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Early adversity increases risk for child mental health difficulties. Stressors in the home environment (e.g., parental mental illness, household socioeconomic challenges) may be particularly impactful. Attending out-of-home childcare may buffer or magnify negative effects of such exposures. Using a longitudinal observational design, we leveraged data from the NIH Environmental influences on Child Health Outcomes Program to test whether number of hours in childcare, defined as 1) any type of nonparental care and 2) center-based care specifically, was associated with child mental health, including via buffering or magnifying associations between early exposure to psychosocial and socioeconomic risks (age 0–3 years) and later internalizing and externalizing symptoms (age 3–5.5 years), in a diverse sample of N = 2,024 parent–child dyads. In linear regression models, childcare participation was not associated with mental health outcomes, nor did we observe an impact of childcare attendance on associations between risk exposures and symptoms. Psychosocial and socioeconomic risks had interactive effects on internalizing and externalizing symptoms. Overall, the findings did not indicate that childcare attendance positively or negatively influenced child mental health and suggested that psychosocial and socioeconomic adversity may need to be considered as separate exposures to understand child mental health risk in early life.
The Magellanic Stream (MS), a tail of diffuse gas formed from tidal and ram pressure interactions between the Small and Large Magellanic Clouds (SMC and LMC) and the Halo of the Milky Way, is primarily composed of neutral atomic hydrogen (HI). The deficiency of dust and the diffuse nature of the present gas make molecular formation rare and difficult, but if present, could lead to regions potentially suitable for star formation, thereby allowing us to probe conditions of star formation similar to those at high redshifts. We search for $\text{HCO}^{+}$, HCN, HNC, and C$_2$H using the highest sensitivity observations of molecular absorption data from the Atacama Large Millimeter Array (ALMA) to trace these regions, comparing with HI archival data from the Galactic Arecibo L-Band Feed Array (GALFA) HI Survey and the Galactic All Sky Survey (GASS) to compare these environments in the MS to the HI column density threshold for molecular formation in the Milky Way. We also compare the line of sight locations with confirmed locations of stars, molecular hydrogen, and OI detections, though at higher sensitivities than the observations presented here.
We find no detections to a 3$\sigma$ significance, despite four sightlines having column densities surpassing the threshold for molecular formation in the diffuse regions of the Milky Way. Here we present our calculations for the upper limits of the column densities of each of these molecular absorption lines, ranging from $3 \times 10^{10}$ to $1 \times 10^{13}$ cm$^{-2}$. The non-detection of $\text{HCO}^{+}$ suggests that at least one of the following is true: (i) $X_{\text{HCO}^{+}{}, \mathrm{MS}}$ is significantly lower than the Milky Way value; (ii) that the widespread diffuse molecular gas observed by Rybarczyk (2022b, ApJ, 928, 79) in the Milky Way’s diffuse interstellar medium (ISM) does not have a direct analogue in the MS; (iii) the HI-to-$\text{H}_{2}$ transition occurs in the MS at a higher surface density in the MS than in the LMC or SMC; or (iv) molecular gas exists in the MS, but only in small, dense clumps.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Irritability and anxiety frequently co-occur in pediatric populations. Studies separately looking at the neural correlates of these symptoms have identified engagement of similar neural systems – particularly those implicated in emotional processing. Both irritability and anxiety can be considered negative valence emotional states that might relate to emotion dysregulation. However, previous work has not examined the neural responding during the performance of an emotion regulation task as a function of interaction between irritability and anxiety simultaneously.
Methods
This fMRI study involved 155 participants (90 with significant psychopathologies and 92 male) who performed the Affective Stroop Task, designed to engage emotion regulation as a function of task demands. The Affective Reactivity Index (ARI) was used to index irritability and the Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to index anxiety.
Results
Levels of irritability, but not anxiety, was positively correlated with responses to visual images within the right rostro-medial prefrontal cortex and left anterior cingulate cortex during view trials. The second region of ventral anterior cingulate cortex showed a condition-by-emotion-by-ARI score-by-SCARED score interaction. Specifically, anxiety level was significantly correlated with a decreased differential BOLD response to negative relative to neutral view trials but only in the presence of relatively high irritability.
Conclusions
Atypical maintenance of emotional stimuli within the rostro-medial prefrontal cortex may exacerbate the difficulties faced by adolescents with irritability. Moreover, increased anxiety combined with significant irritability may disrupt an automatic emotional conflict-based form of emotion regulation that is particularly associated with the ventral anterior cingulate cortex.
