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The Southern dietary pattern, derived within the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, is characterised by high consumption of added fats, fried food, organ meats, processed meats and sugar-sweetened beverages and is associated with increased risk of several chronic diseases. The aim of the present study was to identify characteristics of individuals with high adherence to this dietary pattern. We analysed data from REGARDS, a national cohort of 30 239 black and white adults ≥45 years of age living in the USA. Dietary data were collected using the Block 98 FFQ. Multivariable linear regression was used to calculate standardised beta coefficients across all covariates for the entire sample and stratified by race and region. We included 16 781 participants with complete dietary data. Among these, 34·6 % were black, 45·6 % male, 55·2 % resided in stroke belt region and the average age was 65 years. Black race was the factor with the largest magnitude of association with the Southern dietary pattern (Δ = 0·76 sd, P < 0·0001). Large differences in Southern dietary pattern adherence were observed between black participants and white participants in the stroke belt and non-belt (stroke belt Δ = 0·75 sd, non-belt Δ = 0·77 sd). There was a high consumption of the Southern dietary pattern in the US black population, regardless of other factors, underlying our previous findings showing the substantial contribution of this dietary pattern to racial disparities in incident hypertension and stroke.
The UK Biobank contains data with varying degrees of reliability and completeness for assessing depression. A third of participants completed a Mental Health Questionnaire (MHQ) containing the gold-standard Composite International Diagnostic Interview (CIDI) criteria for assessing mental health disorders.
Aims
To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of major depressive disorder (MDD).
Method
In participants who did not complete the MHQ, we calculated the number of other depression measures endorsed, for example from hospital episode statistics and interview data. We compared cases defined this way with CIDI-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, single nucleotide polymorphisms (SNPs)-based heritability and genetic correlations with summary statistics from the Psychiatric Genomics Consortium MDD genome-wide association study.
Results
The strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% in participants who endorsed only one measure of depression, to 21% in those who endorsed four or five measures of depression. The strength of the genetic contribution to cases defined by at least two measures approximated that for CIDI-defined cases. Most genetic correlations between UK Biobank and the Psychiatric Genomics Consortium MDD study exceeded 0.7, but there was variability between pairwise comparisons.
Conclusions
Multiple measures of depression can serve as a reliable approximation for case status where the CIDI measure is not available, indicating sample size can be optimised using the entire suite of UK Biobank data.
Understanding the physics of viscoelastic liquid jets is relevant to jet-based printing and deposition techniques. In this paper we study the behaviour of jets induced from viscoelastic liquid films, using the mechanical impulse provided by a laser pulse to actuate jet formation. We present direct numerical simulations of viscoelastic liquid jets solving the two-phase flow problem, accounting for the Oldroyd-B rheology. We describe how the jet extension time and length are controlled by the Deborah number (ratio of the elastic and inertia-capillary time scales), the viscous dissipation described by the Ohnesorge number (ratio of the viscous-capillary and inertia-capillary time scales), as well as the ratio of laser impulse energy to the energy required to create free surface during jet formation and propagation. Using the droplet ejection laser threshold energy of a Newtonian liquid, we investigate the influence of increasing viscoelastic effects. We show that viscoelastic effects can modify the effective drop size at the tip of the jet, while the maximum jet length increases with increasing Deborah number. Using the simulations, we identify a high-Deborah-number regime, where the time of maximum jet extension can be described as $t_{max} = c_1 De^{1/4}$, with $c_1$ depending on the Ohnesorge number and blister geometry, while the length of maximum extension reaches an asymptotic value $L_{max}^{\infty }$ for $De>100$, $L_{max}^{\infty }$ depending on the Ohnesorge number and laser energy. The observed asymptotic relationships are in good agreement with experiments performed at much higher Deborah numbers.
The menopausal transition (MT) poses an increased risk for major depression (MD), but not for all women. Current and past stress are toxic risk factors for depression throughout life. The MT may be a time of increased sensitivity to stress, especially among women with a lifetime history of major depressive disorder (MDD). We evaluated whether women who experienced childhood maltreatment (CM) or current stressful events or ongoing problems were at increased risk for MD during the MT.
Methods
At the Pittsburgh site of the Study of Women's Health Across the Nation, 333 midlife women were interviewed approximately annually over 15 years with the Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders and provided health and psychosocial data including the Childhood Trauma Questionnaire. Repeated measures logistic regression analyses were conducted separately for women with and without lifetime MDD at study entry.
