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The effect of sheared E × B flow on the blob dynamics in the scrape-off layer (SOL) of HL-2A tokamak has been studied during the plasma current ramp-up in ohmically heated deuterium plasmas by the combination of poloidal and radial Langmuir probe arrays. The experimental results indicate that the SOL sheared E × B flow is substantially enhanced as the plasma current exceeds a certain value and the strong sheared E × B flow has the ability to slow the blob radial motion via stretching its poloidal correlation length. The locally accumulated blobs are suggested to be responsible for the increase of plasma density just outside the Last Closed Flux Surface (LCFS) observed in this experiment. The results presented here reveal the significant role played by the strong sheared E × B flow on the blob dynamics, which provides a potential method to control the SOL width by modifying the sheared E × B flow in future tokamak plasmas.
Although aberrant brain regional responses are reported in social anxiety disorder (SAD), little is known about resting-state functional connectivity at the macroscale network level. This study aims to identify functional network abnormalities using a multivariate data-driven method in a relatively large and homogenous sample of SAD patients, and assess their potential diagnostic value.
Forty-six SAD patients and 52 demographically-matched healthy controls (HC) were recruited to undergo clinical evaluation and resting-state functional MRI scanning. We used group independent component analysis to characterize the functional architecture of brain resting-state networks (RSNs) and investigate between-group differences in intra-/inter-network functional network connectivity (FNC). Furtherly, we explored the associations of FNC abnormalities with clinical characteristics, and assessed their ability to discriminate SAD from HC using support vector machine analyses.
SAD patients showed widespread intra-network FNC abnormalities in the default mode network, the subcortical network and the perceptual system (i.e. sensorimotor, auditory and visual networks), and large-scale inter-network FNC abnormalities among those high-order and primary RSNs. Some aberrant FNC signatures were correlated to disease severity and duration, suggesting pathophysiological relevance. Furthermore, intrinsic FNC anomalies allowed individual classification of SAD v. HC with significant accuracy, indicating potential diagnostic efficacy.
SAD patients show distinct patterns of functional synchronization abnormalities both within and across large-scale RSNs, reflecting or causing a network imbalance of bottom-up response and top-down regulation in cognitive, emotional and sensory domains. Therefore, this could offer insights into the neurofunctional substrates of SAD.
Morbidity and mortality from coronavirus disease 2019 (COVID-19) have been significant among elderly residents of residential aged-care services (RACS). To prevent incursions of COVID-19 in RACS in Australia, visitors were banned and aged-care workers were encouraged to work at a single site. We conducted a review of case notes and a social network analysis to understand how workplace and social networks enabled the spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) among RACS.
Retrospective outbreak review.
Setting and participants:
Staff involved in COVID-19 outbreaks in RACS in Victoria, Australia, May–October 2020.
The Victorian Department of Health COVID-19 case and contact data were reviewed to construct 2 social networks: (1) a work network connecting RACS through workers and (2) a household network connecting to RACS through households. Probable index cases were reviewed to estimate the number and size (number of resident cases and deaths) of outbreaks likely initiated by multisite work versus transmission via households.
Among 2,033 cases linked to an outbreak as staff, 91 (4.5%) were multisite staff cases. Forty-three outbreaks were attributed to multisite work and 35 were deemed potentially preventable had staff worked at a single site. In addition, 99 staff cases were linked to another RACS outbreak through their household contacts, and 21 outbreaks were attributed to staff–household transmission.
Limiting worker mobility through single-site policies could reduce the chances of SARS-CoV-2 spreading from one RACS to another. However, initiatives that reduce the chance of transmission via household networks would also be needed.
The corticotropin-releasing hormone receptor 2 (CRHR2) gene encodes CRHR2, which is an important element in the hypothalamic-pituitary-adrenal physiologic response towards stress culminating in hyperglycemia, insulin resistance, mood disorders and depression (MDD). CRHR2-/- mice are hypersensitive to stress, and the CRHR2 locus in humans has been linked to type 2 diabetes (T2D) and MDD.
