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Individuals with Generalised Anxiety Disorder (GAD) have an attentional bias towards threatening information. It is not known whether this results from facilitated engagement (faster orientation) or delayed disengagement (shifting attention away) from threat. Recent research has developed a new methodology designed to modify attentional disengagement from threat.
Using this paradigm, the present study assessed the causal role of attentional disengagement from threat and its impact on worry.
Twenty-four university students scoring below 56 on the Penn-State-Worry-Questionnaire were randomly assigned to either threat disengagement training, or non-threat disengagement training. Training was assessed using threat and non-threat test-trials. All participants then completed a novel worry task, assessing tendency, ability and persistency of worry. The hypothesis was that training to disengage from threat rather than non-threat stimuli would affect tendency, ability or persistence of worry.
Accuracy and test-trial reaction-time data indicated disengagement training was successful; compared to the non-threat disengagement group, the threat disengagement group had faster reaction-times for non-threat valence test-trials, experienced marginally non-significantly more negative intrusions during active worry, and found it significantly more difficult to worry, when required to engage solely with worry without interruption in the worry task.
It is possible to manipulate attentional bias to disengage from threat information, leading to fewer negative thought intrusions during active worry and increased difficulty in engaging solely with worry, thus suggesting that impaired disengagement has a causal role in the ability to worry.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Introduction: Cardioactive steroid poisoning occurs worldwide with the use of pharmaceutical digoxin and botanical cardiac glycosides. The wholesale price of the antidote, digoxin immune fab, has increased over 300% from 2010 to 2015. Our objective was to identify gaps in the existing literature with respect to the use of digoxin immune fab in cardioactive steroid toxicity in acute care settings. Methods: We used scoping study methodology, as described by Arksey and O'Malley, to assess the range and scope of empiric research and will report: 1) sources of cardioactive steroid toxicity in acute settings; 2) doses of digoxin immune fab used in treatment; and, 3) intervention outcomes of acute cardioactive steroid toxicity following the administration of digoxin immune fab as first or second-line therapy. We collaborated with a library scientist to devise search strategies for PubMed, CINAHL, EMBASE, CENTRAL and Toxnet. We sought unpublished literature through the Canadian Electronic Library, Proquest, and Scopus and searched reference lists of included studies. We hand searched relevant conference proceedings and applicable guidelines. Two reviewers independently reviewed titles and abstracts using predetermined criteria. Using a structured data abstraction form, two reviewers independently extracted data. All discrepancies were resolved through consensus. Results: Our search strategy yielded 3458 results. After screening titles and abstracts 384 underwent full text screening. We included 147 studies and are currently extracting data from 12 French studies and 135 English studies. To date we have extracted data from 90 case reports and case series. Conclusion: Given concerns over rising costs, our findings will shed light on the extent of the evidence for use of digoxin immune fab in acute care settings.
Little is known about the effect of natural disasters on children's neural development. Additionally, despite evidence that stress and parenting may both influence the development of neural systems underlying reward and threat processing, few studies have brought together these areas of research. The current investigation examined the effect of parenting styles and hurricane-related stress on the development of neural reactivity to reward and threat in children. Approximately 8 months before and 9 months after Hurricane Sandy, 74 children experiencing high and low levels of hurricane-related stress completed tasks that elicited the reward positivity and error-related negativity, event-related potentials indexing sensitivity to reward and threat, respectively. At the post-Hurricane assessment, children completed a self-report questionnaire to measure promotion- and prevention-focused parenting styles. Among children exposed to high levels of hurricane-related stress, lower levels of promotion-focused, but not prevention-focused, parenting were associated with a reduced post-Sandy reward positivity. In addition, in children with high stress exposure, greater prevention-focused, but not promotion-focused, parenting was associated with a larger error-related negativity after Hurricane Sandy. These findings highlight the need to consider contextual variables such as parenting when examining how exposure to stress alters the development of neural reactivity to reward and threat in children.
