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Owing to its high magnetic field, high power, and compact size, the SPARC experiment will operate with divertor conditions at or above those expected in reactor-class tokamaks. Power exhaust at this scale remains one of the key challenges for practical fusion energy. Based on empirical scalings, the peak unmitigated divertor parallel heat flux is projected to be greater than 10 GW m−2. This is nearly an order of magnitude higher than has been demonstrated to date. Furthermore, the divertor parallel Edge-Localized Mode (ELM) energy fluence projections (~11–34 MJ m−2) are comparable with those for ITER. However, the relatively short pulse length (~25 s pulse, with a ~10 s flat top) provides the opportunity to consider mitigation schemes unsuited to long-pulse devices including ITER and reactors. The baseline scenario for SPARC employs a ~1 Hz strike point sweep to spread the heat flux over a large divertor target surface area to keep tile surface temperatures within tolerable levels without the use of active divertor cooling systems. In addition, SPARC operation presents a unique opportunity to study divertor heat exhaust mitigation at reactor-level plasma densities and power fluxes. Not only will SPARC test the limits of current experimental scalings and serve for benchmarking theoretical models in reactor regimes, it is also being designed to enable the assessment of long-legged and X-point target advanced divertor magnetic configurations. Experimental results from SPARC will be crucial to reducing risk for a fusion pilot plant divertor design.
Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated.
Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences.
More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified.
Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.
Prevention and control of respiratory disease is a major contributor to antibiotic use in swine. A systematic review was conducted to address the question, ‘What is the comparative efficacy of antimicrobials for the prevention of swine respiratory disease?’ Eligible studies were controlled trials published in English evaluating prophylactic antibiotics in swine, where clinical morbidity, mortality, or total antibiotic use was assessed. Four databases and the gray literature were searched for relevant articles. Two reviewers working independently screened titles and abstracts for eligibility followed by full-text articles, and then extracted data and evaluated risk of bias for eligible trials. There were 44 eligible trials from 36 publications. Clinical morbidity was evaluated in eight trials where antibiotics were used in nursery pigs and 10 trials where antibiotics were used in grower pigs. Mortality was measured in 22 trials in nursery pigs and 12 trials in grower pigs. There was heterogeneity in the antibiotic interventions and comparisons published in the literature; thus, there was insufficient evidence to allow quantification of the efficacy, or relative efficacy, of antibiotic interventions. Concerns related to statistical non-independence and quality of reporting were noted in the included trials.
A systematic review and network meta-analysis (MA) was conducted to address the question, ‘What is the efficacy of bacterial vaccines to prevent respiratory disease in swine?’ Four electronic databases and the grey literature were searched to identify clinical trials in healthy swine where at least one intervention arm was a commercially available vaccine for one or more bacterial pathogens associated with respiratory disease in swine, including Mycoplasma hyopneumoniae, Actinobacillus pleuropneumonia, Actinobacillus suis, Bordetella bronchiseptica, Pasteurella multocida, Stretococcus suis, Haemophils parasuis, and Mycoplasma hyorhinis. To be eligible, trials had to measure at least one of the following outcomes: incidence of clinical morbidity, mortality, lung lesions, or total antibiotic use. There were 179 eligible trials identified in 146 publications. Network MA was undertaken for morbidity, mortality, and the presence or absence of non-specific lung lesions. However, there was not a sufficient body of research evaluating the same interventions and outcomes to allow a meaningful synthesis of the comparative efficacy of the vaccines. To build this body of research, additional rigor in trial design and analysis, and detailed reporting of trial methods and results are warranted.
Gyrokinetic simulations of drift waves in low-magnetic-shear stellarators reveal that simulation domains comprised of multiple turns can be required to properly resolve critical mode structures important in saturation dynamics. Marginally stable eigenmodes important in saturation of ion temperature gradient modes and trapped electron modes in the Helically Symmetric Experiment (HSX) stellarator are observed to have two scales, with the envelope scale determined by the properties of the local magnetic shear and an inner scale determined by the interplay between the local shear and magnetic field-line curvature. Properly resolving these modes removes spurious growth rates that arise for extended modes in zero-magnetic-shear approximations, enabling use of a zero-magnetic-shear technique with smaller simulation domains and attendant cost savings. Analysis of subdominant modes in trapped electron mode (TEM)-driven turbulence reveals that the extended marginally stable modes play an important role in the nonlinear dynamics, and suggests that the properties induced by low magnetic shear may be exploited to provide another route for turbulence saturation.
Adolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.
Environmental exposures during pregnancy may increase breast cancer risk for mothers and female offspring. Tumor tissue assays may provide insight regarding the mechanisms. This study assessed the feasibility of obtaining tumor samples and pathology reports from mothers (F0) who were enrolled in the Child Health and Development Studies during pregnancy from 1959 to 1967 and their daughters (F1) who developed breast cancer over more than 50 years of follow-up. Breast cancer cases were identified through linkage to the California Cancer Registry and self-report. Written consent was obtained from 116 F0 and 95 F1 breast cancer survivors to access their pathology reports and tumor blocks. Of those contacted, 62% consented, 13% refused and 24% did not respond. We obtained tissue samples for 57% and pathology reports for 75%, and if diagnosis was made ⩽10 years we obtained tissue samples and pathology reports for 91% and 79%, respectively. Obtaining pathology reports and tumor tissues of two generations is feasible and will support investigation of the relationship between early-life exposures and molecular tumor markers. However, we found that more recent diagnosis increased the accessibility of tumor tissue. We recommend that cohorts request consent for obtaining future tumor tissues at study enrollment and implement real-time tissue collection to enhance success of collecting tumor samples and data.
The decline in age of pubertal timing has serious public health implications ranging from psychosocial adjustment problems to a possible increase in reproductive cancers. One biologically plausible explanation for the decline is a decrease in exposures to infections. To systematically review studies that assess the role of infection in pubertal timing, Medline, Web of Science and EMBASE were systematically searched and retrieved studies were reviewed for eligibility. Eligible studies examined the association between infections, including microbial exposures, and physical pubertal characteristics (breast, genitalia and pubic hair development) or age at menarche. We excluded studies that were published in a language other than English, focused on precocious puberty, were case studies, and/or included youth with autoimmune diseases. We report on study design, population characteristics, measurement of infection and puberty and the main effects of infection on pubertal development. Based on our search terms we identified 1372 unique articles, of which only 15 human and five animal studies met our eligibility criteria. Not all studies examined all outcomes. Infection was associated with later breast development (4/4 human studies), with less consistent evidence for genitalia and pubic hair development. Seven studies assessed age at menarche with inconsistent findings (three supporting later, four no association). We conclude that a small but consistent literature supports that infection is associated with later breast development; the evidence for other pubertal events and age at menarche is less clear. Where fewer childhood infections coincide with the rise in incidence of hormone-related cancers.
Studies have produced conflicting evidence regarding whether cognitive
control deficits in patients with schizophrenia result from dysfunction
within the cognitive control network (CCN; top-down) and/or unisensory
To investigate CCN and sensory cortex involvement during multisensory
cognitive control in patients with schizophrenia.
Patients with schizophrenia and healthy controls underwent functional
magnetic resonance imaging while performing a multisensory Stroop task
involving auditory and visual distracters.
Patients with schizophrenia exhibited an overall pattern of response
slowing, and these behavioural deficits were associated with a pattern of
patient hyperactivation within auditory, sensorimotor and posterior
parietal cortex. In contrast, there were no group differences in
functional activation within prefrontal nodes of the CCN, with small
effect sizes observed (incongruent–congruent trials). Patients with
schizophrenia also failed to upregulate auditory cortex with concomitant
increased attentional demands.
Results suggest a prominent role for dysfunction within auditory,
sensorimotor and parietal areas relative to prefrontal CCN nodes during
multisensory cognitive control.
Research reveals mixed results regarding the utility of standardized cognitive and academic tests to predict educational outcomes in youth following a traumatic brain injury (TBI). Yet, deficits in everyday school-based outcomes are prevalent after pediatric TBI. The current study used path modeling to test the hypothesis that parent ratings of adolescents’ daily behaviors associated with executive functioning (EF) would predict long-term functional educational outcomes following pediatric TBI, even when injury severity and patient demographics were included in the model. Furthermore, we contrasted the predictive strength of the EF behavioral ratings with that of a common measure of verbal memory. A total of 132 adolescents who were hospitalized for moderate to severe TBI were recruited to participate in a randomized clinical intervention trial. EF ratings and verbal memory were measured within 6 months of the injury; functional educational outcomes were measured 12 months later. EF ratings and verbal memory added to injury severity in predicting educational competence post injury but did not predict post-injury initiation of special education. The results demonstrated that measurement of EF behaviors is an important research and clinical tool for prediction of functional outcomes in pediatric TBI. (JINS, 2013, 19, 1–9)
This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959–1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the ‘core’ EDAH sample to address specific questions.
