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OBJECTIVE: The Emergency Severity Index (ESI) is the most commonly used system in over 70% of all U.S. emergency departments (ED) that uses predicted resource utilization as a means to triage [1], Mistriage, which includes both undertriage and overtriage has been a persistent issue, affecting 32.2% of total ED visits [2]. Our goal is to develop a machine learning framework that predicts patients' resource needs, thereby improving resource allocation during triage. METHODS: This retrospective study analyzed ED visits from the Medical Information Mart for Intensive Care IV, dividing the data into training (80%) and testing (20%) cohorts. We utilized data available during triage, including patient vital signs, age, gender, mode of arrival, medication history, and chief complaint. Azure AutoML was used to create different machine learning models trained to predict the 144 target columns including laboratory panels and imaging modalities as well as medications required during patients' ED visits. The 144 models' performance was evaluated using the area under the receiver operating characteristic curve (AUROC), F1 score, accuracy, precision and recall. RESULTS: A total of 391,472 ED visits were analyzed. 144 Voting ensemble models were created for each target. All frameworks achieved on average an AUC score of 0.82 and accuracy of 0.76. We gathered the feature importance for each target and observed that 'chief complaint', among others, had a high aggregate feature importance across different targets. CONCLUSION: This study shows the high accuracy in predicting resource needs for patients in the ED using a machine learning model. This can greatly improve patient flow and resource allocation in already resource limited emergency departments.
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In tactile sensing, decoding the journey from afferent tactile signals to efferent motor commands is a significant challenge primarily due to the difficulty in capturing population-level afferent nerve signals during active touch. This study integrates a finite element hand model with a neural dynamic model by using microneurography data to predict neural responses based on contact biomechanics and membrane transduction dynamics. This research focuses specifically on tactile sensation and its direct translation into motor actions. Evaluations of muscle synergy during in -vivo experiments revealed transduction functions linking tactile signals and muscle activation. These functions suggest similar sensorimotor strategies for grasping influenced by object size and weight. The decoded transduction mechanism was validated by restoring human-like sensorimotor performance on a tendon-driven biomimetic hand. This research advances our understanding of translating tactile sensation into motor actions, offering valuable insights into prosthetic design, robotics, and the development of next-generation prosthetics with neuromorphic tactile feedback.
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Tato , Humanos , Tato/fisiologia , Mãos/fisiologia , Fenômenos Biomecânicos , Força da Mão/fisiologia , Percepção do Tato/fisiologia , Músculo Esquelético/fisiologia , Retroalimentação Sensorial/fisiologia , Modelos Neurológicos , Robótica , MasculinoRESUMO
AIMS: To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra-epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings. METHODS: Skin biopsies (n = 274) from 100 participants (fibromyalgia syndrome n = 62; idiopathic small fibre neuropathy: n = 16; healthy volunteers: n = 22) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two-way mixed-effects model to evaluate inter- and intra-observer variability. RESULTS: The automated staining system reproduced intra-epidermal nerve fibre density (IENFD) counts consistent with free-floating sections (mean ± standard deviation: free-floating: 5.6 ± 3.4 fibres/mm; automated: 5.9 ± 3.2 fibres/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at -0.00005 established non-inferiority against a margin of -0.4 (p = .08). Specifically, the inter-class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9-1), indicating excellent agreement between free-floating and automated methods. The inter- and intra-class coefficient between examiners were both 99% (95% CI: 0.9-0.1) for IENFD, demonstrating high reliability using sections stained using the automated method. INTERPRETATION: Automated immunohistochemistry provides high-throughput reliable and reproducible intra-epidermal nerve fibre quantification. This method, although currently proof-of-concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies.
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Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.
