cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene expression profiling and activation status of signaling pathways in pediatric gliomas and correlation with clinical outcome

1837 Background: Gliomas are the most common central nervous system (CNS) tumor during childhood. About 30% of these tumors are malignant and have a dismal prognosis with only third of patients surviving after aggressive treatment. Very little is known about the molecular basis for malignant progression of pediatric gliomas, which might facilitate targeted therapeutic interventions in the future. The objective of this study was to investigate whether pediatric gliomas that overexpress either epidermal-growth-factor receptor (EGFR) or platelet-derived growth-factor receptor beta (PDGFRβ), as well as their active signaling pathways, were more likely to exhibit aggressive behavior and be associated with worse clinical grade (WHO I-IV) and outcome, with the goal of identifying the most suitable targets for future therapeutic interventions. Methods: High throughput tissue microarrays (TMA) were prepared from tumors from 88 patients seen at CNMC from 1980 to 2004 with a new diagnosis of glioma (22 WHO grade III-IV (HGG), 66 WHO grade I-II (LGG)). Immunohistochemistry was applied to assess the expression levels of phosphorylated-EGFR (p-EGFR), total-EGFR, PDGFRβ, p-AKT, p-MAPK, and p-mTOR. Expression of the targets was evaluated by 3 investigators separately and correlated with clinical data including progression free survival (PFS), overall survival (OS), tumor grade, dissemination, proliferation index and age. Results: 32 out of 88 patients had tumor progression (15 LGG and 17 HGG) median 10 months (range 0-87 months) after diagnosis and 12 of these died (11 HGG, 1 LGG) median 14 months (range 0-42 months) after diagnosis. High expression of EGFR, p-EGFR and PDGFRβ was seen in 78.9%, 47.4% and 78.9% of HGG and 87.3%, 52.6% and 41.7% of LGG respectively. Forty patients with high expression of PDGFRβ had significantly worse OS compared to that of 39 patients with low expression (5 year OS 69.0% and 96.9% respectively, p=0.0084). High expression of EGFR, p-EGFR and their signaling pathways was not associated with worse PFS or OS. High proliferation index (MIB>10%) and disseminated disease at diagnosis correlated with worse clinical outcome for HGG patients. Conclusion: High expression of PDGFRβ was significantly associated with lower overall survival in 88 pediatric glioma patients, primarily due to worse OS of patients with malignant histology and high PDGFRβ expression compared to patients with malignant histology and low PDGFRβ expression. Our results suggest that an approach to stratify pediatric glioma patients upfront for targeted PDGFR-kinase inhibitor therapy may be warranted. Furthermore, high expression of EGFR and its active signaling pathways was not shown to be a significant biological marker for predicting adverse clinical outcome in either low-grade or high-grade pediatric gliomas.
Alternative (un)stable states in a stochastic predator–prey model

Abstract Stochastic models sometimes behave qualitatively differently from their deterministic analogues. We explore the implications of this in ecosystems that shift suddenly from one state to another. This phenomenon is usually studied through deterministic models with multiple stable equilibria under a single set of conditions, with stability defined through linear stability analysis. However, in stochastic systems, some unstable states can trap stochastic dynamics for long intervals, essentially masquerading as additional stable states. Using a predator–prey model, we demonstrate that this effect is sufficient to make a stochastic system with one stable state exhibit the same characteristics as an analogous system with alternative stable states. Although this result is surprising with respect to how stability is defined by standard analyses, we show that it is well-anticipated by an alternative approach based on the system's “quasi-potential.” Broadly, understanding the risk of sudden state shifts will require a more holistic understanding of stability in stochastic systems.
When sensing is gambling: An experimental system reveals how plasticity can generate tunable bet-hedging strategies.

Genotypes can persist in unpredictable environments by ‘hedging their bets’ and producing diverse phenotypes. Theoretical studies have shown that the phenotypic variability needed for a bet-hedging strategy can be generated by factors either inside or outside an organism. However, sensing the environment and bet hedging are frequently treated as distinct evolutionary strategies. Furthermore, nearly all empirical studies of the molecular underpinnings of bet-hedging strategies to date have focused on internal sources of variability. We took a synthetic approach and constructed an experimental system where a phenotypic trade-off is mediated by actively sensing a cue present in the environment. We show that active sensing can generate a diversified bet-hedging strategy. Mutations affecting the norm of reaction to the cue alter the diversification strategy, indicating that bet hedging by active sensing is evolvable. Our results indicate that a broader class of biological systems should be considered as potential examples of bet-hedging strategies, and that research into the structure of environmental variability is needed to distinguish bet-hedging strategies from adaptive plasticity. This article is protected by copyright. All rights reserved
MAPK3/1 Participates in the Activation of Primordial Follicles through mTORC1-KITL Signaling.

