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We measure the top quark mass in dilepton final states of tt¯ events in pp¯ collisions at s=1.96 TeV, using data corresponding to an integrated luminosity of 9.7 fb−1 at the Fermilab Tevatron Collider. The analysis features a comprehensive optimization of the neutrino weighting method to minimize the statistical uncertainties. We also improve the calibration of jet energies using the calibration determined in tt¯→lepton+jets events, which reduces the otherwise limiting systematic uncertainty from the jet energy scale. The measured top quark mass is mt=173.32±1.36(stat)±0.85(syst) GeV.

Basic and retrospective translational research has shown that the magnitude of resurgence is determined by the size of the decrease in alternative reinforcement, with larger decreases producing more resurgence. However, this finding has not been evaluated prospectively with a clinical population. In Experiment 1, five participants experienced a fixed progression of reinforcement schedule-thinning steps during treatment of their destructive behavior. Resurgence occurred infrequently across steps and participants, and when resurgence did occur, its clinical meaningfulness was often minimal. In Experiment 2, five new participants experienced these same schedule-thinning steps but in a counterbalanced order. Resurgence occurred most often and was generally largest with larger decreases in alternative reinforcement programmed earlier in the evaluation. Large decreases in alternative reinforcement may be more problematic clinically when they occur earlier in treatment. Whether larger transitions can be recommended in the clinic following the success of smaller ones will require additional research.

While research suggests that social emotional competencies (SECs) influence students' disciplinary outcomes, less is known of their potential to explain racial disparities or grade level differences in those outcomes. This study used survey and administrative data from 30,494 students in grades 3-12 to examine the degree to which SECs were related to discipline outcomes, and whether the relationship differed by race or grade tier. Results indicated that students with higher SEC had fewer behavior incidents, in-school suspensions, and out-of-school suspensions. Further analyses revealed that race and grade tier were predictive of all discipline outcomes. Regardless of SEC level, Black and mixed-race students had higher behavior incidents. When race and grade tier were included as factors, the relationship between SEC and discipline was diminished. Results suggest that SECs cannot explain racial disparities in discipline, but students who report low SEC in middle and high school could potentially benefit from intervention.

We present a measurement of the cross sections for the associated production of a W boson with at least one heavy quark jet, b or c, in proton–antiproton collisions. Data corresponding to an integrated luminosity of 8.7 fb−1 recorded with the D0 detector at the Fermilab Tevatron pp¯ Collider at s=1.96 TeV are used to measure the cross sections differentially as a function of the jet transverse momenta in the range 20 to 150 GeV. These results are compared to calculations of perturbative QCD theory as well as predictions from Monte Carlo generators.

We present the first measurements of the differential cross section dσ/dpTγ for the production of an isolated photon in association with at least two b-quark jets. The measurements consider photons with rapidities |yγ|15 GeV and |yjet|

Abstract Despite the significant burden, cost, and worse prognosis of Alzheimer’s disease (AD) with behavioral and psychological symptoms of dementia (BPSD), little is known about the molecular causes of these symptoms. Using antemortem assessments of BPSD in AD, we demonstrate that individual BPSD can be grouped into 4 domain factors in our cohort: affective, apathy, agitation, and psychosis. Then, we performed a transcriptome-wide analysis for each domain utilizing bulk RNA-seq of post-mortem anterior cingulate cortex (ACC) tissues. Though all 4 domains are associated with a predominantly downregulated pattern of hundreds of differentially expressed genes (DEGs), most DEGs are unique to each domain, with only 22 DEGs being common to all BPSD domains, including TIMP1. Weighted gene co-expression network analysis (WGCNA) yielded multiple transcriptional modules that were shared between BPSD domains or unique to each domain, and NetDecoder was used to analyze context-dependent information flow through the biological network. For the agitation domain, we found that all DEGs and a highly associated transcriptional module were functionally enriched for ECM-related genes including TIMP1, TAGLN, and FLNA. Another unique transcriptional module also associated with the agitation domain was enriched with genes involved in post-synaptic signaling, including DRD1, PDE1B, CAMK4, and GABRA4. By comparing context-dependent changes in DEGs between cases and control networks, ESR1 and PARK2 were implicated as two high-impact genes associated with agitation that mediated significant information flow through the biological network. Overall, our work establishes unique targets for future study of the biological mechanisms of BPSD and resultant drug development.

