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Irritability and anxiety are two common clinical phenotypes that involve high-arousal negative affect states (anger and fear), and that frequently co-occur. Elucidating how these two forms of emotion dysregulation relate to perturbed neurodevelopment may benefit from alternate phenotyping strategies. One such strategy applies a bifactor latent variable approach that can parse shared versus unique mechanisms of these two phenotypes. Here, we aim to replicate and extend this approach and examine associations with neural structure in a large transdiagnostic sample of youth (N = 331; M = 13.57, SD = 2.69 years old; 45.92% male). FreeSurfer was used to extract cortical thickness, cortical surface area, and subcortical volume. The current findings replicated the bifactor model and demonstrate measurement invariance as a function of youth age and sex. There were no associations of youth's factor scores with cortical thickness, surface area, or subcortical volume. However, we found strong convergent and divergent validity between parent-reported irritability and anxiety factors with clinician-rated symptoms and impairment. A general negative affectivity factor was robustly associated with overall functional impairment across symptom domains. Together, these results support the utility of the bifactor model as an alternative phenotyping strategy for irritability and anxiety, which may aid in the development of targeted treatments.
Theory of mind, the ability to represent the mental states of others, is an important social cognitive process, which contributes to the development of social competence. Recent research suggests that interactions between gene and environmental factors, such as oxytocin receptor gene (OXTR) polymorphisms and maternal parenting behavior, may underlie individual differences in children's theory of mind. However, the potential influence of DNA methylation of OXTR remains unclear. The current study investigated the roles of OXTR methylation, maternal behavior, and their statistical interaction on toddlers’ early emerging theory of mind abilities. Participants included a community sample of 189 dyads of mothers and their 2- to 3-year-old children, whose salivary DNA was analyzed. Results indicated that more maternal structuring behavior was associated with better performance, on a battery of three theory of mind tasks, while higher OXTR methylation within exon 3 was associated with poorer performance. A significant interaction also emerged, such that OXTR methylation was related to theory of mind among children whose mothers displayed less structuring, when controlling for children's age, sex, ethnicity, number of child-aged siblings, verbal ability, and maternal education. Maternal structuring behavior may buffer the potential negative impact of hypermethylation on OXTR gene expression and function.
Individuals with schizophrenia have deficits in social cognition that are associated with poor functional outcome. Unfortunately, current treatments result in only modest improvement in social cognition. Oxytocin, a neuropeptide with pro-social effects, has significant benefits for social cognition in the general population. However, studies examining the efficacy of oxytocin in schizophrenia have yielded inconsistent results. One reason for inconsistency may be that oxytocin has typically not been combined with psychosocial interventions. It may be necessary for individuals with schizophrenia to receive concurrent psychosocial treatment while taking oxytocin to have the context needed to make gains in social cognitive skills.
The current study tested this hypothesis in a 24-week (48 session) double-blind, placebo-controlled trial that combined oxytocin and Cognitive-Behavioral Social Skills Training (CBSST), which included elements from Social Cognition and Interaction Training (SCIT). Participants included 62 outpatients diagnosed with schizophrenia (placebo n = 31; oxytocin n = 31) who received 36 IU BID, with supervised administration 45 min prior to sessions on CBSST group therapy days. Participants completed a battery of measures administered at 0, 12, and 24 weeks that assessed social cognition.
CBSST generally failed to enhance social cognition from baseline to end of study, and there was no additive benefit of oxytocin beyond the effects of CBSST alone.
Findings suggest that combined CBSST and oxytocin had minimal benefit for social cognition, adding to the growing literature indicating null effects of oxytocin in multi-dose trials. Methodological and biological factors may contribute to inconsistent results across studies.
Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.
A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.
At baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).
Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.
The principal engineering problems requiring knowledge concerning the properties of ice are prediction of the maximum force that ice might exert on a structure and determination of the load that can be placed safely on an ice cover. The properties of ice relevant to these problems are discussed. Particular attention is given to the dependence of Young's modulus on the frequency of the stress, strain-rate dependence of the yield and fracture strengths, and the ductile to brittle transition. It is shown that the strain-rate dependence of these properties is consistent with information on the stress dependence of dislocation velocity on the basal plane. The tensile and compressive strengths are also shown to be consistent with current theories of crack initiation and propagation.
