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1.
J Chem Phys ; 160(15)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38619456

RESUMO

Owing to ring strain, cyclic ketones exhibit complex excited state dynamics with multiple competing photochemical channels active on the ultrafast timescale. While the excited state dynamics of cyclobutanone after π* ← n excitation into the lowest-energy excited singlet (S1) state has been extensively studied, the dynamics following 3s ← n excitation into the higher-lying singlet Rydberg (S2) state are less well understood. Herein, we employ fully quantum multiconfigurational time-dependent Hartree (MCTDH) simulations using a model Hamiltonian as well as "on-the-fly" trajectory-based surface-hopping dynamics (TSHD) simulations to study the relaxation dynamics of cyclobutanone following 3s ← n excitation and to predict the ultrafast electron diffraction scattering signature of these relaxation dynamics. Our MCTDH and TSHD simulations indicate that relaxation from the initially-populated singlet Rydberg (S2) state occurs on the timescale of a few hundreds of femtoseconds to a picosecond, consistent with the symmetry-forbidden nature of the state-to-state transition involved. There is no obvious involvement of excited triplet states within the timeframe of our simulations (<2 ps). After non-radiative relaxation to the electronic ground state (S0), vibrationally hot cyclobutanone has sufficient internal energy to form multiple fragmented products including C2H4 + CH2CO (C2; 20%) and C3H6 + CO (C3; 2.5%). We discuss the limitations of our MCTDH and TSHD simulations, how these may influence the excited state dynamics we observe, and-ultimately-the predictive power of the simulated experimental observable.

2.
Rev Sci Tech ; 42: 31-41, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37232321

RESUMO

Business-centric solutions to data-related problems often yield the greatest positive impacts and improvements for private enterprises but are challenging to design and implement at scale within government agencies. The core mission of the Veterinary Services of the United States Department of Agriculture (USDA) Animal Plant Health Inspection Service is to safeguard animal agriculture in the United States of America, and effective data management underpins these efforts. As this agency works to assist data-driven decision-making in animal health management, it continues to use a blend of best practices from Federal Data Strategy initiatives and the International Data Management Association framework. This paper describes three case studies that focus on strategies to improve animal health data collection, integration, reporting and governance for animal health authorities. These strategies have enhanced the way USDA's Veterinary Services execute their mission and core operational activities for prevention, detection and early response to support disease containment and control.


S'agissant des problèmes en lien avec les données, les solutions centrées sur l'activité sont souvent celles qui génèrent le plus d'effets positifs et d'améliorations pour les entreprises du secteur privé, mais elles sont difficiles à concevoir et à mettre en oeuvre à grande échelle au sein des agences gouvernementales. Les Services vétérinaires du Service d'inspection de la santé animale et végétale du département américain de l'Agriculture (USDA) ont pour mission centrale de préserver les productions animales états-uniennes ; une gestion efficace des données vient soutenir cet effort. Dans leur action d'appui aux processus décisionnels de gestion de la santé animale fondés sur les données, ces Services recourent à une combinaison de bonnes pratiques mises en oeuvre aussi bien par les initiatives de la Stratégie fédérale sur les données que dans le cadre de l'Association internationale de gestion des données. Les auteurs décrivent trois études de cas sur des stratégies visant à améliorer la collecte, l'intégration, la notification et la gouvernance des données de santé animale afin de répondre aux besoins des autorités compétentes dans ce domaine. Ces stratégies ont permis aux Services vétérinaires de l'USDA de mieux s'acquitter de leur mission et d'améliorer leurs activités opérationnelles de prévention, de détection et de réaction rapide afin d'endiguer et contrôler les maladies.


