 6·2 g/d n-3 PUFA (−1000 (sd 460) ml, −29 (sd 17) % v. −690 (sd 460) ml, −20 (sd 15) %) and 3·1 g/d n-3 PUFA (−970 (sd 480) ml, −28 (sd 18) % v. −700 (sd 420) ml, −21 (sd 15) %) (P<0·001). Baseline fraction of exhaled nitric oxide was reduced by 24 % (P=0·020) and 31 % (P=0·018) after 6·2 and 3·1 g/d n-3 PUFA, respectively. Peak increases in 9α, 11β PGF2 after EVH were reduced by 65 % (P=0·009) and 56 % (P=0·041) after 6·2 and 3·1 g/d n-3 PUFA, respectively. In conclusion, 3·1 g/d n-3 PUFA supplementation attenuated HIB and markers of airway inflammation to a similar extent as a higher dose. Lower doses of n-3 PUFA thus represent a potentially beneficial adjunct treatment for adults with asthma and EIB.
The present study addresses the reaction zone structure and burning mechanism of unstable detonations. Experiments investigated mainly two-dimensional methane–oxygen cellular detonations in a thin channel geometry. The sufficiently high temporal resolution permitted the determination of the probability density function of the shock distribution, a power law with an exponent of $-3$, and the burning rate of unreacted pockets from their edges – through surface turbulent flames with a speed approximately 3–7 times larger than the laminar one at the local conditions. Numerical simulations were performed using a novel large-eddy simulation method where the reactions due to both autoignition and turbulent transport were treated exactly at the subgrid scale in a reaction–diffusion formulation. The model is an extension of Kerstein and Menon’s linear eddy model for large-eddy simulation to treat flows with shock waves and rapid gas-dynamic transients. The two-dimensional simulations recovered well the amplification of the laminar flame speed due to the turbulence generated mainly by the shear layers originating from the triple points and subsequent Richtmyer–Meshkov instability associated with the internal pressure waves. The simulations clarified how the level of turbulence generated controlled the burning rate of the pockets, the hydrodynamic thickness of the wave, the cellular structure and its distribution. Three-dimensional simulations were found to be in general good agreement with the two-dimensional ones, in that the subgrid-scale model captured the ensuing turbulent burning once the scales associated with the cellular dynamics, where turbulent kinetic energy is injected, are well resolved.
Gut microbes have a substantial influence on systemic immune function and allergic sensitisation. Manipulation of the gut microbiome through prebiotics may provide a potential strategy to influence the immunopathology of asthma. This study investigated the effects of prebiotic Bimuno-galactooligosaccharide (B-GOS) supplementation on hyperpnoea-induced bronchoconstriction (HIB), a surrogate for exercise-induced bronchoconstriction, and airway inflammation. A total of ten adults with asthma and HIB and eight controls without asthma were randomised to receive 5·5 g/d of either B-GOS or placebo for 3 weeks separated by a 2-week washout period. The peak fall in forced expiratory volume in 1 s (FEV1) following eucapnic voluntary hyperpnoea (EVH) defined HIB severity. Markers of airway inflammation were measured at baseline and after EVH. Pulmonary function remained unchanged in the control group. In the HIB group, the peak post-EVH fall in FEV1 at day 0 (−880 (sd 480) ml) was unchanged after placebo, but was attenuated by 40 % (−940 (sd 460) v. −570 (sd 310) ml, P=0·004) after B-GOS. In the HIB group, B-GOS reduced baseline chemokine CC ligand 17 (399 (sd 140) v. 323 (sd 144) pg/ml, P=0·005) and TNF-α (2·68 (sd 0·98) v. 2·18 (sd 0·59) pg/ml, P=0·040) and abolished the EVH-induced 29 % increase in TNF-α. Baseline C-reactive protein was reduced following B-GOS in HIB (2·46 (sd 1·14) v. 1·44 (sd 0·41) mg/l, P=0·015) and control (2·16 (sd 1·02) v. 1·47 (sd 0·33) mg/l, P=0·050) groups. Chemokine CC ligand 11 and fraction of exhaled nitric oxide remained unchanged. B-GOS supplementation attenuated airway hyper-responsiveness with concomitant reductions in markers of airway inflammation associated with HIB.
N- and p-type filled-skutterudite materials prepared for thermoelectric power generation modules were analyzed by neutron diffraction at the POWGEN beam line of the Spallation Neutron Source (SNS) and X-ray diffraction (XRD). The skutterudite powders were processed by melt spinning, followed by ball milling and annealing. The n-type material consists of Ba–Yb–Co–Sb and the p-type material consists of Di–Fe–Ni–Sb or Di–Fe–Co–Sb (Di = didymium, an alloy of Pr and Nd). Powders for prototype module fabrication from General Motors and Marlow Industries were analyzed in this study. XRD and neutron diffraction studies confirm that both the n- and p-type materials have cubic symmetry. Structural Rietveld refinements determined the lattice parameters and atomic parameters of the framework and filler atoms. The cage filling fraction was found to depend linearly on the lattice parameter, which in turn depends on the average framework atom size. This knowledge may allow the filling fraction of these skutterudite materials to be purposefully adjusted, thereby tuning the thermoelectric properties.