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To understand the neural basis of behavior, it is essential to measure spiking dynamics across many interacting brain regions. Although new technologies, such as Neuropixels probes, facilitate multi-regional recordings, significant surgical and procedural hurdles remain for these experiments to achieve their full potential. Here, we describe skull-shaped hemispheric implants enabling large-scale electrophysiology datasets (SHIELD). These 3D-printed skull-replacement implants feature customizable insertion holes, allowing dozens of cortical and subcortical structures to be recorded in a single mouse using repeated multi-probe insertions over many days. We demonstrate the procedure's high success rate, biocompatibility, lack of adverse effects on behavior, and compatibility with imaging and optogenetics. To showcase SHIELD's scientific utility, we use multi-probe recordings to reveal novel insights into how alpha rhythms organize spiking activity across visual and sensorimotor networks. Overall, this method enables powerful, large-scale electrophysiological experiments for the study of distributed neural computation.
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When sensory information is incomplete or ambiguous, the brain relies on prior expectations to infer perceptual objects. Despite the centrality of this process to perception, the neural mechanism of sensory inference is not known. Illusory contours (ICs) are key tools to study sensory inference because they contain edges or objects that are implied only by their spatial context. Using cellular resolution, mesoscale two-photon calcium imaging and multi-Neuropixels recordings in the mouse visual cortex, we identified a sparse subset of neurons in the primary visual cortex (V1) and higher visual areas that respond emergently to ICs. We found that these highly selective 'IC-encoders' mediate the neural representation of IC inference. Strikingly, selective activation of these neurons using two-photon holographic optogenetics was sufficient to recreate IC representation in the rest of the V1 network, in the absence of any visual stimulus. This outlines a model in which primary sensory cortex facilitates sensory inference by selectively strengthening input patterns that match prior expectations through local, recurrent circuitry. Our data thus suggest a clear computational purpose for recurrence in the generation of holistic percepts under sensory ambiguity. More generally, selective reinforcement of top-down predictions by pattern-completing recurrent circuits in lower sensory cortices may constitute a key step in sensory inference.
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PURPOSE: Exposures early in life, beginning in utero, have long-term impacts on mental and physical health. The ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) was established to examine the independent and combined impact of pregnancy and childhood chemical exposures and psychosocial stressors on child neurodevelopment and airway health, as well as the placental mechanisms underlying these associations. PARTICIPANTS: The ECHO-PATHWAYS consortium harmonises extant data from 2684 mother-child dyads in three pregnancy cohort studies (CANDLE [Conditions Affecting Neurocognitive Development and Learning in Early Childhood], TIDES [The Infant Development and Environment Study] and GAPPS [Global Alliance to Prevent Prematurity and Stillbirth]) and collects prospective data under a unified protocol. Study participants are socioeconomically diverse and include a large proportion of Black families (38% Black and 51% White), often under-represented in research. Children are currently 5-15 years old. New data collection includes multimodal assessments of primary outcomes (airway health and neurodevelopment) and exposures (air pollution, phthalates and psychosocial stress) as well as rich covariate characterisation. ECHO-PATHWAYS is compiling extant and new biospecimens in a central biorepository and generating the largest placental transcriptomics data set to date (N=1083). FINDINGS TO DATE: Early analyses demonstrate adverse associations of prenatal exposure to air pollution, phthalates and maternal stress with early childhood airway outcomes and neurodevelopment. Placental transcriptomics work suggests that phthalate exposure alters placental gene expression, pointing to mechanistic pathways for the developmental toxicity of phthalates. We also observe associations between prenatal maternal stress and placental corticotropin releasing hormone, a marker of hormonal activation during pregnancy relevant for child health. Other publications describe novel methods for examining exposure mixtures and the development of a national spatiotemporal model of ambient outdoor air pollution. FUTURE PLANS: The first wave of data from the unified protocol (child age 8-9) is nearly complete. Future work will leverage these data to examine the combined impact of early life social and chemical exposures on middle childhood health outcomes and underlying placental mechanisms.
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Exposição Ambiental , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Gravidez , Estudos de Coortes , Hormônio Liberador da Corticotropina , Exposição Ambiental/efeitos adversos , Placenta , Estudos ProspectivosRESUMO
INTRODUCTION: This study evaluates the impact of baseline e-cigarette use on smoking cessation rates in a national sample of two-year college student smokers. METHODS: Participants were 1400 students from over 60 two-year colleges across 25 states who were current smokers enrolled in a web-assisted tobacco intervention (WATI) trial. Survey data were collected at baseline, 1-, 6-, and 12-months, with primary outcomes evaluated at 6-months. RESULTS: At 6-months, baseline e-cigarette users were more likely to report cessation of traditional cigarettes compared to non-users (OR 1.39, 95% CI 1.002-1.92). Cessation was also associated with higher baseline confidence in quitting and greater time to first cigarette in the morning. Baseline e-cigarette use was not found to be associated with self-reported cessation of all nicotine/tobacco products (OR 1.09, 95% CI 0.75-1.58) nor biochemically verified cessation of all nicotine/tobacco products (OR 0.83, 95% CI 0.47-1.47). Higher confidence was again associated with both self-reported and biochemically verified cessation of all nicotine/tobacco products. Female gender was associated only with biochemically verified cessation of all nicotine/tobacco products at 6-months. CONCLUSIONS: Two-year college students represent a priority population for cessation interventions. The findings from this study highlight the complexities of evaluating the impact of e-cigarette use on cessation.