Previous research has discovered different subtypes of social withdrawal based on motivations to approach or avoid social interactions. Each of these motivations are uniquely related to indices of maladjustment during emerging adulthood, including aspects of the self. However, research has yet to investigate whether or not relationship quality moderates these associations. The purpose of this study was to examine whether relationship quality with best friends, romantic partners, mothers, and fathers, respectively, serve as protective factors in the negative links between shyness and avoidance and self-worth. The participants included 519 college students (Mage = 19.87, SD = 1.99, 61% female) from four universities across the United States. Results revealed that relationship quality with both best friends and romantic partners moderated the relation between shyness and self-worth. The differences between parent and peer relationships are discussed.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
The purpose of this study was to investigate the 10-year impact of Hurricane Katrina on the incidence of acute myocardial infarction (AMI) along with contributing risk factors and any alteration in chronobiology of AMI.
A single-center, retrospective, comparison study of AMI incidence was performed at Tulane University Health Sciences Center from 2 years before Hurricane Katrina to 10 years after Hurricane Katrina. A 6-year, pre-Katrina and 10-year, post-Katrina cohort were also compared according to pre-specified demographic, clinical, and chronobiological data.
AMI incidence increased from 0.7% (150/21,079) to 2.8% (2,341/84,751) post-Katrina (P<0.001). The post-Katrina cohort had higher rates of coronary artery disease (36.4% vs. 47.9%, P=0.01), diabetes mellitus (31.3% vs. 39.9%, P=0.04), hyperlipidemia (45.4% vs. 59.3%, P=0.005), smoking (34.4% vs. 53.8%, P<0.001), drug abuse (10.2% vs. 15.4%, P=0.02), psychiatric illness (6.7% vs. 14.9%, P<0.001), medication non-adherence (7.3% vs. 15.3%, P<0.001), and lack of employment (7.2% vs. 16.4%, P<0.001). The post-Katrina group had increased rates of AMI during nights (29.8% vs. 47.8%, P<0.001) and weekends (16.1% vs. 29.1%, P<0.001).
Even 10 years after the storm, Hurricane Katrina continues to be associated with increased incidence of AMI, higher prevalence of traditional cardiovascular and psychosocial risk factors, and an altered chronobiology of AMI toward nights and weekends. (Disaster Med Public Health Preparedness. 2019;13:217–222)
J. E. Colwell, University of Central Florida Orlando, Florida, USA,
J. Blum, Technische Universität Braunschweig Braunschweig, GERMANY,
R. N. Clark, Planetary Science Institute Tucson, Arizona, USA,
S. Kempf, University of Colorado Boulder, Colorado, USA,
R. M. Nelson, Planetary Science Institute Tucson, Arizona, USA
The surface area of Saturn's rings is greater than that of any of the planets in the solar system, yet, aside from dust, we have never observed or sampled an individual ring particle. Rings are unique in the solar system in that they are a complex dynamical system whose individual constituents interact not only with the light that we use to sense them remotely, but also with each other through gravitational and contact forces. These dynamical interactions play as large a role in determining the appearance of the ring system as do the optical properties of the individual ring particles. In this chapter we review the experimental work that has been done to help us understand both aspects of planetary rings: their collective dynamical behavior and their optical properties.
We have a wealth of data on the behavior of ensembles of particles, both dynamically and their optical properties. Laboratory measurements of the behavior of various likely ring particle analogs are a critical link in connecting these bulk observations with the nature of individual ring particles, and understanding the properties of individual ring particles should provide clues to the outstanding unanswered questions about the age and origin of rings.
