561 research outputs found
Are Biological Science Knowledge, Interests, and Science Identity Framed by Religious and Political Perspectives in the United States?
Science trust and views of science differ by political and religious orientations. In this study we examine whether political and religious perspectives are also associated with biological science knowledge, science interest, and general science identity. Results show that conservative Protestants have lower biological science knowledge than other religious groups on several specific topics. Party affiliation is associated with vaccine knowledge but not science interest and identity. Adjusting for demographic characteristics explains some political and religious group differences, but not all. We discuss implications regarding attention to potential political and religious framings of science topics in public education efforts
Duration of Posttraumatic Amnesia Predicts Neuropsychological and Global Outcome in Complicated Mild Traumatic Brain Injury.
OBJECTIVES: Examine the effects of posttraumatic amnesia (PTA) duration on neuropsychological and global recovery from 1 to 6 months after complicated mild traumatic brain injury (cmTBI).
PARTICIPANTS: A total of 330 persons with cmTBI defined as Glasgow Coma Scale score of 13 to 15 in emergency department, with well-defined abnormalities on neuroimaging.
METHODS: Enrollment within 24 hours of injury with follow-up at 1, 3, and 6 months.
MEASURES: Glasgow Outcome Scale-Extended, California Verbal Learning Test II, and Controlled Oral Word Association Test. Duration of PTA was retrospectively measured with structured interview at 30 days postinjury.
RESULTS: Despite all having a Glasgow Coma Scale Score of 13 to 15, a quarter of the sample had a PTA duration of greater than 7 days; half had PTA duration of 1 of 7 days. Both cognitive performance and Extended Glasgow Outcome Scale outcomes were strongly associated with time since injury and PTA duration, with those with PTA duration of greater than 1 week showing residual moderate disability at 6-month assessment.
CONCLUSIONS: Findings reinforce importance of careful measurement of duration of PTA to refine outcome prediction and allocation of resources to those with cmTBI. Future research would benefit from standardization in computed tomographic criteria and use of severity indices beyond Glasgow Coma Scale to characterize cmTBI
Some simple thin-layer chromatographic systems for the separation of purines and purine nucleosides
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33914/1/0000179.pd
The quest for sustained multiple morbidity reduction in very low-birth-weight infants: the Antifragility project.
OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities?
STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always employ this therapy for VLBW infants, (2) never use this therapy, (3) employ this questionable therapy thoughtfully, only in certain circumstances and (4) this therapy has insufficient evidence of efficacy and safety. Extensive staff education emphasized evidence-based potentially better practice (PBP) selection with compliance checks, appreciation of intertwined co-morbidities and prioritizing infant risk reduction strategies.
RESULTS: Control included 221 infants, mean (s.d.) age 29 (2.6) weeks, birth weight 1129 (257) g and Study included 197 infants, 29 (2.7) weeks, 1093 (292) g. One hundred and four distinct therapies were placed into categories 1 to 4, with 32 specific compliance checks. Overall mean compliance with the process checks during the second era was 70%, high: 100% (exclusive breast milk use), low: 24% (correct pulse oximetry alarm settings). Morbidity and mortality rates did not significantly change during the second era.
CONCLUSIONS: In our NICU with favorable morbidity rates, an expanded effort using a comprehensive therapy guideline for VLBW infants did not further improve outcomes. We need deeper understanding of continuous quality improvement (CQI) fundamentals, therapy compliance, co-morbidity relationships and enhanced sensitivity of risk assessment. Our innovative Antifragility PBP guideline could be useful to other NICUs seeking improvement in VLBW infant morbidities, as we offer a reasoned and concise template of a broad array of therapies categorized efficiently for transparency and review, designed to enhance responsible CQI decision-making
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Attitudes toward risk among emergency physicians and advanced practice clinicians in Massachusetts
Objective
Risk aversion is a personality trait influential to decision making in medicine. Little is known about how emergency department (ED) clinicians differ in their attitudes toward risk taking. Methods
We conducted a cross-sectional survey of practicing ED clinicians (physicians and advanced practice clinicians [APCs]) in Massachusetts using the following 4 existing validated scales: the Risk-Taking Scale (RTS), Stress from Uncertainty Scale (SUS), the Fear of Malpractice Scale (FMS), and the Need for (Cognitive) Closure Scale (NCC). We used Cronbach\u27s α to assess the reliability of each scale and performed multivariable linear regressions to analyze the association between the score for each scale and clinician characteristics. Results