Abstract Depression is a common and devastating neuropsychiatric symptom in the elderly and in patients with dementia. In particular, nearly 80% of patients with Alzheimer’s Disease dementia experience depression during disease development and progression. However, it is unknown whether the depression in patients with dementia shares the same molecular mechanisms as depression presenting as primary psychiatric disease or occurs and persists through alternative mechanisms. In this review, we discuss how the clinical presentation and treatment differ between depression in dementia and as a primary psychiatric disease, with a focus on major depressive disorder. Then, we hypothesize several molecular mechanisms that may be unique to depression in dementia such as neuropathological changes, inflammation, and vascular events. Finally, we discuss existing issues and future directions for investigation and treatment of depression in dementia.

The objective of this Campbell systematic review is to examine the relationship between school-based law enforcement (SBLE) presence and school-related outcomes. The past several decades has witnessed a steady growth of the presence of SBLE around the world. There is no standard definition for SBLE, nor is there a common training, job description, or chain of authority. In the USA, the two most common approaches are to contract officers from a local law enforcement agency to work in the school, and school district police departments, in which the local school or district employs its own sworn police force. There is debate about whether SBLE is effective or harmful. This study synthesizes the empirical literature that examined the relationship between SBLE presence and school-related outcomes including: (a) crime and behavior problems; (b) perceptions of school; and (c) student learning.

Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (Ih) were recently identified in mature OLG and shown to play a role in regulating myelin length. Here we provide a biochemical and electrophysiological characterization of HCN channels in cells of the oligodendrocyte lineage. We observed that mice with a nonsense mutation in the Hcn2 gene (Hcn2ap/ap) have less white matter than their wild type counterparts with fewer OLG and fewer oligodendrocyte progenitor cells (OPCs). Hcn2ap/ap mice have severe motor impairments, although these deficits were not observed in mice with HCN2 conditionally eliminated only in oligodendrocytes (Cnpcre/+; Hcn2F/F). However, Cnpcre/+; Hcn2F/F mice develop motor impairments more rapidly in response to experimental autoimmune encephalomyelitis (EAE). We conclude that HCN2 channels in OLG may play a role in regulating metabolism.

Rosacea is a chronic inflammatory skin condition associated with a significant health and economic burden from costs and loss of productivity due to seeking medical treatment. The disease encompasses multiple phenotypic manifestations involving a complex and multi-variate pathogenesis. Although the pathophysiology of rosacea is not completely understood, ongoing research is continually elucidating its mechanisms. In this review, current concepts of rosacea pathogenesis will be addressed which involve skin barrier and permeability dysfunction, the innate and adaptive immune systems, and the neurovascular system. More specifically, the cathelicidin pathway, transient potential receptor channels, mast cells, and the NLRP3 inflammasome pathway are various targets of current pharmacologic regimens. Future therapies may seek different mechanisms to act on current treatment targets, like the potential use of JAK/STAT inhibitors in ameliorating skin barrier dysfunction or TLR antagonists in alleviating cathelicidin mediated inflammation. Other potential treatments aim for entirely different molecular targets such as microvesicle particle mediated local and systemic inflammation. Ultimately rosacea is associated with a significant health and economic burden which warrants deeper research into its pathogenesis and resultant new treatment discovery.

Sediment Barriers (SBs) are crucial for effective erosion control, and understanding their capacities and limitations is essential for environmental protection. This study compares the accuracy and effectiveness of Terrestrial Laser Scanning (TLS) and Robotic Total Station (RTS) techniques for quantifying sediment retention in SBs. To achieve this, erosion tests were conducted in a full-scale testing apparatus with TLS and RTS methods to collect morphological data of sediment retention surfaces before and after each experiment. The acquired datasets were processed and integrated into a Building Information Modeling (BIM) platform to create Digital Elevation Models (DEMs). These were then used to calculate the volume of accumulated sediment upstream of the SB system. The results indicated that TLS and RTS techniques could effectively measure sediment retention in a full-scale testing environment. However, TLS proved to be more accurate, exhibiting a standard deviation of 0.41 ft3 in contrast to 1.94 ft3 for RTS and more efficient, requiring approximately 15% to 50% less time per test than RTS. The main conclusions of this study highlight the benefits of using TLS over RTS for sediment retention measurement and provide valuable insights for improving erosion control strategies and sediment barrier design.

