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1.
Nature ; 585(7825): 357-362, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32939066

RESUMO

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves1 and in the first imaging of a black hole2. Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.


Assuntos
Biologia Computacional/métodos , Matemática , Linguagens de Programação , Design de Software
2.
Hepatology ; 79(5): 1129-1140, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37870278

RESUMO

BACKGROUND AND AIMS: Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive. APPROACH AND RESULTS: A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)]. CONCLUSIONS: The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Vírus Delta da Hepatite/genética , Antígenos de Superfície da Hepatite B , Cirrose Hepática/complicações , Morbidade , RNA Viral , Progressão da Doença , Vírus da Hepatite B/genética
3.
J Urol ; : 101097JU0000000000004032, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38785259

RESUMO

PURPOSE: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach. MATERIALS AND METHODS: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities. RESULTS: The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01). CONCLUSIONS: PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations. CLINICALTRIALS.GOV IDENTIFIER: NCT04936334.

4.
Psychol Med ; 53(10): 4424-4433, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35711146

RESUMO

BACKGROUND: Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear. METHODS: We recruited a sample of adolescents (n = 82; ages 12-18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life. RESULTS: Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome. CONCLUSIONS: Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.


Assuntos
Anedonia , Corpo Estriado , Humanos , Adolescente , Córtex Pré-Frontal/diagnóstico por imagem , Aprendizagem , Recompensa , Imageamento por Ressonância Magnética
5.
Am J Public Health ; 112(3): 397-400, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35196042

RESUMO

During the COVID-19 pandemic, media accounts emerged describing faith-based organizations (FBOs) working alongside health departments to support the COVID-19 response. In May 2021, the Department of Health and Human Services, Centers for Disease Control and Prevention, and the Association of State and Territorial Health Officials (ASTHO) sent an electronic survey to the 59 ASTHO member jurisdictions and four major US cities to assess state and territorial engagement with FBOs. Findings suggest that public health officials in many jurisdictions were able to work effectively with FBOs during the COVID-19 pandemic to provide essential education and mitigation tools to diverse communities. (Am J Public Health. 2022;112(3):397-400. https://doi.org/10.2105/AJPH.2021.306620).


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/etnologia , COVID-19/prevenção & controle , Organizações Religiosas/organização & administração , Promoção da Saúde/organização & administração , Relações Comunidade-Instituição , Organizações Religiosas/economia , Equidade em Saúde , Promoção da Saúde/economia , Humanos , Pandemias , Administração em Saúde Pública , SARS-CoV-2 , Governo Estadual , Estados Unidos/epidemiologia , Hesitação Vacinal/etnologia
6.
MMWR Morb Mortal Wkly Rep ; 71(43): 1374-1378, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36301741

RESUMO

Vaccination with JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to prevent monkeypox commenced shortly after confirmation of the first monkeypox case in the current outbreak in the United States on May 17, 2022 (1). To date, more than 27,000 cases have been reported across all 50 states, the District of Columbia (DC), and Puerto Rico.* JYNNEOS vaccine is licensed by the Food and Drug Administration (FDA) as a 0.5-mL 2-dose series administered subcutaneously 28 days apart to prevent smallpox and monkeypox infections (2) and has been found to provide protection against monkeypox infection during the current outbreak (3). The U.S. Department of Health and Human Services (HHS) allocated 1.1 million vials of JYNNEOS vaccine from the Strategic National Stockpile, with doses allocated to jurisdictions based on case counts and estimated size of population at risk (4). However, initial vaccine supplies were severely constrained relative to vaccine demand during the expanding outbreak. Some jurisdictions with highest incidence responded by prioritizing first dose administration during May-July (5,6). The FDA emergency use authorization (EUA) of 0.1 mL dosing for intradermal administration of JYNNEOS for persons aged ≥18 years on August 9, 2022, substantially expanded available vaccine supply† (7). The U.S. vaccination strategy focuses primarily on persons with known or presumed exposures to monkeypox (8) or those at high risk for occupational exposure (9). Data on monkeypox vaccine doses administered and reported to CDC by U.S. jurisdictions were analyzed to assess vaccine administration and completion of the 2-dose series. A total of 931,155 doses of JYNNEOS vaccine were administered and reported to the CDC by 55 U.S. jurisdictions during May 22-October 10, 2022. Among persons who received ≥1 dose, 51.4% were non-Hispanic White (White), 22.5% were Hispanic or Latino (Hispanic), and 12.6% were non-Hispanic Black or African American (Black). The percentages of vaccine recipients who were Black (5.6%) and Hispanic (15.5%) during May 22-June 25 increased to 13.3% and 22.7%, respectively, during July 31-October 10. Among 496,888 persons who received a first dose and were eligible for a second dose during the study period, 57.6% received their second dose. Second dose receipt was highest among older adults, White persons, and those residing in the South U.S. Census Bureau Region. Tracking and addressing disparities in vaccination can reduce inequities, and equitable access to and acceptance of vaccine should be an essential factor in planning vaccination programs, events, and strategies. Receipt of both first and second doses is necessary for optimal protection against Monkeypox virus infection.


