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1.
Headache ; 62 Suppl 1: 1-170, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35593880
2.
BMC Med Res Methodol ; 22(1): 148, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597908

RESUMO

BACKGROUND: Missing data prove troublesome in data analysis; at best they reduce a study's statistical power and at worst they induce bias in parameter estimates. Multiple imputation via chained equations is a popular technique for dealing with missing data. However, techniques for combining and pooling results from fitted generalized additive models (GAMs) after multiple imputation have not been well explored. METHODS: We simulated missing data under MCAR, MAR, and MNAR frameworks and utilized random forest and predictive mean matching imputation to investigate a variety of rules for combining GAMs after multiple imputation with binary and normally distributed outcomes. We compared multiple pooling procedures including the "D2" method, the Cauchy combination test, and the median p-value (MPV) rule. The MPV rule involves simply computing and reporting the median p-value across all imputations. Other ad hoc methods such as a mean p-value rule and a single imputation method are investigated. The viability of these methods in pooling results from B-splines is also examined for normal outcomes. An application of these various pooling techniques is then performed on two case studies, one which examines the effect of elevation on a six-minute walk distance (a normal outcome) for patients with pulmonary arterial hypertension, and the other which examines risk factors for intubation in hospitalized COVID-19 patients (a dichotomous outcome). RESULTS: In comparison to the results from generalized additive models fit on full datasets, the median p-value rule performs as well as if not better than the other methods examined. In situations where the alternative hypothesis is true, the Cauchy combination test appears overpowered and alternative methods appear underpowered, while the median p-value rule yields results similar to those from analyses of complete data. CONCLUSIONS: For pooling results after fitting GAMs to multiply imputed datasets, the median p-value is a simple yet useful approach which balances both power to detect important associations and control of Type I errors.


Assuntos
COVID-19 , Hipertensão Pulmonar , COVID-19/epidemiologia , Colorado , Hospitalização , Humanos , Hipertensão Pulmonar/diagnóstico , Modelos Estatísticos , Sistema de Registros
4.
Sci Rep ; 12(1): 6451, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468982

RESUMO

Probainognathia is a derived lineage of cynodonts which encompass Mammalia as their crown-group. The rich record of probainognathians from the Carnian of Argentina contrasts with their Norian representation, with only one named species. Here we describe a new probainognathian, Tessellatia bonapartei gen. et sp. nov., from the Norian Los Colorados Formation of the Ischigualasto-Villa Unión Basin of Argentina. The new taxon, represented by a partial cranium with associated lower jaws, was analyzed through neutron and X-rays micro-tomography (µCT). The high-resolution neutron µCT data allowed the identification of a unique character combination, including features inaccessible through traditional techniques. We constructed the largest phylogenetic data matrix of non-mammalian cynodonts. The new species and its sister taxon, the Brazilian Therioherpeton cargnini, are recovered as probainognathians, closely related to Mammaliamorpha. We conducted the first quantitative paleobiogeographic analysis of non-mammalian cynodonts, focusing in probainognathians. The results indicate that Probainognathia and Mammaliamorpha originated in southwestern Gondwana (in the Brazilian Paraná Basin), which was an important center of diversification during the Triassic. Finally, the Chinese Lufeng Basin is identified as the ancestral area of Mammaliaformes. These new findings, besides adding to the knowledge of the poorly represented Norian cynodonts from the Los Colorados Formation, are significant to improve our understanding of probainognathian diversity, evolution, and paleobiogeographic history.


Assuntos
Fósseis , Mamíferos , Animais , Argentina , Brasil , Colorado , Filogenia
11.
Biol Lett ; 18(4): 20210519, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35382585

RESUMO

Understanding the causes and consequences of insect declines has become an important goal in ecology, particularly in the tropics, where most terrestrial diversity exists. Over the past 12 years, the ForestGEO Arthropod Initiative has systematically monitored multiple insect groups on Barro Colorado Island (BCI), Panama, providing baseline data for assessing long-term population trends. Here, we estimate the rates of change in abundance among 96 tiger moth species on BCI. Population trends of most species were stable (n = 20) or increasing (n = 62), with few (n = 14) declining species. Our analysis of morphological and climatic sensitivity traits associated with population trends shows that species-specific responses to climate were most strongly linked with trends. Specifically, tiger moth species that are more abundant in warmer and wetter years are more likely to show population increases. Our study contrasts with recent findings indicating insect decline in tropical and temperate regions. These results highlight the significant role of biotic responses to climate in determining long-term population trends and suggest that future climate changes are likely to impact tropical insect communities.