Of 1458 ED clinicians recruited for participation, 1116 (76.5%) responded from 93% of acute care hospitals in Massachusetts. Each of the 4 scales demonstrated high internal consistency reliability with Cronbach\u27s αs ranging from 0.76 to 0.92. The 4 scales also were moderately correlated with one another (0.08 to 0.54; all P \u3c 0.05). The multivariable results demonstrated differences between physicians and APCs, with physicians showing a greater tolerance for risk or uncertainty (NCC difference, −3.58 [95% confidence interval, CI, −5.26 to −1.90]; SUS difference, −3.14 [95% CI: −4.99 to −1.29]) and a higher concern about malpractice (FMS difference, 1.14 [95% CI, 0.11–2.17]). Differences were also observed based on clinician age (a proxy for years of experience), with greater age associated with greater tolerance of risk or uncertainty (age older than 50 years compared with age 35 years and younger; NCC difference, −2.84 [95% CI, −4.69 to −1.00]; SUS difference, −4.71 [95% CI, −6,74 to −2.68]) and less concern about malpractice (FMS difference, −3.19 [95% CI, −4.31 to −2.06]). There were no appreciable differences based on sex, and there were no consistent associations between scale scores and the practice and payment characteristics assessed. Conclusion
We found that risk attitudes of ED clinicians were associated with type of training (physician vs APC) and age (experience). These differences suggest one possible explanation for the observed differences in decision making
Mandibular and Neural Crest Cell Deficits Seen in TsDn65 Down Syndrome Mouse Model Rescued By Green Tea Polyphenol, EGCG
poster abstractDown Syndrome (DS) is caused by trisomy of the human chromosome 21 (Hsa21) and occurs in
~1 of every 700 births. DS is distinguished by over 80 phenotypic abnormalities including
skeletal deficits and craniofacial phenotypes characterized by a flattened skull, slanted eyes, and a
smaller mandible. To study these abnormalities, we utilize the Ts65Dn DS mouse model
containing a triplication of approximately half of the gene homologues found on Hsa21 and
mirrors the skeletal and mandibular phenotypes observed in DS. In Ts65Dn mice, the origin of
the mandibular deficits were traced to a reduction in size of the 1st branchial arch (BA1), the
developmental precursor to the mandible, occurring at embryonic day 9.5 (E9.5). At E9.5, we
observe a lack of proliferation and migration of neural crest cells (NCC) from the neural tube
(NT) into the BA1, causing a reduced BA1. We hypothesize that an overexpression of Dyrk1a, a
Hsa21 homologue, contributes to the mandibular deficit seen in E9.5 Ts65Dn embryos. We
propose that EGCG, a green tea polyphenol, will inhibit DYRK1a activity, rescuing the BA1
deficit. To test our hypothesis, Ts65Dn mothers were treated with EGCG from E0-E9.5 and
sacrificed to retrieve the E9.5 embryos. Our results from unbiased stereological assessments
show that E0-E9.5 EGCG in vivo treatment has the potential to increase NCC number, BA1
volume, and embryo volume of trisomic embryos. This data provide preclinical testing for a
potential therapy of DS craniofacial disorders, which may extend to treating bone deficits in DS
and osteoporosis
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Estimation of hourly near surface air temperature across Israel using an ensemble model
Mapping of near-surface air temperature (Ta) at high spatio-temporal resolution is essential for unbiased assessment of human health exposure to temperature extremes, not least given the observed trend of urbanization and global climate change. Data constraints have led previous studies to focus merely on daily Ta metrics, rather than hourly ones, making them insufficient for intra-day assessment of health exposure. In this study, we present a three-stage machine learning-based ensemble model to estimate hourly Ta at a high spatial resolution of 1 × 1 km2, incorporating remotely sensed surface skin temperature (Ts) from geostationary satellites, reanalysis synoptic variables, and observations from weather stations, as well as auxiliary geospatial variables, which account for spatio-temporal variability of Ta. The Stage 1 model gap-fills hourly Ts at 4 × 4 km2 from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI), which are subsequently fed into the Stage 2 model to estimate hourly Ta at the same spatio-temporal resolution. The Stage 3 model downscales the residuals between estimated and measured Ta to a grid of 1 × 1 km2, taking into account additionally the monthly diurnal pattern of Ts derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) data. In each stage, the ensemble model synergizes estimates from the constituent base learners—random forest (RF) and extreme gradient boosting (XGBoost)—by applying a geographically weighted generalized additive model (GAM), which allows the weights of results from individual models to vary over space and time. Demonstrated for Israel for the period 2004–2017, the proposed ensemble model outperformed each of the two base learners. It also attained excellent five-fold cross-validated performance, with overall root mean square error (RMSE) of 0.8 and 0.9 °C, mean absolute error (MAE) of 0.6 and 0.7 °C, and R2 of 0.95 and 0.98 in Stage 1 and Stage 2, respectively. The Stage 3 model for downscaling Ta residuals to 1 km MODIS grids achieved overall RMSE of 0.3 °C, MAE of 0.5 °C, and R2 of 0.63. The generated hourly 1 × 1 km2 Ta thus serves as a foundation for monitoring and assessing human health exposure to temperature extremes at a larger geographical scale, helping to further minimize exposure misclassification in epidemiological studies
