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While research knowledge of bias-based bullying is increasing, there has been only limited research comparing in-person and online bias-based victimization incidents. The current study presents data on 521 bias-based incidents experienced by a large sample of youth (n = 854), 13-21 years old, examining differences between incidents that occurred solely online, solely in-person, or both online and in-person. Specifically, we examined whether the three types of incidents differed by: (a) respondents' sociodemographic characteristics (i.e., gender, race/ethnicity, immigrant status, religion, any disability, sexual orientation); (b) incident-level characteristics (i.e., victimization type, perpetrator relationship, number of perpetrators, physical injury, any weapon used, duration of the incident, location of the incident, and disclosure); and (c) negative impact (emotional distress, school-related problems, and physical symptoms). Results indicated that online-only bias-based victimization incidents occurred less frequently, and impacted victims less negatively, than either in-person only or combined online/in-person bias victimization. Incidents that were a mix of online and in-person bias-based victimization were the most distressing type of incident for youth, even controlling for other aggravating features (e.g., the number of perpetrators). Findings highlight the importance of asking vulnerable youth about the context of bias-based victimization they may have experienced and suggest that prevention initiatives will need to incorporate strategies to address the different environments in which bias-based victimization incidents occur.

Research on adverse childhood experiences and resilience (the process of overcoming trauma) has been dominated by studies originating in wealthy democracies of the global north. We call for more global and ecological approaches not only for documenting the true global burden of childhood adversity, but also for advancing the science of resilience and understanding pathways to overcoming trauma. We identify several forms of trauma that need better consideration in prevalence estimates, including state, political, and institutional violence, crisis migration, climate change and related natural disasters, and global health crises such as the COVID-19 pandemic. We also need more nuanced analyses of culture and place and to recognize that the global south and global north are not monolithic concepts. We offer illustrative examples of how more global, ecological approaches can enhance our understanding of pathways to overcoming even high dosages of childhood adversity. One of the key insights of ACEs research, the dose-response relationship between trauma burden and outcomes, has been extended to research on resilience. Concepts that capture the total “dose” of positive assets and resources (people's resilience portfolios) are showing how people might overcome even high doses of trauma. This work can become more global by including incorporating strengths and healing processes common in collectivist, versus individualistic, cultures. It can become more ecological by recognizing that physical environments—both natural and human-made built aspects—play key roles in resilience. Recognizing the intersectionality among these elements can take us to the next generation of trauma and resilience science.

This study investigates how adults who faced childhood adversity develop resilience, using the Resilience Portfolio Model to assess the impact of early victimization on adult well-being and posttraumatic growth. A sample of 689 adults aged 18 to 60 (average age 25.2 years, SD = 9.62) was recruited online in Kosovo, a collectivist and post-conflict society. Participants completed a survey on youth victimization, psychosocial strengths, subjective well-being and posttraumatic growth. Findings from the study show that 93% experienced some form of victimization, including 40% who were exposed to parental violence. Blockwise logistic regressions indicated that poly-strengths (an indicator of the breadth of one's resilience portfolio), sense of purpose, optimism, and religious meaning making were associated with higher levels of posttraumatic growth, controlling for polyvictimization and demographics (total R2 = 0.39). Poly-strengths, sense of purpose, optimism, and psychological endurance were associated with higher subjective well-being (total R2 = 0.34). Unexpectedly, some strengths were associated with lower posttraumatic growth, including coping, anger management, and moral-based meaning making. Findings from this highly victimized sample show that several strengths seem promising in promoting resilience. Intervention and prevention programs should consider focusing on promoting a sense of purpose or broadening resilience portfolios. More research is needed in other collectivist and post-conflict societies.

Background: Thoracic aortic dissection (TAD) is an uncommon complication in patients with Tetralogy of Fallot (TOF). Information concerning risk factors for TAD in patients with TOF is very limited. Methods: We report a case of Stanford type A TAD in a female patient with previously repaired TOF. Whole exome sequencing (WES); Novogene UK, Agilent V6 capture kit, Illumina HiSeq 100x depth) was performed to identify genetic variants in genes known to be associated with TAD. A systematic literature review was performed in the NCBI PubMed database to identify case reports of TAD in patients with TOF. Results: The patient was a 31-year-old female who developed Stanford type A aortic dissection having had TOF repair at the age of four years. The thoracic aorta was only minimally dilated (sinus of Valsalva 43 mm) on clinical review 16 months prior to TAD. Of note the patient had completed pregnancy 5 months prior to the dissection. There were no other high-risk features predisposing to TAD. WES identified rare genetic variant in a gene previously associated with TAD: MYLK (p.Arg1405His). The literature review identified nine other case reports of TAD in patients with TOF. The reported patients, had no clinical characteristics that distinguished them from the wider population of patients with TOF. Conclusions: The presence of a rare genetic variant in MYLK is a plausible explanation for the clinical presentation. The variant will need further verification to confirm pathogenicity. Pathogenic MYLK variants have been previously reported in context of dissection with minimally dilated aortas.