The majority of ovarian primordial follicles are preserved in a dormant state to maintain the female reproductive lifespan, and only a few primordial follicles are activated to enter the growing follicle pool in each wave. Recent studies have shown that primordial follicular activation depends on mammalian target of rapamycin complex 1 (mTORC1)-KIT ligand (KITL) signaling in pre-granulosa cells and its receptor (KIT)-phosphoinositol 3 kinase (PI3K) signaling in oocytes. However, the upstream regulator of mTORC1 signaling is unclear. The results of the present study showed that the phosphorylated mitogen-activated protein kinase3/1 (MAPK3/1) protein is expressed in some primordial follicles and all growing follicles. Culture of 3 days post-parturition (dpp) ovaries with the MAPK3/1 signaling inhibitor U0126 significantly reduced the number of activated follicles and was accompanied by dramatically reduced granulosa cell proliferation and increased oocyte apoptosis. Western blot and immunofluorescence analyses showed that U0126 significantly decreased the phosphorylation levels of Tsc2, S6K1, and rpS6 and the expression of KITL, indicating that U0126 inhibits mTORC1-KITL signaling. Furthermore, U0126 decreased the phosphorylation levels of Akt, resulting in a decreased number of oocytes with Foxo3 nuclear export. To further investigate MAPK3/1 signaling in primordial follicle activation, we used phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor bpV(HOpic) to promote primordial follicle activation. In this model, U0126 also inhibited the activation of primordial follicles and mTORC1 signaling. Thus, these results suggest that MAPK3/1 participates in primordial follicle activation through mTORC1-KITL signaling.
Suppression Effectiveness of Aerosols: The Effect of Size and Flame Type

This paper summarizes efforts to identify properties of aerosols (liquids and solids) leading to effective fire suppression. It is part of the US Department of Defense’s Next Generation Fire Suppression Technology Program (NGP) supported by the DoD Strategic Environmental Research and Development Program (SERDP) for identifying suitable replacements for Halon 1301. The number of gas-phase compounds that meet the now stringent list of requirements for suitable replacements is not very large, but there are several condensed phase compounds that offer good fire protection including water and alkali and transition metal compounds. However efficient implementation of liquid or powder aerosol systems is hampered by the lack of a suitable technical database on their fire suppression behavior. Although it is known that size is an important parameter in suppression effectiveness, a quantitative understanding as to the exact role size plays is lacking. Because of this, separating any possible chemical effects from the physical effects which are almost always present is difficult. This project was undertaken to address the lack of quantitative information on aerosol suppression behavior, particularly targeting the effects of size and physical and chemical properties of liquid and powder aerosols. Although the original goals of this project as part of the NGP were specifically targeted for military platforms, the findings are applicable to fire suppression by aerosols in general.
Allergic-like contrast reactions in the ED: Incidence, management, and impact on patient disposition.

Abstract Purpose Determine the incidence, management, and impact on patient disposition of allergic-like contrast reactions (ALCR) to intravenous iodinated contrast in the emergency department (ED). Methods All ED patients who developed an ALCR following contrast-enhanced CT (CECT) from June 2011–December 2016 were retrospectively identified. Medical records were reviewed and reaction severity, management, and disposition were quantified using descriptive statistics. The total number of consecutive CECTs performed in the ED were available from June 2011–March 2016 and were used to derive ALCR incidence over that time period. Results A total of 90 patients developed an ALCR during the study period. An ALCR incidence of 0.2% was derived based on 74 ALCRs occurring out of 47,059 consecutive contrast injections in ED patients from June 2011–April 2016. Reaction severity was mild in 63/90 (70%) and moderate in 27/90 (30%) cases; no patient developed a severe reaction by American College of Radiology criteria. The most commonly administered treatments were diphenhydramine in 67/90 (74%), corticosteroid in 24/90 (27%), and epinephrine in 13/90 (14%); symptoms subsequently resolved in all cases. No patient required inpatient admission for contrast reaction alone, and 5 patients were sent to the ED observation unit for post-epinephrine monitoring and subsequently discharged. Conclusion ALCR among ED patients undergoing CECT are rare, generally of mild severity, respond well to pharmacologic management, and do not alter patient disposition in most cases. Familiarity with symptoms, management, and prevention strategies is increasingly relevant to the emergency physician given the ubiquity of CECT.
Adverse childhood experiences: Evidence for screening beyond preventive visits

Primary efforts to screen for adverse childhood experiences (ACE/ACEs) are often focused on the well child/adolescent visit. The purpose of this study was to examine relationships between ACEs and youth likelihood of receiving preventive care. Data are from 126,868 students in the 8th, 9th, and 11th grades who participated in the 2016 Minnesota Student Survey, an anonymous, self-report questionnaire examining youth behaviors, experiences, and perceptions. Logistic regression models were used to determine if 10 types of ACEs, including abuse, household dysfunction, and food and housing insecurity were associated with receipt of recommended preventive medical and dental care after adjustment for demographic covariates and self-reported health. ACEs scores were entered into regression models to test for cumulative impact of adversities on preventive care outcomes. More than one third (38.5%) of youth identified at least one ACE, most commonly having a parent or guardian who had ever been in jail or prison. Each type of ACE was significantly associated with reduced odds of receiving preventive care in the last year. Associations with food insecurity were of greatest magnitude, associated with 0.32 [CI: 0.64-0.72] to 0.54 [CI: 0.44-0.49] decreased odds of receiving care. Each one point increase in the total ACE score was associated with 0.07 [CI: 0.92-0.94] to 0.15 [CI: 0.84-0.86] decreased odds of having had a preventive care visit in the last year. Findings add to the growing literature documenting significant relationships between ACEs and health, in this case, youth missing opportunities to receive recommended surveillance and anticipatory guidance.
Alterations in Mitochondrial Function in Blood Cells Obtained From Patients With Sepsis Presenting to an Emergency Department.