Assuntos
Mpox , Vacina Antivariólica , Vacinas , Vacínia , Estados Unidos/epidemiologia , Humanos , Adolescente , Adulto , Idoso , Mpox/epidemiologia , Mpox/prevenção & controle , Vacinação
7.
Cereb Cortex ; 31(9): 4006-4023, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-33895807

RESUMO

What role do domain-general executive functions play in human language comprehension? To address this question, we examine the relationship between behavioral measures of comprehension and neural activity in the domain-general "multiple demand" (MD) network, which has been linked to constructs like attention, working memory, inhibitory control, and selection, and implicated in diverse goal-directed behaviors. Specifically, functional magnetic resonance imaging data collected during naturalistic story listening are compared with theory-neutral measures of online comprehension difficulty and incremental processing load (reading times and eye-fixation durations). Critically, to ensure that variance in these measures is driven by features of the linguistic stimulus rather than reflecting participant- or trial-level variability, the neuroimaging and behavioral datasets were collected in nonoverlapping samples. We find no behavioral-neural link in functionally localized MD regions; instead, this link is found in the domain-specific, fronto-temporal "core language network," in both left-hemispheric areas and their right hemispheric homotopic areas. These results argue against strong involvement of domain-general executive circuits in language comprehension.


Assuntos
Compreensão/fisiologia , Idioma , Rede Nervosa/fisiologia , Adulto , Atenção/fisiologia , Encéfalo/diagnóstico por imagem , Função Executiva/fisiologia , Feminino , Fixação Ocular , Lateralidade Funcional , Humanos , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Psicolinguística , Desempenho Psicomotor/fisiologia , Leitura , Adulto Jovem
8.
J Neurosci ; 40(1): 107-130, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31704785

RESUMO

Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, we showed that mice (both females and males) with a heterozygous mutation in the first coding exon of Hnrnph1 (H1+/-) showed reduced methamphetamine reinforcement and intake and dose-dependent changes in methamphetamine reward as measured via conditioned place preference. Furthermore, H1+/- mice showed a robust decrease in methamphetamine-induced dopamine release in the NAc with no change in baseline extracellular dopamine, striatal whole-tissue dopamine, dopamine transporter protein, dopamine uptake, or striatal methamphetamine and amphetamine metabolite levels. Immunohistochemical and immunoblot staining of midbrain dopaminergic neurons and their forebrain projections for TH did not reveal any major changes in staining intensity, cell number, or forebrain puncta counts. Surprisingly, there was a twofold increase in hnRNP H protein in the striatal synaptosome of H1+/- mice with no change in whole-tissue levels. To gain insight into the mechanisms linking increased synaptic hnRNP H with decreased methamphetamine-induced dopamine release and behaviors, synaptosomal proteomic analysis identified an increased baseline abundance of several mitochondrial complex I and V proteins that rapidly decreased at 30 min after methamphetamine administration in H1+/- mice. In contrast, the much lower level of basal synaptosomal mitochondrial proteins in WT mice showed a rapid increase. We conclude that H1+/- decreases methamphetamine-induced dopamine release, reward, and reinforcement and induces dynamic changes in basal and methamphetamine-induced synaptic mitochondrial function.SIGNIFICANCE STATEMENT Methamphetamine dependence is a significant public health concern with no FDA-approved treatment. We discovered a role for the RNA binding protein hnRNP H in methamphetamine reward and reinforcement. Hnrnph1 mutation also blunted methamphetamine-induced dopamine release in the NAc, a key neurochemical event contributing to methamphetamine addiction liability. Finally, Hnrnph1 mutants showed a marked increase in basal level of synaptosomal hnRNP H and mitochondrial proteins that decreased in response to methamphetamine, whereas WT mice showed a methamphetamine-induced increase in synaptosomal mitochondrial proteins. Thus, we identified a potential role for hnRNP H in basal and dynamic mitochondrial function that informs methamphetamine-induced cellular adaptations associated with reduced addiction liability.