THE ARCHETYPE OF THE DYING AND RISING GOD IN WORLD MYTHOLOGY. Paul R. Rovang. Lanham MD: Lexington Books, 2023. 224p. 9781666917086. $100. Additional Keywords archetype Long considered an important concept [...]

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

CT1812 is a novel, brain penetrant small molecule modulator of the sigma-2 receptor (S2R) that is currently in clinical development for the treatment of Alzheimer's disease (AD). Preclinical and early clinical data show that, through S2R, CT1812 selectively prevents and displaces binding of amyloid beta (Aβ) oligomers from neuronal synapses and improves cognitive function in animal models of AD. SHINE is an ongoing phase 2 randomized, double-blind, placebo-controlled clinical trial (COG0201) in participants with mild to moderate AD, designed to assess the safety and efficacy of 6 months of CT1812 treatment. To elucidate the mechanism of action in AD patients and pharmacodynamic biomarkers of CT1812, the present study reports exploratory cerebrospinal fluid (CSF) biomarker data from 18 participants in an interim analysis of the first set of patients in SHINE (part A). Untargeted mass spectrometry-based discovery proteomics detects >2000 proteins in patient CSF and has documented utility in accelerating the identification of novel AD biomarkers reflective of diverse pathophysiologies beyond amyloid and tau, and enabling identification of pharmacodynamic biomarkers in longitudinal interventional trials. We leveraged this technique to analyze CSF samples taken at baseline and after 6 months of CT1812 treatment. Proteome-wide protein levels were detected using tandem mass tag-mass spectrometry (TMT-MS), change from baseline was calculated for each participant, and differential abundance analysis by treatment group was performed. This analysis revealed a set of proteins significantly impacted by CT1812, including pathway engagement biomarkers (i.e., biomarkers tied to S2R biology) and disease modification biomarkers (i.e., biomarkers with altered levels in AD vs. healthy control CSF but normalized by CT1812, and biomarkers correlated with favorable trends in ADAS-Cog11 scores). Brain network mapping, Gene Ontology, and pathway analyses revealed an impact of CT1812 on synapses, lipoprotein and amyloid beta biology, and neuroinflammation. Collectively, the findings highlight the utility of this method in pharmacodynamic biomarker identification and providing mechanistic insights for CT1812, which may facilitate the clinical development of CT1812 and enable appropriate pre-specification of biomarkers in upcoming clinical trials of CT1812.

In recent years, there has been an increase in the adventive establishment and spread of parasitoid wasps outside of their native range. However, lack of taxonomic tools can hinder the efficient screening of field-collected samples to document the establishment and range expansion of parasitoids on continent-wide geographic scales. Here we report that Leptopilina japonica (Hymenoptera, Figitidae), a parasitoid of the globally invasive fruit pest Drosophila suzukii (Diptera, Drosophilidae), is now widespread in much of North America despite not having been intentionally introduced. Surveys in 2022 using a variety of methods detected L. japonica in 10 of 11 surveyed USA States and one Canadian Province where it was not previously known to occur. In most surveys, L. japonica was the most common species of D. suzukii parasitoid found. The surveys also resulted in the detection of Ganaspis cf. brasiliensis (Hymenoptera, Figitidae), the recently-released biological control agent of D. suzukii, in six USA States where it had not previously been found. These new detections are likely a result of intentional biological control introductions rather than spread of adventive populations. A species-specific multiplex PCR assay was developed as a rapid, accurate and cost-effective method to distinguish L. japonica, G. cf. brasiliensis, the closely-related cosmopolitan parasitoid Leptopilina heterotoma (Hymenoptera, Figitidae) and other native parasitoid species. This dataset and the associated molecular tools will facilitate future studies of the spread and ecological impacts of these introduced parasitoids on multiple continents.