Las soluciones eminentemente empresariales a problemas relacionados con los datos deparan con frecuencia los mejores frutos y resultados a la empresa privada, pero son difíciles de diseñar y aplicar a escala dentro de las administraciones públicas. Los Servicios Veterinarios adscritos al Servicio de Inspección Sanitaria de Animales y Plantas del Departamento de Agricultura de los Estados Unidos (USDA) tienen por principal cometido salvaguardar la producción animal estadounidense, labor que pasa en parte por una eficaz gestión de los datos. En su función de apoyo a la adopción de decisiones de gestión zoosanitaria basadas en los datos, este organismo sigue empleando una combinación de prácticas óptimas tomadas de iniciativas de la Estrategia Federal de Datos y de las pautas marcadas por la Asociación Internacional de Gestión de Datos. Los autores presentan y analizan tres ejemplos de estrategias para mejorar la obtención, integración, notificación y administración de datos zoosanitarios para las autoridades del ramo. Estas estrategias han conferido mayor eficacia a los Servicios Veterinarios del USDA en el cumplimiento de su misión y en la ejecución de sus principales actividades operativas de prevención, detección y pronta respuesta para ayudar a contener y combatir enfermedades.


Assuntos
Agricultura , Animais , Estados Unidos
3.
Ann Oncol ; 31(10): 1386-1396, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32561401

RESUMO

BACKGROUND: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Antígeno B7-H1/uso terapêutico , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Feminino , Seguimentos , Hospitalização/tendências , Humanos , Hidroxicloroquina/uso terapêutico , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Estudos Retrospectivos , SARS-CoV-2 , Tratamento Farmacológico da COVID-19
4.
Faraday Discuss ; 216(0): 395-413, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31012872

RESUMO

Excited state energy transfer in disordered systems has attracted significant attention owing to the importance of this phenomenon in both artificial and natural systems that operate in electronically excited states. Of particular interest, especially in the context of organic electronics, is the dynamics of triplet excited states. Due to their weak coupling to the singlet manifold they can often act as low energy trapping sites and are therefore detrimental to device performance. Alternatively, by virtue of their long lifetime they can lead to enhanced diffusion lengths important for organic photovoltaics (OPV). Herein, we explore the triplet energy transfer mechanism from dichlorobenzene to thioxanthone in methanol solution. We rationalise previous experimental observations as arising from preferential population transfer into the lowest triplet state rather than the higher lying triplet state that is closer in energy. The reason for this is a delicate balance between the electronic coupling, reorganisation energy and the energy gap involved. The present results provide the understanding to potentially develop a hot exciton mechanism in materials for organic light emitting diodes (OLED) to achieve higher device efficiencies.

5.
J Phys Chem A ; 123(13): 2640-2649, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30848598

RESUMO

Thermally activated delayed fluorescence (TADF) has shown great potential as a mechanism for harvesting low-lying triplet excited states in organic molecules and is therefore of great interest in the context of organic electronics, especially organic light emitting diodes (OLEDs). Herein we study the mechanism for triplet harvesting in triquinolonobenzene (TQB), which instead of relying upon the well-established donor-acceptor (D-A) scheme uses excited-state intramolecular proton transfer (ESIPT). We demonstrate that upon photoexcitation into the lowest singlet excited state the proton is transferred within 20 fs, suggesting it plays little role in triplet harvesting, which occurs on the nano- to microsecond time scale. However, TQB exhibits multiple low-lying triplet states that are strongly coupled along this proton transfer coordinate. The majority of these states favor the structure prior to proton transfer (TQB-TA) and this means that the proton transfer dynamics (3TQB-TA → 1TQB-TB) plays a crucial role in triplet harvesting. This mechanism yields an energy gap in good agreement with that reported experimentally and is consistent with previous photophysical characterization. Finally, a discussion upon extending this understanding into a device context is also presented.