The new conodont genus Magnigondolella is recognized based on specimens recovered from the Anisian (Middle Triassic) of British Columbia in Canada, and Nevada in the USA. This new genus encompasses problematic specimens with high carinas, which have recently been collectively referred to as Neogondolella ex gr. regalis Mosher. Ten species from North America are herein assigned to Magnigondolella n. gen., including the eight new species M. alexanderi, M. cyri, M. julii, M. nebuchadnezzari, M. salomae, M. n. sp. A, M. n. sp. B, and M. n. sp. C, as well as the two existing species M. regalis (Mosher) and M. dilacerata (Golding and Orchard). Other species from the Tethys region are also tentatively assigned to Magnigondolella n. gen. Based on published records, the genus appears to range from the Spathian to the upper Anisian in North America. The recognition of eight new species from the Anisian significantly increases the conodont biodiversity of this period, which has previously been regarded as a time of low diversity. Although some of the species included within Magnigondolella n. sp. have relatively long stratigraphic ranges, many have been identified in both British Columbia and Nevada, and therefore show potential for biostratigraphic correlation on a regional scale.
Seafood intake in pregnancy has been positively associated with childhood cognitive outcomes which could potentially relate to the high vitamin D content of oily fish. However, whether higher maternal vitamin D status (serum 25-hydroxyvitamin D (25(OH)D)) in pregnancy is associated with a reduced risk of offspring suboptimal neurodevelopmental outcomes is unclear. A total of 7065 mother–child pairs were studied from the Avon Longitudinal Study of Parents and Children cohort who had data for both serum total 25(OH)D concentration in pregnancy and at least one measure of offspring neurodevelopment (pre-school development at 6–42 months; ‘Strengths and Difficulties Questionnaire’ scores at 7 years; intelligence quotient (IQ) at 8 years; reading ability at 9 years). After adjustment for confounders, children of vitamin D-deficient mothers (<50·0 nmol/l) were more likely to have scores in the lowest quartile for gross-motor development at 30 months (OR 1·20; 95 % CI 1·03, 1·40), fine-motor development at 30 months (OR 1·23; 95 % CI 1·05, 1·44) and social development at 42 months (OR 1·20; 95 % CI 1·01, 1·41) than vitamin D-sufficient mothers (≥50·0 nmol/l). No associations were found with neurodevelopmental outcomes, including IQ, measured at older ages. However, our results suggest that deficient maternal vitamin D status in pregnancy may have adverse effects on some measures of motor and social development in children under 4 years. Prevention of vitamin D deficiency may be important for preventing suboptimal development in the first 4 years of life.
Observations were carried out on each significant layer of the snow cover at Ottawa (lat. 45° 24′ N., long. 75° 43′ W.) on the thickness of the layer, and the density, grain size distribution and degree of bonding of the snow in each layer. A logarithmic dependence on time was found for the layer thickness, and the density and grain size distribution. The product of layer thickness times the corresponding snow density was found to be constant when no melting occurred.
An unusual humped formation of floating ice, about 10 m. high, 100 m. wide and 1,200 m. long. was observed on the Ottawa River, Canada. Some characteristics of this formation are described. The cause of the humps was found to be frazil ice deposited in a trench about 90 m. wide, 90 m. deep and 1,200 m. long. The frazil ice was formed in rapids up-stream from the humps.
An investigation was undertaken of the creep of columnar-grained ice under constant compressive stresses of 98 and 59 kPa in order to extend the observed relationship between strain-rate and stress further into the low-stress region. Stress was applied perpendicular to the long direction of the grains. Observations were made for temperatures between -5 and -40°C. The steady-state creep rate for secondary creep was not yet attained for strain of 1.4% and stress of 98 kPa. An initial yield was observed at that stress in the strain range of 0.2 to 0.3%, similar to that seen at higher stress. The observations showed that the strain-rate tended to a linear dependence on stress below 49 kPa and that more than one dislocation process with different values for the stress exponent may contribute to the strain at higher stresses. An activation energy of 63 kJ mol−1 was consistent with the observed temperature dependence of the strain-rate. Straining ice to a given strain under a stress of about 0.3 MPa and then reducing the load may be a convenient way to study the stress, strain and temperature dependence of the strain-rate at low stress.
