Higher-order dimensions of psychopathology in a neurodevelopmental transdiagnostic sample.

Funder: Brain Sciences Unit University of CambridgeHierarchical dimensional models of psychopathology derived for adult and child community populations offer more informative and efficient methods for assessing and treating symptoms of mental ill health than traditional diagnostic approaches. It is not yet clear how many dimensions should be included in models for youth with neurodevelopmental conditions. The aim of this study was to delineate the hierarchical dimensional structure of psychopathology in a transdiagnostic sample of children and adolescents with learning-related problems, and to test the concurrent predictive value of the model for clinically, socially, and educationally relevant outcomes. A sample of N = 403 participants from the Centre for Attention Learning and Memory (CALM) cohort were included. Hierarchical factor analysis delineated dimensions of psychopathology from ratings on the Conner's Parent Rating Short Form, the Revised Children's Anxiety and Depression Scale, and the Strengths and Difficulties Questionnaire. A hierarchical structure with a general p factor at the apex, broad internalizing and broad externalizing spectra below, and three more specific factors (specific internalizing, social maladjustment, and neurodevelopmental) emerged. The p factor predicted all concurrently measured social, clinical, and educational outcomes, but the other dimensions provided incremental predictive value. The neurodevelopmental dimension, which captured symptoms of inattention, hyperactivity, and executive function and emerged from the higher-order externalizing factor, was the strongest predictor of learning. This suggests that in struggling learners, cognitive and affective behaviors may interact to influence learning outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Roles of hCG in Advancing Follicular Growth to Ovulation after Concurrent Injections of PGF2α and GnRH in Postpubertal Holstein Heifers Bearing a CL

A study was conducted to test the hypothesis that injecting Gonadotropin-releasing hormone (GnRH) concurrently with Prostaglandin F2 alpha (PGF2α) followed by an injection of human Chorionic Gonadotropin (hCG), would advance follicular growth to ovulation in Holstein heifers bearing a corpus luteum (CL). After manual examination of the CL, group 1 (PGF; n = 12) received an injection of PGF2α (25 mg, im). Group 2 (PGF + GnRH; n = 13) received an injection of GnRH (100 μg, im) immediately after an injection of PGF2α. Group 3 (PGF + GnRH + hCG; n = 12) received concurrent injections of PGF2α and GnRH followed with hCG (1500 IU, im) two days later. Follicular size and day of ovulation were monitored by daily ultrasonographic examination from days 1 to 10. Blood was collected on days-7, 0 (PGF2α administration), 2, and 7. Progesterone was not different (P > .05) on days-7, 0, and 2 between the experimental groups. However, it was higher (P < .005) in the PGF + GnRH + hCG group on day 7 compared to PGF + GnRH heifers, but not significantly higher than the PGF. Additionally, heifers in the PGF + GnRH + hCG group ovulated earlier (P < .05) than heifers in the PGF + GnRH and the PGF group. This data indicates that hCG advances follicular growth to ovulation in spite of high levels of progesterone when injected 48 h after concurrent treatments of GnRH and PGF2α on heifers bearing a CL

Hydra: software for tailored processing of H/D exchange data from MS or tandem MS analyses

<p>Abstract</p> <p>Background</p> <p>Hydrogen/deuterium exchange mass spectrometry (H/DX-MS) experiments implemented to characterize protein interaction and protein folding generate large quantities of data. Organizing, processing and visualizing data requires an automated solution, particularly when accommodating new tandem mass spectrometry modes for H/DX measurement. We sought to develop software that offers flexibility in defining workflows so as to support exploratory treatments of H/DX-MS data, with a particular focus on the analysis of very large protein systems and the mining of tandem mass spectrometry data.</p> <p>Results</p> <p>We present a software package ("Hydra") that supports both traditional and exploratory treatments of H/DX-MS data. Hydra's software architecture tolerates flexible data analysis procedures by allowing the addition of new algorithms without significant change to the underlying code base. Convenient user interfaces ease the organization of raw data files and input of peptide data. After executing a user-defined workflow, extracted deuterium incorporation values can be visualized in tabular and graphical formats. Hydra also automates the extraction and visualization of deuterium distribution values. Manual validation and assessment of results is aided by an interface that aligns extracted ion chromatograms and mass spectra, while providing a means of rapidly reprocessing the data following manual adjustment. A unique feature of Hydra is the automated processing of tandem mass spectrometry data, demonstrated on a large test data set in which 40,000 deuterium incorporation values were extracted from replicate analysis of approximately 1000 fragment ions in one hour using a typical PC.</p> <p>Conclusion</p> <p>The customizable workflows and user-friendly interfaces of Hydra removes a significant bottleneck in processing and visualizing H/DX-MS data and helps the researcher spend more time executing new experiments and interpreting results. This increased efficiency will encourage the analysis of larger protein systems. The ability to accommodate the tandem MS dimension supports alternative data collection and analysis strategies, as well as higher resolution localization of deuteration where permitted by the fragmentation mechanism.</p