6.
Soft Matter ; 14(28): 5775-5785, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-29987298

RESUMO

Using a lattice model of polymers in a tube, we define one way to characterise different configurations of a given knot as either "local" or "non-local", based on a standard approach for measuring the "size" of a knot within a knotted polymer chain. The method involves associating knot-types to subarcs of the chain, and then identifying a knotted subarc with minimal arclength; this arclength is then the knot-size. If the resulting knot-size is small relative to the whole length of the chain, then the knot is considered to be localised or "local"; otherwise, it is "non-local". Using this definition, we establish that all but exponentially few sufficiently long self-avoiding polygons (closed chains) in a tubular sublattice of the simple cubic lattice are "non-locally" knotted. This is shown to also hold for the case when the same polygons are subject to an external tensile force, as well as in the extreme case when they are as compact as possible (no empty lattice sites). We also provide numerical evidence for small tube sizes that at equilibrium non-local knotting is more likely than local knotting, regardless of the strength of the stretching or compressing force. The relevance of these results to other models and recent experiments involving DNA knots is also discussed.

7.
Epidemiol Infect ; 146(9): 1071-1078, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29739483

RESUMO

Giardia duodenalis is the most common intestinal parasite of humans in the USA, but the risk factors for sporadic (non-outbreak) giardiasis are not well described. The Centers for Disease Control and Prevention and the Colorado and Minnesota public health departments conducted a case-control study to assess risk factors for sporadic giardiasis in the USA. Cases (N = 199) were patients with non-outbreak-associated laboratory-confirmed Giardia infection in Colorado and Minnesota, and controls (N = 381) were matched by age and site. Identified risk factors included international travel (aOR = 13.9; 95% CI 4.9-39.8), drinking water from a river, lake, stream, or spring (aOR = 6.5; 95% CI 2.0-20.6), swimming in a natural body of water (aOR = 3.3; 95% CI 1.5-7.0), male-male sexual behaviour (aOR = 45.7; 95% CI 5.8-362.0), having contact with children in diapers (aOR = 1.6; 95% CI 1.01-2.6), taking antibiotics (aOR = 2.5; 95% CI 1.2-5.0) and having a chronic gastrointestinal condition (aOR = 1.8; 95% CI 1.1-3.0). Eating raw produce was inversely associated with infection (aOR = 0.2; 95% CI 0.1-0.7). Our results highlight the diversity of risk factors for sporadic giardiasis and the importance of non-international-travel-associated risk factors, particularly those involving person-to-person transmission. Prevention measures should focus on reducing risks associated with diaper handling, sexual contact, swimming in untreated water, and drinking untreated water.


Assuntos
Giardíase/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Estudos de Casos e Controles , Criança , Pré-Escolar , Colorado/epidemiologia , Feminino , Giardíase/epidemiologia , Giardíase/transmissão , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
8.
J Chem Phys ; 149(1): 014304, 2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29981553

RESUMO

The intersystem crossing (ISC) mechanism of a cyclic (alkyl)(amino) carbene gold (I) complex (CMA1) is studied using quantum dynamics. A model spin-vibronic Hamiltonian is developed, which includes 10 excited states and two important nuclear degrees of freedom. The quantum dynamics reveals that ISC from S1 → T1 occurs on the tens of picosecond time scale, consistent with recent experiments. It is driven by motion along the torsional degree of freedom of the carbazole (Cz) ligand, which causes orthogonality between the donor and acceptor groups closing the gap between the initial (S1) and final (T1) states. The role of higher triplet states through spin-vibronic interactions is also discussed. Although previous calculations, evaluated in the Condon approximation, yield large ISC rates, our present dynamical treatment, taking into account the large amplitude torsional motion, increases the calculated rate by an order of magnitude improving the agreement with experiments. The model spin-vibronic Hamiltonian developed can also be used to understand the properties of related linear metal carbene compounds, facilitating molecular design.