Images of Saturn's rings and optical depth profiles from occultations show features at a variety of spatial scales, from the resolution limit of tens of meters for occultations up to thousands of kilometers, and including most scales in between (Colwell et al., 2009; Chapter 3). A frustratingly small fraction of these structures is well understood. Many that remain puzzling, such as the large optical depth fluctuations in Saturn's central B ring, the complex structure in the B ring and the inner A ring, the long-wavelength low-amplitude undulations in optical depth in the C ring, and the plateaus in the C ring, are likely linked to either the collective behavior of the ring particles governed in part by their collisional properties (see e.g. Schmidt et al., 2009, for a review) or by ballistic transport of material due to extrinsic micrometeoroid bombardment (Chapter 9). The mechanical properties of individual ring particles are critical in both types of process.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
While our fascination with understanding the past is sufficient to warrant an increased focus on synthesis, solutions to important problems facing modern society require understandings based on data that only archaeology can provide. Yet, even as we use public monies to collect ever-greater amounts of data, modes of research that can stimulate emergent understandings of human behavior have lagged behind. Consequently, a substantial amount of archaeological inference remains at the level of the individual project. We can more effectively leverage these data and advance our understandings of the past in ways that contribute to solutions to contemporary problems if we adapt the model pioneered by the National Center for Ecological Analysis and Synthesis to foster synthetic collaborative research in archaeology. We propose the creation of the Coalition for Archaeological Synthesis coordinated through a U.S.-based National Center for Archaeological Synthesis. The coalition will be composed of established public and private organizations that provide essential scholarly, cultural heritage, computational, educational, and public engagement infrastructure. The center would seek and administer funding to support collaborative analysis and synthesis projects executed through coalition partners. This innovative structure will enable the discipline to address key challenges facing society through evidentially based, collaborative synthetic research.
Reports in the literature of treatment with recombinant tissue plasminogen activator following cardiac surgery are limited. We reviewed our experience to provide a case series of the therapeutic use of tissue plasminogen activator for the treatment of venous thrombosis in children after cardiac surgery. The data describe the morbidity, mortality, and clinical outcomes of tissue plasminogen activator administration for treatment of venous thrombosis in children following cardiac surgery.
The study was designed as a retrospective case series.
The study was carried out in a 25-bed cardiac intensive care unit in an academic, free-standing paediatric hospital.
All children who received tissue plasminogen activator for venous thrombosis within 60 days of cardiac surgery, a total of 13 patients, were included.
Data was collected, collated, and analysed as a part of the interventions of this study.
Measurements and main results
Patients treated with tissue plasminogen activator were principally young infants (median 0.2, IQR 0.07–0.58 years) who had recently (22, IQR 12.5–27.3 days) undergone cardiac surgery. Hospital mortality was high in this patient group (38%), but there was no mortality attributable to tissue plasminogen activator administration, occurring within <72 hours. There was one major haemorrhagic complication that may be attributable to tissue plasminogen activator. Complete or partial resolution of venous thrombosis was confirmed using imaging in 10 of 13 patients (77%), and tissue plasminogen activator administration was associated with resolution of chylous drainage, with no drainage through chest tubes, at 10 days after tissue plasminogen activator treatment in seven of nine patients who had upper-compartment venous thrombosis-associated chylothorax.
On the basis of our experience with administration of tissue plasminogen activator in children after cardiac surgery, tissue plasminogen activator is both safe and effective for resolution of venous thrombosis in this high-risk population.
Population-based registries report 95% 5-year survival for children undergoing surgery for CHD. This study investigated paediatric cardiac surgical outcomes in the Australian indigenous population.
All children who underwent cardiac surgery between May, 2008 and August, 2014 were studied. Demographic information including socio-economic status, diagnoses and co-morbidities, and treatment and outcome data were collected at time of surgery and at last follow-up.
A total of 1528 children with a mean age 3.4±4.6 years were studied. Among them, 123 (8.1%) children were identified as indigenous, and 52.7% (62) of indigenous patients were in the lowest third of the socio-economic index compared with 28.2% (456) of non-indigenous patients (p⩽0.001). The indigenous sample had a significantly higher Comprehensive Aristotle Complexity score (indigenous 9.4±4.2 versus non-indigenous 8.7±3.9, p=0.04). The probability of having long-term follow-up did not differ between groups (indigenous 93.8% versus non-indigenous 95.6%, p=0.17). No difference was noted in 30-day mortality (indigenous 3.2% versus non-indigenous 1.4%, p=0.13). The 6-year survival for the entire cohort was 95.9%. The Cox survival analysis demonstrated higher 6-year mortality in the indigenous group – indigenous 8.1% versus non-indigenous 5.0%; hazard ratio (HR)=2.1; 95% confidence intervals (CI): 1.1, 4.2; p=0.03. Freedom from surgical re-intervention was 79%, and was not significantly associated with the indigenous status (HR=1.4; 95% CI: 0.9, 1.9; p=0.11). When long-term survival was adjusted for the Comprehensive Aristotle Complexity score, no difference in outcomes between the populations was demonstrated (HR=1.6; 95% CI: 0.8, 3.2; p=0.19).