Summary: Short polypeptides encoded by small open reading frames (smORFs) are ubiquitously found in eukaryotic genomes and are important regulators of physiology, development, and mitochondrial processes. Here, we focus on a subset of 298 smORFs that are evolutionarily conserved between Drosophila melanogaster and humans. Many of these smORFs are conserved broadly in the bilaterian lineage, and ∼182 are conserved in plants. We observe remarkably heterogeneous spatial and temporal expression patterns of smORF transcripts—indicating wide-spread tissue-specific and stage-specific mitochondrial architectures. In addition, an analysis of annotated functional domains reveals a predicted enrichment of smORF polypeptides localizing to mitochondria. We conduct an embryonic ribosome profiling experiment and find support for translation of 137 of these smORFs during embryogenesis. We further embark on functional characterization using CRISPR knockout/activation, RNAi knockdown, and cDNA overexpression, revealing diverse phenotypes. This study underscores the importance of identifying smORF function in disease and phenotypic diversity.

Abstract Background Nonalcoholic fatty liver disease affects about 24% of the world’s population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC can develop in lean individuals. The mechanisms by which HCC develops and the role of epigenetic changes in the context of obesity and normal weight are not well understood. Methods In this study, we used previously generated mouse models of lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to evaluate methylation differences in HCC progression in lean versus obese mice. Differentially methylated regions were determined using reduced representation bisulfite sequencing. Results A larger number of differentially methylated regions (DMRs) were seen in NASH-HCC progression in the obese mice compared to the non-obese mice. No overlap existed in the DMRs with the largest methylation differences between the two models. In lean NASH-HCC, methylation differences were seen in genes involved with cancer progression and prognosis (including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and lipid metabolism, including PNPLA6 and LDLRAP1. In obese NASH- HCC, methylation differences were seen in genes known to be associated with HCC, including RNF217, GJA8, PTPRE, PSAPL1, and LRRC8D. Genes involved in Wnt-signaling pathways were enriched in hypomethylated DMRs in the obese NASH-HCC. Conclusions These data suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice may drive progression of HCC, while progression of HCC in lean mice may be driven through other signaling pathways, including lipid metabolism.

The bacterial pathogen Candidatus Liberibacter asiaticus (CLas) is the causal agent of citrus greening disease. This unusual plant pathogenic bacterium also infects its psyllid host, the Asian citrus psyllid (ACP). To investigate gene expression profiles with a focus on genes involved in infection and circulation within the psyllid host of CLas, RNA-seq libraries were constructed from CLas-infected and CLas-free ACP representing the five different developmental stages, namely, nymphal instars 1-2, 3, and 4-5, and teneral and mature adults. The Gbp paired-end reads (296) representing the transcriptional landscape of ACP across all life stages and the official gene set (OGSv3) were annotated based on the chromosomal-length v3 reference genome and used for de novo transcript discovery resulting in 25,410 genes with 124,177 isoforms. Differential expression analysis across all ACP developmental stages revealed instar-specific responses to CLas infection, with greater overall responses by nymphal instars, compared to mature adults. More genes were over-or under-expressed in the 4-5th nymphal instars and young (teneral) adults than in instars 1-3, or mature adults, indicating that late immature instars and young maturing adults were highly responsive to CLas infection. Genes identified with potential for direct or indirect involvement in the ACP-CLas circulative, propagative transmission pathway were predominantly responsive during early invasion and infection processes and included canonical cytoskeletal remodeling and endo-exocytosis pathway genes. Genes with predicted functions in defense, development, and immunity exhibited the greatest responsiveness to CLas infection. These results shed new light on ACP-CLas interactions essential for pathogenesis of the psyllid host, some that share striking similarities with effector protein-animal host mechanisms reported for other culturable and/or fastidious bacterial- or viral- host pathosystems.

The use of lattice structure in the Design for Additive Manufacturing (DfAM) engineering practice offers the ability to tailor the properties (and therefore the response) of an engineered component independent of the material and overall geometry. The selection of a lattice topology is critical in maximizing the value of the lattice structure and its unique properties for the intended application. To support this, we have compiled a catalog of lattice structures from the literature that includes all Triply Periodic Minimal Surfaces (TPMS) for which a low-order Fourier series fit is known (so that they can be modeled and manufactured). We also include equations that do not directly correspond to known TPMS but do produce a triply periodic structure without sharp corners that would give rise to stress concentrations. This catalog includes images, elastic mechanical property data, and CAD models useful for the visualization, selection, and implementation of these lattice structures for any engineered structure.