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Florestas , Herbivoria , Insetos , Nitrogênio , Folhas de Planta , Temperatura , Herbivoria/fisiologia , Animais , Insetos/fisiologia , Folhas de Planta/metabolismo , Nitrogênio/metabolismo , Carbono/metabolismo , Ciclo do Carbono , Fósforo/metabolismo , Ecossistema , Árvores/metabolismoRESUMO
Thermophilization is the directional change in species community composition towards greater relative abundances of species associated with warmer environments. This process is well-documented in temperate and Neotropical plant communities, but it is uncertain whether this phenomenon occurs elsewhere in the tropics. Here we extend the search for thermophilization to equatorial Africa, where lower tree diversity compared to other tropical forest regions and different biogeographic history could affect community responses to climate change. Using re-census data from 17 forest plots in three mountain regions of Africa, we find a consistent pattern of thermophilization in tree communities. Mean rates of thermophilization were +0.0086 °C·y-1 in the Kigezi Highlands (Uganda), +0.0032 °C·y-1 in the Virunga Mountains (Rwanda-Uganda-Democratic Republic of the Congo) and +0.0023 °C·y-1 in the Udzungwa Mountains (Tanzania). Distinct from other forests, both recruitment and mortality were important drivers of thermophilzation in the African plots. The forests studied currently act as a carbon sink, but the consequences of further thermophilization are unclear.
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Mudança Climática , Florestas , Árvores , Clima Tropical , Biodiversidade , Temperatura , Uganda , Tanzânia , Ruanda , República Democrática do Congo , Sequestro de CarbonoRESUMO
Importance: Adolescence is a period in which mental health problems emerge. Research suggests that the COVID-19 lockdown may have worsened emotional and behavioral health. Objective: To examine whether socioeconomic status was associated with mental health outcomes among youths during the COVID-19 pandemic. Design, Setting, and Participants: The Adolescent Brain Cognitive Development (ABCD) Study is a multisite 10-year longitudinal study of youth neurocognitive development in the US. Recruitment was staggered where the baseline visit (ages 9 to 10 years) occurred from 2016 to 2018, and visits occurred yearly. The COVID-19 lockdown halted research collection during the 2-year follow-up visits (ages 11 to 12 years), but eventually resumed. As some youths already underwent their 2-year visits prior to lockdown, this allowed for a natural experiment-like design to compare prepandemic and intrapandemic groups. Thus, data were gathered from the 1-year follow-up (pre-COVID-19 lockdown for all youths) and the 2-year follow-up, of which a portion of youths had data collected after the lockdown began, to compare whether a period of near social isolation was associated with mental health symptoms in youths. The prepandemic group consisted of youths with a 2-year follow-up visit collected prior to March 11, 2020, and the intrapandemic group had their 2-year follow-up visit after lockdown restrictions were lifted. Main Outcomes and Measures: Assessments included measures on income-to-needs ratio (INR; derived from total household income), the Child Behavior Checklist (a measure of mental health symptomology), and the Family Environmental Scale. Results: The final sample included 10â¯399 youths; 3947 (52.3%) were male; 2084 (20.3%) were Latinx/Hispanic; 6765 (66.0%) were White; 4600 (44.2%) reported caregiver education levels below a 4-year college degree; and 2475 (26.2%) had INR either below 100% (indicating poverty) or between 100% and less than 200% (near poverty). Among youths in the intrapandemic group, worse mental health symptoms (eg, more total problems, greater depression, and greater anxiety) over time were associated with being from a household with higher socioeconomic status (eg, when comparing individuals who differed by 1 unit on INR between prepandemic and intrapandemic groups from 1-year to 2-year follow-up, their expected difference in total problems score was 0.79 [95% CI, 0.37-1.22]; false discovery rate-corrected P < .001). Conclusions and Relevance: This cohort study found that the COVID-19 lockdown was associated with disproportionately negative mental health outcomes among youths from higher socioeconomic status backgrounds. Although this study does not shed light on the direct mechanisms driving these associations, it does provide some support for positive outcomes for youths. Future studies are needed to understand whether these associations persist over longer periods of time.