Assuntos
Dopamina/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo F-H/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Metanfetamina/farmacologia , Mitocôndrias/efeitos dos fármacos , Reforço Psicológico , Recompensa , Sinaptossomos/metabolismo , Animais , Ansiedade/fisiopatologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Éxons/genética , Comportamento Exploratório/efeitos dos fármacos , Feminino , Heterozigoto , Masculino , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Metanfetamina/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Mutação , Reflexo de Sobressalto/efeitos dos fármacos , Teste de Desempenho do Rota-Rod , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia
9.
Arterioscler Thromb Vasc Biol ; 39(11): 2411-2430, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31554421

RESUMO

OBJECTIVE: Clinical evidence has linked low HDL (high-density lipoprotein) cholesterol levels with high cardiovascular disease risk; however, its significance as a therapeutic target remains unestablished. We hypothesize that HDLs functional heterogeneity is comprised of metabolically distinct proteins, each on distinct HDL sizes and that are affected by diet. Approach and Results: Twelve participants were placed on 2 healthful diets high in monounsaturated fat or carbohydrate. After 4 weeks on each diet, participants completed a metabolic tracer study. HDL was isolated by Apo (apolipoprotein) A1 immunopurification and separated into 5 sizes. Tracer enrichment and metabolic rates for 8 HDL proteins-ApoA1, ApoA2, ApoC3, ApoE, ApoJ, ApoL1, ApoM, and LCAT (lecithin-cholesterol acyltransferase)-were determined by parallel reaction monitoring and compartmental modeling, respectively. Each protein had a unique, size-specific distribution that was not altered by diet. However, carbohydrate, when replacing fat, increased the fractional catabolic rate of ApoA1 and ApoA2 on alpha3 HDL; ApoE on alpha3 and alpha1 HDL; and ApoM on alpha2 HDL. Additionally, carbohydrate increased the production of ApoC3 on alpha3 HDL and ApoJ and ApoL1 on the largest alpha0 HDL. LCAT was the only protein studied that diet did not affect. Finally, global proteomics showed that diet did not alter the distribution of the HDL proteome across HDL sizes. CONCLUSIONS: This study demonstrates that HDL in humans is composed of a complex system of proteins, each with its own unique size distribution, metabolism, and diet regulation. The carbohydrate-induced hypercatabolic state of HDL proteins may represent mechanisms by which carbohydrate alters the cardioprotective properties of HDL.


Assuntos
Dieta Hiperlipídica , Carboidratos da Dieta/administração & dosagem , Gorduras Insaturadas na Dieta/administração & dosagem , Lipoproteínas HDL/sangue , Proteoma , Apolipoproteína A-I/sangue , Apolipoproteína A-II/sangue , Apolipoproteína C-III/sangue , Apolipoproteína L1/sangue , Apolipoproteínas E/sangue , Apolipoproteínas M/sangue , Clusterina/sangue , Feminino , Humanos , Lipoproteínas HDL/química , Masculino , Fosfatidilcolina-Esterol O-Aciltransferase/sangue
10.
Blood ; 128(24): 2819-2823, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27760759