Several variants in the CRHR2 gene have been reported in patients with bipolar disorder, post-traumatic stress disorder, and T2D, but variants in the gene have not been investigated in families with T2D and MDD.
We genotyped 212 Italian families with T2D and MDD. We tested 17 SNPs in the CRHR2 gene using two-point parametric-linkage and linkage-disequilibrium (LD) analysis with the following models: dominant with complete-penetrance (D1), dominant with incomplete-penetrance (D2), recessive with complete-penetrance (R1) and recessive with incomplete-penetrance (R2).
We detected linkage to and/or LD with: MDD for 3 SNPs/D1, 2 SNPs/D2, 3 SNPs/R1, and 3 SNPs/R2; and, T2D for 3 SNPs/D1, 2 SNPs/D2, 2 SNPs/R1 and 1 SNP/R2. Two independent SNPs were comorbid. Interestingly, the variants linked to or in LD with MDD had in general higher statistical significance level than the variants linked to T2D, despite that the families were primarily ascertained for T2D.
Our study shows for the first time that the CRHR2 gene which encodes CRHR2 is in linkage to and linkage disequilibrium with MDD and T2D, thereby contributing, in families with T2D, to both disorders and underlying the shared genetic pathogenesis of their comorbidity
Despite theoretical accounts asserting the importance of children for the wellbeing of individuals as they age, research evidence suggests that children may be inconsequential when it comes to loneliness. Yet, there is reason to expect some subgroups may be more vulnerable to the impact of childlessness than others and this may also differ depending on the type of loneliness being assessed. This paper addresses the relationship between childlessness and social and emotional loneliness in middle and later life, including differential vulnerability associated with age, gender and marital/partner status. The study drew on data from three waves (2007, 2012 and 2018) of the Canadian General Social Survey for a nationally representative sample of adults aged 45 and older (N = 49,892). In general, childlessness assumed greater importance with regard to social than emotional loneliness. Women reported lower levels of social loneliness in conjunction with childlessness than men. Further, childlessness was associated with higher levels of overall and social loneliness among older than middle-aged adults. Fewer interactions were evident between marital/partner status and childlessness. Among women specifically, those who were co-habiting, separated/divorced or never married reported lower levels of social loneliness than their married counterparts. In contrast, childlessness was linked to greater emotional loneliness only among separated/divorced men and widowed women. Overall, our results suggest that having children available does matter for feelings of loneliness in middle and later life but that the relationship varies and is contingent on the social contexts (age, gender, marital/partner status) and the type of loneliness (social, emotional) involved.
Emotional dysregulation (ED) is a common characteristic of both attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD), especially in adolescents. However, whether ADHD and MDD may share the specific ED-related neural networks remains unknown.
In total, 43 adolescents with clinical ED (22 adolescents with ADHD and 21 with MDD) were recruited; in addition, 29 sex- and age-matched healthy controls (HCs) were included. Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient. In addition, we determined the significant regions of interest in patients with ED due to ADHD and MDD as compared with HCs and tested their correlations with clinical rating scale scores.
Compared with HCs, patients with ED had greater RSFC in the cerebellum and supramarginal gyrus (SMG), especially between vermis VI and the SMG in the attention networks, and lower RSFC between the right supplementary motor area and right lateral parietal area. Lower gray matter (GM) volume in the SMG was also found. RSFC was significantly correlated with clinical rating scale scores for all patients with ED due to ADHD or MDD. GM change was correlated with ED and MDD rating scale scores.
The cerebellum and attention networks might play major roles in ED pathophysiology in adolescents with ADHD and MDD. Increased connectivity of the vermis to the SMG serves as a possible underlying neural network.