Eight new species of the conodont Neogondolella are described from the Anisian (Middle Triassic) of northeastern British Columbia. The subtlety of morphological variation in this conodont genus has hampered biostratigraphical correlation, but large, often independently dated collections have enabled the description of N. cuneiforme, N. curva, N. hastata, N. dilacerata, N. indicta, N. panlaurentia, N. tenera, and N. vellicata n. spp. Several of these species are widespread, as specimens of N. curva, N. hastata, N. indicta, N. panlaurentia, N. tenera, and N. vellicata are found in contemporary collections from Nevada, whereas N. panlaurentia has also been recovered from the Canadian Arctic. This distribution promises to significantly improve correlation among Anisian sections in North America.
This paper provides an overview of the U.S. Department of Energy’s (DOE) hydrogen and fuel cell activities within the Office of Energy Efficiency and Renewable Energy (EERE), focusing on key targets, progress towards meeting those targets, and materials-related issues that need to be addressed. The most recent, state-of-the-art data on metrics such as cost, durability, and performance of fuel cell and hydrogen technologies are presented. Key technical accomplishments to date include a 50% reduction in the modeled high volume cost of fuel cells since 2006, and an 80% cost reduction for electrolyzers since 2002. The statuses of various hydrogen production, delivery, and storage technologies are also presented along with a summary of materials-related challenges for hydrogen infrastructure technologies such as compression, dispensing, seals, pipeline materials/embrittlement, and storage materials. Specific examples and areas requiring more research are discussed. Finally, future plans including EERE’s lab consortium approach such as HyMARC (Hydrogen Storage Materials Advanced Research Consortium) and FC-PAD (Fuel Cell Performance and Durability) Consortia, are summarized.
The emergence of hydrogen and fuel cell technologies in transportation and stationary power sectors offers the world important and potentially transformative environmental and energy security benefits. In recent years, research supported by the U.S. Department of Energy’s (DOE) Fuel Cell Technologies Office has contributed substantially to the development of these technologies. Enhanced performance and reduced cost in automotive fuel cells are important examples of achievement. The research investments are clearly paying off, as commercial fuel-cell electric vehicles (FCEVs) are being rolled out by major car manufacturers today. With increasing market penetration of FCEVs, enabling technologies for the affordable and widespread production, storage and delivery of renewable hydrogen are becoming increasingly important. Long term commercial viability of hydrogen and fuel cells in the commercial marketplace will rely on continued materials research on several important fronts. Examples include the discovery and development of: (1) non-platinum-group-metal catalysts for next-generation fuel cells; (2) durable, high-performance photocatalytic materials systems for direct solar water splitting; (3) advanced materials-based systems for low-pressure, high-volumetric-density hydrogen storage; and (4) low-cost, hydrogen-compatible pipeline materials for hydrogen delivery and distribution. Research innovations in macro-, meso- and nano-scale materials are all needed for pushing forward the state-of-the-art in these areas. New approaches in accelerated materials development facilitated by a national Energy Materials Network of advanced scientific resources in theory, computation and experimentation are being adopted at DOE. Application of these approaches to address the key materials challenges in hydrogen and fuel cell technologies are discussed.
The number of separable cognitive dimensions in schizophrenia has been debated. Guided by the extant factor analytic literature, the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative selected seven cognitive domains relevant to treatment studies in schizophrenia: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These domains are assessed in the MATRICS Consensus Cognitive Battery (MCCB). The aim of this study was to conduct a confirmatory factor analysis (CFA) of the beta battery of the MCCB to compare the fit of the MATRICS consensus seven-domain model to other models in the current literature on cognition in schizophrenia.
Using data from 281 schizophrenia outpatients, we compared the seven correlated factors model with alternative models. Specifically, we compared the 7-factor model to (a) a single-factor model, (b) a three correlated factors model including speed of processing, working memory, and general cognition, and (c) a hierarchical model in which seven first-order factors loaded onto a second-order general cognitive factor.
Multiple fit indices indicated the seven correlated factors model was the best fit for the data and provided significant improvement in model fit beyond the comparison models.
