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The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
This study evaluated the efficacy of a family-centered preventive intervention, the Family Check-Up (FCU), delivered as an online, eHealth model to middle school families. To increase accessibility of family-centered prevention in schools, we adapted the evidence-based FCU to an online format, with the goal of providing a model of service delivery that is feasible, given limited staffing and resources in many schools. Building on prior research, we randomly assigned participants to waitlist control (n = 105), FCU Online as a web-based intervention (n = 109), and FCU Online with coaching support (n = 108). We tested the effects of the intervention on multiple outcomes, including parental self-efficacy, child self-regulation, and child behavior, in this registered clinical trial (NCT03060291). Families engaged in the intervention at a high rate (72% completed the FCU assessment) and completed 3-month posttest assessments with good retention (94% retained). Random assignment to the FCU Online with coaching support was associated with reduced emotional problems for children (p = .003, d = −0.32) and improved parental confidence and self-efficacy (p = .018, d = 0.25) when compared with waitlist controls. Risk moderated effects: at-risk youth showed stronger effects than did those with minimal risk. The results have implications for online delivery of family-centered interventions in schools.
The aim of this study was to explore the clinical decisions that health care students would make if faced with an active shooter event while providing patient care.
A cross-sectional study design was used to survey 245 students from 6 different professional programs. Participants read 4 case-based scenarios, selected 1 of 4 actions in a multiple-choice format, and responded to an open-ended question. Demographic questions asked whether participants had been a victim of violence and whether they have taken a certified active shooter course. Statistical analysis included descriptive statistics and chi-square testing.
For each case, most students chose “patient-centric” versus “provider-centric” actions (range: 66%–94% and 4%–17%, respectively). The gender of the patient made no difference in actions. Those who attended a certified active shooter course tended to act with more “provider-centric” concerns than those who did not take such a course.
A significant majority of interprofessional health care students, when presented with specific case-scenarios, declared they would act to protect themselves and their patients during an active shooter event. This “patient-centric” attitude transcends the oversimplified “Run-Hide-Fight” axiom and must be addressed by all health care educational institutions.
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.
“Uncertain futures” refers to a set of policy problems that possess some combination of the following characteristics: (i) they potentially cause irreversible changes; (ii) they are widespread, so that policy responses may make sense only on a global scale; (iii) network effects are difficult to understand and may amplify (or moderate) consequences; (iv) time horizons are long; and (v) the likelihood of catastrophic outcomes is unknown or even unknowable. These characteristics tend to make uncertain futures intractable to market solutions because property rights are not clearly defined and essential information is unavailable. These same factors also pose challenges for benefit-cost analysis (BCA) and other traditional decision analysis tools. The diverse policy decisions confronting decision-makers today demand “dynamic BCA,” analytic frameworks that incorporate uncertainties and trade-offs across policy areas, recognizing that: perceptions of risks can be uninformed, misinformed, or inaccurate; risk characterization can suffer from ambiguity; and experts’ tendency to focus on one risk at a time may blind policymakers to important trade-offs. Dynamic BCA – which recognizes trade-offs, anticipates the need to learn from experience, and encourages learning – is essential for lowering the likelihoods and mitigating the consequences of uncertain futures while encouraging economic growth, reducing fragility, and increasing resilience.
Natural living conductive biofilms transport electrons between electrodes and cells, as well as among cells fixed within the film, catalyzing an array of reactions from acetate oxidation to CO2 reduction. Synthetic biology offers tools to modify or improve electron transport through biofilms, creating a new class of engineered living conductive materials. Engineered living conductive materials could be used in a range of applications for which traditional conducting polymers are not appropriate, including improved catalytic coatings for microbial fuel-cell electrodes, self-powered sensors for austere environments, and next-generation living components of bioelectronic devices that interact with the human microbiome.
Mismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity (‘repetition positivity’; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity (‘deviant negativity’; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC).
Electroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains.
Compared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects.
MMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.
Prior evolutionary theory provided reason to suspect that measures of development and reproduction would be correlated with antisocial behaviours in human and non-human species. Behavioural genetics has revealed that most quantitative traits are heritable, suggesting that these phenotypic correlations may share genetic aetiologies. We use genome-wide association study data to estimate the genetic correlations between various measures of reproductive development (N = 52 776–318 863) and antisocial behaviour (N = 31 968). Our genetic correlation analyses demonstrate that alleles associated with higher reproductive output (number of children ever born, rg = 0.50, P = 0.0065) were positively correlated with alleles associated with antisocial behaviour, whereas alleles associated with more delayed reproductive onset (age at first birth, rg = −0.64, P = 0.0008) were negatively associated with alleles linked to antisocial behaviour. Ultimately, these findings coalesce with evolutionary theories suggesting that increased antisocial behaviours may partly represent a faster life history approach, which may be significantly calibrated by genes.
During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds. Previously, we found attenuated vocalization-related auditory cortical suppression in psychosis and a similar trend in the psychosis risk syndrome. Here, we report data from the final sample of early illness schizophrenia patients (ESZ), individuals at clinical high risk for psychosis (CHR), and healthy controls (HC).
Event-related potentials (ERP) were recorded from ESZ (n = 84), CHR (n = 71), and HC (n = 103) participants during a vocalization paradigm. The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Age effects on N1 suppression (Talk–Listen), Talk N1, and Listen N1 were compared across groups. N1 measures were adjusted for normal aging before testing for group differences.
