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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.
The fossil record is notoriously imperfect and biased in representation, hindering our ability to place fossil specimens into an evolutionary context. For groups with fossil records mostly consisting of disarticulated parts (e.g., vertebrates, echinoderms, plants), the limited morphological information preserved sparks concerns about whether fossils retain reliable evidence of phylogenetic relationships and lends uncertainty to analyses of diversification, paleobiogeography, and biostratigraphy in Earth's history. To address whether a fragmentary past can be trusted, we need to assess whether incompleteness affects the quality of phylogenetic information contained in fossil data. Herein, we characterize skeletal incompleteness bias in a large dataset (6585 specimens; 14,417 skeletal elements) of fossil squamates (lizards, snakes, amphisbaenians, and mosasaurs). We show that jaws + palatal bones, vertebrae, and ribs appear more frequently in the fossil record than other parts of the skeleton. This incomplete anatomical representation in the fossil record is biased against regions of the skeleton that contain the majority of morphological phylogenetic characters used to assess squamate evolutionary relationships. Despite this bias, parsimony- and model-based comparative analyses indicate that the most frequently occurring parts of the skeleton in the fossil record retain similar levels of phylogenetic signal as parts of the skeleton that are rarer. These results demonstrate that the biased squamate fossil record contains reliable phylogenetic information and support our ability to place incomplete fossils in the tree of life.
Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.
Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear.
To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS).
The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22–1.45; p = 5.03 × 10−11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25–1.37; p = 6.88 × 10−31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23–1.40; p = 1.42 × 10−16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03–1.10, p = 7.85 × 10−4 for PTSD; OR = 1.37, 95% CI 1.14–1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed.
Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.
We report on experimental observation of non-laminar proton acceleration modulated by a strong magnetic field in laser irradiating micrometer aluminum targets. The results illustrate the coexistence of ring-like and filamentation structures. We implement the knife edge method into the radiochromic film detector to map the accelerated beams, measuring a source size of 30–110 μm for protons of more than 5 MeV. The diagnosis reveals that the ring-like profile originates from low-energy protons far off the axis whereas the filamentation is from the near-axis high-energy protons, exhibiting non-laminar features. Particle-in-cell simulations reproduced the experimental results, showing that the short-term magnetic turbulence via Weibel instability and the long-term quasi-static annular magnetic field by the streaming electric current account for the measured beam profile. Our work provides direct mapping of laser-driven proton sources in the space-energy domain and reveals the non-laminar beam evolution at featured time scales.
Our study was conducted to assess the sepsis-associated hospitalisations and antimicrobials prescribed for sepsis inpatients in Hong Kong. Demographic, diagnostic and antimicrobial prescription data were analysed for patients admitted to public hospitals with a diagnosis of septicaemia from 2000 to 2015. A total of 223 250 sepsis hospitalisations were recorded in Hong Kong from 2000 to 2015 during which the hospitalisation rate increased by 85.6%. The majority of the sepsis hospitalisations occurred in adults ≥65 years and children aged 0–4 years. Adults with a secondary diagnosis of sepsis were often admitted with a primary diagnosis of urological conditions or pneumonia; whereas diabetes mellitus was the most common secondary diagnosis among those with primary sepsis. Paediatric sepsis patients aged 0–4 years were often diagnosed with disorders relating to short gestation and low birthweight. Antimicrobial prescriptions increased by 51.1% and 34.4% for primary and secondary sepsis patients, respectively. β-Lactam and β-lactamase inhibitor combinations were the most used antibiotics whereas the usage of carbapenems increased more than 10 times over the study period. A substantial burden of hospitalisations was attributable to sepsis in Hong Kong, particularly in the extremes of age. Broad-spectrum and last-resort antibiotics had been increasingly dispensed for sepsis inpatients.