Estimation of hourly near surface air temperature across Israel using an ensemble model
Mapping of near-surface air temperature (Ta) at high spatio-temporal resolution is essential for unbiased assessment of human health exposure to temperature extremes, not least given the observed trend of urbanization and global climate change. Data constraints have led previous studies to focus merely on daily Ta metrics, rather than hourly ones, making them insufficient for intra-day assessment of health exposure. In this study, we present a three-stage machine learning-based ensemble model to estimate hourly Ta at a high spatial resolution of 1 × 1 km2, incorporating remotely sensed surface skin temperature (Ts) from geostationary satellites, reanalysis synoptic variables, and observations from weather stations, as well as auxiliary geospatial variables, which account for spatio-temporal variability of Ta. The Stage 1 model gap-fills hourly Ts at 4 × 4 km2 from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI), which are subsequently fed into the Stage 2 model to estimate hourly Ta at the same spatio-temporal resolution. The Stage 3 model downscales the residuals between estimated and measured Ta to a grid of 1 × 1 km2, taking into account additionally the monthly diurnal pattern of Ts derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) data. In each stage, the ensemble model synergizes estimates from the constituent base learners—random forest (RF) and extreme gradient boosting (XGBoost)—by applying a geographically weighted generalized additive model (GAM), which allows the weights of results from individual models to vary over space and time. Demonstrated for Israel for the period 2004–2017, the proposed ensemble model outperformed each of the two base learners. It also attained excellent five-fold cross-validated performance, with overall root mean square error (RMSE) of 0.8 and 0.9 °C, mean absolute error (MAE) of 0.6 and 0.7 °C, and R2 of 0.95 and 0.98 in Stage 1 and Stage 2, respectively. The Stage 3 model for downscaling Ta residuals to 1 km MODIS grids achieved overall RMSE of 0.3 °C, MAE of 0.5 °C, and R2 of 0.63. The generated hourly 1 × 1 km2 Ta thus serves as a foundation for monitoring and assessing human health exposure to temperature extremes at a larger geographical scale, helping to further minimize exposure misclassification in epidemiological studies
Treatment with a Green Tea Polyphenol Corrects Craniofacial Deficits Associated with Down Syndrome
poster abstractDown syndrome (DS) is caused by trisomy of human chromosome 21 (HSA21). Individuals with DS present craniofacial abnormalities including an undersized, dismorphic mandible leading to difficulty with eating, breathing, and swallowing. Using the Ts65Dn DS mouse model (three copies of ~50% HSA21 homologs), we have traced the mandibular deficit to a neural crest cell (NCC) deficiency and reduction in first pharyngeal arch (PA1 or mandibular precursor) size at embryonic day 9.5. At E9.5, Dyrk1A, a triplicated DS candidate gene, is overexpressed and may cause the NCC and PA1 deficits. We hypothesize that treatment of pregnant Ts65Dn mothers with Epigallocatechin gallate (EGCG), a known Dyrk1A inhibitor, will correct NCC deficits and rescue the undersized PA1 in trisomic E9.5 embryos. To test our hypothesis, we treated pregnant Ts65Dn mothers with EGCG from either E7-E8 or E0-E9.5. Our preliminary study found an increase in PA1 volume and NCC number in trisomic E9.5 embryos after treatment, but observed differences between treatment regimens. Differential gene expression was also quantified in trisomic treated embryos. This preliminary data suggests EGCG treatment has the potential to rescue the mandibular phenotype caused by trisomy. These findings provide preclinical testing for a potential therapy for craniofacial disorders linked to DS
Down-regulation of PLCγ2-β-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer
Myeloid-derived suppressor cells (MDSCs) favor tumor promotion, mainly by suppressing antitumor T cell responses in many cancers. Although the mechanism of T cell inhibition is established, the pathways leading to MDSC accumulation in bone marrow and secondary lymphoid organs of tumor-bearing hosts remain unclear. We demonstrate that down-regulation of PLCγ2 signaling in MDSCs is responsible for their aberrant expansion during tumor progression. PLCγ2(−/−) MDSCs show stronger immune-suppressive activity against CD8(+) T cells than WT MDSCs and potently promote tumor growth when adoptively transferred into WT mice. Mechanistically, PLCγ2(−/−) MDSCs display reduced β-catenin levels, and restoration of β-catenin expression decreases their expansion and tumor growth. Consistent with a negative role for β-catenin in MDSCs, its deletion in the myeloid population leads to MDSC accumulation and supports tumor progression, whereas expression of β-catenin constitutively active reduces MDSC numbers and protects from tumor growth. Further emphasizing the clinical relevance of these findings, MDSCs isolated from pancreatic cancer patients show reduced p-PLCγ2 and β-catenin levels compared with healthy controls, similar to tumor-bearing mice. Thus, for the first time, we demonstrate that down-regulation of PLCγ2–β-catenin pathway occurs in mice and humans and leads to MDSC-mediated tumor expansion, raising concerns about the efficacy of systemic β-catenin blockade as anti-cancer therapy
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