Assuntos
Mariposas , Clima Tropical , Animais , Mudança Climática , Colorado , Ecologia , Mariposas/fisiologia , Árvores
12.
Int J Drug Policy ; 104: 103685, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35429874

RESUMO

BACKGROUND: Emergency department (ED) visits involving psychosis and schizophrenia have increased at a rate exceeding population growth in the United States over the past decade. Research shows a strong dose-response relationship between chronic use of high-potency cannabis and odds of developing symptoms of psychosis. The aim of this study was to evaluate the impact of cannabis legalization on psychosis and schizophrenia-related ED visits in Colorado. METHODS: Using administrative data from Colorado Hospital Association (CHA) on county-level quarterly ED visits between January 1, 2013, and December 31, 2018, we applied a difference-in-difference analysis to examine how new exposure to recreational cannabis dispensaries after 2014 differentially influenced the rate of ED visits for psychosis and schizophrenia, comparing counties with no prior medical cannabis dispensary exposure to counties with low or high medical dispensary exposure. RESULTS: As recreational dispensaries per 10,000 residents increased, there was no significant association with the rate of schizophrenia ED visits per capita (incidence rate ratio or IRR: 0.95, 95% CI [0.69, 1.30]) while the rate of psychosis visits increased 24% (IRR: 1.24, 95% CI [1.02, 1.49]). Counties with no previous medical dispensaries experienced larger increases in schizophrenia ED visits than counties already exposed to a low level of medical dispensaries, but this effect was not significant. Counties with low baseline medical exposure had lower increases in rates of psychosis visits than counties with high baseline medical exposure (IRR 0.83, 95% CI [0.69, 0.99]). CONCLUSIONS: There was a positive association between the number of cannabis dispensaries and rates of psychosis ED visits across all counties in Colorado. Although it is unclear whether it is access to products, or the types of products that may be driving this association, our findings suggest there is a potential impact on the mental health of the local population that is observed after cannabis legalization.


Assuntos
Cannabis , Alucinógenos , Transtornos Psicóticos , Esquizofrenia , Analgésicos , Cannabis/efeitos adversos , Colorado/epidemiologia , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Transtornos Psicóticos/epidemiologia , Esquizofrenia/epidemiologia , Estados Unidos
13.
Sci Rep ; 12(1): 4602, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35301399

RESUMO

The identification of sex in larvae of insects is usually challenging or even impossible, while in adults the sexual dimorphism is usually evident. Here, we used copy number analysis to develop a method of sex detection in Colorado potato beetle (Leptinotarsa decemlineata), which has an X0 sex determination system. The X linked gene LdVssc and autosomal gene LdUBE3B were identified as appropriate target and reference loci, respectively. The copy numbers (CNV) of LdVssc in males and females were estimated using standard droplet digital PCR (ddPCR) and real-time PCR (qPCR). With both methods, CNVs were bimodally distributed (BAddPCR = 0.709 and BAqPCR = 0.683) with 100% ability to distinguish females from males. The use of qPCR-based sex detection in a broad collection of 448 random CPB adults showed a perfect association (Phi = 1.0, p < 0.05) with the true sexes of adults, with mean CNV in females of 2.032 (SD = 0.227) and 0.989 in males (SD = 0.147). In the collection of 50 random 4th instar larvae, 27 females and 23 males were identified, consistent with the expected 1:1 sex ratio (p = 0.689). The method is suitable for sexing in all stages of ontogenesis. The optimal cost-effective application of the method in large populations requires the DNA extraction using CTAB, the qPCR assay in one biological replicate and three technical replicates of each marker, and the use of one randomly chosen male per run to calibrate calculation of CNV.


Assuntos
Besouros , Solanum tuberosum , Animais , Besouros/genética , Colorado , Variações do Número de Cópias de DNA , Feminino , Larva/genética , Masculino
15.
Behav Med ; 48(2): 72-84, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35318900

RESUMO

The COVID-19 pandemic has drawn greater attention to social determinants of health and associated health inequities, which disproportionately affect vulnerable populations and places in the U.S. In this study, we explored geographic patterns of local-level COVID-19 vulnerability and associations with social and health determinants across Colorado. To conceptualize social and health determinants and how together they generate risk and exposure, we integrated the concepts of social vulnerability and syndemic to situate COVID-19 vulnerability within a broader hazards of place framework. Using geospatial statistics and GIS, we estimated census tract-level rates of COVID-19, which are not yet available in Colorado, and mapped areas of high and low incidence risk. We also developed composite indices that characterized social and health vulnerabilities to measure multivariate associations with COVID-19 rates. The findings revealed hotspots of persistent risk in mountain communities since the pandemic emerged in Colorado, as well as clusters of risk in the Urban Front Range's central and southern counties, and across many parts of eastern Colorado. Vulnerability analyses indicate that COVID-19 rates were associated with mental health and chronic conditions along with social determinants that represent inequities in education, income, healthcare access, and race/ethnicity (minority percent of population), which may have disproportionately exposed some communities more than others to infection and severe health outcomes. Overall, the findings provide geographic health information about COVID-19 and vulnerability context, which may better inform local decision-making for interventions and policies that support equity of social determinants of health.Supplemental data for this article is available online at https://doi.org/10.1080/08964289.2021.2021382 .