9.
Med J Malaysia ; 73(1): 46-48, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29531203

RESUMO

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma. It is commonly reported in the younger population with no underlying chronic liver disease and free of viral Hepatitis B and C. Local recurrence and distant metastasis are common despite better prognosis compared to conventional hepatocellular carcinoma. Complete surgical resection is associated with higher median survival and is the mainstay treatment option for localized FL-HCC. Multi-modality therapies such as TACE can be used to downstage upfront unresectable FL-HCC. Complete response with GEMOX chemotherapy has been reported in advanced metastatic FL-HCC and should be considered in upfront unresectable or metastatic disease. We present a case of biopsied proven relapse FL-HCC with oligo- left lung metastasis who successfully underwent a left lung lobectomy after neo-adjuvant GEMOX chemotherapy, and is disease free at 24 months follow up.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/terapia , Desoxicitidina/análogos & derivados , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundário , Carcinoma Hepatocelular/patologia , Terapia Combinada , Desoxicitidina/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos Organoplatínicos/uso terapêutico , Tomografia Computadorizada por Raios X
10.
Spinal Cord ; 55(2): 172-179, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27752057

RESUMO

STUDY DESIGN: Longitudinal observational study. OBJECTIVE: To quantify the amount of upper- and lower-extremity movement repetitions (that is, voluntary movements as part of a functional task or specific motion) occurring during inpatient spinal cord injury (SCI), physical (PT) and occupational therapy (OT), and examine changes over the inpatient rehabilitation stay. SETTING: Two stand-alone inpatient SCI rehabilitation centers. METHODS: Participants: A total of 103 patients were recruited through consecutive admissions to SCI rehabilitation. INTERVENTIONS: Trained assistants observed therapy sessions and obtained clinical outcome measures in the second week following admission and in the second to last week before discharge. MAIN OUTCOME MEASURES: PT and OT time, upper- and lower-extremity repetitions and changes in these outcomes over the course of rehabilitation stay. RESULTS: We observed 561 PT and 347 OT sessions. Therapeutic time comprised two-thirds of total therapy time. Summed over PT and OT, the median upper-extremity repetitions in patients with paraplegia were 7 repetitions and in patients with tetraplegia, 42 repetitions. Lower-extremity repetitions and steps primarily occurred in ambulatory patients and amounted to 218 and 115, respectively (summed over PT and OT sessions at discharge). Wilcoxon-signed rank tests revealed that most repetition variables did not change significantly over the inpatient rehabilitation stay. In contrast, clinical outcomes for the arm and leg improved over this time period. CONCLUSIONS: Repetitions of upper- and lower-extremity movements are markedly low during PT and OT sessions. Despite improvements in clinical outcomes, there was no significant increase in movement repetitions over the course of inpatient rehabilitation stay.


Assuntos
Movimento , Manipulações Musculoesqueléticas/métodos , Terapia Ocupacional/métodos , Centros de Reabilitação , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/reabilitação , Atividades Cotidianas , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Manipulações Musculoesqueléticas/tendências , Terapia Ocupacional/tendências , Alta do Paciente/tendências , Centros de Reabilitação/tendências , Traumatismos da Medula Espinal/epidemiologia , Resultado do Tratamento
11.
Osteoarthritis Cartilage ; 24(4): 597-604, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26564576

RESUMO

OBJECTIVES: To determine the association between the long-term use of analgesics and progression of osteoarthritis (OA) as evidenced by up to 3-years follow-up worsening of radiographic Kellgren-Lawrence (KL) grade and incidence of knee replacement (KR). DESIGN: Using nearest neighbor matching of the propensity scores with caliper in the Osteoarthritis Initiative (OAI) cohort, 173 index (Analgesic +) and 173 referent (Analgesic -) subjects were included. Analgesic + and - subjects had analgesics in all and none of their visits, respectively. Analgesic + and - subjects were balanced in their demographics, baseline, first, second and third year body mass index (BMI), Western Ontario and McMaster (WOMAC) total score, Physical and Mental health summary scales (SF-12), Physical Activity Scale for the Elderly (PASE) and Charleston Comorbidity Scale. Analgesic + and - subjects were also matched for baseline radiographic KL grade. Interval increase in the KL grade and incidence of KR were defined as the outcome. RESULTS: Included subjects had average 6.5 years of follow-up. By the third year, 44 subjects had an interval increase in the KL grade; 29 in Analgesic + and 15 among Analgesic - subjects (P = 0.024). By the eighth-year, 41 subjects had their first KR; 29 in Analgesic + and 12 among Analgesic - subjects (P = 0.005). Hazard Ratio (HR) of OA progression and KR for Analgesic + subjects was 1.91 (1.02-3.57) and 2.57 (1.31-5.04), respectively. CONCLUSIONS: Long-term use of analgesics may be associated with radiographic progression of knee OA and increased risk of future KR.