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COVID-19 , Saúde Mental , Pandemias , SARS-CoV-2 , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Masculino , Feminino , Criança , Estudos Longitudinais , Saúde Mental/estatística & dados numéricos , Adolescente , Estados Unidos/epidemiologia , Classe Social , Isolamento Social/psicologia , Controle de Doenças Transmissíveis/métodos , Quarentena/psicologia , Ansiedade/epidemiologia , Disparidades Socioeconômicas em SaúdeRESUMO
BACKGROUND: To investigate relationships among different physical health problems in a large, sociodemographically diverse sample of 9-to-10-year-old children and determine the extent to which perinatal health factors are associated with childhood physical health problems. METHODS: A cross-sectional study was conducted utilizing the Adolescent Brain Cognitive Developmentâ (ABCD) Study (n = 7613, ages 9-to-10-years-old) to determine the associations among multiple physical health factors (e.g., prenatal complications, current physical health problems). Logistic regression models controlling for age, sex, pubertal development, household income, caregiver education, race, and ethnicity evaluated relationships between perinatal factors and childhood physical health problems. RESULTS: There were significant associations between perinatal and current physical health measures. Specifically, those who had experienced perinatal complications were more likely to have medical problems by 9-to-10 years old. Importantly, sleep disturbance co-occurred with several physical health problems across domains and developmental periods. CONCLUSION: Several perinatal health factors were associated with childhood health outcomes, highlighting the importance of understanding and potentially improving physical health in youth. Understanding the clustering of physical health problems in youth is essential to better identify which physical health problems may share underlying mechanisms. IMPACT: Using a multivariable approach, we investigated the associations between various perinatal and current health problems amongst youth. Our study highlights current health problems, such as sleep problems at 9-to-10 years old, that are associated with a cluster of factors occurring across development (e.g., low birth weight, prenatal substance exposure, pregnancy complications, current weight status, lifetime head injury). Perinatal health problems are at large, non-modifiable (in this retrospective context), however, by identifying which are associated with current health problems, we can identify potential targets for intervention and prevention efforts.
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Eliciting an antihapten antibody response to vaccination typically requires the use of constructs where multiple copies of the hapten are covalently attached to a larger carrier molecule. The carrier is required to elicit T cell help via presentation of peptide epitopes on major histocompatibility complex (MHC) class II molecules; as such, attachment to full-sized proteins, alone or in a complex, is generally used to account for the significant MHC diversity in humans. While such carrier-based vaccines have proven extremely successful, particularly in protecting against bacterial diseases, they can be challenging to manufacture, and repeated use can be compromised by pre-existing immunity against the carrier. One approach to reducing these complications is to recruit help from type I natural killer T (NKT) cells, which exhibit limited diversity in their antigen receptors and respond to glycolipid antigens presented by the highly conserved presenting molecule CD1d. Synthetic vaccines for universal use can, therefore, be prepared by conjugating haptens to an NKT cell agonist such as α-galactosylceramide (αGalCer, KRN7000). An additional advantage is that the quality of NKT cell help is sufficient to overcome the need for an extra immune adjuvant. However, while initial studies with αGalCer-hapten conjugate vaccines report strong and rapid antihapten antibody responses, they can fail to generate lasting memory. Here, we show that antibody responses to the hapten 4-hydoxy-3-nitrophenyl acetyl (NP) can be improved through additional attachment of a fusion peptide containing a promiscuous helper T cell epitope (Pan DR epitope, PADRE) that binds diverse MHC class II molecules. Such αGalCer-hapten-peptide tricomponent vaccines generate strong and sustained anti-NP antibody titers with increased hapten affinity compared to vaccines without the helper epitope. The tricomponent vaccine platform is therefore suitable for further exploration in the pursuit of efficacious antihapten immunotherapies.