As the primary risk factor for cardiovascular disease (CVD), hypertension is the leading cause of preventable, premature mortality globally. Hypertension, or elevated blood pressure (BP), has a number of well-established risk factors, including genetics. A common C677T polymorphism in the gene encoding the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) affects 10–12% of UK and Irish populations and has been linked with 24–87% increased risk of hypertension globally. Evidence from randomised controlled trials (RCTs) conducted at this Centre has shown BP to be highly responsive (by 5–13 mmHg) to supplementation with riboflavin (MTHFR co-factor), an effect confined to homozygous individuals (TT genotype). To date, our trials have focused on peripheral BP; however, additional measures of vascular health such as central pressure are reported to be more closely correlated with CVD risk. Investigation of central BP, augmentation index (AIx) and pulse pressure amplification (PPA) may thus offer further insight into the role of this gene-nutrient interaction in blood pressure. The present study aims to investigate BP, and measures of vascular health in healthy adults stratified by MTHFR 677 genotype. Apparently healthy adults aged 18–60 years were recruited from workplaces across Northern Ireland and screened for MTHFR genotype via buccal swab. Clinic BP, anthropometry and blood sample were measured in TT individuals (n 209) and age and sex-matched CC (n 98) and CT (n 102) controls. AIx and central BP were assessed using SphygmoCor® (AtCor Medical, Australia). Preliminary results demonstrate higher BP in individuals with the MTHFR 677TT genotype compared to non-TT controls (systolic BP 134.7 ± 13.8 mmHg vs 129.7 ± 12.4 mmHg, P < 0.001; diastolic BP 81.6 ± 9.5 mmHg vs 79.7 mmHg ± 8.9 mmHg, P = 0.023, respectively). The MTHFR 677TT genotype group had significantly higher central systolic BP (119.4 ± 11.8 vs 116.7 ± 10.9 mmHg, P = 0.018), central pulse pressure (P = 0.006) and central mean pressure (P = 0.011) compared to the non-TT group. No significant differences for central diastolic BP, pulse pressure amplification, pulse pressure ratio and augmentation index were observed. This study confirms the phenotype of elevated BP in individuals with the C677T polymorphism in the gene encoding MTHFR. For the first time, this study reports that individuals with the MTHFR 677TT genotype have higher central systolic BP, central mean pressure and pulse pressure. Further investigations through RCTs investigating the effect of the MTHFR cofactor, riboflavin, on central blood pressure in these genetically at-risk adults are warranted.
Gut microbiota data obtained by DNA sequencing are not only complex because of the number of taxa that may be detected within human cohorts, but also compositional because characteristics of the microbiota are described in relative terms (e.g., “relative abundance” of particular bacterial taxa expressed as a proportion of the total abundance of taxa). Nutrition researchers often use standard principal component analysis (PCA) to derive dietary patterns from complex food data, enabling each participant's diet to be described in terms of the extent to which it fits their cohort's dietary patterns. However, compositional PCA methods are not commonly used to describe patterns of microbiota in the way that dietary patterns are used to describe diets. This approach would be useful for identifying microbiota patterns that are associated with diet and body composition. The aim of this study is to use compositional PCA to describe gut microbiota profiles in 5 year old children and explore associations between microbiota profiles, diet, body mass index (BMI) z-score, and fat mass index (FMI) z-score. This study uses a cross-sectional data for 319 children who provided a faecal sample at 5 year of age. Their primary caregiver completed a 123-item quantitative food frequency questionnaire validated for foods of relevance to the gut microbiota. Body composition was determined using dual-energy x-ray absorptiometry, and BMI and FMI z-scores calculated. Compositional PCA identified and described gut microbiota profiles at the genus level, and profiles were examined in relation to diet and body size. Three gut microbiota profiles were found. Profile 1 (positive loadings on Blautia and Bifidobacterium; negative loadings on Bacteroides) was not related to diet or body size. Profile 2 (positive loadings on Bacteroides; negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was associated with a lower BMI z-score (r = -0.16, P = 0.003). Profile 3 (positive loadings on Faecalibacterium, Eubacterium and Roseburia) was associated with higher intakes of fibre (r = 0.15, P = 0.007); total (r = 0.15, P = 0.009), and insoluble (r = 0.13, P = 0.021) non-starch polysaccharides; protein (r = 0.12, P = 0.036); meat (r = 0.15, P = 0.010); and nuts, seeds and legumes (r = 0.11, P = 0.047). Further regression analyses found that profile 2 and profile 3 were independently associated with BMI z-score and diet respectively. We encourage fellow researchers to use compositional PCA as a method for identifying further links between the gut, diet and obesity, and for developing the next generation of research in which the impact on body composition of dietary interventions that modify the gut microbiota is determined.
Alterations in reinforcement-based decision making may be associated with increased psychiatric vulnerability in children who have experienced maltreatment. A probabilistic passive avoidance task and a model-based functional magnetic resonance imaging analytic approach were implemented to assess the neurocomputational components underlying decision making: (a) reinforcement expectancies (the representation of the outcomes associated with a stimulus) and (b) prediction error signaling (the ability to detect the differences between expected and actual outcomes). There were three main findings. First, the maltreated group (n = 18; mean age = 13), relative to nonmaltreated peers (n = 19; mean age = 13), showed decreased activity during expected value processing in a widespread network commonly associated with reinforcement expectancies representation, including the striatum (especially the caudate), the orbitofrontal cortex, and medial temporal structures including the hippocampus and insula. Second, consistent with previously reported hyperresponsiveness to negative cues in the context of childhood abuse, the maltreated group showed increased prediction error signaling in the middle cingulate gyrus, somatosensory cortex, superior temporal gyrus, and thalamus. Third, the maltreated group showed increased activity in frontodorsal regions and in the putamen during expected value representation. These findings suggest that early adverse environments disrupt the development of decision-making processes, which in turn may compromise psychosocial functioning in ways that increase latent vulnerability to psychiatric disorder.
Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder.
Method
Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future.
Results
As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both).
Conclusions
The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.
Field experiments from 1997 to 1999 examined cotton cv. ‘Coker 312’ that was genetically transformed to tolerate glufosinate. None of the glufosinate treatments caused visible injury to the glufosinate-tolerant cotton, but treatments were lethal to nontransformed or nonexpressing cotton. No glufosinate treatment adversely affected plant height at maturity, total number of nodes, bolls per plant, or boll positions. Glufosinate applications of 0.6 kg ha−1 made at eight stages of growth, ranging from cotyledon stage to 50% open boll, did not adversely affect yield or fiber quality as measured by micronaire or fiber length and strength. Sequential glufosinate applications up to four stages of growth from the zero- to one-leaf stage to the 14- to 15-leaf stage or individual glufosinate applications at 3.3 kg ha−1 made at the two- to three-leaf stage of growth also did not adversely affect yield or fiber quality. Overall yields in these studies were low relative to normal Texas Southern High Plains cotton yield because these studies were conducted using a Coker 312 parental line, which is generally a poor performer in this region. This research indicated that the transformation events for glufosinate tolerance in cotton were successful and the glufosinate-tolerance gene was expressed throughout the growing season. Transformation and field testing of other cotton varieties are needed to improve varietal performance on the Texas Southern High Plains.
The foetal mammary gland is sensitive to maternal weight and nutrition during gestation, which could affect offspring milk production. It has previously been shown that ewes born to dams offered maintenance nutrition during pregnancy (day 21 to 140 of gestation) produced greater milk, lactose and CP yields in their first lactation when compared with ewes born to dams offered ad libitum nutrition. In addition, ewes born to heavier dams produced greater milk and lactose yields when compared with ewes born to lighter dams. The objective of this study was to analyse and compare the 5-year lactation performance of the previously mentioned ewes, born to heavy or light dams that were offered maintenance or ad libitum pregnancy nutrition. Ewes were milked once per week, for the first 6 weeks of their lactation, for 5 years. Using milk yield and composition data, accumulated yields were calculated over a 42-day period for each year for milk, milk fat, CP, true protein, casein and lactose using a Legendre orthogonal polynomial model. Over the 5-year period, ewes born to heavy dams produced greater average milk (P=0.04), lactose (P=0.01) and CP (P=0.04) yields than offspring born to light dams. In contrast, over the 5-year period dam nutrition during pregnancy did not affect average (P>0.05) offspring milk yields or composition, but did increase milk and lactose accumulated yield (P=0.03 and 0.01, respectively) in the first lactation. These results indicate that maternal gestational nutrition appears to only affect the first lactational performance of ewe offspring. Neither dam nutrition nor size affected grand-offspring live weight gain to, or live weight at weaning (P>0.05). Combined these data indicate that under the conditions of the present study, manipulating dam weight or nutrition in pregnancy can have some effects of offspring lactational performance, however, these effects are not large enough to alter grand-offspring growth to weaning. Therefore, such manipulations are not a viable management tool for farmers to influence lamb growth to weaning.
Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions?
Method
A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions.
Results
During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions.
Conclusions
These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.
Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)
The Perth Astronomy Research Group (PARG), consisting of members from Curtin University of Technology, Perth Observatory and the University of Western Australia, is in the process of developing an automated supernova search system, using the 61-cm Lowell-Perth reflector, a CCD camera and an 80386-based computer for image analysis. Computer control of the telescope and dome, a liquid-nitrogen-cooled CCD camera, and modified VISTA image analysis software will be completed in late 1990, allowing initial semi-automatic searching of external galaxies, together with CCD photometry of flare stars and newly discovered supernovae. Full-scale automation will be introduced subsequently, in collaboration with the Berkeley group. This paper describes the project, and reports on its current status.
To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10–18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits.
Method
Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data.
Results
Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD.
Conclusions
These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.
The new 1 m f/4 fast-slew Zadko Telescope was installed in June 2008 about 70 km north of Perth, Western Australia. It is the only metre-class optical facility at this southern latitude between the east coast of Australia and South Africa, and can rapidly image optical transients at a longitude not monitored by other similar facilities. We report on first imaging tests of a pilot program of minor planet searches, and Target of Opportunity observations triggered by the Swift satellite. In 12 months, 6 gamma-ray burst afterglows were detected, with estimated magnitudes; two of them, GRB 090205 (z = 4.65) and GRB 090516 (z = 4.11), are among the most distant optical transients imaged by an Australian telescope. Many asteroids were observed in a systematic 3-month search. In September 2009, an automatic telescope control system was installed, which will be used to link the facility to a global robotic telescope network; future targets will include fast optical transients triggered by high-energy satellites, radio transient detections, and LIGO gravitational wave candidate events. We also outline the importance of the facility as a potential tool for education, training, and public outreach.