We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor.
Tobacco smoke has both carcinogenic effects and anti-estrogenic properties and its inconsistent association with breast cancer risk in observational studies may be because of these competing effects across the lifecourse. We conducted a prospective study of prenatal smoke exposure, childhood household smoke exposure, and adult active smoke exposure and mammographic density, a strong intermediate marker of breast cancer risk, in an adult follow-up of existing US birth cohorts. Specifically, we followed up women who were born between 1959 and 1967 and whose mothers participated in either the Collaborative Perinatal Project (Boston and Providence sites) or the Childhood Health and Development Study in California. Of the 1134 women interviewed in adulthood (ranging in age from 39 to 49 years at interview), 79% had a screening mammogram. Cigarette smoking was reported by mothers at the time of their pregnancy; 40% of mothers smoked while pregnant. Women whose mothers smoked during pregnancy had a 3.1% (95% confidence interval (CI) = −6.0%, −0.2%) lower mammographic density than women whose mothers did not smoke during pregnancy. When we further accounted for adult body mass index and adult smoking status, the association remained (β = −2.7, 95% CI = −5.0, −0.3). When we examined patterns of smoking, prenatal smoke exposure without adult smoke exposure was associated with a 5.6% decrease in mammographic density (β = −5.6, 95% CI = −9.6, −1.6). Given the strength of mammographic density as an intermediate marker for breast cancer, the inverse associations between mammographic density and smoking patterns across the lifecourse may help explain the complex association between cigarette smoking and breast cancer risk.
Growing evidence suggests obesity may have its roots in early life but it is still uncertain whether prenatal factors operate primarily though altering early infant growth. It is also still unclear if rapid growth during selected time periods is more important than other time periods in predicting future body size. Using prospectively collected data on 20,523 participants born from 1959 to 1966 (10,327 boys; 10,196 girls) of the Collaborative Perinatal Project, we investigated the associations between pre- and postnatal factors and childhood body size at age 7 years and compared these associations across linear, logistic and quantile regression models. Maternal body mass index (BMI), maternal pregnancy weight gain, birth weight and postnatal weight change for three time periods (birth to 4 months; 4–12 months; 1–4 years) were all positively and independently associated with BMI at age 7 years. Rapid growth during each time period had a similar association BMI at age 7 years. For example, a 10-percentile increase in weight increased the probability of being overweight at age 7 years by approximately two-fold regardless of time period (OR = 1.8–2.2 for boys and girls). Using same-sex siblings (n = 571 boy sets; n = 651 girl sets) from the same cohort, we observed that siblings with higher BMI at age 7 years than their same-sex siblings were more likely to have higher maternal pregnancy weight gain, higher maternal pre-pregnancy BMI, higher birth weight and increased rate of weight gain during the three time periods. These consistent findings both from the overall cohort and the sibling analyses suggest that there are multiple, rather than specific critical periods of influence shaping childhood body size.
Hydrogenated amorphous silicon (a-Si:H) thin-film transistors (TFTs) are widely used in many areas and the most important application is in active matrix liquid crystal display. However, the instability of the a-Si:H TFTs constrains their usability. These TFTs have been annealed at higher temperatures in hope of improving their electrical performance. But, higher anneal temperatures become a constraint when the TFTs are grown on polymer-based flexible substrates. This study investigates the effect of anneal time on the performance of the a-Si:H TFTs on PEN. Thin-film transistors are annealed at different anneal times (4 h, 24 h, and 48 h) and were stressed under different bias conditions. Sub-threshold slope and the off-current improved with anneal time. Off-current was reduced by two orders of magnitude for 48 hours annealed TFT and sub-threshold slope became steeper with longer annealing. At positive gate-bias-stress (20 V), threshold voltage shift (∆Vt) values are positive and exhibit a power-law time dependence. High temperature measurements indicate that longer annealed TFTs show improved performance and stability compared to unannealed TFTs. This improvement is due to reduction of interface trap density and good a-Si:H/insulator interface quality with anneal time.