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Haptenos , Vacinas Conjugadas , Animais , Haptenos/imunologia , Haptenos/química , Camundongos , Vacinas Conjugadas/imunologia , Peptídeos/imunologia , Peptídeos/química , Formação de Anticorpos/imunologia , Camundongos Endogâmicos C57BL , Galactosilceramidas/imunologia , Galactosilceramidas/química , Feminino , Células T Matadoras Naturais/imunologia , Glicolipídeos/imunologia , Glicolipídeos/químicaRESUMO
Terrestriality is relatively rare in the predominantly arboreal primate order. How frequently, and when, terrestriality appears in primate evolution, and the factors that influence this behavior, are not well understood. To investigate this, we compiled data describing terrestriality in 515 extant nonhuman primate taxa. We describe the geographic and phylogenetic distribution of terrestriality, including an ancestral state reconstruction estimating the frequency and timing of evolutionary transitions to terrestriality. We review hypotheses concerning the evolution of primate terrestriality and test these using data we collected pertaining to characteristics including body mass and diet, and ecological factors including forest structure, food availability, weather, and predation pressure. Using Bayesian analyses, we find body mass and normalized difference vegetation index are the most reliable predictors of terrestriality. When considering subsets of taxa, we find ecological factors such as forest height and rainfall, and not body mass, are the most reliable predictors of terrestriality for platyrrhines and lemurs.
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Antropologia Física , Primatas , Animais , Primatas/fisiologia , Evolução Biológica , Dieta , Filogenia , Ecossistema , Teorema de Bayes , FlorestasRESUMO
One hundred years ago, Erlanger and Gasser demonstrated that conduction velocity is correlated with the diameter of a peripheral nerve axon. Later, they also demonstrated that the functional role of the axon is related to its diameter: touch is signalled by large-diameter axons, whereas pain and temperature are signalled by small-diameter axons. Certain discoveries in recent decades prompt a modification of this canonical classification. Here, we review the evidence for unmyelinated (C) fibres signalling touch at a slow conduction velocity and likely contributing to affective aspects of tactile information. We also review the evidence for large-diameter Aß afferents signalling pain at ultrafast conduction velocity and likely contributing to the rapid nociceptive withdrawal reflex. These discoveries imply that conduction velocity is not as clear-cut an indication of the functional role of the axon as previously thought. We finally suggest that a future taxonomy of the peripheral afferent nervous system might be based on the combination of the axons molecular expression and electrophysiological response properties.
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Condução Nervosa , Nervos Periféricos , Humanos , Animais , Nervos Periféricos/fisiopatologia , Nervos Periféricos/fisiologia , Condução Nervosa/fisiologia , Tato/fisiologia , Dor/fisiopatologia , Dor/classificação , Fibras Nervosas Amielínicas/fisiologia , Axônios/fisiologiaRESUMO
By using geospatial information such as participants' residential history along with external datasets of environmental exposures, ongoing studies can enrich their cohorts to investigate the role of the environment on brain-behavior health outcomes. However, challenges may arise if clear guidance and key quality control steps are not taken at the outset of data collection of residential information. Here, we detail the protocol development aimed at improving the collection of lifetime residential address information from the Adolescent Brain Cognitive Development (ABCD) Study. This protocol generates a workflow for minimizing gaps in residential information, improving data collection processes, and reducing misclassification error in exposure estimates.
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Coleta de Dados , Exposição Ambiental , Humanos , Adolescente , Coleta de Dados/métodos , Exposição Ambiental/efeitos adversos , Feminino , Masculino , Características de ResidênciaAssuntos
Estudos Cross-Over , Humanos , Recém-Nascido , Lactente , Oxigenoterapia/métodos , Feminino , Masculino , Oxigênio/administração & dosagemRESUMO
A proportion of people with fibromyalgia demonstrate small fibre pathology (SFP). However, it is unclear how SFP directly relates to pain phenomenology. Thirty-three individuals with FMS and ten healthy volunteers underwent assessment of SFP and sensory phenotyping using corneal confocal microscopy, validated questionnaires and quantitative sensory testing (QST). Corneal nerve fibre length was used to stratify participants with fibromyalgia into with SFP [SFP+] and without SFP [SFP-]. SFP was detected in 50% of the fibromyalgia cohort. Current pain score and QST parameters did not differ between SFP+ and SFP-. Mechanical pain sensitivity (MPS) demonstrated a significant gain-of-function in the SFP- cohort compared to healthy-volunteers (p = 0.014, F = 4.806, η2 = 0.22). Further stratification revealed a cohort without structural SFP but with symptoms compatible with small fibre neuropathy symptoms and a significant gain in function in MPS (p = 0.020 Chi-square). Additionally, this cohort reported higher scores for both depression (p = 0.039, H = 8.483, η2 = 0.312) and anxiety (p = 0.022, F = 3.587, η2 = 0.293). This study confirms that SFP is present in a proportion of people with fibromyalgia. We also show that in a proportion of people with fibromyalgia, small fibre neuropathy symptoms are present in the absence of structural SFP. Greater mechanical pain sensitivity, depression and anxiety are seen in these individuals.