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BACKGROUND: Personal smoke-free policies (home and vehicle) reduce secondhand smoke exposure, improve health, and increase quitting among smokers. Overall, 83.0% and 78.1% of Americans report smoke-free homes and vehicles, respectively. However, little is known about such policies among 2-year community college (CC) students, who represent a large, diverse population with higher smoking rates and less negative attitudes toward smoking than 4-year college students. METHODS: Prevalence of, and factors associated with, personal smoke-free policies were examined for 2,475 CC smokers enrolled in a national trial of web-assisted tobacco intervention. RESULTS: Few students had smoke-free home policies (20.7%), smoke-free vehicles (17.0%), both smoke-free home and vehicle policy (4.2%), or any policy (home or vehicle; 31.2%). In logistic regression models, having children was associated with a smoke-free home or any policy but not with a smoke-free vehicle, and among participants who had children, only 20% reported a smoke-free home, and only 15% had a smoke-free vehicle. In addition, not living with other smokers, living with parents or roommates/siblings (vs. alone), smoking later than 30 minutes after awakening, believing that smoking affects the health of others, and confidence in quitting were associated with presence of a smoke-free home or any policy; no variables were significantly associated with presence of a smoke-free vehicle. CONCLUSIONS: CC students represent a priority population for intervention regarding smoke-free homes and vehicles. Such intervention can decrease exposure of others, including children, and potentially increase the likelihood of quitting in this high-risk population.
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Política Antifumo , Fumantes/estatística & dados numéricos , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Universidades , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , New York/epidemiologia , Prevalência , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/prevenção & controle , Adulto JovemRESUMO
BACKGROUND: United States college students, particularly those attending community colleges, have higher smoking rates than the national average. Recruitment of such smokers into research studies has not been studied in depth, despite a moderate amount information on study recruitment success with smokers from traditional four-year colleges. Recruitment channels and success are evolving as technology evolves, so it is important to understand how to best target, implement, and evaluate recruitment strategies. OBJECTIVE: The aim of this paper is to both qualitatively and quantitatively explore recruitment channels (eg, mass email, in-person referral, posted materials) and their success with enrollment into a Web-Assisted Tobacco Intervention study in this priority population of underserved and understudied smokers. METHODS: Qualitative research methods included key informant interviews (n=18) and four focus groups (n=37). Quantitative research methods included observed online responsiveness to any channel (n=10,914), responses from those completing online screening and study consent (n=2696), and responses to a baseline questionnaire from the fully enrolled study participants (n=1452). RESULTS: Qualitative results prior to recruitment provided insights regarding the selection of a variety of recruitment channels proposed to be successful, and provided context for the unique attributes of the study sample. Quantitative analysis of self-reported channels used to engage with students, and to enroll participants into the study, revealed the relative utilization of channels at several recruitment points. The use of mass emails to the student body was reported by the final sample as the most influential channel, accounting for 60.54% (879/1452) of the total enrolled sample. CONCLUSIONS: Relative channel efficiency was analyzed across a wide variety of channels. One primary channel (mass emails) and a small number of secondary channels (including college websites and learning management systems) accounted for most of the recruitment success. TRIAL REGISTRATION: ClinicalTrials.gov NCT01692730; https://clinicaltrials.gov/ct2/show/NCT01692730 (Archived by WebCite at http://www.webcitation.org/6qEcFQN9Q).
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INTRODUCTION: Tobacco use among United States college-aged students remains higher than that of the national average. While a majority of public health literature has explained smoking programs and policies at traditional four-year colleges and universities, little research exists on programs and policies at two-year community colleges. It is important to understand such efforts at these institutions as they have vastly different infrastructures and enroll a more diverse and at-risk student body compared to traditional four-year colleges. METHODS: The role of community colleges in health efforts aimed at smoking was examined at four community colleges. Qualitative research methods included 18 interviews and four focus groups (N=55), document review, and direct environmental observation. RESULTS: Community colleges offered a limited number of smoking cessation and secondhand smoke prevention initiatives. All colleges provided cessation literature, though additional programming varied by college. Indoor and outdoor smoking policies existed on all campuses though enforcement was problematic. Little evidence was found that current program and policy approaches are based upon best practices or are being employed successfully. CONCLUSIONS: Future tobacco control initiatives at community colleges need to require little infrastructure and minimal staffing, and be low cost. Cessation tools for students must be convenient, understandable, and accessible from multiple locations. Feasible approaches for future initiatives could include testing low cost technology such as Web Assisted Tobacco Interventions (WATI) and outside partnerships with community organizations and health agencies. Policy enforcement could be improved with tobacco policy education at orientation for students, faculty and staff.