Assuntos
Analgésicos/efeitos adversos , Artroplastia do Joelho/estatística & dados numéricos , Osteoartrite do Joelho/induzido quimicamente , Idoso , Analgésicos/administração & dosagem , Estudos de Coortes , Progressão da Doença , Esquema de Medicação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Medição da Dor/métodos , Pontuação de Propensão , Radiografia , Índice de Gravidade de Doença
12.
Spinal Cord ; 52(8): 578-87, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24796445

RESUMO

OBJECTIVE: To conduct a systematic review examining the effectiveness of knowledge translation (KT) interventions in changing clinical practice and patient outcomes. METHODS: MEDLINE/PubMed, CINAHL, EMBASE and PsycINFO were searched for studies published from January 1980 to July 2012 that reported and evaluated an implemented KT intervention in spinal cord injury (SCI) care. We reviewed and summarized results from studies that documented the implemented KT intervention, its impact on changing clinician behavior and patient outcomes as well as the facilitators and barriers encountered during the implementation. RESULTS: A total of 13 articles featuring 10 studies were selected and abstracted from 4650 identified articles. KT interventions included developing and implementing patient care protocols, providing clinician education and incorporating outcome measures into clinical practice. The methods (or drivers) to facilitate the implementation included organizing training sessions for clinical staff, introducing computerized reminders and involving organizational leaders. The methodological quality of studies was mostly poor. Only 3 out of 10 studies evaluated the success of the implementation using statistical analyses, and all 3 reported significant behavior change. Out of the 10 studies, 6 evaluated the effect of the implementation on patient outcomes using statistical analyses, with 4 reporting significant improvements. The commonly cited facilitators and barriers were communication and resources, respectively. CONCLUSION: The field of KT in SCI is in its infancy with only a few relevant publications. However, there is some evidence that KT interventions may change clinician behavior and improve patient outcomes. Future studies should ensure rigorous study methods are used to evaluate KT interventions.


Assuntos
Conhecimento , Traumatismos da Medula Espinal/terapia , Pesquisa Translacional Biomédica , Animais , Bases de Dados Factuais/estatística & dados numéricos , Humanos
13.
Med J Malaysia ; 69(4): 199-201, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25500854

RESUMO

Kimura's disease is rare chronic inflammatory disease with a distinct clinicopathological entity. It has three major components; inflammatory, vascular and fibrosis. It has to be considered as a differential diagnosis in young patient presenting with head and neck swelling. Although of unknown aetiology many hypothesis has been postulated. Inflammation is the most prominent and predominating characteristic in this disease. Although reported to be predominant in Asian literature regarding this disease is scanty. We report a complete clinical-radiological and pathological picture of this disease.

14.
Hong Kong Med J ; 19(5): 447-50, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24088589

RESUMO

We report on a preterm male newborn with complete ectopia cordis associated with Cantrell's syndrome. The neonate had an ectopia cordis involving defects of the lower sternum, supraumbilical abdominal wall, anterior portion of the diaphragm, and diaphragmatic portion of the pericardium associated with complex congenital heart defects. The infant died shortly after birth. We discuss this case and review the literature.