One of the most promising tools for the control of fungal plant diseases is spray-induced gene silencing (SIGS). In SIGS, small interfering RNA (siRNA) or double-stranded RNA (dsRNA) targeting essential or virulence-related pathogen genes are exogenously applied to plants and postharvest products to trigger RNA interference (RNAi) of the targeted genes, inhibiting fungal growth and disease. However, SIGS is limited by the unstable nature of RNA under environmental conditions. The use of layered double hydroxide or clay particles as carriers to deliver biologically active dsRNA, a formulation termed BioClay™, can enhance RNA durability on plants, prolonging its activity against pathogens. Here, we demonstrate that dsRNA delivered as BioClay can prolong protection against Botrytis cinerea, a major plant fungal pathogen, on tomato leaves and fruit and on mature chickpea plants. BioClay increased the protection window from 1 to 3 weeks on tomato leaves and from 5 to 10 days on tomato fruits, when compared with naked dsRNA. In flowering chickpea plants, BioClay provided prolonged protection for up to 4 weeks, covering the critical period of poding, whereas naked dsRNA provided limited protection. This research represents a major step forward for the adoption of SIGS as an eco-friendly alternative to traditional fungicides.

IntroductionDegenerin proteins, such as βENaC and ASIC2, have been implicated in cardiovascular function. However, their role in metabolic syndrome have not been studied. To begin to assess this interaction, we evaluated the impact of a high fat diet (HFD) on mice lacking normal levels of ASIC2 (ASIC2-/-) and βENaC (βENaCm/m).MethodsTwenty-week-old male and female mice were placed on a 60% HFD for 12 weeks. Body weight was measured weekly, and body composition by non-invasive ECHO MRI and fasting blood glucose were measured at 0, 4, 8 and 12 weeks. A glucose tolerance test was administered after 12 weeks. Differences between ASIC2-/-/βENaCm/m and WT groups were compared using independent t-tests or ANOVA where appropriate within each sex. Data are presented as mean ± SEM and ASIC2-/-/βENaCm/m vs. WT. ResultsAt 20 weeks of age, ASIC2-/-/βENaCm/m mice (n=9F/10M) weighed less and gained less weight than WT (n=12F/16M). Total body fat and lean body masses were reduced in female and male ASIC2-/-/βENaCm/m mice. Total body fat and lean body masses as % control were identical at the end of 12 weeks. Fasting blood glucoses were lower in female and male ASIC2-/-/βENaCm/m vs. WT mice after 12 weeks HFD. The area under the curve for the glucose tolerance test was reduced in female and tended (p=.079) to decrease in male ASIC2-/-/βENaCm/m. Plasma leptin and insulin were reduced in female and male ASIC2-/-/βENaCm/m vs. WT mice. Plasma insulin in female ASIC2-/-/βENaCm/m mice remained unchanged throughout the HFD period. Liver and liver fat masses, as well as percent liver fat, were reduced in both female and male ASIC2-/-/βENaCm/m mice after HFD. Plasma triglycerides, cholesterol, LDL- and HDL-cholesterols were markedly improved in male and/or female ASIC2-/-/βENaCm/m following the HFD.DiscussionThese novel findings suggest that loss of ASIC2 and βENaC offer a significant protection against HFD-induced metabolic syndrome.

PurposeTo describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions.MethodsIn May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods.Results236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews.ConclusionVirtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

Abstract Background Effective, disease-modifying therapeutics for the treatment of Alzheimer’s disease (AD) remain a large unmet need. Extensive evidence suggests that amyloid beta (Aβ) is central to AD pathophysiology, and Aβ oligomers are among the most toxic forms of Aβ. CT1812 is a novel brain penetrant sigma-2 receptor ligand that interferes with the binding of Aβ oligomers to neurons. Preclinical studies of CT1812 have demonstrated its ability to displace Aβ oligomers from neurons, restore synapses in cell cultures, and improve cognitive measures in mouse models of AD. CT1812 was found to be generally safe and well tolerated in a placebo-controlled phase 1 clinical trial in healthy volunteers and phase 1a/2 clinical trials in patients with mild to moderate dementia due to AD. The unique objective of this study was to incorporate synaptic positron emission tomography (PET) imaging as an outcome measure for CT1812 in AD patients. Methods The present phase 1/2 study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted in 23 participants with mild to moderate dementia due to AD to primarily evaluate the safety of CT1812 and secondarily its pharmacodynamic effects. Participants received either placebo or 100 mg or 300 mg per day of oral CT1812 for 24 weeks. Pharmacodynamic effects were assessed using the exploratory efficacy endpoints synaptic vesicle glycoprotein 2A (SV2A) PET, fluorodeoxyglucose (FDG) PET, volumetric MRI, cognitive clinical measures, as well as cerebrospinal fluid (CSF) biomarkers of AD pathology and synaptic degeneration. Results No treatment differences relative to placebo were observed in the change from baseline at 24 weeks in either SV2A or FDG PET signal, the cognitive clinical rating scales, or in CSF biomarkers. Composite region volumetric MRI revealed a trend towards tissue preservation in participants treated with either dose of CT1812, and nominally significant differences with both doses of CT1812 compared to placebo were found in the pericentral, prefrontal, and hippocampal cortices. CT1812 was safe and well tolerated. Conclusions The safety findings of this 24-week study and the observed changes on volumetric MRI with CT1812 support its further clinical development. Trial registration The clinical trial described in this manuscript is registered at clinicaltrials.gov (NCT03493282).