Both ESZ and CHR groups showed reduced Talk–Listen N1 suppression relative to HC, but did not differ from each other. Listen N1 was reduced in ESZ, but not in CHR, relative to HC. Deficient Talk–Listen N1 suppression was associated with greater unusual thought content in CHR individuals. N1 suppression increased with age in HC (12–36 years), and while CHR individuals showed a similar age-related increase, no such relationship was evident in ESZ.
Putative efference copy/corollary discharge-mediated auditory cortical suppression during vocalization is deficient in ESZ and precedes psychosis onset, particularly in CHR individuals with greater unusual thought content. Furthermore, this suppression increases from adolescence through early adulthood, likely reflecting the effects of normal brain maturation. This maturation effect is disrupted in ESZ, presumably due to countervailing illness effects.
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.
Introduction: Each year about two thirds of U.S. smokers make a quit attempt. Yet, less than 5% remain abstinent three months post-quit date. One factor that may affect abstinence is negative feelings about the self-associated with being a smoker (disequilibrium), particularly if smoking is important to the sense of self and one is trying to quit.
Aims: We evaluated a multivariate structural equation model proposing that smoking's subjective importance to a smoker would influence carbon monoxide verified smoking abstinence at 24 weeks (post-quit date). Further, we assessed whether the relation would be moderated by the smoker's experience of disequilibrium.
Methods: Participants were 440 regular smokers taking part in a clinical trial assessing the effectiveness of different durations of nicotine replacement therapy use. Participants completed the subjective importance of smoking survey at baseline and were assessed for carbon monoxide verified seven-day point prevalence abstinence at 24 weeks
Results: Using exploratory structural equation modelling, the subjective importance of smoking was associated with point prevalence abstinence at 24 weeks, but only for smokers with high disequilibrium.
Conclusions: The results of this study suggest that experiencing negative feelings about being a smoker could motivate smokers to remain abstinent, despite the importance of smoking to the smoker's sense of self.
To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing.
A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network.
The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing.
In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48–72 hours, but only 55% reported “always” doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care.
Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs.
This article compares the law and practice of the European Union and Australia in respect to the search and rescue (SAR) of boat migrants, concluding that the response to individuals in peril at sea in both jurisdictions is becoming increasingly securitized. This has led to the humanitarian purpose of SAR being compromised in the name of border security. Part I contrasts the unique challenge posed by SAR operations involving migrants and asylum seekers, as opposed to other people in distress at sea. Part II analyses the relevant international legal regime governing SAR activities and its operation among European States and in offshore Australia. Part III introduces the securitization framework as the explanatory paradigm for shifting State practice and its impact in Europe and Australia. It then examines the consequences of increasing securitization of SAR in both jurisdictions and identifies common trends, including an increase in militarization and criminalization, a lack of transparency and accountability, developments relating to disembarkation and non-refoulement, and challenges relating to cooperation and commodification.
We describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.
The relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood.
The aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension in hospitalised infants.
We extracted information on sildenafil dosing and clinical characteristics from electronic health records of 348 neonatal ICUs from 1997 to 2013, and we predicted drug exposure using a population pharmacokinetic model.
We identified 232 infants receiving sildenafil at a median dose of 3.2 mg/kg/day (2.0, 6.0). The median steady-state area under the concentration–time curve over 24 hours (AUC24,SS) and maximum concentration of sildenafil (Cmax,SS,SIL) were 712 ng×hour/ml (401, 1561) and 129 ng/ml (69, 293), respectively. Systemic hypotension occurred in 9% of the cohort. In multivariable analysis, neither dosing nor exposure were associated with systemic hypotension: odds ratio=0.96 (95% confidence interval: 0.81, 1.14) for sildenafil dose; 0.87 (0.59, 1.28) for AUC24,SS; 1.19 (0.78, 1.82) for Cmax,SS,SIL.
We found no association between sildenafil dosing or exposure with systemic hypotension. Continued assessment of sildenafil’s safety profile in infants is warranted.
This paper presents the thermospheric winds and temperature properties measured with a Fabry-Pérot interferometer (FPI) over Oukaimeden observatory (31.2°N, 7.8°W, 22.8°N magnetic) in Morocco. After Three years of successful functioning from 2014 to 2017, we can address the seasonal behavior of the temperature and the winds (vertical, zonal and meridional). The dependence of the thermospheric winds and temperature on the solar cycle is also presented. The day-to-day variations of the quiet time wind pattern exhibits the importance of other type of waves superposed to the main diurnal tides. The storm time wind and temperature exhibits also a variety of ways to react to the storm. However, there is seasonal effect to the storm that will be illustrated in this paper. The signature of the MTM phenomenon is also present in the winds and temperature in geomagnetically quiet and disturbed nights. The occurrence of this phenomenon over the studied area is also addressed.
We investigated the frequency and determinants of guideline-discordant antibiotic prescribing in outpatients with respiratory infections or cystitis. Antibiotic prescribing was guideline discordant in 60% of patients. The most common reason for discordance was prescribing an antibiotic when not indicated. In a multivariate analysis, physicians in training had the highest likelihood of guideline-concordant antibiotic prescribing.