Results
Among women with lifetime MDD, CM, but not current stress, interacted with menopausal status to increase the risk for MD during postmenopause (ORs ranged from 2.71 to 8.04). All stressors were associated with increased odds of MD. Among women without lifetime MDD, current stress was related to risk for MD, but the effect did not vary by menopausal status.
Conclusions
Women with MDD prior to midlife and who experienced CM were at greatest risk for MD after the MT. Women without prior MDD were at increased risk for MD during peri- and postmenopause. Healthcare providers should monitor women at risk for MD even after the MT.
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 SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
In order to inform core performance projections and divertor design, the baseline SPARC tokamak plasma discharge is evaluated for its expected H-mode access, pedestal pressure and edge-localized mode (ELM) characteristics. A clear window for H-mode access is predicted for full field DT plasmas, with the available 25 MW of design auxiliary power. Additional alpha heating is likely needed for H-mode sustainment. Pressure pedestal predictions in the developed H-mode are surveyed using the EPED model. The projected SPARC pedestal would be limited dominantly by peeling modes and may achieve pressures in excess of 0.3 MPa at a density of approximately 3 × 1020 m−3. High pedestal pressure is partially enabled by strong equilibrium shaping, which has been increased as part of recent design iterations. Edge-localized modes (ELMs) with >1 MJ of energy are projected, and approaches for reducing the ELM size, and thus the peak energy fluence to divertor surfaces, are under consideration. The high pedestal predicted for SPARC provides ample margin to satisfy its high fusion gain (Q) mission, so that even if ELM mitigation techniques result in a 2× reduction of the pedestal pressure, Q > 2 is still predicted.
We tested for plague (Yersinia pestis) in a puma population in the Greater Yellowstone Ecosystem (GYE) over 9 years, overlapping a case when a boy in the area became infected with plague. Antibodies to Y. pestis were detected in 8 of 17 (47%) pumas tested by complement-enzyme-linked immunosorbent assay, and the organism itself was detected in 4 of 11 (36%) pumas tested after necropsy. Neither puma sex nor age was significantly associated with Y. pestis exposure or mortality, although our sample size was small. The overall prevalence of exposure we recorded was similar to that found along the western slope of Colorado, which is adjacent to the Four Corners region, a known plague hotspot in the USA. This suggests that: (1) Y. pestis may be present at higher levels in the GYE than previously assumed; (2) plague is a significant source of mortality for local pumas (6.6% of sub-adult and adult mortality); and (3) pumas may be a useful sentinel for potential risk of plague exposure to humans throughout the West. We would also emphasize that hunters and others handling pumas in this region should be made aware of the possibility of exposure.
To determine the effect of an electronic medical record (EMR) nudge at reducing total and inappropriate orders testing for hospital-onset Clostridioides difficile infection (HO-CDI).
Design:
An interrupted time series analysis of HO-CDI orders 2 years before and 2 years after the implementation of an EMR intervention designed to reduce inappropriate HO-CDI testing. Orders for C. difficile testing were considered inappropriate if the patient had received a laxative or stool softener in the previous 24 hours.
Setting:
Four hospitals in an academic healthcare network.
Patients:
All patients with a C. difficile order after hospital day 3.
Intervention:
Orders for C. difficile testing in patients administered a laxative or stool softener in <24 hours triggered an EMR alert defaulting to cancellation of the order (“nudge”).
Results:
Of the 17,694 HO-CDI orders, 7% were inappropriate (8% prentervention vs 6% postintervention; P < .001). Monthly HO-CDI orders decreased by 21% postintervention (level-change rate ratio [RR], 0.79; 95% confidence interval [CI], 0.73–0.86), and the rate continued to decrease (postintervention trend change RR, 0.99; 95% CI, 0.98–1.00). The intervention was not associated with a level change in inappropriate HO-CDI orders (RR, 0.80; 95% CI, 0.61–1.05), but the postintervention inappropriate order rate decreased over time (RR, 0.95; 95% CI, 0.93–0.97).
Conclusion:
An EMR nudge to minimize inappropriate ordering for C. difficile was effective at reducing HO-CDI orders, and likely contributed to decreasing the inappropriate HO-CDI order rate after the intervention.
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.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
Methods:
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
Results:
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Conclusion:
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.
Methods
Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.
Results
Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.
Conclusions
Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.
Maternal mental health during pregnancy and postpartum predicts later emotional and behavioural problems in children. Even though most perinatal mental health problems begin before pregnancy, the consequences of preconception maternal mental health for children's early emotional development have not been prospectively studied.