The indigenous population experienced higher late mortality. This apparent relationship is explained by increased patient complexity, which may reflect negative social and environmental factors.
We hypothesised that infants with ventricular dysfunction after cardiac surgery have impaired haemodynamic response to arginine–vasopressin therapy. We retrospectively reviewed the medical records of neonates and infants treated with arginine–vasopressin within 48 hours of corrective or palliative cardiac surgery who underwent echocardiographic assessment of ventricular function before initiation of therapy. Patients were classified as “responders” if their systolic blood pressure increased by ⩾10% without increase in catecholamine score or if it was maintained with decreased catecholamine score. Response was assessed 1 hour after maximum upward titration of arginine–vasopressin. A total of 36 children (15 neonates) were reviewed (17 male). The median (interquartile) age was 10.4 weeks (1.1–26.9), and the median weight was 4.3 kg (3.2–5.8). Diagnoses included single ventricle (eight), arch abnormalities (five), atrioventricular septal defect (four), double-outlet right ventricle (three), tetralogy of Fallot (three), and others (13). In all, 12 patients (33%) had ventricular dysfunction. Only 15 (42%) responded favourably according to our definition 1 hour after the “target” arginine–vasopressin dose was achieved. Ventricular dysfunction was not associated with poor response. The overall mortality was 25%, but mortality in patients with ventricular dysfunction was 42%. Favourable response was associated with shorter ICU stay (9.5 days versus 19.5 days, p=0.01). We conclude that arginine–vasopressin fails to increase blood pressure in ~50% of hypotensive children after cardiac surgery. The response rate does not increase with duration of therapy. Ventricular function does not predict haemodynamic response. The mortality in this group is very high. Prospective comparison of vasopressin with other vasoactive agents and/or inotropes is warranted.
Information about the health and economic impact of infections caused by vancomycin-resistant enterococci (VRE) can inform investments in infection prevention and development of novel therapeutics.
To systematically review the incidence of VRE infection in the United States and the clinical and economic outcomes.
We searched various databases for US studies published from January 1, 2000, through June 8, 2015, that evaluated incidence, mortality, length of stay, discharge to a long-term care facility, readmission, recurrence, or costs attributable to VRE infections. We included multicenter studies that evaluated incidence and single-center and multicenter studies that evaluated outcomes. We kept studies that did not have a denominator or uninfected controls only if they assessed postinfection length of stay, costs, or recurrence. We performed meta-analysis to pool the mortality data.
Five studies provided incidence data and 13 studies evaluated outcomes or costs. The incidence of VRE infections increased in Atlanta and Detroit but did not increase in national samples. Compared with uninfected controls, VRE infection was associated with increased mortality (pooled odds ratio, 2.55), longer length of stay (3-4.6 days longer or 1.4 times longer), increased risk of discharge to a long-term care facility (2.8- to 6.5-fold) or readmission (2.9-fold), and higher costs ($9,949 higher or 1.6-fold more).
VRE infection is associated with large attributable burdens, including excess mortality, prolonged in-hospital stay, and increased treatment costs. Multicenter studies that use suitable controls and adjust for time at risk or confounders are needed to estimate the burden of VRE infections.
The Pandemic Risk Assessment Model (PRAM) is a mathematical model developed to analyse two pandemic influenza control measures available to public health: antiviral treatment and immunization. PRAM is parameterized using surveillance data from Alberta, Canada during pandemic H1N1. Age structure and risk level are incorporated in the compartmental, deterministic model through a contact matrix. The model characterizes pandemic influenza scenarios by transmissibility and severity properties. Simulating a worst-case scenario similar to the 1918 pandemic with immediate stockpile release, antiviral demand is 20·3% of the population. With concurrent, effective and timely immunization strategies, antiviral demand would be significantly less. PRAM will be useful in informing policy decisions such as the size of the Alberta antiviral stockpile and can contribute to other pandemic influenza planning activities and scenario analyses.