The efficacy of youth violence prevention policies, programs, and practices partly depends on understanding the reasons for why students are targeted for victimization. However, what is known about why some students are targeted for victimization over others is limited to researcher-generated reasons and therefore may risk ecological validity. This study used a qualitative open-coding content analyses to make sense of 8531 students' open-ended responses about the reasons why they were targeted for victimization at school. Results identified 35 commonly reported reasons, many of which are underrepresented in previous literature. Students primarily reported reasons related to relational dynamics, physical characteristics, non-physical personal characteristics, and characteristics external to themselves. These results portray reasons for being targeted as a social phenomenon with both individual and contextual components. Implications for theory, research, and practitioners are discussed.

Antipsychotic drugs are still widely prescribed to control various severe neuropsychiatric symptoms in the elderly and dementia patients although they are off-label use in the United States. However, clinical practice shows greater side effects and lower efficacy of antipsychotics for this vulnerable population and the mechanisms surrounding this aged-related sensitivity are not well understood. Our previous studies have shown that aging-induced epigenetic alterations may be involved in the increasing severity of typical antipsychotic haloperidol induced side effects in aged mice. Still, it is unknown if similar epigenetic mechanisms extend to atypical antipsychotics, which are most often prescribed to dementia patients combined with severe neuropsychiatric symptoms. In this study, we report that atypical antipsychotic risperidone also causes increased motor side effect behaviors in aged mice and 5xFAD mice. Histone deacetylase (HDAC) inhibitor Valproic Acid and Entinostat can mitigate the risperidone induced motor side effects. We further showed besides D2R, reduced expression of 5-HT2A, one of the primary atypical antipsychotic targets in the striatum of aged mice that are also mitigated by HDAC inhibitors. Finally, we demonstrate that specific histone acetylation mark H3K27 is hypoacetylated at the 5htr2a and Drd2 promoters in aged mice and can be reversed with HDAC inhibitors. Our work here establishes evidence for a mechanism where aging reduces expression of 5-HT2A and D2R, the key atypical antipsychotic drug targets through epigenetic alteration. HDAC inhibitors can restore 5-HT2A and D2R expression in aged mice and decrease the motor side effects in aged and 5xFAD mice.

Introduction Multiple abortions are consistently associated with adverse health consequences. Prior abortion is a known risk factor for another abortion. Objective To determine the persistence of the association of a first-pregnancy abortion with the likelihood of subsequent pregnancy outcomes. Methods Data was extracted for a study population of 5453 continuously eligible Medicaid beneficiaries in states which funded and reported elective abortions 1999–2015. Women age 16 in 1999 were organized into three cohorts based upon the first pregnancy outcome: abortion, birth, natural loss. Results Women in the abortion cohort are more likely than those in the birth cohort to experience another abortion rather than a birth or natural loss, and less likely to experience a live birth rather than an abortion or natural loss, for every subsequent pregnancy. The tendency toward abortion (OR 2.99, CL 2.02-4.43) and away from birth (OR 0.49, CL 0.39-0.63) peaks at the sixth pregnancy, but persists throughout the reproductive period ages 16–32. The pattern is reversed, but similarly consistent, for women in the birth cohort. They remain likelier to have another birth rather than an abortion or natural loss in subsequent pregnancies. Compared to the birth cohort, the abortion cohort had 1.35 times as many pregnancies: 4.31 times the abortions, 1.53 times the natural losses, but only 0.52 times the births. They were 4.3 and 5.0 times as likely to have 2-plus and 3-plus abortions, but only 0.47 times and 0.31 times as likely to have 2-plus and 3-plus births. Of the abortion cohort, 37.1% had no births. By contrast, 73.6% of the birth cohort had no abortions. Conclusion The first-pregnancy abortion maintains a strong and persistent association with the likelihood of another abortion in subsequent pregnancies, enabling a cascade of adverse events associated with multiple abortions.