Assuntos
Anormalidades Múltiplas/fisiopatologia , Ectopia Cordis/fisiopatologia , Pentalogia de Cantrell/fisiopatologia , Ectopia Cordis/etiologia , Evolução Fatal , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Adulto Jovem
15.
Mhealth ; 9: 12, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37089273

RESUMO

Background: The rising prevalence of type 2 diabetes in Australia is a public health concern, contributing to significant disease burden and economic costs. Text-message programs have been shown to improve health outcomes for people with type 2 diabetes, however they remain underutilized, and no evidence exists on their cost-effectiveness or costs of scale up to a population level in Australia. This study aimed to determine the cost-effectiveness and cost-utility of a 6-month text-message intervention (DTEXT) to improve glycated hemoglobin (HbA1c) and self-management behaviors for Australian adults with type 2 diabetes. Methods: A within-trial economic evaluation was conducted on the DTEXT randomized controlled trial. Incremental cost-effectiveness ratios (ICERs) were determined per 11 mmol/mol (1%) reduced HbA1c and per quality adjusted life year (QALY) gained, compared to usual care. Cost-effectiveness acceptability curves (CEAC) determined the probability of the intervention being cost-effective over a range of willingness to pay thresholds. A scenario analysis was conducted to determine how cost-effectiveness was impacted by using current implementation costs. Results: The DTEXT intervention cost AU$36 (INT$24) per participant, with an ICER of AU$311 (INT$211) per 11 mmol/mol (1%) reduced HbA1c. Based on HbA1c outcomes, DTEXT had a 33% probability of being effective and cost-saving. Based on the QALY outcomes, the intervention had only a 24% probability of being cost-effective. Scenario analysis indicated costs per participant of AU$13 (INT$9) to deliver the intervention, with a reduced incremental cost effectiveness ratio of AU$151 (INT$103) per 11 mmol/mol (1%) reduced HbA1c and a 38% probability of being effective and cost-saving. Conclusions: DTEXT was low cost and potentially scalable, but only had a low to moderate probability of being effective and cost saving. Further research should determine more targeted approaches that may improve cost-effectiveness. Trial Registration: ACTRN12617000416392.

17.
Spinal Cord ; 50(8): 570-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22450883

RESUMO

STUDY DESIGN: Systematic review. OBJECTIVES: To identify changes in subjective quality of life (QoL) as one ages with a spinal cord injury (SCI). SETTING: Vancouver, Canada. METHODS: Electronic databases were searched for studies reporting on age-related QoL changes over time. Data from relevant studies were transcribed into data extraction forms and analyzed by years post injury (YPI) and chronologic age. Each study was assigned a level of evidence based on a modified Sackett scale. RESULTS: In all, 21 studies, each with a low level of evidence, were included for review. The results indicated that regardless of chronologic age, individuals with relatively new SCI have the potential to improve their QoL. Among individuals with advanced YPI, overall QoL is consistently reported as good or excellent over time, however, with variations in different QoL domains. CONCLUSION: The QoL of individuals aging with a SCI has the potential to improve, and remain high and stable over time. As the identified studies provide low levels of evidence, more longitudinal research with greater methodological and measurement rigor is needed to corroborate the findings and conclusions of this review.


Assuntos
Envelhecimento/fisiologia , Qualidade de Vida , Traumatismos da Medula Espinal/psicologia , Medicina Baseada em Evidências , Humanos , Projetos de Pesquisa , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo
18.
Spinal Cord ; 49(6): 684-701, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21151191

RESUMO

STUDY DESIGN: Systematic review. OBJECTIVE: To systematically review evidence on aging of the body systems after spinal cord injury (SCI). SETTING: Toronto, Ontario and Vancouver, British Columbia, Canada. METHODS: Electronic databases (MEDLINE/PubMed, CINAHL, EMBASE and PsycINFO), were searched for studies published between 1980 and 2009. The search was augmented by reviewing the reference lists of relevant papers. Non-intervention studies that were longitudinal or cross-sectional with able-bodied controls that were at minimum matched on chronological age were included for review. Levels of evidence were assigned to the study design using a modified Sackett scale. RESULTS: Of the 74 studies selected for inclusion, 16 were longitudinal in design. The hypothesis that SCI represents a model for premature aging is supported by a large proportion of level 5 evidence for the cardiovascular and endocrine systems, level 2, 4 and 5 evidence for the musculoskeletal system, and limited level 5 evidence for the immune system. Only a few level 4 and 5 studies for the respiratory system were found. The evidence on the genitourinary system, gastrointestinal system, and for skin and subcutaneous tissues provide level 4 and 5 evidence that premature aging may not be occurring. The evidence on the nervous system does not provide evidence of premature aging as a result of SCI. CONCLUSIONS: Premature aging appears to occur in some systems after SCI. Additional longitudinal studies are required to confirm these findings.


