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1.
SSM Popul Health ; 26: 101675, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38711568

RESUMO

Health equity is fundamental to improving the health of populations, but in recent decades progress towards this goal has been mixed. To better support this mission, a deeper understanding of the local heterogeneity within population-level health equity is vital. This analysis presents trends in average health and health equity in the United States at the local level from 1990 to 2019 using three different health outcomes: mortality, self-reported health status, and healthy days. Furthermore, it examines the association between these measures of average health and health equity with several structural factors. Results indicate growing levels of geographic inequality disproportionately impacting less urbanized parts of the country, with rural counties experiencing the largest declines in health equity, followed by Medium and Small Metropolitan counties. Additionally, lower levels of health equity are associated with poorer local socioeconomic context, including several measures that are proxies for structural racism. Altogether, these findings strongly suggest social and economic factors play a pivotal role in explaining growing levels of geographic health inequality in the United States. Policymakers invested in improving health equity must adopt holistic and upstream approaches to improve and equalize economic opportunity as a means of fostering health equity.

2.
Dev Psychopathol ; : 1-10, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738358

RESUMO

Substance use disorders among juveniles are a major public health concern and are often intertwined with other psychosocial risk factors including antisocial behavior. Identifying etiological risks and mechanisms promoting substance use disorders remains a high priority for informing more focused interventions in high-risk populations. The present study examined brain gray matter structure in relation to substance use severity among n = 152 high-risk, incarcerated boys (aged 14-20). Substance use severity was positively associated with gray matter volume across several frontal/striatal brain regions including amygdala, pallidum, putamen, insula, and orbitofrontal cortex. Effects were apparent when using voxel-based-morphometric analysis, as well as in whole-brain, data-driven, network-based approaches (source-based morphometry). These findings support the hypothesis that elevated gray matter volume in striatal reward circuits may be an endogenous marker for vulnerability to severe substance use behaviors among youth.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38659338

RESUMO

BACKGROUND: Young children involved in the child welfare system (CWS) are at high risk for suicidal ideation (SI) at a time when overall rates of suicide death in this age group are rising. Yet risk factors for and changes in SI over time are poorly understood in this population. METHOD: We combined data from two large representative longitudinal studies of children involved in the United States CWS. We examined patterns of SI among children who were between ages 7 and 12 years at the initial survey wave (N = 2,186), assessed at three waves using a measure of SI in the past 2 weeks. We conducted a multinomial regression to understand the baseline demographic, child maltreatment, and mental health characteristics that distinguish the trajectories. RESULTS: There were eight different subgroups (Non-Ideators, Late Ideators, Boomerang Ideators, Delayed Ideators, Desisters, Boomerang Non-Ideators, Late Desisters, and Persisters). Differences in race, type of maltreatment, sex, and mental health symptoms were identified when comparing Persisters (SI at all three waves) to other groups. CONCLUSIONS: These findings can help researchers and practitioners to develop strategies for better identifying CWS-involved children who are in greatest need of suicide risk monitoring and intervention.

4.
J Vis Exp ; (206)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38647320

RESUMO

Fuel treatments and other forest restoration thinning practices aim to reduce wildfire risk while building forest resilience to drought, insects, and diseases and increasing aboveground carbon (C) sequestration. However, fuel treatments generate large amounts of unmerchantable woody biomass residues that are often burned in open piles, releasing significant quantities of greenhouse gases and particulates, and potentially damaging the soil beneath the pile. Air curtain burners offer a solution to mitigate these issues, helping to reduce smoke and particulates from burning operations, more fully burn biomass residues compared to pile burning, and eliminate the direct and intense fire contact that can harm soil beneath the slash pile. In an air curtain burner, burning takes place in a controlled environment. Smoke is contained and recirculated by the air curtain, and therefore burning can be conducted under a variety of climatic conditions (e.g., wind, rain, snow), lengthening the burning season for disposal of slash material. The mobile pyrolysis unit that continuously creates biochar was specifically designed to dispose of residual woody biomass at log landings, green wood at landfills, or salvaged logged materials and create biochar in the process. This high-carbon biochar output can be used to enhance soil resilience by improving its chemical, physical, and biological properties and has potential applications in remediating contaminated soils, including those at abandoned mine sites. Here, we describe the general use of this equipment, appropriate siting, loading methods, quenching requirements, and lessons learned about operating this new technology.