These results support the assessment of these seven cognitive dimensions in clinical trials of interventions to improve cognition in schizophrenia. Because these cognitive factors are separable to some degree, it is plausible that specific interventions may have differential effects on the domains.
A method of diamond heteroepitaxial lateral overgrowth is demonstrated which utilizes a photolithographic metal mask to pattern a thin (001) epitaxial diamond surface. Significant structural improvement was found, with a threading dislocation density reduced by two orders of magnitude at the top surface of a thick overgrown diamond layer. In the initial stage of overgrowth, a reduction of diamond Raman linewidth in the overgrown area was also realized. Thermally-induced stress and internal stress were determined by Raman spectroscopy of adhering and delaminated diamond films. The internal stress is found to decrease as sample thickness increases.
Antimicrobial therapy for asymptomatic bacteriuria (ASB) is recommended for pregnant patients and those undergoing genitourinary procedures. In other populations, treatment has not been demonstrated to confer benefit and is associated with adverse drug reactions, selection for infection with increasingly drug-resistant bacteria, and Clostridium difficile infection. We undertook a prospective audit of urine culture ordering practices among medical and surgical inpatients at 2 acute care teaching hospitals to identify the proportion of urine cultures ordered without clinical indication that lead to antimicrobial therapy for ASB.
During August and September 2012, consecutive urine cultures from nonpregnant ward patients were identified within 24 hours of culture ordering. Each patient was interviewed by the study team to determine the presence of urinary tract infection (UTI) using standard surveillance criteria. Non-catheterized patients met clinical indications for UTI if they had fever (temperature >38°C) without another explanation or at least 1 urinary symptom (dysuria, urgency, frequency, costovertebral angle tenderness, or suprapubic pain or tenderness). Catheterized patients met clinical indications for UTI if they had fever, suprapubic pain, or costovertebral angle tenderness. Other reasons for ordering cultures were documented on the basis of care provider interviews before culture results were known. Culture results and antimicrobial prescriptions were documented 72 hours later. The study was approved by the research ethics boards of Mount Sinai Hospital (472 beds) and University Health Network (408 beds; Toronto General Hospital site).
Patients with enlarged lymph nodes present to a number of different specialties and diagnosis is often made following a biopsy.
This study aimed to establish department waiting times for cervical lymph node biopsy, and compare these to the cancer services guidelines.
A retrospective audit was carried out to record patient waiting times (defined as the number of days from referral to biopsy) between May and December 2010. A proforma for referral was introduced. In addition, appointments for biopsies were arranged by a co-ordinator. A prospective re-audit was carried out from March to September 2011.
The first audit showed that national guidelines were not met; there was a median waiting time of 74 days (interquartile range, 47–113). Re-audit demonstrated a significant reduction in waiting times using the proforma; the median waiting time had decreased to 18 days (interquartile range, 9–22).
A proforma for lymph node biopsy and a designated co-ordinator streamlined the service, significantly reducing waiting times. Together, these can aid referral for meeting guidelines and improve patient care.
While impaired memory and altered cortisol secretion are characteristic features of major depression, much less is known regarding the impact of antidepressant medication. We examined whether the cortisol awakening response (CAR) is increased in depressed patients with and without medication compared with healthy controls (HC) and whether CAR is associated with memory function in each group.
We examined 21 patients with major depression without medication, 20 depressed patients on antidepressant treatment, and 41 age-, sex- and education-matched healthy subjects. We tested verbal (Auditory Verbal Learning Task) and visuospatial (Rey figure) memory and measured CAR on two consecutive days.
Patient groups did not differ in severity of depression. We found a significant effect of group (p = 0.03) for CAR. Unmedicated patients exhibited a greater CAR compared with medicated patients (p = 0.04) with no differences between patient groups and HC. We found a significant effect of group for verbal (p = 0.03) and non-verbal memory (p = 0.04). Unmedicated patients performed worse compared with medicated patients and HC in both memory domains. Medicated patients and HC did not differ. Regression analyses revealed a negative association between CAR and memory function in depressed patients, but not in HC.
While in unmedicated depressed patients the magnitude of CAR is associated with impaired memory, medicated patients showed a smaller CAR and unimpaired cognitive function compared with HC. Our findings are compatible with the idea that antidepressants reduce CAR and partially restore memory function even if depressive psychopathology is still present.