Our objective was to estimate the per-infection and cumulative mortality and cost burden of multidrug-resistant (MDR) Acinetobacter healthcare-associated infections (HAIs) in the United States using data from published studies.
We identified studies that estimated the excess cost, length of stay (LOS), or mortality attributable to MDR Acinetobacter HAIs. We generated estimates of the cost per HAI using 3 methods: (1) overall cost estimates, (2) multiplying LOS estimates by a cost per inpatient-day ($4,350) from the payer perspective, and (3) multiplying LOS estimates by a cost per inpatient-day from the hospital ($2,030) perspective. We deflated our estimates for time-dependent bias using an adjustment factor derived from studies that estimated attributable LOS using both time-fixed methods and either multistate models (70.4% decrease) or matching patients with and without HAIs using the timing of infection (47.4% decrease). Finally, we used the incidence rate of MDR Acinetobacter HAIs to generate cumulative incidence, cost, and mortality associated with these infections.
Our estimates of the cost per infection were $129,917 (method 1), $72,025 (method 2), and $33,510 (method 3). The pooled relative risk of mortality was 4.51 (95% CI, 1.10–32.65), which yielded a mortality rate of 10.6% (95% CI, 2.5%–29.4%). With an incidence rate of 0.141 (95% CI, 0.136–0.161) per 1,000 patient-days at risk, we estimated an annual cumulative incidence of 12,524 (95% CI, 11,509–13,625) in the United States.
The estimates presented here are relevant to understanding the expenditures and lives that could be saved by preventing MDR Acinetobacter HAIs.
Herpes simplex virus (HSV) is one of the most commonly identified infectious aetiologies of encephalitis in North America and Europe. The epidemiology of encephalitis beyond these regions, however, is poorly defined. During 2009–2012 we enrolled 313 patients in a multicentre prospective study of encephalitis in Peru, 45 (14·4%) of whom had confirmed HSV infection. Of 38 patients with known HSV type, 84% had HSV-1 and 16% had HSV-2. Patients with HSV infection were significantly more likely to present in the summer months (44·4% vs. 20·0%, P = 0·003) and have nausea (60·0% vs. 39·8%, P = 0·01) and rash (15·6% vs. 5·3%, P = 0·01) compared to patients without HSV infection. These findings highlight differences in the epidemiology and clinical presentation of HSV encephalitis outside of the Northern Hemisphere that warrant further investigation. Furthermore, there is an urgent need for improved HSV diagnostic capacity and availability of intravenous acyclovir in Peru.
Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD.
A sample of 136 children (aged 6–30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners’ offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity.
Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years.
Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.
Childhood maltreatment (CM) has consistently been linked with adverse outcomes including substance use disorders and adult sexual revictimization. Adult sexual victimization itself has been linked with psychopathology but has predominately been studied in women. The current investigation examines the impact of CM and co-occurring psychopathology on adult sexual victimization in men and women, replicating findings in three distinct samples.
We investigated the association between continuous CM factor scores and adult sexual victimization in the Childhood Trauma Study (CTS) sample (N = 2564). We also examined the unique relationship between childhood sexual abuse (CSA) and adult sexual victimization while adjusting for co-occurring substance dependence and psychopathology. We replicated these analyses in two additional samples: the Comorbidity and Trauma Study (CATS; N = 1981) and the Australian Twin-Family Study of Alcohol Use Disorders (OZ-ALC; N = 1537).
Analyses revealed a significant association with CM factor scores and adult sexual victimization for both men and women across all three samples. The CSA factor score was strongly associated with adult sexual victimization after adjusting for substance dependence and psychopathology; higher odds ratios were observed in men (than women) consistently across the three samples.
A continuous measure of CSA is independently associated with adult sexual trauma risk across samples in models that included commonly associated substance dependence and psychopathology as covariates. The strength of the association between this CSA measure and adult sexual victimization is higher in magnitude for men than women, pointing to the need for further investigation of sexual victimization in male community samples.