RESUMO

Myelodysplastic syndromes (MDSs) are a group of hematopoietic disorders affecting the myeloid lineage, characterized by cytopenias and clonal evolution to acute myeloid leukemia (AML). We hypothesized that natural killer (NK) cells and their activating killer immunoglobulin-like receptors (aKIRs) influence the immune surveillance and clinical outcome of patients with MDSs. Here, we first examined the distribution of aKIR genes and haplotype in 2 independent cohorts of MDS and AML patients. The median number of aKIR genes was lower in MDS patients than healthy controls (2 vs 3 genes; P = .001), and lower in patients with secondary AML (progressed from MDSs) compared with de novo AML patients (2 vs 3; P = .008) and healthy controls (2 vs 3; P = .006). In a multivariate analysis, the presence of KIR haplotype A (characterized by low aKIR content 0-1) independently predicted a higher risk of conversion to AML (relative risk [RR] with 95% confidence interval [CI], 2.67 [1.13-6.71]; P = .02) and worse adjusted progression-free survival (RR with 95% CI, 2.96 [1.59-5.52]; P = .001) and overall survival (2.25 [1.17-4.31]; P = .02), compared with KIR haplotype B (multiple aKIR genes). These novel findings may help to identify MDS patients with a high risk of disease progression who would likely benefit from adoptive NK-cell therapy.


Assuntos
Haplótipos/genética , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Receptores KIR/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/patologia , Progressão da Doença , Feminino , Dosagem de Genes , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Prognóstico , Resultado do Tratamento , Adulto Jovem
11.
Int J Gynecol Pathol ; 37(4): 397-400, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28700437

RESUMO

We present a novel case of a 48-yr-old female with a uterine adenomyoma with an unusual pseudoinvasive growth pattern displaying full-thickness penetration beyond the serosal surface in association with a dehisced Caesarian scar. Before hysterectomy, magnetic resonance imaging findings showed an infiltrative lesion suggestive of endometrial carcinoma. An endometrial biopsy was benign but definitive operative management was pursued given the concerning imaging. Gross examination of the uterus demonstrated a 7.2 cm, relatively well-circumscribed polypoid neoplasm with pushing borders extending through the full thickness of the myometrium. A serosal defect with protruding red tissue was noted where the neoplasm penetrated the exterior surface of the uterus. Histologic examination demonstrated benign endometrial glands, associated endometrial stroma, thick-walled vessels, and a prominent smooth muscle component consistent with an adenomyoma. To our knowledge, this unique presentation of a pseudoinvasive adenomyoma extending beyond the serosa is extremely rare and is the first time reported in the literature.


Assuntos
Adenomioma/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico por imagem , Pólipos/diagnóstico por imagem , Adenomioma/patologia , Adenomioma/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Endométrio/diagnóstico por imagem , Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Músculo Liso/diagnóstico por imagem , Músculo Liso/patologia , Músculo Liso/cirurgia , Miométrio/diagnóstico por imagem , Miométrio/patologia , Miométrio/cirurgia , Pólipos/patologia , Pólipos/cirurgia , Útero/diagnóstico por imagem , Útero/patologia , Útero/cirurgia
12.
J Neurosci ; 36(25): 6732-41, 2016 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-27335404