Late blight, caused by the oomycete Phytophthora infestans, poses a significant challenge to organic tomato and potato production systems across the globe. To enhance education and outreach programming pertaining to tomato organic late blight management in Wisconsin, we sought to identify grower strategies and needs through an online survey conducted during spring 2018. Our findings demonstrated that organic growers emphasized crop diversity, crop rotation and soil health in their late blight management decisions. Grower concerns about biopesticides were identified and suggest that the use of input-based products within integrated management programs could be enhanced by further research on effectiveness and modes of actions. Additionally, stronger emphasis on oomycete pathogen biology and the significance of late blight as a community disease were identified as important areas of emphasis in the development of organic disease management education programming and resources that promote more effective cultural and chemical disease management strategies that adhere to the regulation and principles underlying the USDA National Organic Program. The integration of a live polling questionnaire conducted in winter 2019 allowed us to corroborate findings from the online survey and underscored the importance of two-way learning to enhance outreach efforts between Extension and organic growers in Wisconsin and the surrounding upper Midwestern states.
Background: In ALS, determining whether individuals have a substantial response to therapy is a challenge for the field. ALS naturally progresses at variable rates and a personalized approach is required to determine if individuals have a substantial response. A new method to evaluate individual response is proposed and applied to data from the CENTAUR trial of sodium phenylbutyrate/ursodoxicoltaurine (PB/TURSO). Methods: In a post hoc analysis, CENTAUR participants whose actual rate of change from baseline in the ALSFRS-R at week 18 was ≤ their own trial baseline progression rate (ΔFS) were defined as having a substantial individual response in slowing ALS progression. Results: Substantial individual response was observed in a greater proportion of participants receiving PB/TURSO (41%, n=87) vs placebo (19%, n=48; P=0.0076). Conclusions: Response versus ΔFS provides a personalized metric to determine substantial individual response in ALS. ΔFS has been shown to be highly correlated with, but to proportionally underestimate, ALSFRS-R decline in clinical trials. Consequently, those who outperform the ΔFS may be considered to have a substantial individual response. Application to CENTAUR data demonstrates a greater proportion of participants with a substantial individual response in the PB/TURSO arm. These methods may enable greater personalization and analysis of individual response in ALS.
Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04–0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94–2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.
Host density is a key regulatory factor in parasite transmission. The goldfish (Carassius auratus)-Gyrodactylus kobayashii model was used to investigate effects of host density on population growth of gyrodactylids. A donor fish infected by five gravid gyrodactylids was mixed with 11 parasite-free goldfish at five host densities. There was a significant positive correlation between host density and mean abundance of G. kobayashii throughout the 58-day experiment. During early infection (days 15–24), mean abundance in medium high (0.5 fish L−1) and high host density groups (1 and 2 fish L−1) was significantly higher than that in the low host density groups (0.125 and 0.25 fish L−1). At high host density, prevalence increased more rapidly, and the peak prevalence was higher. Fitting of an exponential growth model showed that the population growth rate of the parasite increased with host density. A hypothesis was proposed that higher host density contributed to increased reinfection of detached gyrodactylids. A reinfection experiment was designed to test this hypothesis. Both mean abundance and prevalence at a host density of 1 fish L−1 were significantly higher than those at 0.25 fish L−1 on days 1 and 3, which suggested that more reinfections of G. kobyashii occurred at the higher host density. Density-dependent transmission during the early infection was an important contributor of population growth of G. kobayashii, as well as density-dependent reinfection of the detached gyrodactylids.