Findings from a meta-analysis of meta-analyses of 14 different types of preservice student and beginning teacher preparation practices are described. The research synthesis included 118 meta-analyses and 12 other research studies of preservice practices-preservice student and beginning teacher outcomes. The research reports included between 5000 and 6000 studies and an estimated 2.5 to 3 million study participants. The outcomes included two different teacher quality measures and two different preservice student and beginning teacher measures. Mean difference effect sizes, confidence intervals for the average effect sizes, and generalized patterns of results were used to identify very high impact, high impact, medium impact, low impact, and no impact preservice practices. Results showed that clinically rich field experiences (extended and limited student teaching), learning experiences that included multiple opportunities for deliberate practice, faculty and school-based coaching, clinical supervision and performance feedback, different types of experiences and opportunities to learn to teach, course-based experiential learning experiences, and cooperative learning opportunities stood out as especially important practices that were related to optimal preservice and beginning teacher outcomes. The patterns of results are consistent with a practice-based approach to teacher preparation where the focus of preservice and beginning teacher education is the learning experiences and opportunities to learn and use optimal effective teaching practices.

Findings from a synthesis of technical assistance models and frameworks were used to code the use of 25 core elements of technical assistance in studies and evaluations of implementation interventions to affect program, organization, and systems change. The 25 core elements were group into five components: preparation for the provision of technical assistance, development of a technical assistance plan, implementation of technical assistance, evaluation of the effects of technical assistance, and sustainability of technical assistance-facilitated changes. Results indicated that a subset of 11 core elements was related to between groups and between condition differences in the sizes of effect for program, organization, and systems changes. Results also showed that more intensive technical assistance was associated with larger sizes of effects compared to less intensive technical assistance and that particular combinations of practices were associated with the largest sizes of effect.

The manner in which family-centered capacity-building practices and parenting efficacy beliefs were directly and indirectly related to parent-child interactions and child behavior and development was investigated using meta-analytic structural equation modeling. The participants were 6507 caregivers of young children with identified disabilities and developmental delays in 13 studies. Results showed that capacity-building practices were directly related to parenting efficacy beliefs and indirectly related to parent-child interaction mediated by belief appraisals; parenting efficacy beliefs were directly related to parent-child interactions and indirectly related to child social competence mediated by parenting practices; and parent-child interactions were directly related to both child behavior and child development. Results also indicated these relationships were not moderated by parents' education, severity of child disability, or frequency of practitioner-parent contacts. Implications for investigating the influences of social and family systems intervention practices on parent, family, and child outcomes of early childhood intervention are described.

While prior work has examined the effects of emotions on consumers' attitudes toward ads, little research has explored how the joint presence of positive and negative emotions affects ad-related outcomes and to what extent such ads are common. This research leverages recent advances in emotion recognition technology to identify emotions based on the facial expressions of actors in Super Bowl ads aired over the past five years. We examine how the joint presence of happiness—a basic positive emotion—and sadness, disgust, anger, and fear—basic negative emotions—in these ads predict USA TODAY Ad Meter scores (the premier tracker of public opinion on Super Bowl ads). Results show that the joint presence of happiness and sadness enhances ad liking, the presence of happiness and fear reduces ad liking, while the presence of happiness and anger or happiness and disgust do not affect ad liking. We discuss the theoretical and methodological implications of these findings and future research directions. [ABSTRACT FROM AUTHOR]

Recent discoveries show that fungi can take up environmental RNA, which can then silence fungal genes through environmental RNA interference. This discovery prompted the development of Spray-Induced Gene Silencing (SIGS) for plant disease management. In this study, we aimed to determine the efficacy of SIGS across a variety of eukaryotic microbes. We first examined the efficiency of RNA uptake in multiple pathogenic and non-pathogenic fungi, and an oomycete pathogen. We observed efficient double-stranded RNA (dsRNA) uptake in the fungal plant pathogens Botrytis cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Aspergillus niger and Verticillium dahliae, but no uptake in Colletotrichum gloeosporioides, and weak uptake in a beneficial fungus, Trichoderma virens. For the oomycete plant pathogen, Phytophthora infestans, RNA uptake was limited and varied across different cell types and developmental stages. Topical application of dsRNA targeting virulence-related genes in pathogens with high RNA uptake efficiency significantly inhibited plant disease symptoms, whereas the application of dsRNA in pathogens with low RNA uptake efficiency did not suppress infection. Our results have revealed that dsRNA uptake efficiencies vary across eukaryotic microbe species and cell types. The success of SIGS for plant disease management can largely be determined by the pathogen's RNA uptake efficiency.