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Fibromialgia , Neuropatia de Pequenas Fibras , Humanos , Neuropatia de Pequenas Fibras/diagnóstico , Dor , Limiar da Dor , Fibras Nervosas/patologiaRESUMO
The great apes-bonobos, chimpanzees, gorillas and orangutans-are critically threatened by human activities. We have destroyed their habitats, hunted them and transmitted fatal diseases to them. Yet we also conduct research on them, try to protect them and live alongside them. They are endangered, and time is running out. Here we outline what must be done to ensure that future generations continue to share this planet with great apes. We urge dialogue with those who live with great apes and interact with them often. We advocate conservation plans that acknowledge the realities of climate change, economic drivers and population growth. We encourage researchers to use technology to minimize risks to great apes. Our proposals will require substantial investment, and we identify ways to generate these funds. We conclude with a discussion of how field researchers might alter their work to protect our closest living relatives more effectively.
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Conservação dos Recursos Naturais , Hominidae , Animais , Humanos , Mudança Climática , Espécies em Perigo de Extinção , Ecossistema , Pan troglodytes , Pan paniscusRESUMO
Tactile discrimination has been extensively studied, but mechanical pain discrimination remains poorly characterized. Here, we measured the capacity for mechanical pain discrimination using a two-alternative forced choice paradigm, with force-calibrated indentation stimuli (Semmes-Weinstein monofilaments) applied to the hand and foot dorsa of healthy human volunteers. In order to characterize the relationship between peripheral nociceptor activity and pain perception, we recorded single-unit activity from myelinated (A) and unmyelinated (C) mechanosensitive nociceptors in the skin using microneurography. At the perceptual level, we found that the foot was better at discriminating noxious forces than the hand, which stands in contrast to that for innocuous force discrimination, where the hand performed better than the foot. This observation of superior mechanical pain discrimination on the foot compared to the hand could not be explained by the responsiveness of individual nociceptors. We found no significant difference in the discrimination performance of either the myelinated or unmyelinated class of nociceptors between skin regions. This suggests the possibility that other factors such as skin biophysics, receptor density or central mechanisms may underlie these regional differences.
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Dor , Pele , Humanos , Estimulação Física , Nociceptores , Percepção da DorRESUMO
Growing evidence suggests that liana competition with trees is threatening the global carbon sink by slowing the recovery of forests following disturbance. A recent theory based on local and regional evidence further proposes that the competitive success of lianas over trees is driven by interactions between forest disturbance and climate. We present the first global assessment of liana-tree relative performance in response to forest disturbance and climate drivers. Using an unprecedented dataset, we analysed 651 vegetation samples representing 26,538 lianas and 82,802 trees from 556 unique locations worldwide, derived from 83 publications. Results show that lianas perform better relative to trees (increasing liana-to-tree ratio) when forests are disturbed, under warmer temperatures and lower precipitation and towards the tropical lowlands. We also found that lianas can be a critical factor hindering forest recovery in disturbed forests experiencing liana-favourable climates, as chronosequence data show that high competitive success of lianas over trees can persist for decades following disturbances, especially when the annual mean temperature exceeds 27.8°C, precipitation is less than 1614 mm and climatic water deficit is more than 829 mm. These findings reveal that degraded tropical forests with environmental conditions favouring lianas are disproportionately more vulnerable to liana dominance and thus can potentially stall succession, with important implications for the global carbon sink, and hence should be the highest priority to consider for restoration management.