Methods
We used data from two prospective Australian intergenerational cohorts, with 756 women assessed repeatedly for mental health problems before pregnancy between age 13 and 29 years, and during pregnancy and at 1 year postpartum for 1231 subsequent pregnancies. Offspring infant emotional reactivity, an early indicator of differential sensitivity denoting increased risk of emotional problems under adversity, was assessed at 1 year postpartum.
Results
Thirty-seven percent of infants born to mothers with persistent preconception mental health problems were categorised as high in emotional reactivity, compared to 23% born to mothers without preconception history (adjusted OR 2.1, 95% CI 1.4–3.1). Ante- and postnatal maternal depressive symptoms were similarly associated with infant emotional reactivity, but these perinatal associations reduced somewhat after adjustment for prior exposure. Causal mediation analysis further showed that 88% of the preconception risk was a direct effect, not mediated by perinatal exposure.
Conclusions
Maternal preconception mental health problems predict infant emotional reactivity, independently of maternal perinatal mental health; while associations between perinatal depressive symptoms and infant reactivity are partially explained by prior exposure. Findings suggest that processes shaping early vulnerability for later mental disorders arise well before conception. There is an emerging case for expanding developmental theories and trialling preventive interventions in the years before pregnancy.
Although cognitive-behavioural therapy (CBT) is an effective treatment for depression, less than half of patients achieve satisfactory symptom reduction during treatment. Targeting known psychopathological processes such as rumination may increase treatment efficacy. The aim of this study was to test whether adding group rumination-focused CBT (RFCBT) that explicitly targets rumination to routine medical management is superior to adding group CBT to routine medical management in treating major depression.
Methods
A total of 131 outpatients with major depression were randomly allocated to 12 sessions group RFCBT v. group CBT, each in addition to routine medical management. The primary outcome was observer-rated symptoms of depression at the end of treatment measured on the Hamilton Rating Scale for Depression. Secondary outcomes were rumination at post-treatment and depressive symptoms at 6 months follow-up (Trial registered: NCT02278224).
Results
RFCBT significantly improved observer-rated depressive symptoms (Cohen's d 0.38; 95% CI 0.03–0.73) relative to group CBT at post-treatment on the primary outcome. No post-treatment differences were found in rumination or in depressive symptoms at 6 months follow-up, although these secondary analyses may have been underpowered.
Conclusions
This is the first randomized controlled trial providing evidence of benefits of RFCBT in major depression compared with CBT. Group RFCBT may be a beneficial alternative to group CBT for major depression.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
Methods:
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Results:
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Conclusion:
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
To characterize the microbiology of hepatobiliary surgical site infections (SSIs) and to explore the relationship between specific antimicrobial prophylaxis regimens and the development of SSIs.
Design
Retrospective matched case-control study comparing patient, procedure, and antimicrobial prophylaxis characteristics among patients undergoing a hepatobiliary surgical procedure with and without an SSI.
Setting
A tertiary referral acute-care facility.
Methods
Patients undergoing procedures defined as “BILI” (bile duct, liver, or pancreas surgery) using National Healthcare Safety Network (NHSN) definitions, excluding those undergoing concomitant liver transplantation, from January 2013 through June 2016 were included in the study population. The SSIs were identified through routine infection control surveillance using NHSN definitions. All patients who developed an SSI were considered cases. Controls were selected randomly matched 2:1 with cases based on fiscal quarter of the procedure. Logistic regression modeling was performed to explore variables associated with SSI, including antimicrobial prophylaxis received.
Results
Among 975 procedures, 80 (8.2%) resulted in an SSI. Most cases involved an organism nonsusceptible to standard prophylaxis regimens, including cefazolin (68.8%), cefazolin plus metronidazole (61.3%), and ampicillin-sulbactam (52.5%). In a multivariate model, antimicrobial coverage against Enterococcus spp (aOR, 0.58; 95% confidence interval [CI], 0.17–2.04; P=.40) and against Pseudomonas spp (aOR, 2.40; 95% CI, 0.56–10.29; P=.24) were not protective against the development of an SSI. The presence of a documented β-lactam allergy was significantly associated with the development of an SSI (aOR, 3.54; 95% CI, 1.36–9.19; P=.009).
Conclusions
Although SSIs at the study institution were associated with pathogens nonsusceptible to the most commonly used prophylaxis regimens, broader-spectrum coverage was not associated with a reduction in SSIs.