Objective Mitochondrial dysfunction has been implicated as a key cellular event leading to organ dysfunction in sepsis. Our objective is to measure changes in mitochondrial bioenergetics in subjects with early presentation of sepsis to provide insight into the incompletely understood pathophysiology of the dysregulated host response in sepsis. Design Prospective observational study. Setting Single site tertiary academic emergency department. Subjects We enrolled a total of 48 subjects in the study, 10 with sepsis or septic shock, 10 with infection without sepsis, 14 older and 14 younger healthy controls. Interventions Peripheral blood mononuclear cells were measured with high-resolution respirometry (OROBOROS O2K). Measurements and main results The median age in patients with sepsis, infection only, older control and younger controls were 63, 34, 61, and 29 years old, respectively. In the Sepsis group, the median 1st 24-h SOFA score was 8, and the initial median lactate was 4.2 mmol/dL, compared with 1.1 in the Infection Group. The 30-day mortality of the sepsis/septic shock group was 50%, with a median length of stay of 7-days. The Sepsis Group had significantly lower routine and Max respiration when compared with the other groups as well as uncoupled Complex I respiration. There was also a significant decrease in ATP-linked respiration along with the Spare Reserve Capacity in the Sepsis Group when compared with the other group. There were no age-related differences in respiration between the Older and Younger control group. Conclusions Bedside measurement of mitochondrial respiration can be minimally invasive and performed in a timely manner. Mitochondrial dysfunction, detected by decreased oxygen consumption utilized for energy production and depleted cellular bioenergetics reserve.
Open Versus Endovascular Stent Graft Repair of Abdominal Aortic Aneurysms: A Meta-Analysis of Randomized Trials

Objectives This study sought to evaluate the short-, intermediate-, and longer-term outcomes after endovascular versus open repair of abdominal aortic aneurysms (AAA), including both AAA-related and all-cause mortality. Background Endovascular stent graft placement for AAA has gained broad acceptance as an alternative to open surgical repair due to a lower perioperative morbidity and mortality. The intermediate- and long-term all-cause and aneurysm-related mortality vary among studies. Thus, we sought to perform a meta-analysis of open versus endovascular repair for treating AAA. Methods Electronic databases were queried for identification of prospective, randomized trials of open surgery versus endovascular stent graft repair of AAA. A total of 10 published papers reporting on 6 studies at different follow-up intervals were identified; they involved 2,899 patients with AAA repair procedures, of whom, 1,470 underwent endovascular stent graft AAA exclusion and 1,429 were treated by open AAA repair. Results At 30 days, the pooled relative risk of all-cause mortality was lower in the endovascular group (relative risk [RR]: 0.35, 95% confidence interval [CI]: 0.19 to 0.64) than in the open surgery group. At intermediate follow-up, the all-cause mortality had a nonsignificant difference (RR: 0.78, 95% CI: 0.57 to 1.08), the AAA-related mortality was significantly lower (RR: 0.46, 95% CI: 0.28 to 0.74) and reintervention rates were higher (RR: 1.48, 95% CI: 1.06 to 2.08) in the endovascular group than in the open surgery group. At long-term follow-up, there was no significant difference in all-cause mortality (RR: 0.99, 95% CI: 0.85 to 1.15) or AAA-related mortality (RR: 1.58, 95% CI: 0.20 to 12.74), whereas the significant difference in the rate of reinterventions persisted (RR: 2.54, 95% CI: 1.58 to 4.08). Conclusions In patients randomized to open or endovascular AAA repair, all-cause perioperative mortality, as well as AAA-related mortality at short- and intermediate-term follow-up are lower in patients undergoing endovascular stent graft placement. This was associated with greater reintervention in the endovascular group noted at intermediate follow-up. Long-term survival appears to converge between the 2 groups.
E-Commerce Systems Architecture and Applications

Identify all the major building blocks of an e-commerce system and understand how these building blocks interact to form an effective e-commerce system with E-Commerce Systems: Architecture, Design, and Implementation . This new book presents you with the key tools and technologies in use today, and the complete understanding you need to build an e-commerce architecture for the various types of commercial transactions - business-to-business, business-to-consumer, and intra-business. Plus, it conveys the dramatic impact e-commerce has on an enterprise's IT strategy. You get a close examination of the primary elements of the e-commerce systems architecture, including information appliances, computing networks, e-commerce services and their applications, and electronic payment systems, to help you plan, build, and maintain a vigorous e-commerce site of your own. Going beyond e-commerce via the Internet and World Wide Web, you also learn how online commercial transactions can and will take place utilizing cellular and pager networks. E-Commerce Systems: Architecture, Design, and Implementation also includes: A review of current and emergent technologies providing you with multiple options when planning and building an e-commerce system; Information on the sources for the technology you need to build your e-commerce infrastructure; A method for calculating the costs associated with building an e-commerce system suited to your organization 's needs; The technical know-how you need to understand the inherent complexities and related solutions in e-commerce system design and manufacture; Discussion of e-commerce system security issues, the popular technologies in use to control security, and the strategies you can use to assess the costs and risks associated with security implementation.
Behavioral Insomnias of Childhood: Assessment and Treatment