RESUMO

UNLABELLED: Dopamine D2/3 receptor signaling is critical for flexible adaptive behavior; however, it is unclear whether D2, D3, or both receptor subtypes modulate precise signals of feedback and reward history that underlie optimal decision making. Here, PET with the radioligand [(11)C]-(+)-PHNO was used to quantify individual differences in putative D3 receptor availability in rodents trained on a novel three-choice spatial acquisition and reversal-learning task with probabilistic reinforcement. Binding of [(11)C]-(+)-PHNO in the midbrain was negatively related to the ability of rats to adapt to changes in rewarded locations, but not to the initial learning. Computational modeling of choice behavior in the reversal phase indicated that [(11)C]-(+)-PHNO binding in the midbrain was related to the learning rate and sensitivity to positive, but not negative, feedback. Administration of a D3-preferring agonist likewise impaired reversal performance by reducing the learning rate and sensitivity to positive feedback. These results demonstrate a previously unrecognized role for D3 receptors in select aspects of reinforcement learning and suggest that individual variation in midbrain D3 receptors influences flexible behavior. Our combined neuroimaging, behavioral, pharmacological, and computational approach implicates the dopamine D3 receptor in decision-making processes that are altered in psychiatric disorders. SIGNIFICANCE STATEMENT: Flexible decision-making behavior is dependent upon dopamine D2/3 signaling in corticostriatal brain regions. However, the role of D3 receptors in adaptive, goal-directed behavior has not been thoroughly investigated. By combining PET imaging with the D3-preferring radioligand [(11)C]-(+)-PHNO, pharmacology, a novel three-choice probabilistic discrimination and reversal task and computational modeling of behavior in rats, we report that naturally occurring variation in [(11)C]-(+)-PHNO receptor availability relates to specific aspects of flexible decision making. We confirm these relationships using a D3-preferring agonist, thus identifying a unique role of midbrain D3 receptors in decision-making processes.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Tomada de Decisões/fisiologia , Receptores de Dopamina D3/metabolismo , Reversão de Aprendizagem/fisiologia , Análise de Variância , Animais , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Simulação por Computador , Condicionamento Operante/efeitos dos fármacos , Tomada de Decisões/efeitos dos fármacos , Dopaminérgicos/farmacologia , Privação de Alimentos , Masculino , Modelos Biológicos , Oxazinas/farmacocinética , Tomografia por Emissão de Pósitrons , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Long-Evans , Reversão de Aprendizagem/efeitos dos fármacos , Fatores de Tempo
13.
Hepatology ; 61(5): 1471-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25706754

RESUMO

UNLABELLED: Patients with chronic hepatitis C (CHC) exhibit reduced work productivity owing to their disease. Historically, most regimens indicated for CHC genotype 1 (GT1) patients were administered with pegylated interferon (Peg-IFN) and/or ribavirin (RBV), which further compromised work productivity during treatment. The aim of this study was to model the impact of LDV/SOF (ledipasvir/sofosbuvir), the first Peg-IFN- and RBV-free regimen for CHC GT1 patients, on work productivity from an economic perspective, compared to receiving no treatment. The WPAI-SHP (Work Productivity and Activity Index-Specific Health Problem) questionnaire was administered to patients across the ION clinical trials (N = 1,923 U.S. patients). Before initiation of treatment, patients with CHC GT1 in the ION trials exhibited absenteeism and presenteeism impairments of 2.57% and 7.58%, respectively. Patients with cirrhosis exhibited greater work productivity impairment than patients without cirrhosis. In total, 93.21% of U.S. patients in the ION trials achieved SVR; these patients exhibited absenteeism and presenteeism impairments of 2.62% (P = 0.76, when compared to baseline) and 3.53% (P < 0.0001), respectively. Monetizing these data to the entire U.S. population, our model projects an annual societal cost of $7.1 billion owing to productivity loss in untreated GT1 CHC patients. Our model projects that, when compared to no treatment, treating all CHC GT1 patients with a regimen with very high viral eradication rates (LDV/SOF) would translate to annual productivity loss savings of $2.7 billion over a 1-year time horizon. CONCLUSIONS: Patients with untreated HCV impose a substantial societal burden owing to reduced work productivity. As a result of improvements in work productivity, treatment of CHC GT1 patients with LDV/SOF-based regimens is likely to result in significant cost savings from a societal perspective, relative to no treatment.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Eficiência , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/economia , Modelos Econômicos , Uridina Monofosfato/análogos & derivados , Custos e Análise de Custo , Humanos , Sofosbuvir , Estados Unidos , Uridina Monofosfato/uso terapêutico
14.
Water Sci Technol ; 73(6): 1287-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27003068