Assuntos
Carvão Vegetal , Madeira , Madeira/química , Carvão Vegetal/química , Pirólise , Agricultura Florestal/métodos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38407775

RESUMO

Psychopathic traits have been associated with rearrest in adolescents involved in the criminal legal system. Much of the prior work has focused on White samples, short follow-up windows, and relatively low-risk youth. The current study aimed to evaluate the utility of the Hare Psychopathy Checklist: Youth Version (PCL:YV) for predicting general and violent felony recidivism in a large sample of high-risk, predominantly Hispanic/Latino, male adolescents (n = 254) with a five-year follow-up period. Results indicated higher PCL:YV scores and lower full-scale estimated IQ scores were significantly associated with a shorter time to felony and violent felony rearrest. These effects generalized to Hispanic/Latino adolescents (n = 193)-a group that faces disproportionate risk of being detained or committed to juvenile correctional facilities in the U.S. These results suggest that expert-rated measures of psychopathic traits and IQ are reliable predictors of subsequent felony and violent felony rearrest among high-risk male adolescents.

6.
Children (Basel) ; 11(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38255377

RESUMO

Studies have reported positive associations between youth psychopathy scores and measures of 'fearlessness'. However, prior studies modified fearlessness items to be age appropriate, shifting from assessing hypothetical, extreme forms of physical risk-taking (e.g., flying an airplane) to normative risk-taking (e.g., riding bicycles downhill). We hypothesize that associations between youth psychopathy scores and alternative forms of sensation seeking (i.e., Disinhibition) have been conflated under a false fearlessness label. We tested this hypothesis among incarcerated male adolescents, investigating whether youth psychopathy scores were significantly associated with two different forms of sensation seeking: Disinhibition and Thrill and Adventure Seeking (TAS). Youth psychopathic traits were assessed using the Psychopathy Checklist: Youth Version (PCL:YV), Antisocial Process Screening Device (APSD), Child Psychopathy Scale (CPS), Inventory of Callous and Unemotional Traits (ICU), and Youth Psychopathic Traits Inventory (YPI). Disinhibition and fearlessness (i.e., TAS) were assessed using an unmodified version of the Zuckerman Sensation Seeking Scales (SSS). Consistent with hypotheses, youth psychopathy scores were associated with higher Disinhibition and lower TAS scores. Our results contribute to a growing body of literature suggesting that psychopathic traits, including among adolescents, are not concomitant with physical risk-taking and descriptions of psychopathy including fearlessness distort a precise understanding of psychopathy's core features.

7.
Pers Individ Dif ; 2002023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37937147

RESUMO

Men with elevated psychopathic traits have been characterized by unique patterns of nonverbal communication, including more fixed and focused head positions during clinical interviews, compared to men scoring low on measures of psychopathy. However, it is unclear whether similar patterns of head dynamics help characterize women scoring high on psychopathic traits. Here, we utilized an automated detection algorithm to assess head position and dynamics during a videotaped clinical interview (i.e., the Psychopathy Checklist - Revised [PCL-R]) in a sample of n = 213 incarcerated women. PCL-R Total, Factor 1 (i.e., interpersonal and affective psychopathic traits), and Factor 2 (i.e., lifestyle/behavioral and antisocial/developmental psychopathic traits) scores were associated with a pattern of head dynamics indicative of a rigid head position. The current study extends analyses of nonverbal behavior studies in men to women and highlights how individuals with elevated psychopathic traits demonstrate unique nonverbal behaviors relative to individuals who score low on psychopathic traits. The implications and clinical value of these findings are discussed.

8.
Nat Commun ; 14(1): 5826, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749094

RESUMO

Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observe excessive renin and NOTCH1 signalling mRNAs, with a concomitant non-excess of NRARP expression. Re-analysis of previously published reninoma bulk transcriptomes further corroborates our observation of dysregulated Notch pathway signalling in reninoma. Our findings reveal NOTCH1 rearrangements in reninoma, therapeutically targetable through existing NOTCH1 inhibitors, and indicate that unscheduled Notch signalling may be a disease-defining feature of reninoma.