The Behavioral Insomnias of Childhood (BIC) include a series of problems of sleep initiation, continuity, maintenance, and bedtime resistance. These sleep problems can place a significant burden on the parents who may be required to attend to a child at the beginning or in the middle of the night. The resulting sleep loss can impact parents’ and children’s daytime functioning and can increase bedtime-related conflict. Even when sleep problems do not meet criteria for a disorder, they can increase parental stress and parent–child conflict. Childhood sleep problems can be an indicator of poor regulatory capacity in the infant or child, and there is some evidence that sleep problems presenting in the first few years of life can be a marker of a diathesis for psychopathology. Even though sleep problems in early childhood are quite common and there are well-established interventions for these problems, little is understood about the pathophysiology of childhood sleep disorders. This chapter will review common causes of sleep problems in infants and young children that can persist into the later school years and adolescence. This will be followed by a detailed practical approach to evaluating and treating childhood insomnias.
Threat, Explore, Barter, Puzzle: A Semantically-Informed Algorithm for Extracting Interaction Modes.

In the world of online gaming, not all actions are created equal. For example, when a player's character is confronted with a closed door, it would not make much sense to brandish a weapon, apply a healing potion, or attempt to barter. A more reasonable response would be to either open or unlock the door. The term interaction mode embodies the idea that many potential actions are neither useful nor applicable in a given situation. This paper presents a AEGIM, an algorithm for the automated extraction of game interaction modes via a semantic embedding space. AEGIM uses an image captioning system in conjunction with a semantic vector space model to create a gestalt representation of in-game screenshots, thus enabling it to detect the interaction mode evoked by the game.
Tweets to a Young 1L

A collection of advice for law students, especially first-year law students, expanded from a series of tweets reflecting on the author's reflections upon discovering her law school transcript.
Cannabis Use: Neurobiological, Behavioral, and Sex/Gender Considerations.

To summarize the current literature on the effects of cannabinoids in humans and to discuss the existing literature on the sex- and gender-related differences in the effects of cannabinoids. Cannabis and its constituent cannabinoids are associated with risk of addiction, cognitive deficits, and mood/psychotic disorders. Preclinical and emerging clinical data suggest greater sensitivity to the effects of cannabinoids in women. Cannabis is one of the most commonly used drugs with increasing rates of use. Women in particular may be at a greater risk of adverse outcomes given the previously described “telescoping effect” of substance use in women. Human data examining the sex- and gender-related differences in the effects of cannabinoids and factors underlying these differences are very limited. This represents a critical gap in the literature and needs to be systematically examined in future studies.
Transurethral resection of the ejaculatory ducts: etiology of obstruction and surgical treatment options

Ejaculatory duct obstruction is an uncommon but surgically correctable cause of male infertility. With the advent and increased use of high-resolution transrectal ultrasonography, anomalies of the ejaculatory ducts related to infertility have been well documented. Although there are no pathognomonic findings associated with ejaculatory duct obstruction, the diagnosis should be suspected in an infertile male with oligospermia or azoospermia with low ejaculate volume, normal secondary sex characteristics, testes, and hormonal profile, and dilated seminal vesicles, midline cyst, or calcifications on transrectal ultrasound (TRUS). Although additional larger prospective and comparative studies are needed, it appears that TRUS with aspiration is the most effective method for diagnosis. While intrusive, it is less invasive than vasography. The most robust and published evidence for treatment involves transurethral resection of ejaculatory duct (TURED). More recent experience with antegrade endoscopic approaches are promising and may also be considered. An alternative to surgeries for reversal of obstruction is sperm retrieval for in vitro fertilization/intracytoplasmic sperm injection. A thorough discussion of all alternatives, including risks and benefits, should be held with couples facing this uncommon condition to allow them to make informed decisions regarding management.
Association of a Crime Prevention Program for Boys With Mortality 72 Years After the Intervention: Follow-up of a Randomized Clinical Trial