RESUMO

An anaerobic/ion exchange (AN-IX) system was developed for recovery and reuse of wastewater nitrogen at point-of-origin. AN-IX combines upflow solids blanket anaerobic treatment with ammonium ion adsorption onto granular natural zeolite. AN-IX operates passively and without energy input. A 57 L empty-bed prototype was operated for 355 days on wastewater primary effluent. Total nitrogen removal exceeded 95% over the first 214 days of operation and ammonia reduction exceeded 99%; accumulation of oxidized nitrogen species (NO3(-) + NO2(-)) was not observed. The wastewater flowrate was increased during the last 35 days of operation to deliberately exhaust the ion exchange media. Spent granular media was removed from the AN-IX prototype and deployed in plant chamber experiments for cultivation of Solanum lycopersicum (cherry tomato). Wastewater nitrogen captured on zeolite was capable of supplying the total growth requirement for nitrogen. Canopy volume and plant flowering and fruiting were higher for wastewater nitrogen than for artificial fertilizer. The AN-IX process is a passive, mechanically simple and reliable system for local-scale nitrogen recovery. AN-IX is modular, scalable, adaptable and can be applied in diverse treatment contexts and recycling scenarios. AN-IX benefits include appropriate technology for local-scale nitrogen recovery, low capital and energy costs, and protection of health and the environment.


Assuntos
Nitrogênio/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Adsorção , Compostos de Amônio , Fertilizantes , Troca Iônica , Plantas Comestíveis , Reciclagem , Zeolitas
16.
J Ark Med Soc ; 111(12): 248-51, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25966598

RESUMO

Hepatitis C infection is the most common blood-borne infection in the United States with an estimated 2.7 million individuals suffering from chronic infection. Of those who are infected with Hepatitis C virus, 75-85% develop chronic infection. Without treatment for chronic infection, individuals can develop liver diseases, such as cirrhosis and hepatocellular carcinoma, during many years of asymptomatic infection. To examine the burden of Hepatitis C virus infection in the state, the Arkansas Department of Health created an epidemiologic profile based on data collected in 2013 from several data sources, including the department's Hepatitis C surveillance program. In order to make more Arkansans aware of their infection, the local health units in all 75 counties of the state recently began screening individuals at risk for the disease, including persons born during the years 1945-1965. Despite recent advances in treatment efficacy, identifying infected individuals and connecting patients to affordable HCV treatment and care remain priorities.


Assuntos
Hepatite C Crônica/epidemiologia , Adolescente , Adulto , Idoso , Antivirais/economia , Antivirais/uso terapêutico , Arkansas , Estudos Transversais , Custos de Medicamentos , Feminino , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ribavirina/economia , Ribavirina/uso terapêutico , Fatores de Risco , Sofosbuvir , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/economia , Uridina Monofosfato/uso terapêutico , Adulto Jovem
17.
MMWR Morb Mortal Wkly Rep ; 63(8): 165-8, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24572611

RESUMO

On October 27, 2011, the Arkansas Department of Health (ADH) was notified by a northeast Arkansas primary care provider of a cluster of three histoplasmosis cases. On November 4, ADH was notified by a pediatric infectious diseases specialist regarding seven potential cases of pulmonary histoplasmosis associated with a family gathering that included a bonfire that burned bamboo from a grove that had been a red-winged blackbird roost. These reports prompted an outbreak investigation to ensure that the persons involved received appropriate medical care, to identify whether any novel exposures were associated with illness, and to determine whether any factors were associated with hospitalization. The investigation found that, among the 19 attendees at the family gathering, seven were confirmed with histoplasmosis, 11 were probable, and one did not have histoplasmosis.


Assuntos
Bambusa , Surtos de Doenças , Incêndios , Histoplasmose/diagnóstico , Arkansas/epidemiologia , Criança , Pré-Escolar , Feminino , Histoplasmose/epidemiologia , Humanos , Masculino
18.
MMWR Morb Mortal Wkly Rep ; 63(8): 169-73, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24572612