George MacDonald in the Age of Miracles: Incarnation, DOUBT, and reenchantment. Timothy Larsen. Downers Grove IL: IVP Academic, 2018. 142 p. 9780830853731. $18.00. AS ONE OF THE MOST INFLUENTIAL CHRISTIAN [...]

Results from a metasynthesis of the relationships between 14 different types of preservice teacher preparation practices and teaching quality, preschool to university student performance, and university student and beginning teacher belief appraisals are reported. Each type of preservice practice (e.g., course-based student learning) included different kinds of instructional methods (e.g., problem-based learning, inquiry-based learning, and project-based learning). The metasynthesis included 118 meta-analyses and 12 surveys of more than three million study participants. Findings clearly indicated that active university student and beginning teacher involvement in mastering the use of instructional practices and both knowledge and skill acquisition by far stood out as the most important preservice teacher preparation practices. These included extended student teaching experiences, simulated instructional practices and microteaching, faculty coaching and mentoring, clinical supervision, different types of cooperative learning practices, and course-based active student learning methods. The pattern of results helped identify high leverage and high impact teacher preparation practices. Implications for future research and improving teacher preparation are described.

A review of 25 technical assistance models and frameworks was conducted to identify the core elements of technical assistance practices. The focus of analysis was on generally agreed upon technical assistance practices that were considered essential for planning, implementing and evaluating the effectiveness of technical assistance. Results indicated that there are five major components of technical assistance and 25 different core elements. Analyses of the models and components found considerable variability within and between components in terms of the core elements that are considered most important or essential. Findings were used to define and describe the core elements of the technical assistance models and frameworks and how they can be used in research and evaluation studies to determine if the use of the core elements and practices are related to changes or improvements in program, organizational, or systems practices.

The analyses described in this paper permitted an evaluation of whether capacity-building professional development practices were related to early childhood intervention practitioners' reported use of capacity-building family-centered practices. This was ascertained by structural equation modeling for two different types of family-centered practices (participatory and relational) where the two models were compared to determine the better fitting model and the sizes of effects for the relationships among the variables in the models. Results provided converging evidence that capacity-building professional development engenders practitioners' use of capacity-building family-centered practices. Implications for practice are described.

Abstract Objectives: Evaluate system-wide antimicrobial stewardship program (ASP) update impact on intravenous (IV)-to-oral (PO) antimicrobial conversion in select community hospitals through pre- and postimplementation trend analysis. Methods: Retrospective study across seven hospitals: region one (four hospitals, 827 beds) with tele-ASP managed by infectious diseases (ID)-trained pharmacists and region two (three hospitals, 498 beds) without. Data were collected pre- (April 2022–September 2022) and postimplementation (April 2023–September 2023) on nine antimicrobials for the IV to PO days of therapy (DOTs). Antimicrobial administration route and (DOTs)/1,000 patient days were extracted from the electronical medical record (EMR). Primary outcome: reduction in IV DOTs/1,000 patient days. Secondary outcomes: decrease in IV usage via PO:total antimicrobial ratios and cost reduction. Results: In region one, IV usage decreased from 461 to 209/1,000 patient days (P = < .001), while PO usage increased from 289 to 412/1,000 patient days (P = < .001). Total antimicrobial use decreased from 750 to 621/1,000 patient days (P = < .001). In region two, IV usage decreased from 300 to 243/1,000 patient days (P = .005), and PO usage rose from 154 to 198/1,000 patient days (P = .031). The PO:total antimicrobial ratios increased in both regions, from .42–.52 to .60–.70 in region one and from .36–.55 to .46–.55 in region two. IV cost savings amounted to $19,359.77 in region one and $4,038.51 in region two. Conclusion: The ASP intervention improved IV-to-PO conversion rates in both regions, highlighting the contribution of ID-trained pharmacists in enhancing ASP initiatives in region one and suggesting tele-ASP expansion may be beneficial in resource-constrained settings.