Assuntos
Neoplasias Renais , Renina , Humanos , Renina/metabolismo , Neoplasias Renais/metabolismo , Sistema Justaglomerular/metabolismo , Sistema Justaglomerular/patologia , Glomérulos Renais/patologia , Transdução de Sinais/genética , Receptor Notch1/genética
9.
Child Adolesc Psychiatry Ment Health ; 17(1): 111, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735417

RESUMO

BACKGROUND: Incarcerated youth are characterized by particularly high rates of childhood trauma, a significant risk factor for outcomes including risky behaviors and recidivism. Trauma-based interventions can ameliorate the negative effects of childhood trauma; however, a critical part of success is careful trauma screening. Due to the limitations associated with commonly used self-report trauma assessments, our team developed the Trauma Checklist (TCL), a trained-rater assessment of childhood trauma specifically created for use with forensic populations. The TCL is designed to provide a more comprehensive assessment of trauma, incorporating categories that are of specific relevance for incarcerated individuals (e.g., traumatic loss). Here, we discuss the continued development made to our original trauma assessment and explore the psychometric properties of this expanded assessment (herein termed the TCL 2.0). METHOD: We examined relationships between TCL 2.0 scores, measures of psychopathology, and psychopathic traits in a sample of incarcerated male juvenile offenders (n = 237). In addition, we examined whether TCL 2.0 scores were associated with time to felony re-offense via Cox proportional-hazard regression analyses. RESULTS: We examined dimensionality of the TCL 2.0 using a principal component analysis (PCA), the results of which were confirmed via exploratory structural equation modeling; the PCA yielded a two-component solution (i.e., PC1 and PC2). We observed that PC1 (Experienced Trauma) scores were positively correlated with mood disorder diagnoses. TCL 2.0 total scores were positively correlated with post-traumatic stress disorder symptomatology and psychopathic traits. Finally, higher PC2 (Community Trauma) scores were associated with faster time to felony re-offending. CONCLUSIONS: These results suggest that the TCL 2.0 may be a beneficial screening tool to provide high-risk youth with appropriate trauma-informed treatment.

10.
Front Neuroimaging ; 2: 1216494, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554634

RESUMO

Previous work in incarcerated boys and adult men and women suggest that individuals scoring high on psychopathic traits show altered resting-state limbic/paralimbic, and default mode functional network properties. However, it is unclear whether similar results extend to high-risk adolescent girls with elevated psychopathic traits. This study examined whether psychopathic traits [assessed via the Hare Psychopathy Checklist: Youth Version (PCL:YV)] were associated with altered inter-network connectivity, intra-network connectivity (i.e., functional coherence within a network), and amplitude of low-frequency fluctuations (ALFFs) across resting-state networks among high-risk incarcerated adolescent girls (n = 40). Resting-state networks were identified by applying group independent component analysis (ICA) to resting-state fMRI scans, and a priori regions of interest included limbic, paralimbic, and default mode network components. We tested the association of psychopathic traits (PCL:YV Factor 1 measuring affective/interpersonal traits and PCL:YV Factor 2 assessing antisocial/lifestyle traits) to these three resting-state measures. PCL:YV Factor 1 scores were associated with increased low-frequency and decreased high-frequency fluctuations in components corresponding to the default mode network, as well as increased intra-network FNC in components corresponding to cognitive control networks. PCL:YV Factor 2 scores were associated with increased low-frequency fluctuations in sensorimotor networks and decreased high-frequency fluctuations in default mode, sensorimotor, and visual networks. Consistent with previous analyses in incarcerated adult women, our results suggest that psychopathic traits among incarcerated adolescent girls are associated with altered intra-network ALFFs-primarily that of increased low-frequency and decreased high-frequency fluctuations-and connectivity across multiple networks including paralimbic regions. These results suggest stable neurobiological correlates of psychopathic traits among women across development.

11.
Nat Med ; 29(7): 1700-1709, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37407840

RESUMO

In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. This persistence signature was dominant among circulating CAR-T cells in all children with a long-lived treatment response for which sequencing data were sufficient (4/4, 100%). The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists.