Des preuves de plus en plus nombreuses suggèrent que la competition entre lianes et les arbres menace le puits de carbone mondial en ralentissant la récupération des forêts après une perturbation. Une théorie récente, fondée sur des observations locales et régionales, propose en outre que le succès compétitif des lianes sur les arbres est dû aux interactions entre la perturbation forestière et le climat. Nous présentons la première évaluation mondiale de la performance relative des lianes par rapport aux arbres en réponse aux perturbations forestières et aux facteurs climatiques. En utilisant un ensemble de données sans précédent, nous avons analysé 651 échantillons de végétation représentant 26,538 lianes et 82,802 arbres, issus de 556 emplacements uniques dans le monde entier, tirés de 83 publications. Les résultats montrent que les lianes ont de meilleure performances par rapport aux arbres (augmentation du ratio liane-arbre) lorsque les forêts sont perturbées, sous des zones chaudes aves précipitations faibles, et vers les basses altitudes tropicales. Nous avons également constaté que les lianes peuvent être un facteur critique entravant la récupération des forêts dans les forêts perturbées connaissant des climats favorables aux lianes, car les données de chronoséquence montrent que le succès compétitif élevé des lianes sur les arbres peut persister pendant des décennies après les perturbations, surtout lorsque la température annuelle moyenne dépasse 27.8°C, que les précipitations sont inférieures à 1614 mm et que le déficit hydrique climatique est supérieur à 829 mm. Ces découvertes révèlent que les forêts tropicales dégradées avec des conditions environnementales favorables aux lianes sont disproportionnellement plus vulnérables à la dominance des lianes, et peuvent ainsi potentiellement entraver la succession, avec d'importantes implications pour le puits de carbone mondial et devraient donc être la plus haute priorité à considérer pour la gestion de la restauration.
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Árvores , Clima Tropical , Árvores/fisiologia , Florestas , Sequestro de Carbono , ÁguaRESUMO
OBJECTIVE: The purpose of this study was to test two non-exclusive mechanisms by which parental monitoring might reduce teen substance use. The first mechanism (M1) is that monitoring increases punishment for substance use since parents who monitor more are more likely to find out when substance use occurs. The second mechanism (M2) is that monitoring directly prevents/averts teens from using substances in the first place for fear that parents would find out. METHOD: A total of 4,503 teens ages 11-15 years old in 21 communities across the United States completed a survey reporting on parents' monitoring/knowledge and teens' substance use. RESULTS: We found no support for M1: Parents with greater parental monitoring were not more likely to be aware when the teen had used substances (odds ratios = 0.79-0.93, ps = .34-.85), so they could not have increased the rate of punishment. We found support for M2: When asked directly, teens identified instances in which they planned to or had a chance to use substances but did not because their parents got in the way or would have found out (p < .01). Had all those opportunities for substance use occurred rather than been averted by parents, the prevalence of substance use in the sample would have been 1.4 times higher. CONCLUSIONS: In this community-based sample of teens, we failed to support prior punishment-centric theories of how monitoring might reduce teen substance use. Rather, monitoring may directly discourage teens from using substances regardless of whether it increases parents' awareness of substance use or results in more punishment. Replication in other samples and contexts is needed.