RESUMO

In August 2012, the Arkansas Department of Health (ADH) was notified of gastrointestinal illness outbreaks in two Arkansas state prisons. ADH investigated the outbreaks and conducted case-control studies to identify the source of the illnesses. This report describes the results of these investigations, which identified 528 persons with onset of diarrhea during August 2-18, 2012. Results from the prison A investigation identified chicken salad as the most likely vehicle. At prison B, person-to-person transmission and contamination of multiple foods likely contributed to illness. Analysis of stool specimens from inmates identified eight serotypes and 15 pulsed-field gel electrophoresis (PFGE) patterns of Salmonella. Isolates of Salmonella from eggs produced at prison B matched two outbreak patterns. An additional 69 inmates were positive by culture but were not interviewed or did not report diarrhea, making the total case count 597. Sanitarians identified problems with food preparation, hand washing, and food safety training. ADH tested inmate kitchen workers, excluded infected inmates from work, and provided food safety training. Prison kitchen staff should follow guidelines consistent with state regulations for safe food preparation and pass sanitarian inspection.


Assuntos
Surtos de Doenças , Prisões , Intoxicação Alimentar por Salmonella/microbiologia , Salmonella/classificação , Arkansas/epidemiologia , Estudos de Casos e Controles , Diarreia/epidemiologia , Eletroforese em Gel de Campo Pulsado , Fezes/microbiologia , Contaminação de Alimentos , Manipulação de Alimentos/normas , Humanos , Salmonella/isolamento & purificação , Intoxicação Alimentar por Salmonella/epidemiologia , Intoxicação Alimentar por Salmonella/transmissão , Sorotipagem
19.
J Orthop Case Rep ; 14(2): 131-135, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38420232

RESUMO

Introduction: Intraosseous ganglion cysts are an uncommon variant found in the subchondral bone. We report here the development of an intraosseous ganglion cyst of the proximal tibia in the setting of a prior left total knee arthroplasty (TKA) with an all-polyethylene tibial component. Case Report: The cyst was diagnosed on routine follow-up radiographs approximately 4 years status post-TKA. Although initially asymptomatic, 1 year later the patient presented with progressive knee pain and ambulation limitations, so revision TKA was indicated. Computed tomography confirmed an osteolytic lesion suggestive of a penetrating ganglion. Given the absence of malrotation or malalignment of the well-fixed femoral component, the decision was made to proceed with tibial revision to stemmed component cemented through a porous tantalum cone. Postoperatively, the patient had complete resolution of pain and instability with 0-120° of stable range of motion, which has persisted to the latest follow-up at over 6 months post-operative, with radiographic resolution of the cyst. Conclusion: This case demonstrates a ganglion cyst surrounding total knee implants as a possible source of persistent pain following TKA. To our knowledge, this is the first report of such a case. This case demonstrates that refractory painful knee implants secondary to tibial ganglion cysts can be treated successfully with revision arthroplasty.

20.
IEEE Trans Med Imaging ; 43(7): 2411-2419, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38306263

RESUMO

Positron emission tomography (PET) imaging enables quantitative assessment of tissue physiology. Dynamic pharmacokinetic analysis of PET images requires accurate estimation of the radiotracer plasma input function to derive meaningful parameter estimates, and small discrepancies in parameter estimation can mimic subtle physiologic tissue variation. This study evaluates the impact of input function interpolation method on the accuracy of Patlak kinetic parameter estimation through simulations modeling the pharmacokinetic properties of [68Ga]-PSMA-11. This study evaluated both trained and untrained methods. Although the mean kinetic parameter accuracy was similar across all interpolation models, the trained node weighting interpolation model estimated accurate kinetic parameters with reduced overall variability relative to standard linear interpolation. Trained node weighting interpolation reduced kinetic parameter estimation variance by a magnitude approximating the underlying physiologic differences between normal and diseased prostatic tissue. Overall, this analysis suggests that trained node weighting improves the reliability of Patlak kinetic parameter estimation for [68Ga]-PSMA-11 PET.


Assuntos
Ácido Edético , Isótopos de Gálio , Radioisótopos de Gálio , Oligopeptídeos , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Masculino , Radioisótopos de Gálio/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Isótopos de Gálio/farmacocinética , Oligopeptídeos/farmacocinética , Oligopeptídeos/química , Ácido Edético/análogos & derivados , Ácido Edético/farmacocinética , Próstata/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Compostos Radiofarmacêuticos/farmacocinética
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