Assuntos
Leucemia Linfocítica Crônica de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Antígenos CD19/genética , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T , Indução de Remissão , Linfócitos T
12.
Curr Oncol ; 30(7): 5946-5952, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37503586

RESUMO

ETV6-ABL1 gene fusion is a rare genetic rearrangement in a variety of malignancies, including myeloproliferative neoplasms (MPN), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Here, we report the case of a 16-year-old male diagnosed with a MPN, 7 months post-completion of treatment for Burkitt leukaemia. RNA sequencing analysis confirmed the presence of an ETV6-ABL1 fusion transcript, with an intact, in-frame ABL tyrosine-kinase domain. Of note, secondary ETV6-ABL1-rearranged neoplastic diseases have not been reported to date. The patient was started on a tyrosine kinase inhibitor (TKI; imatinib) and, subsequently, underwent a 10/10 matched unrelated haematopoietic stem cell transplant. He is disease-free five years post-transplant. Definitive evidence of the prognostic influence of the ETV6-ABL1 fusion in haematological neoplasms is lacking; however, overall data suggest that it is a poor prognostic factor, particularly in patients with ALL and AML. The presence of this ETV6-ABL1 fusion should be more routinely investigated, especially in patients with a CML-like picture. More routine use of whole-genome and RNA sequencing analyses in clinical diagnostic care, in conjunction with conventional cytogenetics, will facilitate these investigations.


Assuntos
Linfoma de Burkitt , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Adolescente , Proteínas Tirosina Quinases/genética , Hibridização in Situ Fluorescente , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
13.
Am J Prev Med ; 65(6): 1078-1091, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37385571

RESUMO

INTRODUCTION: Structural racism has clear and pernicious effects on population health. However, there is a limited understanding of how structural racism impacts young people's well-being. The objective of this ecologic cross-sectional study was to assess the relationship between structural racism and well-being for 2,009 U.S. counties from 2010 to 2019. METHODS: Population-based data on demographics, health, and other variables related to young people's ability to thrive are used to construct a previously validated composite index that serves as a proxy of young people's well-being. The index is regressed on several forms of structural racism (segregation, economic, and educational) both independently and jointly while accounting for county-fixed effects, time trends, and state-specific trends as well as weighting for child population. Data were analyzed from November 2021 through March 2023. RESULTS: Higher levels of structural racism are associated with lower well-being. A 1-SD increase in Black-White child poverty disparity is associated with a -0.034 (95% CI= -0.019, -0.050) SD change in index score. When accounting for multiple structural racism measures, associations remain statistically significant. In joint models, only estimates for economic racism measures remain significant when additionally controlling for demographic, socioeconomic, and adult health measures (ß= -0.015; 95% CI= -0.001, -0.029). These negative associations are heavily concentrated in counties where Black and Latinx children are overrepresented. CONCLUSIONS: Structural racism-particularly of the kind that produces racialized poverty outcomes-has a meaningful adverse association with child and adolescent well-being, which may produce lifelong effects. Studies of structural racism among adults should consider a lifecourse perspective.


Assuntos
Racismo , Racismo Sistêmico , Adolescente , Adulto , Criança , Humanos , Estudos Transversais , Escolaridade , Pobreza , Nível de Saúde
14.
Neuroimage Rep ; 3(1)2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37169013

RESUMO

Individuals with acute and chronic traumatic brain injury (TBI) are associated with unique white matter (WM) structural abnormalities, including fractional anisotropy (FA) differences. Our research group previously used FA as a feature in a linear support vector machine (SVM) pattern classifier, observing high classification between individuals with and without acute TBI (i.e., an area under the curve [AUC] value of 75.50%). However, it is not known whether FA could similarly classify between individuals with and without history of chronic TBI. Here, we attempted to replicate our previous work with a new sample, investigating whether FA could similarly classify between incarcerated men with (n = 80) and without (n = 80) self-reported history of chronic TBI. Additionally, given limitations associated with FA, including underestimation of FA values in WM tracts containing crossing fibers, we extended upon our previous study by incorporating neurite orientation dispersion and density imaging (NODDI) metrics, including orientation dispersion (ODI) and isotropic volume (Viso). A linear SVM based classification approach, similar to our previous study, was incorporated here to classify between individuals with and without self-reported chronic TBI using FA and NODDI metrics as separate features. Overall classification rates were similar when incorporating FA and NODDI ODI metrics as features (AUC: 82.50%). Additionally, NODDI-based metrics provided the highest sensitivity (ODI: 85.00%) and specificity (Viso: 82.50%) rates. The current study serves as a replication and extension of our previous study, observing that multiple diffusion MRI metrics can reliably classify between individuals with and without self-reported history of chronic TBI.