The incidence of scarlet fever has increased dramatically in recent years in Chongqing, China, but there has no effective method to forecast it. This study aimed to develop a forecasting model of the incidence of scarlet fever using a seasonal autoregressive integrated moving average (SARIMA) model. Monthly scarlet fever data between 2011 and 2019 in Chongqing, China were retrieved from the Notifiable Infectious Disease Surveillance System. From 2011 to 2019, a total of 5073 scarlet fever cases were reported in Chongqing, the male-to-female ratio was 1.44:1, children aged 3–9 years old accounted for 81.86% of the cases, while 42.70 and 42.58% of the reported cases were students and kindergarten children, respectively. The data from 2011 to 2018 were used to fit a SARIMA model and data in 2019 were used to validate the model. The normalised Bayesian information criterion (BIC), the coefficient of determination (R2) and the root mean squared error (RMSE) were used to evaluate the goodness-of-fit of the fitted model. The optimal SARIMA model was identified as (3, 1, 3) (3, 1, 0)12. The RMSE and mean absolute per cent error (MAPE) were used to assess the accuracy of the model. The RMSE and MAPE of the predicted values were 19.40 and 0.25 respectively, indicating that the predicted values matched the observed values reasonably well. Taken together, the SARIMA model could be employed to forecast scarlet fever incidence trend, providing support for scarlet fever control and prevention.
For a common micro-satellite, orbiting in a circular sun-synchronous orbit (SSO) at an altitude between 500 and 600km, the satellite attitude during off-nadir imaging and staring-imaging operations can be up to ±45 degree on roll and pitch angles. During these off-nadir pointing for both multi-trip operation and staring imaging operations, the spacecraft body is commonly subject to high-rate motion. This posts challenges for a spacecraft attitude determination subsystem called Gyro Stellar Inertial Attitude Estimate (GS IAE), which employs gyros and star sensors to maintain the required attitude knowledge, since star trackers will severely degrade attitude estimation accuracies when the spacecraft is subject to high-rate motion. This paper analyses the star motion-induced errors for a typical star tracker, models the star motion-induced errors to assess the performance impact on the attitude estimation accuracy, and investigates the adaptive extended Kalman filter design in the GS IAE while evaluating its effectiveness.
OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 Î¼g/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 Î¼m thick sagittal sections from each joint, 50 Î¼m apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
The relationships among depression, personality factors, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Presence of neuroticism worsens cognitive decline in depressed older adults. Yet little is known about changes in neuroticism among older adults being treated for depression and the impact of these changes on cognitive decline.
Longitudinal observational study.
Academic Health Center.
We examined 68 participants in the neurobiology of late-life depression (LLD) study to test the hypothesis that older depressed subjects with more improvement in neuroticism would experience less cognitive decline compared with those with less change in neuroticism.
We measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery–Åsberg depression rating scale (MADRS). Global cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer’s disease (CERAD) battery at baseline and annually over 3 years. Regression models of 1-year change in neuroticism and 3-year change in CERAD included sex, age, race, education, and 1-year change in MADRS score as covariates.
We found that among older adults, 1-year change in neuroticism was inversely associated with 3-year change in CERAD total score.
Our findings challenge the notion of longitudinal stability of measures of personality, especially among older depressed individuals. They highlight the importance of repeated personality assessment, especially of neuroticism, in the management of LLD. Future studies in larger samples followed for longer periods are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.
Accurate geometrical calibration between the scan coordinates and the camera coordinates is critical in four-dimensional scanning transmission electron microscopy (4D-STEM) for both quantitative imaging and ptychographic reconstructions. For atomic-resolved, in-focus 4D-STEM datasets, we propose a hybrid method incorporating two sub-routines, namely a J-matrix method and a Fourier method, which can calibrate the uniform affine transformation between the scan-camera coordinates using raw data, without a priori knowledge of the crystal structure of the specimen. The hybrid method is found robust against scan distortions and residual probe aberrations. It is also effective even when defects are present in the specimen, or the specimen becomes relatively thick. We will demonstrate that a successful geometrical calibration with the hybrid method will lead to a more reliable recovery of both the specimen and the electron probe in a ptychographic reconstruction. We will also show that, although the elimination of local scan position errors still requires an iterative approach, the rate of convergence can be improved, and the residual errors can be further reduced if the hybrid method can be firstly applied for initial calibration. The code is made available as a simple-to-use tool to correct affine transformations of the scan-camera coordinates in 4D-STEM experiments.