Assuntos
COVID-19 , Determinantes Sociais da Saúde , COVID-19/epidemiologia , Colorado/epidemiologia , Geografia , Humanos , Pandemias
16.
Transl Vis Sci Technol ; 11(2): 12, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35133404

RESUMO

PURPOSE: To determine if there are sex differences in levels of regulated upon activation, normal T cell expressed and secreted (RANTES) in patients with intermediate age-related macular degeneration (iAMD) and in controls with no AMD. METHODS: Patients with iAMD and controls defined by multi-modal imaging were recruited into a Colorado AMD registry. Plasma levels of the chemokine RANTES were measured using a multiplex assay. A nonparametric (rank-based) regression model was fit to RANTES with a sex by AMD category interaction. RESULTS: The plasma level of RANTES was significantly higher in the control group in comparison with the iAMD group. When moderated by sex, RANTES was significantly lower (P = 0.005) in males (median, 4525.6 pg/mL; interquartile range, 2589-7861 pg/mL) compared with females (median, 6686 pg/mL; interquartile range, 3485-12488 pg/mL) within the iAMD cohort. No significant difference was found in levels of RANTES between males and females in the control group. CONCLUSIONS: We found that levels of RANTES were moderated by sex in cases with iAMD with lower levels in males compared with females. The findings illustrate the importance of including sex as a biological variable in AMD research. There is a need for further studies of RANTES, stratified by sex, in the advanced phenotypes of AMD. TRANSLATIONAL RELEVANCE: The biomarker RANTES identified in the plasma of patients with iAMD reflects systemic alterations when stratified by sex.


Assuntos
Quimiocina CCL5 , Degeneração Macular , Colorado , Feminino , Humanos , Degeneração Macular/genética , Masculino , Caracteres Sexuais , Linfócitos T
17.
Prev Med ; 156: 106993, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35150750

RESUMO

The primary objective of this study was to evaluate the association between presence of recreational cannabis dispensaries and prevalence of cannabis-involved pregnancy hospitalizations in Colorado. This was a retrospective cohort study of pregnancy-related hospitalizations co-coded with cannabis diagnosis codes in the Colorado Hospital Association from January 1, 2011, through December 31, 2018 (recreational cannabis began January 1, 2014). Our primary outcome was cannabis-involved pregnancy hospitalizations per 10 k live births per county. The primary exposure measure was county variation in the number of recreational dispensaries. We controlled for counties' baseline exposure to medical cannabis dispensaries and used Poisson regression to evaluate the association between exposure to recreational cannabis and hospitalizations. During the study period, cannabis-involved pregnancy hospitalizations increased from 429 to 1210. Mean hospitalizations per county (1.7 to 4.7) and per 10 k live births (13.2 to 55.7) increased. Overall, increasing recreational dispensaries were associated with increases in hospitalizations (1.02, CI: 1.00,1.04). When comparing counties with different densities of baseline medical cannabis market, low and high exposure counties had fewer hospitalizations than those counties with no exposure (low: IRR 0.97, CI: 0.96-0.99; high: 0.98, CI: 0.96-0.99). In Colorado, there was more than a two-fold increase in cannabis-involved pregnancy hospitalizations between 2011 and 2018. Counties with no baseline exposure to medical cannabis had a greater increase than other counties, suggesting the recreational market may influence cannabis use among pregnant individuals.


Assuntos
Cannabis , Maconha Medicinal , Cannabis/efeitos adversos , Colorado/epidemiologia , Feminino , Hospitalização , Humanos , Gravidez , Estudos Retrospectivos
18.
Vet Ophthalmol ; 25(3): 240-249, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35226789

RESUMO

OBJECTIVE: In the fall of 2020, Colorado experienced the two largest wildfires in state history. The smoke blanketed the college town of Fort Collins, Colorado, the location of the Veterinary Teaching Hospital at Colorado State University (CSU-VTH). The objective for this cross-sectional observational study was to evaluate how these wildfires and the corresponding elevated air quality index (AQI)) was associated with infected corneal ulcerations in dogs when compared to the two previous years. ANIMALS: Seventeen dogs were included in this study. PROCEDURES: Medical records from dogs presented to the CSU-VTH ophthalmology service with infected corneal ulcerations in August, September, and October of 2020, 2019, and 2018 were evaluated. Only corneal ulcerations with growth on their microbial cultures were included in this study. RESULTS: The study revealed a significant increase in prevalence of infected corneal ulcerations in dogs presented to the CSU-VTH during the three wildfire months of 2020 that is, 3.5% (9/255) when compared with the two previous years, 2019: 1.0% (4/383, p = 0.04), and 2018: 0.9% (4/457) (p = .01). The AQI (mean ± standard error) was also significantly elevated for dogs that presented with infected corneal ulcerations in 2020 (70.2 ± 5.8) compared with 2019 (19.7 ± 8.7) and 2018 (45.6 ± 8.7) (p < .01). CONCLUSIONS AND CLINICAL RELEVANCE: Elevation of AQI from wildfires seems to be correlated with an increased prevalence of infected corneal ulceration in dogs. As the duration and frequency of wildfires continues to rise globally, the effects of these wildfires on animal health should be investigated further.