15.
J Public Health Manag Pract ; 29(4): 529-538, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37200100

RESUMO

CONTEXT: In recent years, stakeholders in public health have emphasized measuring young peoples' well-being as a more holistic and upstream approach to understanding their health and development. However, summarizing the available indicators of well-being in ways that strengthen ongoing policy and community efforts remains a challenge. PROGRAM: Our objective was to develop a measurement framework of young peoples' well-being that would be engaging and actionable to a broad and diverse set of stakeholders in California. IMPLEMENTATION: We began with a scan of the relevant literature documenting previous efforts to measure young peoples' well-being, both within the United States and internationally. Subsequently, we individually interviewed a set of key informants and then convened a multidisciplinary panel of experts to solicit feedback on our approach. Throughout this iterative and collaborative process, we developed and refined a measurement framework based on the information provided across these various sources. EVALUATION: Findings suggest data dashboards are a promising approach for presenting a parsimonious yet holistic picture of young peoples' well-being. Dashboards can highlight well-being's multidimensionality by categorizing indicators over different domains. Our framework organizes indicators over 5 types: child-centric, subjective well-being, contextual determinants, developmental, and equity-focused. The design and flexibility of dashboards can also highlight important gaps in data collection that are of interest to end users such as indicators not yet collected among the broader population. Furthermore, dashboards can include interactive features, such as selecting key data elements, that can help communities articulate priority areas for policy action, thereby generating momentum and enthusiasm for future iterations and improvements. DISCUSSION: Data dashboards are well suited for engaging a variety of stakeholders on complex multidimensional concepts such as young peoples' well-being. However, to fulfill their promise, they should be codesigned and codeveloped through an iterative process with the stakeholders and community members they intend to serve.


Assuntos
Saúde do Adolescente , Adolescente , Humanos , Estados Unidos , California
16.
Milbank Q ; 101(2): 259-286, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37052602

RESUMO

Policy Points Social indicators of young peoples' conditions and circumstances, such as high school graduation, food insecurity, and smoking, are improving even as subjective indicators of mental health and well-being have been worsening. This divergence suggests policies targeting the social indicators may not have improved overall mental health and well-being. There are several plausible reasons for this seeming contradiction. Available data suggest the culpability of one or several common exposures poorly captured by existing social indicators. Resolving this disconnect requires significant investments in population-level data systems to support a more holistic, child-centric, and up-to-date understanding of young people's lives.


Assuntos
Saúde Mental , Adolescente , Humanos , Estados Unidos , Saúde do Adolescente , Saúde da Criança , Criança
17.
Neuroimage Clin ; 37: 103343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36764058

RESUMO

Individuals with history of childhood trauma are characterized by aberrant resting-state limbic and paralimbic functional network connectivity. However, it is unclear whether specific subtypes of trauma (i.e., experienced vs observed or community) showcase differential effects. This study examined whether subtypes of childhood trauma (assessed via the Trauma Checklist [TCL] 2.0) were associated with aberrant intra-network amplitude of fluctuations and connectivity (i.e., functional coherence within a network), and inter-network connectivity across resting-state networks among incarcerated juvenile males (n = 179). Subtypes of trauma were established via principal component analysis of the TCL 2.0 and resting-state networks were identified by applying group independent component analysis to resting-state fMRI scans. We tested the association of subtypes of childhood trauma (i.e., TCL Factor 1 measuring experienced trauma and TCL Factor 2 assessing community trauma), and TCL Total scores to the aforementioned functional connectivity measures. TCL Factor 2 scores were associated with increased high-frequency fluctuations and increased intra-network connectivity in cognitive control, auditory, and sensorimotor networks, occurring primarily in paralimbic regions. TCL Total scores exhibited similar neurobiological patterns to TCL Factor 2 scores (with the addition of aberrant intra-network connectivity in visual networks), and no significant associations were found for TCL Factor 1. Consistent with previous analyses of community samples, our results suggest that childhood trauma among incarcerated juvenile males is associated with aberrant intra-network amplitude of fluctuations and connectivity across multiple networks including predominately paralimbic regions. Our results highlight the importance of accounting for traumatic loss, observed trauma, and community trauma in assessing neurobiological aberrances associated with adverse experiences in childhood, as well as the value of trained-rater trauma assessments compared to self-report.