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Comportamento do Adolescente , Relações Pais-Filho , Poder Familiar , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Feminino , Masculino , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Criança , Poder Familiar/psicologia , Estados Unidos/epidemiologia , Comportamento do Adolescente/psicologia , Punição , PaisRESUMO
AIMS: Amongst elderly people with type 2 diabetes (T2D) over prescribing can result in emergency ambulance call-outs, falls and fractures and increased mortality, particularly in frail patients. Current clinical guidelines, however, remain focused on medication intensification rather than deintensification where appropriate. This study aims to evaluate the effectiveness of an electronic decision-support system and training for the deintensification of potentially inappropriate medications amongst older frail people with T2D, when compared to 'usual' care at 12-months. METHODS: This study is an open-label, multi-site, two-armed pragmatic cluster-randomised trial. GP practices randomised to the 'enhanced care' group have an electronic decision support system installed and receive training on the tool and de-intensification of diabetes medications. The system flags eligible patients for possible deintensification of diabetes medications, linking the health care professional to a clinical algorithm. The primary outcome will be the number of patients at 12-months who have had potentially inappropriate diabetes medications de-intensified. RESULTS: Study recruitment commenced in June 2022. Data collection commenced in January 2023. Baseline data have been extracted from 40 practices (3145 patients). CONCLUSIONS: Digital technology, involving computer decision systems, may have the potential to reduce inappropriate medications and aid the process of de-intensification. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN53221378. Available at: https://www.isrctn.com/ISRCTN53221378.
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Diabetes Mellitus Tipo 2 , Lista de Medicamentos Potencialmente Inapropriados , Humanos , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Idoso Fragilizado , Prescrição Inadequada/prevenção & controle , Coleta de Dados , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The current small study utilised prospective data collection of patterns of prenatal alcohol and tobacco exposure (PAE and PTE) to examine associations with structural brain outcomes in 6-year-olds and served as a pilot to determine the value of prospective data describing community-level patterns of PAE and PTE in a non-clinical sample of children. Participants from the Safe Passage Study in pregnancy were approached when their child was â¼6 years old and completed structural brain magnetic resonance imaging to examine with archived PAE and PTE data (n = 51 children-mother dyads). Linear regression was used to conduct whole-brain structural analyses, with false-discovery rate (FDR) correction, to examine: (a) main effects of PAE, PTE and their interaction; and (b) predictive potential of data that reflect patterns of PAE and PTE (e.g. quantity, frequency and timing (QFT)). Associations between PAE, PTE and their interaction with brain structural measures demonstrated unique profiles of cortical and subcortical alterations that were distinct between PAE only, PTE only and their interactive effects. Analyses examining associations between patterns of PAE and PTE (e.g. QFT) were able to significantly detect brain alterations (that survived FDR correction) in this small non-clinical sample of children. These findings support the hypothesis that considering QFT and co-exposures is important for identifying brain alterations following PAE and/or PTE in a small group of young children. Current results demonstrate that teratogenic outcomes on brain structure differ as a function PAE, PTE or their co-exposures, as well as the pattern (QFT) or exposure.
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Efeitos Tardios da Exposição Pré-Natal , Criança , Gravidez , Feminino , Humanos , Pré-Escolar , Projetos Piloto , África do Sul , Encéfalo/patologia , Imageamento por Ressonância MagnéticaRESUMO
RATIONALE AND OBJECTIVES: The Omicron variant of COVID-19 is less severe than the ancestral strain, leading to the potential for deaths in patients infected with the virus but who die of other causes. This study evaluated the difference in rates of pneumonia among patients who died with SARS-CoV-2 infection in the ancestral vs Omicron eras. MATERIALS AND METHODS: We identified patients who died within 30days of a positive SARS-CoV-2 test, from March 2020 through December 2022; variants were assigned based on the prevalent variant in the US at that time. We also obtained a control group from patients who died within 30days of a negative SARS-CoV-2 test in January 2022. The first CT after the test was reviewed in a blinded fashion and assigned a category from the RSNA Consensus Reporting Guidelines. The primary outcome was the difference in rates of positive (typical or indeterminate) COVID-19 findings in the ancestral vs Omicron eras. RESULTS: A total of 598 patients died during the ancestral era and 400 during the Omicron era, and 347 decedents comprised the control group. The rate of positive COVID-19 findings was 67/81 (83%) in the ancestral era and 43/81 (53%) in the Omicron era (P < .001), an absolute difference of 30% (95% CI 16%-43%). The rate of positive findings in the control group was 23/76 (30%). CONCLUSION: During the Omicron era, 30% fewer SARS-CoV-2-associated deaths were associated with COVID-19 pneumonia and were caused either by nonpulmonary effects of the infection or were unrelated to the infection.