Assuntos
Poluentes Atmosféricos , Incêndios Florestais , Poluentes Atmosféricos/análise , Animais , Colorado/epidemiologia , Estudos Transversais , Cães , Hospitais Veterinários , Hospitais de Ensino , Humanos , Material Particulado/análise , Estações do Ano
19.
Int J Oncol ; 60(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35179215

RESUMO

Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive pediatric brain tumor. Despite radiation, aggressive chemotherapy and autologous stem cell rescue, children usually have a poor survival time. In the present study, the role of TP53/MDM2 interaction in ATRT was investigated. A functional genomic screen identified the TP53/MDM2 axis as a therapeutic target in the central nervous system (CNS) ATRT. Gene expression analysis revealed that all ATRT sub­groups expressed high levels of MDM2, which is a negative regulator of TP53. Using cell viability, colony formation and methylcellulose assays it was found that genetic MDM2 inhibition with short hairpin RNA or chemical MDM2 inhibition with small molecule inhibitors, Nutlin3 and idasanutlin (RG7388) decreased the growth of ATRT cell lines. Furthermore, idasanutlin significantly decreased the growth of intracranial orthotopic ATRT brain tumors, as evaluated using T2 MRI, and prolonged survival time relative to control animals. MRI of intracranial tumors showed that diffusion coefficient, an effective marker for successful treatment, significantly increased with idasanutlin treatment showing tumor necrosis/apoptosis. Immunohistochemistry revealed an increased number of caspase­3­positive cells in the idasanutlin treatment group, confirming the induction of apoptosis in vivo. Using flow cytometry and western blot analysis we show that inhibition of MDM2 enhanced radiation sensitivity in vitro by potentiating DNA damage via the induction of the TP53/Bax/Puma proapoptotic axis. Furthermore, DNA damage was associated with increased mitochondrial reactive oxygen species accumulation. The present study demonstrated that MDM2 expression level was increased in ATRT patient samples and MDM2 inhibition suppressed ATRT cell growth in vitro, and leads to apoptosis in vivo. MDM2 inhibition potentiates DNA damage and sensitizes ATRT cells to radiation. These findings highlight the TP53/MDM2 axis as a rational therapeutic target in CNS ATRT.


Assuntos
Proteínas Proto-Oncogênicas c-mdm2/efeitos dos fármacos , Tolerância a Radiação/efeitos dos fármacos , Tumor Rabdoide/radioterapia , Proteína Supressora de Tumor p53/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Proliferação de Células/efeitos dos fármacos , Colorado , Humanos , Tolerância a Radiação/genética , Teratoma/radioterapia
20.
Artigo em Inglês | MEDLINE | ID: mdl-35206386

RESUMO

Cardiometabolic diseases are a group of interrelated diseases that pose greater burden among socially vulnerable communities. The social vulnerability index (SVI) identifies communities vulnerable to emergencies and may also help determine communities at risk of adverse chronic health outcomes. However, no studies have examined the relationship between the SVI and cardiometabolic health outcomes in Colorado or focused on rural settings. The aim of this ecological study was to determine whether the county-level SVI is associated with county-level cardiometabolic health indicators with a particular focus on rurality and racial/ethnic diversity. We obtained 2014 SVI scores from the Centers for Disease Control and Prevention (scored 0-1; higher = more vulnerable) and 2013-2015 cardiometabolic health estimates from the Colorado Department of Public Health and Environment. The distribution of social determinants of health was spatially evaluated. Bivariate relationships between the SVI and cardiometabolic indicators were estimated using simple linear regression models. The highest SVI scores were observed in rural areas, including the San Luis Valley (mean: 0.78, median: 0.91), Southeast (mean: 0.72, median: 0.73), and Northeast (mean: 0.66, median: 0.76) regions. Across Colorado, the SVI accounted for 41% of the variability in overweight and obesity prevalence (p < 0.001), 17% of the variability in diabetes prevalence (p = 0.001), and 58% of the age-adjusted myocardial infarction hospitalization rate (p < 0.001). SVI values may be useful in determining a community's burden of cardiometabolic diseases.


Assuntos
Doenças Cardiovasculares , Vulnerabilidade Social , Doenças Cardiovasculares/epidemiologia , Colorado/epidemiologia , Humanos
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