Positioning the Root Elongation Zone Is Saltatory and Receives Input from the Shoot

In the root, meristem and elongation zone lengths remain stable, despite growth and division of cells. To gain insight into zone stability, we imaged individual Arabidopsis thaliana roots through a horizontal microscope, and used image analysis to obtain velocity profiles. For a root, velocity profiles obtained every 5 min over 3 h coincided closely, implying that zonation is regulated tightly. However, the position of the elongation zone saltated, by on average 17 μm every 5 min. Saltation was apparently driven by material elements growing faster and then slower, while moving through the growth zone. When the shoot was excised, after about 90 minutes, growth zone dynamics resembled those of intact roots, except that the position of the elongation zone moved, on average, rootward, by several hundred microns in 24 h. We hypothesize that mechanisms determining elongation zone position receive input from the shoot

Invasive cutaneous rhizopus infections in an immunocompromised patient population associated with hospital laundry carts

Mucormycosis is an invasive fungal infection with high morbidity and mortality that most commonly occurs in immunocompromised hosts.1–5 Cutaneous mucormycosis is rare and can be acquired through direct contact of the fungi with non-intact skin or mucous membranes.3,4,7–9 Outbreaks of mucormycosis associated with contaminated adhesive bandages, ostomy supplies, wooden tongue depressors, and linen have been published.1,6–9 This is a report of a cluster of cutaneous mucormycosis with Rhizopus that occurred in 4 immunocompromised inpatients housed primarily in the same intensive care unit (ICU) prior to infection

Discovering the Data of Safety: Embry-Riddle’s Aviation Safety and Security Archives

The path to the sky and beyond has not been simple or obstacle-free, but dedicated dreamers have worked to overcome obstacles, learn from mishaps, and develop new technologies to achieve their goals. As the leading university for aviation and aerospace education, Embry-Riddle Aeronautical University maintains a firm commitment to the practice and study of safety. As part of this mission, the university has established the Aviation Safety and Security Archives (ASASA) which is a national treasure of aviation safety history and information

Face valid phenotypes in a mouse model of the most common mutation in EEF1A2 related neurodevelopmental disorder, E122K

De novo heterozygous missense mutations in EEF1A2, encoding neuromuscular translation-elongation factor eEF1A2, are associated with developmental and epileptic encephalopathies. We used CRISPR/Cas9 to recapitulate the most common mutation, E122K, in mice. Although E122K heterozygotes were not observed to have convulsive seizures, they exhibited frequent electrographic seizures and EEG abnormalities, transient early motor deficits and growth defects. Both E122K homozygotes and Eef1a2-null mice developed progressive motor abnormalities, with E122K homozygotes reaching humane endpoints by P31. The null phenotype is driven by progressive spinal neurodegeneration; however, no signs of neurodegeneration were observed in E122K homozygotes. The E122K protein was relatively stable in neurons yet highly unstable in skeletal myocytes, suggesting that the E122K/E122K phenotype is instead driven by loss of function in muscle. Nevertheless, motor abnormalities emerged far earlier in E122K homozygotes than in nulls, suggesting a toxic gain of function and/or a possible dominant-negative effect. This mouse model represents the first animal model of an EEF1A2 missense mutation with face-valid phenotypes and has provided mechanistic insights needed to inform rational treatment design.</p

Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians