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1.
J Environ Radioact ; 255: 107012, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36126488

RESUMO

On May 15th of 2019, an anomalous emission of selenium-75 was detected at the stack of the Belgian Reactor 2 (BR2) in Mol. Although the release exceeded the prescribed limits for BR2, there was no harm to the population or food chain and so the event was classified as INES 1. However, it was very interesting from the perspective of near-range atmospheric dispersion. This publication brings together all available information at the near range - stack-monitored source term data, on-site meteorological data, ambient dose equivalent rates, deposition and concentration measurements - in one dataset that covers the initial puff release on May 15th, 2019 as well as a residual release through early November 2019. To demonstrate the consistency of this dataset, supporting atmospheric transport and dispersion calculations are performed using a Gaussian plume model. These calculations, in turn, are supported by near-range Flexpart calculations in the context of the residual release.


Assuntos
Monitoramento de Radiação , Modelos Teóricos
2.
Subst Abus ; 43(1): 892-900, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35192446

RESUMO

Background: The opioid epidemic continues to erode communities across Pennsylvania (PA). Federal and PA state programs developed grants to establish Hub and Spoke programs for the expansion of medications for opioid use disorders (MOUD). Employing the telementoring platform Project ECHO (Extension for Community Health Outcomes), Penn State Health engaged the other seven grant awardees in a Collaborative Health Systems (CHS) ECHO. We conducted key informant interviews to better understand impact of the CHS ECHO on health systems collaboration and opioid crisis efforts. Methods: For eight one-hour sessions, each awardee presented their unique strategies, challenges, and opportunities. Using REDCap, program characteristics, such as number of waivered prescribers and number of patients served were collected at baseline. After completion of the sessions, key informant interviews were conducted to assess the impact of CHS ECHO on awardee's programs. Results: Analysis of key informant interviews revealed important themes to address opioid crisis efforts, including the need for strategic and proactive program reevaluation and the convenience of collaborative peer learning networks. Participants expressed benefits of the CHS ECHO including allowing space for discussion of challenges and best practices and facilitating conversation on collaborative targeted advocacy and systems-level improvements. Participants further reported bolstered motivation and confidence. Conclusions: Utilizing Project ECHO provided a bidirectional platform of learning and support that created important connections between institutions working to combat the opioid epidemic. CHS ECHO was a unique opportunity for productive and convenient peer learning across external partners. Open dialogue developed during CHS ECHO can continue to direct systems-levels improvements that benefit individual and population outcomes.


Assuntos
Buprenorfina , Administração Financeira , Analgésicos Opioides/uso terapêutico , Buprenorfina/uso terapêutico , Comunicação , Humanos , Pennsylvania , Atenção Primária à Saúde
3.
Ann Oncol ; 32(10): 1267-1275, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34293461

RESUMO

BACKGROUND: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. PATIENTS AND METHODS: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. RESULTS: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895). CONCLUSION: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.


Assuntos
Neoplasias do Colo , Extensão Extranodal , Neoplasias do Colo/patologia , Humanos , Linfonodos/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
4.
Transl Psychiatry ; 11(1): 54, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446638

RESUMO

Neurodevelopmental abnormalities in neural connectivity have been long implicated in the etiology of schizophrenia (SCZ); however, it remains unclear whether these neural connectivity patterns are associated with genetic risk for SCZ in unaffected individuals (i.e., an absence of clinical features of SCZ or a family history of SCZ). We examine whether polygenic risk scores (PRS) for SCZ are associated with functional neural connectivity in adolescents and young adults without SCZ, whether this association is moderated by sex and age, and if similar associations are observed for genetically related neuropsychiatric PRS. One-thousand four-hundred twenty-six offspring from 913 families, unaffected with SCZ, were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort (median age at first interview = 15.6 (12-26), 51.6% female, 98.1% European American, 41% with a family history of alcohol dependence). Participants were followed longitudinally with resting-state EEG connectivity (i.e., coherence) assessed every two years. Higher SCZ PRS were associated with elevated theta (3-7 Hz) and alpha (7-12 Hz) EEG coherence. Associations differed by sex and age; the most robust associations were observed between PRS and parietal-occipital, central-parietal, and frontal-parietal alpha coherence among males between ages 15-19 (B: 0.15-0.21, p < 10-4). Significant associations among EEG coherence and Bipolar and Depression PRS were observed, but differed from SCZ PRS in terms of sex, age, and topography. Findings reveal that polygenic risk for SCZ is robustly associated with increased functional neural connectivity among young adults without a SCZ diagnosis. Striking differences were observed between men and women throughout development, mapping onto key periods of risk for the onset of psychotic illness and underlining the critical importance of examining sex differences in associations with neuropsychiatric PRS across development.


Assuntos
Transtorno Bipolar , Esquizofrenia , Adolescente , Adulto , Transtorno Bipolar/genética , Depressão , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Estudos Prospectivos , Esquizofrenia/genética , Caracteres Sexuais , Adulto Jovem
5.
Eur Cell Mater ; 40: 239-258, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206993

RESUMO

Discogenic back pain is a common condition without approved intervertebral disc (IVD) repair therapies. Cell delivery using injectable biomaterial carriers offers promise to restore disc height and biomechanical function, while providing a functional niche for delivered cells to repair degenerated tissues. This systematic review advances the injectable IVD cell delivery biomaterials field by characterising its current state and identifying themes of promising strategies. Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) guidelines were used to screen the literature and 183 manuscripts met the inclusion criteria. Cellular and biomaterial inputs, and biological and biomechanical outcomes were extracted from each study. Most identified studies targeted nucleus pulposus (NP) repair. No consensus exists on cell type or biomaterial carrier, yet most common strategies used mesenchymal stem cell (MSC) delivery with interpenetrating network/co-polymeric (IPN/CoP) biomaterials composed of natural biomaterials. All studies reported biological outcomes with about half the studies reporting biomechanical outcomes. Since the IVD is a load-bearing tissue, studies reporting compressive and shear moduli were analysed and two major themes were found. First, a competitive balance, or 'seesaw' effect, between biomechanical and biological performance was observed. Formulations with higher moduli had inferior cellular performance, and vice versa. Second, several low-modulus biomaterials had favourable biological performance and matured throughout culture duration with enhanced extracellular matrix synthesis and biomechanical moduli. Findings identify an opportunity to develop next-generation biomaterials that provide high initial biomechanical competence to stabilise and repair damaged IVDs with a capacity to promote cell function for long-term healing.


Assuntos
Materiais Biocompatíveis/farmacologia , Injeções , Disco Intervertebral/fisiopatologia , Regeneração/fisiologia , Fenômenos Biomecânicos/efeitos dos fármacos , Humanos
6.
J Perinatol ; 39(2): 193-202, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353080

RESUMO

OBJECTIVE: To compare neurodevelopmental outcomes in linear growth-restricted (LGR) infants born <29 weeks with and without weight gain out of proportion to linear growth. STUDY DESIGN: We compared 2-year neurodevelopmental outcomes between infants with and without LGR and between LGR infants with and without weight gain out of proportion to linear growth. The outcomes were Bayley-III cognitive, motor, and language scores, cerebral palsy, Gross Motor Function Classification System (GMFCS) level ≥ 2, and neurodevelopmental impairment. RESULT: In total, 1227 infants were analyzed. LGR infants were smaller and less mature at birth, had higher BMI, and had lower Bayley-III language scores (82.3 vs. 85.0, p < 0.05). Among infants with LGR, infants with high BMI had lower language scores compared with those with low-to-normal BMI (80.8 vs. 83.3, p < 0.05), and were more likely to have GMFCS level ≥2 and neurodevelopmental impairment. CONCLUSION: Among infants with LGR, weight gain out of proportion to linear growth was associated with poorer neurodevelopmental outcomes.


Assuntos
Lactente Extremamente Prematuro/crescimento & desenvolvimento , Testes Neuropsicológicos , Aumento de Peso , Paralisia Cerebral/diagnóstico , Transtornos Cognitivos/diagnóstico , Bases de Dados Factuais , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Masculino , Transtornos Motores/diagnóstico , National Institute of Child Health and Human Development (U.S.) , Estudos Retrospectivos , Estados Unidos
7.
Eur J Cancer ; 91: 99-106, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29353165

RESUMO

Indication for primary tumour resection (PTR) in asymptomatic metastatic colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses suggest a survival benefit for patients who underwent PTR. The aim was to evaluate the prognostic value of PTR in patients with synchronous mCRC by analysis of recent large RCTs including systemic therapy with modern targeted agents. Individual patient data (IPD) of 3423 patients enrolled into 8 randomised controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analysed. The number of patients with unresected synchronous mCRC, resected synchronous mCRC and metachronous mCRC was 710 (21%), 1705 (50%) and 1008 (29%), respectively. Adjusting for age, gender, performance status (PS) and prior chemotherapy, the unresected group had a significantly worse median overall survival (16.4 m) compared with the synchronous resected (22.2 m; hazard ratio [HR] 1.60, 95% CI 1.43-1.78) and metachronous (22.4 m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, median progression-free survival was significantly worse for the unresected group compared with the synchronous resected (HR 1.31, 95% CI 1.19-1.44) and metachronous (HR 1.47, 95% CI 1.30-1.66) groups. In a multivariate analysis, the observed associations remained significant. This largest IPD analysis of mCRC trials to date demonstrates an improved survival in synchronous mCRC patients after PTR. These results may be subject to bias since reasons for (non)resection were not available. Until results of ongoing RCTs are available, both upfront PTR followed by systemic treatment and upfront systemic treatment are considered appropriate treatment strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Colectomia/efeitos adversos , Colectomia/mortalidade , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Metástase Neoplásica , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
8.
Mol Psychiatry ; 23(5): 1293-1302, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29112194

RESUMO

Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations.


Assuntos
Cromossomos Humanos Par 10/genética , Abuso de Maconha/genética , Adulto , Negro ou Afro-Americano/genética , Alelos , Cannabis , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , População Branca/genética , Adulto Jovem
9.
Chem Commun (Camb) ; 53(61): 8529-8532, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28703825

RESUMO

The future of 89Zr-based immuno-PET is reliant upon the development of new chelators with improved stability compared to the currently used deferoxamine (DFO). Herein, we report the evaluation of the octadentate molecule DFO-HOPO (3) as a suitable chelator for 89Zr and a more stable alternative to DFO. The molecule showed good potential for the future development of a DFO-HOPO-based bifunctional chelator (BFC) for the radiolabelling of biomolecules with 89Zr. This work broadens the selection of available chelators for 89Zr in search of improved successors to DFO for clinical 89Zr-immuno-PET.

10.
Epidemiol Infect ; 145(10): 2109-2121, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28462763

RESUMO

Individuals with chronic respiratory conditions may be at increased risk for pertussis. We conducted a retrospective administrative claims analysis to examine the incidence and economic burden of diagnosed pertussis among adolescents and adults in the USA with chronic obstructive pulmonary disease (COPD) or asthma. Patients aged ⩾11 years with diagnosed pertussis and pre-existing COPD (n = 343) or asthma (n = 1041) were matched 1:1 to patients with diagnosed pertussis but without COPD or asthma. Differences in all-cause costs ('excess' costs) during the 45-day and 3-month and 6-month periods before and after the pertussis index date were calculated; adjusted excess costs were estimated via multivariate regressions. The incidence of diagnosed pertussis was higher among patients with COPD or asthma than among matched patients. Compared with matched patients, patients with pertussis and pre-existing COPD or asthma accrued greater all-cause adjusted costs across study periods ($3694 and $1193 more, respectively, in the 45-day period; $4173 and $1301 more in the 3-month period; and $6154 and $1639 more in the 6-month period; all P < 0·0001). Patients with pre-existing COPD or asthma experience an increased economic burden after diagnosed pertussis and may especially benefit from targeted tetanus, diphtheria, and acellular pertussis vaccination strategies.


Assuntos
Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Asma/economia , Asma/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asma/etiologia , Criança , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
11.
Philos Trans A Math Phys Eng Sci ; 375(2091)2017 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-28265024

RESUMO

Complex turbine wake interactions play an important role in overall energy extraction in large wind farms. Current control strategies optimize individual turbine power, and lead to significant energy losses in wind farms compared with lone-standing wind turbines. In recent work, an optimal coordinated control framework was introduced (Goit & Meyers 2015 J. Fluid Mech.768, 5-50 (doi:10.1017/jfm.2015.70)). Here, we further elaborate on this framework, quantify the influence of optimization parameters and introduce new simulation results for which gains in power production of up to 21% are observed.This article is part of the themed issue 'Wind energy in complex terrains'.

12.
Ann Oncol ; 28(6): 1183-1190, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28184420

RESUMO

BACKGROUND: Collection and reporting of adverse events (AEs) and their relatedness to study treatment, known commonly as attribution, in clinical trials is mandated by regulatory agencies (the National Cancer Institute and the Food and Drug Administration). Attribution is assigned by the treating physician using judgment based on various factors including patient's baseline status, disease history, and comorbidity as well as knowledge about the safety profile of the study treatments. We evaluate the patterns of AE attribution (unrelated, unlikely, possibly, probably, and definitely related to the treatment) in treatment, symptom intervention (cancer patients) and cancer prevention (participants at high risk for cancer) setting. MATERIALS AND METHODS: Nine multicenter placebo-controlled trials (two treatment, two symptom intervention, and five cancer prevention) were analysed separately (2155 patients). Frequency and severity of AEs were summarized by arm. Attribution and percentage of repeated AEs whose attribution changed overtime were summarized for the placebo arms. Percentage of physician over- or under-reporting of AE relatedness was calculated for the treatment arms using the placebo arm as the reference. RESULTS: Across all trials and settings, a very high proportion of AEs reported as related to treatment were classified as possibly related, a significant proportion of AEs in the placebo arm were incorrectly reported as related to treatment, and clinician-reported attribution over-estimated the rate of AEs related to treatment. Fatigue, nausea, vomiting, diarrhea, constipation, and neurosensory were the common AEs that were over reported by clinician as related to treatment. CONCLUSIONS: These analyses demonstrate that assigning causality to AE is a complex and difficult process that produces unreliable and subjective data. In randomized double-blind placebo-controlled trials where data are available to objectively assess relatedness of AE to treatment, attribution assignment should be eliminated.


Assuntos
Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Duplo-Cego , Feminino , Humanos , Masculino , Neoplasias/fisiopatologia , Neoplasias/prevenção & controle , Placebos
13.
Mol Psychiatry ; 22(12): 1767-1775, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28070124

RESUMO

Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (ß: -0.124; P<4.5 × 10-9), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.


Assuntos
Alcoolismo/genética , Alcoolismo/fisiopatologia , Negro ou Afro-Americano/genética , Eletroencefalografia , Endofenótipos , Predisposição Genética para Doença , Adulto , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/fisiopatologia , Alcoolismo/diagnóstico , População Negra/genética , Encéfalo/fisiopatologia , Butirilcolinesterase/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
14.
Psychol Med ; 47(1): 103-114, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27667499

RESUMO

BACKGROUND: Religiosity is a protective factor against many health problems, including alcohol use disorders (AUD). Studies suggest that religiosity has greater buffering effects on mental health problems among US Blacks and Hispanics than Whites. However, whether race/ethnic differences exist in the associations of religiosity, alcohol consumption and AUD is unclear. METHOD: Using 2004-2005 NESARC data (analytic n = 21 965), we examined the relationship of public religiosity (i.e. frequency of service attendance, religious social group size), and intrinsic religiosity (i.e. importance of religious/spiritual beliefs) to frequency of alcohol use and DSM-IV AUD in non-Hispanic (NH) Blacks, Hispanics and NH Whites, and whether associations differed by self-identified race/ethnicity. RESULTS: Only public religiosity was related to AUD. Frequency of religious service attendance was inversely associated with AUD (NH Whites ß: -0.103, p 0.05) or Hispanics (ß: -0.002, p > 0.05). CONCLUSIONS: US adults reporting greater public religiosity were at lower risk for AUD. Public religiosity may be particularly important among NH Blacks, while intrinsic religiosity may be particularly important among NH Whites, and among Hispanics who frequently attend religious services. Findings may be explained by variation in drinking-related norms observed among these groups generally, and in the context of specific religious institutions.


Assuntos
Consumo de Bebidas Alcoólicas/etnologia , População Negra/etnologia , Hispânico ou Latino/estatística & dados numéricos , Religião e Psicologia , População Branca/etnologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/etnologia , Adulto Jovem
15.
J Perinatol ; 36(12): 1116-1121, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27629374

RESUMO

OBJECTIVE: To compare neurodevelopmental outcomes in postnatal growth-restricted infants born <29 weeks with and without postnatal head-sparing (PHS). STUDY DESIGN: We analyzed developmental outcomes at 2 years of age among postnatally growth-restricted infants with and without head-sparing. The primary outcome was Bayley III cognitive composite score; secondary outcomes included Bayley III motor composite score, moderate/severe cerebral palsy, gross motor functional classification scale level⩾2, and presence or absence of neurodevelopmental impairment (NDI). RESULTS: Of 1098 infants evaluated at 18 to 22 months, 658 were postnatally growth restricted, of whom 301 had head-sparing. In the multivariate model including independent risk factors for poor growth and poor developmental outcome, infants with head-sparing had higher adjusted motor composite scores (mean difference 4.65, P<0.01), but no differences in other neurodevelopmental outcomes. CONCLUSION: PHS is associated with improved neurodevelopmental outcome in extremely preterm infants, specifically Bayley III motor scores, but whether beneficial effects of PHS persist later in life is unknown.


Assuntos
Desenvolvimento Infantil , Deficiências do Desenvolvimento/diagnóstico , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Estudos de Casos e Controles , Pré-Escolar , Feminino , Retardo do Crescimento Fetal/terapia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Deficiência Intelectual/diagnóstico , Masculino , Destreza Motora , Estudos Prospectivos
16.
Ann Oncol ; 27(2): 339-44, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26578722

RESUMO

BACKGROUND: Carboplatin (C) and paclitaxel (P) are standard treatments for carcinoma of unknown primary (CUP). Everolimus, an mTOR inhibitor, exhibits activity in diverse cancer types. We did a phase II trial combining everolimus with CP for CUP. We also evaluated whether a gene expression profiling (GEP) test that predicts tissue of origin (TOO) could identify responsive patients. PATIENTS AND METHODS: A tumor biopsy was required for central confirmation of CUP and GEP. Patients with metastatic, untreated CUP received everolimus (30 mg weekly) with P (200 mg/m(2)) and C (area under the curve 6) every 3 weeks. The primary end point was response rate (RR), with 22% needed for success. The GEP test categorized patients into two groups: those having a TOO where CP is versus is not considered standard therapy. RESULTS: Of 45 assessable patients, the RR was 36% (95% confidence interval 22% to 51%), which met criteria for success. Grade ≥3 toxicities were predominantly hematologic (80%). Adequate tissue for GEP was available in 38 patients and predicted 10 different TOOs. Patients with a TOO where platinum/taxane is a standard (n = 19) tended to have higher RR (53% versus 26%) and significantly longer PFS (6.4 versus 3.5 months) and OS (17.8 versus 8.3 months, P = 0.005), compared with patients (n = 19) with a TOO where platinum/taxane is not standard. CONCLUSIONS: Everolimus combined with CP demonstrated promising antitumor activity and an acceptable side-effect profile. A tumor biomarker identifying TOO may be useful to select CUP patients for specific antitumor regimens. CLINICALTRIALSGOV: NCT00936702.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Everolimo/uso terapêutico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neoplasias Primárias Desconhecidas/genética , Paclitaxel/uso terapêutico , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/patologia , Estudos Prospectivos , Resultado do Tratamento
18.
Transl Psychiatry ; 5: e586, 2015 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-26101849

RESUMO

Rodent models implicate metabotropic glutamate receptors (mGluRs) and downstream signaling pathways in addictive behaviors through metaplasticity. One way mGluRs can influence synaptic plasticity is by regulating the local translation of AMPA receptor trafficking proteins via eukaryotic elongation factor 2 (eEF2). However, genetic variation in this pathway has not been examined with human alcohol use phenotypes. Among a sample of adults living in Detroit, Michigan (Detroit Neighborhood Health Study; n = 788; 83% African American), 206 genetic variants across the mGluR-eEF2-AMPAR pathway (including GRM1, GRM5, HOMER1, HOMER2, EEF2K, MTOR, EIF4E, EEF2, CAMK2A, ARC, GRIA1 and GRIA4) were found to predict number of drinking days per month (corrected P-value < 0.01) when considered as a set (set-based linear regression conducted in PLINK). In addition, a CpG site located in the 3'-untranslated region on the north shore of EEF2 (cg12255298) was hypermethylated in those who drank more frequently (P < 0.05). Importantly, the association between several genetic variants within the mGluR-eEF2-AMPAR pathway and alcohol use behavior (i.e., consumption and alcohol-related problems) replicated in the Grady Trauma Project (GTP), an independent sample of adults living in Atlanta, Georgia (n = 1034; 95% African American), including individual variants in GRM1, GRM5, EEF2, MTOR, GRIA1, GRIA4 and HOMER2 (P < 0.05). Gene-based analyses conducted in the GTP indicated that GRM1 (empirical P < 0.05) and EEF2 (empirical P < 0.01) withstood multiple test corrections and predicted increased alcohol consumption and related problems. In conclusion, insights from rodent studies enabled the identification of novel human alcohol candidate genes within the mGluR-eEF2-AMPAR pathway.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Fator de Iniciação 2 em Eucariotos/genética , Receptores de AMPA/genética , Receptores de Glutamato Metabotrópico/genética , Adulto , Idoso , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteínas de Transporte/genética , Proteínas do Citoesqueleto/genética , Quinase do Fator 2 de Elongação/genética , Fator de Iniciação 4E em Eucariotos/genética , Feminino , Proteínas de Arcabouço Homer , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Plasticidade Neuronal/genética , Polimorfismo de Nucleotídeo Único , Receptor de Glutamato Metabotrópico 5/genética , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética
19.
J Diabetes Complications ; 29(4): 529-33, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25660136

RESUMO

AIMS: To obtain costs of episodes of care for type 2 diabetes mellitus (T2DM)-related comorbidities. METHODS: Data from the MarketScan Commercial Claims and Encounters Database were analyzed with the Medical Episode Grouper software, which uses proprietary algorithms to identify episodes of care. Episodes relevant to the T2DM population were examined, including: coronary artery disease with acute myocardial infarction, ventricular fibrillation, shock, and/or cardiac arrest (CAD episodes); cerebrovascular disease with stroke (CVD episodes); hypoglycemia; T2DM with complications (complication episodes); and renal failure. RESULTS: 45,350 CAD; 85,287 CVD; 29,886 hypoglycemia; 40,339 complication; and 211,673 renal failure episodes were identified. Mean (SD) episode durations were 15.2 (39.1), 25.5 (55.0), 5.9 (24.0), 21.2 (54.6), and 364.0 (0.0) days, respectively. Inpatient visits were the largest component of unadjusted costs for CAD, CVD, and complication episodes (93.4%, 78.3%, and 91.9%, respectively). Other ancillary care represented the largest component of unadjusted costs for hypoglycemia (53.3%) and renal failure (80.5%) episodes. Mean adjusted total costs were $16,435; $4558; $445; $5675; and $8765 for CAD, CVD, hypoglycemia, complication, and renal failure episodes, respectively. CONCLUSIONS: This study adds important information to the literature regarding costs of episodes of care for patients with T2DM in the US.


Assuntos
Complicações do Diabetes/economia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/terapia , Cuidado Periódico , Custos de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia
20.
Zoology (Jena) ; 117(4): 227-36, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24703241

RESUMO

Within a year of hatching, chameleons can grow by up to two orders of magnitude in body mass. Rapid growth of the feeding mechanism means that bones, muscles, and movements change as chameleons grow while needing to maintain function. A previous morphological study showed that the musculoskeletal components of the feeding apparatus grow with negative allometry relative to snout-vent length (SVL) in chameleons. Here, we investigate the scaling of prey capture kinematics and muscle physiological cross-sectional area in the veiled chameleon, Chamaeleo calyptratus. The chameleons used in this study varied in size from approximately 3 to 18 cm SVL (1-200 g). Feeding sequences of 12 chameleons of different sizes were filmed and the timing of movements and the displacements and velocities of the jaws, tongue, and the hyolingual apparatus were quantified. Our results show that most muscle cross-sectional areas as well as tongue and hyoid mass scaled with isometry relative to mandible length, yet with negative allometry relative to SVL. Durations of movement also scaled with negative allometry relative to SVL and mandible length. Distances and angles generally scaled as predicted under geometric similarity (slopes of 1 and 0, respectively), while velocities generally scaled with slopes greater than 0 relative to SVL and mandible length. These data indicate that the velocity of jaw and tongue movements is generally greater in adults compared to juveniles. The discrepancy between the scaling of cross-sectional areas versus movements suggests changes in the energy storage and release mechanisms implicated in tongue projection.


Assuntos
Lagartos/anatomia & histologia , Lagartos/fisiologia , Músculos/fisiologia , Língua/fisiologia , Animais , Fenômenos Biomecânicos , Comportamento Alimentar/fisiologia , Lagartos/crescimento & desenvolvimento , Masculino , Mandíbula/anatomia & histologia , Língua/anatomia & histologia , Língua/crescimento & desenvolvimento
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