Assuntos
Experiências Adversas da Infância , Criminosos , Masculino , Humanos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Criminosos/psicologia , Imageamento por Ressonância Magnética/métodos
18.
Front Public Health ; 11: 856940, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825137

RESUMO

Background: U.S. school closures due to the coronavirus disease 2019 (COVID-19) pandemic led to extended periods of remote learning and social and economic impact on families. Uncertainty about virus dynamics made it difficult for school districts to develop mitigation plans that all stakeholders consider to be safe. Methods: We developed an agent-based model of infection dynamics and preventive mitigation designed as a conceptual tool to give school districts basic insights into their options, and to provide optimal flexibility and computational ease as COVID-19 science rapidly evolved early in the pandemic. Elements included distancing, health behaviors, surveillance and symptomatic testing, daily symptom and exposure screening, quarantine policies, and vaccination. Model elements were designed to be updated as the pandemic and scientific knowledge evolve. An online interface enables school districts and their implementation partners to explore the effects of interventions on outcomes of interest to states and localities, under a variety of plausible epidemiological and policy assumptions. Results: The model shows infection dynamics that school districts should consider. For example, under default assumptions, secondary infection rates and school attendance are substantially affected by surveillance testing protocols, vaccination rates, class sizes, and effectiveness of safety education. Conclusions: Our model helps policymakers consider how mitigation options and the dynamics of school infection risks affect outcomes of interest. The model was designed in a period of considerable uncertainty and rapidly evolving science. It had practical use early in the pandemic to surface dynamics for school districts and to enable manipulation of parameters as well as rapid update in response to changes in epidemiological conditions and scientific information about COVID-19 transmission dynamics, testing and vaccination resources, and reliability of mitigation strategies.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Reprodutibilidade dos Testes , SARS-CoV-2 , Quarentena , Instituições Acadêmicas
19.
Immunity ; 56(1): 11-13, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36630910

RESUMO

In a study recently in Nature, Galeano Niño et al. use spatial profiling and single-cell RNA sequencing to delineate the spatial organization of microbiota in cancer. Their findings demonstrate that tumor-associated microbiota coalesce in micro-niches where they may mediate immune and epithelial oncogenic roles.


Assuntos
Microbiota , Neoplasias , Humanos , Bactérias/genética
20.
Nat Commun ; 14(1): 77, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604421

RESUMO

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline TP53 pathogenic variants. Here, we perform whole-genome sequence (WGS) analysis of tumors from 22 patients with TP53 germline pathogenic variants. We observe somatic mutations affecting Wnt, PI3K/AKT signaling, epigenetic modifiers and homologous recombination genes as well as mutational signatures associated with prior chemotherapy. We identify near-ubiquitous early loss of heterozygosity of TP53, with gain of the mutant allele. This occurs earlier in these tumors compared to tumors with somatic TP53 mutations, suggesting the timing of this mark may distinguish germline from somatic TP53 mutations. Phylogenetic trees of tumor evolution, reconstructed from bulk and multi-region WGS, reveal that LFS tumors exhibit comparatively limited heterogeneity. Overall, our study delineates early copy number gains of mutant TP53 as a characteristic mutational process in LFS tumorigenesis, likely arising years prior to tumor diagnosis.


Assuntos
Síndrome de Li-Fraumeni , Síndromes Neoplásicas Hereditárias , Humanos , Proteína Supressora de Tumor p53/genética , Predisposição Genética para Doença , Variações do Número de Cópias de DNA/genética , Fosfatidilinositol 3-Quinases/genética , Filogenia , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/genética , Mutação em Linhagem Germinativa/genética , Mutação
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