Importance Mortality is an important outcome in evaluating crime prevention programs, but little is known about the effects on mortality during the full life course. Objective To determine the long-term outcomes of a crime prevention program on mortality and whether the iatrogenic effects on mortality observed in middle age persist or change in old age. Design This longitudinal follow-up was conducted in a cohort of boys included in a matched-pair randomized clinical trial (the Cambridge-Somerville Youth Study). Six hundred fifty boys aged 5 to 13 years who lived and attended public and parochial schools in working-class areas of Cambridge and Somerville, Massachusetts, and were identified as at risk for antisocial behavior were matched by age and demographic characteristics. One member of each pair was randomly allocated to the treatment condition. The original trial was performed from June 1, 1939, to December 1945. Follow-up in the present analysis was performed from January 2016 through June 2018. Interventions Treatment group participants received individual counseling through a range of activities and home visits for an extended duration (mean, 5.5 years). Control group participants received no special services. Main Outcomes and Measures The 4 outcomes of interest include age at mortality, mortality at latest follow-up, premature mortality (younger than 40 years), and cause of mortality (natural vs unnatural). Results In the original analysis, 650 participants were matched and randomized to treatment or control conditions, of whom 506 were retained in the analysis (mean [SD] age, 9.8 [1.7] years). Through early 2018, records for 488 participants (96.4%) were located. A total of 446 participants were confirmed dead (88.1%) and 42 alive (8.3%). Matched-pairs analyses showed no significant differences between the treatment and control groups for mortality at latest follow-up (relative risk [RR], 1.05; 95% CI, 0.99-1.11), premature mortality (RR, 1.15; 95% CI, 0.55-2.43), or cause of mortality (RR, 1.19; 95% CI, 0.65-2.18) (P > .05 for all). Cox proportional hazard regression indicated no difference in time to death between groups (hazard ratio, 1.18; 95% CI, 0.98-1.41;P = .09). Conclusions and Relevance Iatrogenic effects on mortality were not detected in this long-term follow-up. The longitudinal analysis provides information on the utility of life-long assessments of crime prevention programs and draws attention to the need for quality-of-life assessments of participants and their children.
Restraint use and injury in forward and rear-facing infants and toddlers involved in a fatal motor vehicle crash on a U. S. Roadway

Use of appropriate child passenger safety restraints reduces injury in infants, with rear facing restraints favored over forward facing. In 2011, the American Academy of Pediatrics (AAP) began recommending that infants and children under the age of 2 years be restrained in a rear-facing seat installed in the vehicle’s rear seat. This study examines the practice of rear-facing restraints pre- and post-AAP recommendations for children under 2 years. Data from the Fatality Analysis Reporting System (FARS) from 2008 to 2015 were used to examine restraint status and injuries in rear-seated infants and toddlers aged 0 to less than 2 years involved in fatal collisions (n = 4966). Subpopulation analyses were conducted on 1557 children with seat facing direction recorded. Multivariable logistic regression was used to generate odds ratios (OR) with 95% confidence intervals (CI). Covariates considered for inclusion in the multivariable model included passenger characteristics (age, gender, seating position), driver characteristics (age, gender, seat belt status, alcohol status, drug status, previous traffic violations), vehicle characteristics (vehicle type), and crash-level characteristics (day/night, weekday/weekend, rush hour, expressway/surface street, urban/rural). Approximately 6.7% (330 of 4996) of infants and toddlers were unrestrained with mortality that was approximately triple that of restrained infants (40.0% vs 13.7%, P < 0.0001). In multivariable adjusted models, predictors of an infant being unrestrained included unrestrained driver (OR: 3.17, 95% CI: 2.38–4.21), driver aged less than 20 years (OR: 2.18, 95% CI: 1.42–3.34), driver alcohol use (OR: 2.21, 95% CI: 1.42–3.44), center-seated infant (OR: 1.55, 95% CI: 1.19–2.03) and weekday crash (OR: 1.52, 95% CI: 1.12–2.01). Of all rear-seated children whose restraint status were reported (4966), rear-facing restraint use increased from 5.0% to 23.2% between 2008 and 2015 (P < 0.0001). The odds of rear-facing restraint use increased after introduction of the AAP guideline among infants aged 0 to < 1 year old (OR: 2.12, 95% CI: 1.46–3.10) and among toddlers aged 1 to < 2 years old (OR: 1.97, 95% CI: 1.03–3.79). Trends in the use of rear-facing child restraints improved over the timeframe of this study, but remain low despite the introduction of AAP guidelines and the strengthening of child restraint laws.
Tale of two curricula: The performance of 2000 students in introductory electromagnetism

The performance of over 2000 students in introductory calculus-based electromagnetism EM M&I averages were significantly higher in each topic. The results suggest that the M&I curriculum is more effective than the traditional curriculum at teaching E&M concepts to students, possibly because the learning progression in M&I reorganizes and augments the traditional sequence of topics, for example, by increasing early emphasis on the vector field concept and by emphasizing the effects of fields on matter at the microscopic level. DOI: 10.1103/PhysRevSTPER.5.020105 PACS numbers: 01.40.Fk, 01.40.gb
Do Race and Everyday Discrimination Predict Mortality Risk? Evidence From the Health and Retirement Study.