Background Despite an elevated risk of psychopathology stemming from COVID-19-related stress, many essential workers stigmatise and avoid psychiatric care. This randomised controlled trial was designed to compare five versions of a social-contact-based brief video intervention for essential workers, differing by protagonist gender and race/ethnicity. Aims We examined intervention efficacy on treatment-related stigma (‘stigma’) and openness to seeking treatment (‘openness’), especially among workers who had not received prior mental healthcare. We assessed effectiveness and whether viewer/protagonist demographic concordance heightened effectiveness. Method Essential workers (N = 2734) randomly viewed a control video or brief video of an actor portraying an essential worker describing hardships, COVID-related anxiety and depression, and psychotherapy benefits. Five video versions (Black/Latinx/White and male/female) followed an identical 3 min script. Half the intervention group participants rewatched their video 14 days later. Stigma and openness were assessed at baseline, post-intervention, and at 14- and 30-day follow-ups. Trial registration: NCT04964570. Results All video intervention groups reported immediately decreased stigma (P < 0.0001; Cohen's d = 0.10) and increased openness (P < 0.0001; d = 0.23). The initial increase in openness was largely maintained in the repeated-video group at day 14 (P < 0.0001; d = 0.18), particularly among viewers without history of psychiatric treatment (P < 0.0001; d = 0.32). Increases were not sustained at follow-up. Female participants viewing a female protagonist and Black participants viewing a Black protagonist demonstrated greater openness than other demographic pairings. Conclusions Brief video-based interventions improved immediate stigma and openness. Greater effects among female and Black individuals viewing demographically matched protagonists emphasise the value of tailored interventions, especially for socially oppressed groups. This easily disseminated intervention may proactively increase care-seeking, encouraging treatment among workers in need. Future studies should examine intervention mechanisms and whether linking referrals to psychiatric services generates treatment-seeking.

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

Introduction: The prevalence of induced abortion among women with children has been estimated indirectly by projections derived from survey research. However, an empirically derived, population-based conclusion on this question is absent from the published literature. Objective: The objective of this study was to describe the period prevalence of abortion among all other possible pregnancy outcomes within the reproductive histories of Medicaid-eligible women in the U.S. Methods: A retrospective, cross-sectional, longitudinal analysis of the pregnancy outcome sequences of eligible women over age 13 from the 17 states where Medicaid included coverage of most abortions, with at least one identifiable pregnancy between 1999 and 2014. A total of 1360 pregnancy outcome sequences were grouped into 8 categories which characterize various combinations of the 4 possible pregnancy outcomes: birth, abortion, natural loss, and undetermined loss. The reproductive histories of 4,884,101 women representing 7,799,784 pregnancy outcomes were distributed into these categories. Results: Women who had live births but no abortions or undetermined pregnancy losses represented 74.2% of the study population and accounted for 87.6% of total births. Women who have only abortions but no births constitute 6.6% of the study population, but they are 53.5% of women with abortions and have 51.5% of all abortions. Women with both births and abortions represent 5.7% of the study population and have 7.2% of total births. Conclusion: Abortion among low-income women with children is exceedingly uncommon, if not rare. The period prevalence of mothers without abortion is 13 times that of mothers with abortion.

Introduction/Objectives: Although a majority of women who have an abortion report having 1 or more children, there is no published research on the number of abortions which occur between live births, after a first child but before the last. The objectives of this research, therefore, were to estimate the period prevalence of an induced abortion separating live births in a population of Medicaid eligible enrollees and to identify the characteristics of enrollees significantly associated with the use of abortion to enable child spacing. Methods: A retrospective, cross-sectional, longitudinal analysis of the pregnancy outcome sequences of eligible enrollees over age 13 from the 17 states where Medicaid included coverage of all abortions, with at least one identifiable pregnancy outcome between 1999 and 2014. Eligibles with a defined sequence of birth-abortion-birth within up to 5 consecutive pregnancies were identified to estimate the number of eligibles who could have practiced birth spacing by abortion. Logistic regression was applied to identify the significant predictor variables of the birth-abortion-birth sequence. Results: There were 50 012 (1.02%) of 4 875 511 Medicaid eligible enrollees exhibited a birth-abortion-birth sequence. Eligibles with the birth-abortion-birth sequence are more likely to be Black than White (OR 2.641, CL 2.581-2.702), less likely to be Hispanic than White (OR 0.667, CL 0.648-0.687), and more likely to have received contraceptive counseling (OR 1.14, CL 1.118-1.163). Increases in months of Medicaid eligibility (OR 1.004, CL 1.003-1.004) and months from first pregnancy to second live birth (OR 1.015, CL 1.015-1.016) are associated with the likelihood of undergoing live births separated by one or more induced abortions. Increases in the age at first pregnancy are associated with a decreased likelihood of the birth-abortion-birth sequence (OR 0.962, CL 0.959-0.964). Conclusion: Birth spacing via abortion is uncommon among a low-income population for whom the financial barriers to abortion are somewhat alleviated.