Everyday discrimination is a potent source of stress for racial minorities, and is associated with a wide range of negative health outcomes, spanning both mental and physical health. Few studies ha...
Care of Transgender Individuals

Transgender (trans) people experience many challenges in health-care settings including difficult access to care and discrimination from health-care personnel. Providers often lack the knowledge, vocabulary, or experience to optimally care for trans individuals. Providers who care for trans individuals perioperatively can improve patient care by developing an awareness of the challenges that trans patients experience in health-care settings, knowing and using appropriate terminology, and providing recommendations regarding perioperative management for patients on hormonal therapy.
Reversal of synaptic and behavioral deficits in a 16p11.2 duplication mouse model via restoration of the GABA synapse regulator Npas4

The human 16p11.2 gene locus is a hot spot for copy number variations, which predispose carriers to a range of neuropsychiatric phenotypes. Microduplications of 16p11.2 are associated with autism spectrum disorder (ASD), intellectual disability (ID), and schizophrenia (SZ). Despite the debilitating nature of 16p11.2 duplications, the underlying molecular mechanisms remain poorly understood. Here we performed a comprehensive behavioral characterization of 16p11.2 duplication mice (16p11.2dp/+) and identified social and cognitive deficits reminiscent of ASD and ID phenotypes. 16p11.2dp/+ mice did not exhibit the SZ-related sensorimotor gating deficits, psychostimulant-induced hypersensitivity, or motor impairment. Electrophysiological recordings of 16p11.2dp/+ mice found deficient GABAergic synaptic transmission and elevated neuronal excitability in the prefrontal cortex (PFC), a brain region critical for social and cognitive functions. RNA-sequencing identified genome-wide transcriptional aberrance in the PFC of 16p11.2dp/+ mice, including downregulation of the GABA synapse regulator Npas4. Restoring Npas4 expression in PFC of 16p11.2dp/+ mice ameliorated the social and cognitive deficits and reversed GABAergic synaptic impairment and neuronal hyperexcitability. These findings suggest that prefrontal cortical GABAergic synaptic circuitry and Npas4 are strongly implicated in 16p11.2 duplication pathology, and may represent potential targets for therapeutic intervention in ASD.
On the Modeling and Design of Modular Multilevel Converters With Parametric and Model-Form Uncertainty Quantification

Modeling and design with parametric and model-form uncertainty quantification is an alternative to conventional model-based design approaches as it improves the existing modeling practice and validates the model used in the design of power converters. However, in the case of modular multilevel converters (MMCs), uncertainty quantification, as the main step in this design methodology, becomes challenging due to the inherent complexity and sheer size of such units. In this article, these limitations are discussed and a systematic study for developing a simplified testbed for uncertainty quantification of an MMC is presented. To this end, first sensitivity analysis is conducted to identify the key parameters whose tolerances contribute the most to the parametric uncertainty of the selected design variables. Second, the effect of increasing the number of power cells in each arm on the estimated total uncertainty, and thus the predictive capability of the MMC simulation models for medium- and high-voltage applications is studied. A simplified testbed for model validation of the power cell in the design of an MMC is developed accordingly. The development of this simplified testbed allows validating the models used and estimating uncertainties in the design with less computational cost and hardware prototyping.
Post-Vietnam Syndrome: Psychiatry, Anti-War Politics, and the Reconstitution of the Vietnam Veteran

Using primary source materials from medical, government, and journalism archives, this study of public medical discourse reveals the role of argumentation in posi­tively shaping public perceptions of traumatized soldiers and locates the contem­porary origins of the trope of “soldier as psychological victim of war”—a perception that continues to inform public policy and medical research. Using Jasinski’s (1998) concepts of interior and exterior constitutive potential to analyze the public writ­ings, interviews, and Congressional testimony of VVAW-affiliated psychiatrists, the study finds that the radical psychiatrists’ interior (directed at veterans) and exte­rior (directed at public and medical institutions) rhetorics were (and arguably remain) mutually effective in creating an identity for veterans to occupy that exculpated them from their involvement in war, while allowing them to garner benefits for their ser­vice. The article concludes with two examples of the “veteran as psychological vic­tim of war” trope as it shapes the contemporary rhetorical ecology of former servicemembers.
Prediction and evaluation of deleterious and disease causing non-synonymous SNPs (nsSNPs) in human NF2 gene responsible for neurofibromatosis type 2 (NF2)

The majority of genetic variations in the human genome that lead to variety of different diseases are caused by non-synonymous single nucleotide polymorphisms (nsSNPs). Neurofibromatosis type 2 (NF...
Computational And Experimental Investigation Of Cathodic Protection Distribution In Reinforced Concrete Marine Piling

A detailed computer model of corrosion distribution in reinforced concrete has been used to predict the extent of cathodic protection provided for partiafly submerged piles by a combination of bulk sacrificial anodes placed below water and surface anodes above water. The model predictions are directly compared with the experimental response to cathodic protection in laboratory piles having active corrosion in progress. INTRODUCTION Chloride penetration of the concrete cover is a leading cause of significant corrosion damage in steel reinforced concrete marine structures. It is possible however, to intervene in this deterioration by the installation of cathodic protection systems. The goal of the present paper is to introduce a quantitative model to analyze the effectiveness of cathodic protection in marine piling by combining bulk and surface anodes. This investigation involves initial model calibration by comparison between results obtained in a laboratory investigation of small scale pilings and a computer generated model. Ultimately, it is hoped that a study of this nature will lead to improved techniques of application of cathodic protection, based on initial field data and a predictive model.
Decontaminating N95 respirators during the Covid-19 pandemic: simple and practical approaches to increase decontamination capacity, speed, safety and ease of use.

Summary Background The COVID-19 pandemic has caused a severe shortage of personal protective equipment (PPE), especially N95 respirators. Efficient, effective and economically feasible methods for large-scale PPE decontamination are urgently needed. Aims (1) to develop protocols for effectively decontaminating PPE using vaporized hydrogen peroxide (VHP); (2) to develop novel approaches that decrease set up and take down time while also increasing decontamination capacity (3) to test decontamination efficiency for N95 respirators heavily contaminated by makeup or moisturizers. Methods We converted a decommissioned Biosafety Level 3 laboratory into a facility that could be used to decontaminate N95 respirators. N95 respirators were hung on metal racks, stacked in piles, placed in paper bags or covered with makeup or moisturizer. A VHP®VICTORYTM unit from STERIS was used to inject VHP into the facility. Biological and chemical indicators were used to validate the decontamination process. Findings N95 respirators individually hung on metal racks were successfully decontaminated using VHP. N95 respirators were also successfully decontaminated when placed in closed paper bags or if stacked in piles of up to six. Stacking reduced the time needed to arrange N95 respirators for decontamination by approximately two-thirds while almost tripling facility capacity. Makeup and moisturizer creams did not interfere with the decontamination process. Conclusions Respirator stacking can reduce the hands-on time and increase decontamination capacity. When personalization is needed, respirators can be decontaminated in labeled paper bags. Make up or moisturizers do not appear to interfere with VHP decontamination.
Critical Issues in the Training of Bilingual School Psychologists

There are over five million bilingual learners in the US public school system as reported by the National Center for Education Statistics (2020) and this number has increased dramatically over the past several decades. Shortages of well-trained bilingual school psychologists (BSP) can negatively influence the provision of culturally and linguistically responsive services, contribute to potential misidentification or delayed special education identification of bilingual learners, and reduce home-school collaboration among bilingual families. The training of BSPs is complex, and there are currently no professional standards for competencies required for this specialized profession. This article provides a research-based review of recommended training components for BSPs. Most importantly, a foundational training in cultural responsiveness, advocacy, and equity must permeate all training. BSPs must also have advanced language proficiency in another language that aligns with the provision of school psychology practice. Recommended competencies for BSPs in the areas of assessment, counseling, intervention, and consultation are provided as well as suggestions for supervision and field-based experiences. Implications for the field of bilingual school psychology are provided as well as areas for future research.
Gut Microbial Signature of Hepatocellular Cancer in Men With Cirrhosis.

The gut microbiome is altered in cirrhosis. Recent evidence has suggested a key role for the gut microbiota in the progression of cirrhosis and the development of hepatocellular carcinoma (HCC). We studied the differences in the microbial composition in patients with cirrhosis with prior and future HCC in the context of other complications (eg, infections, hepatic encephalopathy). The following 2 cohorts were recruited prospectively: the prior HCC cohort, in which outpatients with HCC within 2 years were age-matched, sex-matched, and Model for End-Stage Liver Disease (MELD) score-matched with those without HCC; and the future HCC cohort, in which patients were followed for 2 years and divided into future HCC versus no HCC after age, sex, and MELD-score matching and other complications were also recorded. Microbiota composition and predicted function were analyzed with ribosomal RNA sequencing and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PiCRUST)and compared between (1) prior HCC versus none and (2) future HCC versus none, and in the future cohort, comparisons were also made between those patients who developed (1) HCC only versus without complications, (2) HCC only versus non-HCC complications only, and (3) HCC + other complications versus non-HCC complications only. A total of 142 men (76 total in the prior cohort [38 with/38 without HCC] and 66 total in the future cohort [33 with/33 without future HCC]) were included. The groups had similar etiology, lactulose/rifaximin/proton pump inhibitor use, diabetes mellitus, and non-HCC complications. Microbial diversity was similar between prior HCC/not or future HCC/not. On DESeq2 higher Clostridium sensu stricto and Anaerotruncus were significantly associated with protection from HCC, whereas the reverse was seen with Raoultella and Haemophilus regardless of prior/future HCC comparisons. Functions focused on urea cycle, bioenergetics, tryptophan, and toluene metabolism were different between the groups. Rothia was specific for other complications. Despite age, sex, and MELD-score matching and accounting for other complications, gut microbiota composition and the predicted function are different in men with cirrhosis with and without prior HCC and can be extended toward future HCC development.
An Analysis of Medical Malpractice Litigations in Coronary Artery Bypass Grafting from 1994-2019.

Abstract Background Cardiothoracic surgery is one of the more highly litigated medical specialties, and coronary artery bypass grafting (CABG) constitutes a substantial portion of cardiothoracic surgery cases. Therefore, understanding litigations relating to CABG would be of benefit to surgeons working to uphold the standards of care that their patients seek and minimize their own legal liability. This study analyzed CABG litigations to identify predictive factors of litigation and verdict type. Methods This study utilized the Westlaw legal database to compile litigations from 1994-2019 across the United States, and resulted in 307 total litigations. After individual screening, 211 litigations met the criteria for inclusion, and were analyzed for demographic, clinical, chronological, and verdict characteristics. Results Litigations were present in 33 US states, with California, New York, and Florida having the most litigations. Defendant verdicts were reached in 67.78% of litigations, followed by 20.38% of plaintiff verdicts, and 11.85% of settlements. Plaintiff verdicts were associated with the incidence of myocardial infarction during hospitalization. The winter season had the most litigations (42.18%), and the most defendant verdicts (37.76%). Patient mortality occurred in 47.39% of litigations. The most common alleged reason for litigation was a procedural error (55.45%). Conclusions Defendant verdicts were significantly associated with an alleged reason of procedural errors, an alleged reason of a failure to monitor, and congestive heart failure present in patients. The common nature of defendant verdicts, and the significantly greater occurrence of defendant verdicts during the highly litigated winter season, suggest that surgeons frequently satisfy the legal standard of care.
Initial evaluation of domain-specific episodic future thinking on delay discounting and cannabis use.

Episodic Future Thinking (EFT), mental simulation of personally relevant and positive future events, may modulate delay discounting (DD) in cannabis users. Whether EFT impacts cannabis use, whether DD mediates this effect, and whether EFT can be enhanced by prompting future events across specific life domains is unknown. Active, adult cannabis users (n = 90) recruited from Amazon mTurk and Qualtrics Panels were administered an Episodic Specificity Induction (ESI) to enhance quality of imagined events before being randomized to EFT, domain-specific-EFT (DS-EFT), or Episodic Recent Thinking (ERT). All participants created four, positive life events; DS-EFT participants imagined social, leisure, health, and financial events. Event-quality ratings were assessed (e.g., enjoyment). DD was assessed at baseline (Day 1), post-intervention (Days 2-4), and follow-up (Days 9-12). Cannabis use was assessed at baseline and follow-up. Differences in change in days and grams of cannabis use between conditions and mediation of changes in use by DD were examined. No differences in DD were observed between conditions. DS-EFT, but not EFT, showed significantly greater reductions in grams (d = .54) and days of cannabis use (d = .50) than ERT. DS-EFT and EFT demonstrated significantly greater event-quality ratings than ERT (ds > .55). EFT-based interventions showed potential for reducing cannabis use. Unexpectedly, effects on DD did not mediate this effect. Further testing with larger samples of cannabis users is needed to better understand EFT's mechanisms of action and determine optimal implementation strategies. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Nothing’s Changed but Me: Reintegration Plans Meet the Inner City

This chapter draws on an ethnographic study of 15 young men of color returning to Philadelphia after release from “Mountain Ridge Academy,” a therapeutic facility designed to target “criminal thinking errors.” I describe the disjuncture between the young men’s plans to “fall back” or refrain from further offending and the realities they faced when returning to impoverished urban neighborhoods. Although they were trained to view their post-release trajectories in terms of improved weighing of risks and rewards, their good intentions were dwarfed by marginal positions in the labor market, limited human capital, and stigma linking men of color to criminality. They often “fell back” on old ways of solving problems. When they returned home, they realized “nothing’s changed but me.” Helpful reintegration professionals and well-thought-out reentry plans were insufficient to overcome real material conditions their communities and families presented. Because the juvenile justice system is ill equipped to address these realities, it must define the problem of criminal offending as the product of the young men’s individual deficits, creating a mismatch between services and needs.
Generalized Deep Learning EEG Models for Cross-Participant and Cross-Task Detection of the Vigilance Decrement in Sustained Attention Tasks

Tasks which require sustained attention over a lengthy period of time have been a focal point of cognitive fatigue research for decades, with these tasks including air traffic control, watchkeeping, baggage inspection, and many others. Recent research into physiological markers of mental fatigue indicate that markers exist which extend across all individuals and all types of vigilance tasks. This suggests that it would be possible to build an EEG model which detects these markers and the subsequent vigilance decrement in any task (i.e., a task-generic model) and in any person (i.e., a cross-participant model). However, thus far, no task-generic EEG cross-participant model has been built or tested. In this research, we explored creation and application of a task-generic EEG cross-participant model for detection of the vigilance decrement in an unseen task and unseen individuals. We utilized three different models to investigate this capability: a multi-layer perceptron neural network (MLPNN) which employed spectral features extracted from the five traditional EEG frequency bands, a temporal convolutional network (TCN), and a TCN autoencoder (TCN-AE), with these two TCN models being time-domain based, i.e., using raw EEG time-series voltage values. The MLPNN and TCN models both achieved accuracy greater than random chance (50%), with the MLPNN performing best with a 7-fold CV balanced accuracy of 64% (95% CI: 0.59, 0.69) and validation accuracies greater than random chance for 9 of the 14 participants. This finding demonstrates that it is possible to classify a vigilance decrement using EEG, even with EEG from an unseen individual and unseen task.