Assuntos
Medicina Baseada em Evidências/métodos , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/fisiopatologia , Senilidade Prematura/epidemiologia , Senilidade Prematura/patologia , Senilidade Prematura/fisiopatologia , Comorbidade , Medicina Baseada em Evidências/tendências , Humanos , Traumatismos da Medula Espinal/patologia
19.
Neuroscience ; 460: 13-30, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33571596

RESUMO

Because hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels modulate the excitability of cortical and hippocampal principal neurons, these channels play a key role in the hyperexcitability that occurs during the development of epilepsy after a brain insult, or epileptogenesis. In epileptic rats generated by pilocarpine-induced status epilepticus, HCN channel activity is downregulated by two main mechanisms: a hyperpolarizing shift in gating and a decrease in amplitude of the current mediated by HCN channels, Ih. Because these mechanisms are modulated by various phosphorylation signaling pathways, we hypothesized that phosphorylation changes occur at individual HCN channel amino acid residues (phosphosites) during epileptogenesis. We collected CA1 hippocampal tissue from male Sprague Dawley rats made epileptic by pilocarpine-induced status epilepticus, and age-matched naïve controls. We also included resected human brain tissue containing epileptogenic zones (EZs) where seizures arise for comparison to our chronically epileptic rats. After enrichment for HCN1 and HCN2 isoforms by immunoprecipitation and trypsin in-gel digestion, the samples were analyzed by mass spectrometry. We identified numerous phosphosites from HCN1 and HCN2 channels, representing a novel survey of phosphorylation sites within HCN channels. We found high levels of HCN channel phosphosite homology between humans and rats. We also identified a novel HCN1 channel phosphosite S791, which underwent significantly increased phosphorylation during the chronic epilepsy stage. Heterologous expression of a phosphomimetic mutant, S791D, replicated a hyperpolarizing shift in Ih gating seen in neurons from chronically epileptic rats. These results show that HCN1 channel phosphorylation is altered in epilepsy and may be of pathogenic importance.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Animais , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Masculino , Espectrometria de Massas , Fosforilação , Canais de Potássio/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Osteoporos Int ; 21(6): 997-1007, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19882095

RESUMO

SUMMARY: The purpose of this study was to identify the determinants of the bone strength index of the distal tibia epiphysis in chronic stroke patients. The results showed that lower cardiovascular fitness, more muscle atrophy, poorer mobility, and more severe spasticity were independently associated with lower tibial bone strength index. INTRODUCTION: To identify the determinants of the bone strength index (BSI) at the distal tibia in chronic stroke patients METHODS: Sixty-three chronic stroke survivors underwent scanning of the distal tibia at the 4% site on both sides using peripheral quantitative computed tomography. The primary outcomes were trabecular bone mineral density (BMD; milligram per cubic centimeter), total BMD (milligram per cubic centimeter), total bone area (square millimeter), and BSI (square gram per centimeter to the power of four). Cardiovascular fitness, leg lean mass, gait velocity, and spasticity were also measured. RESULTS: Scans from 45 subjects were deemed to have acceptable quality and were included for subsequent analysis. The paretic side had significantly lower trabecular BMD, total BMD, and BSI than the nonparetic side (p < 0.05). However, the total bone area demonstrated no significant side-to-side difference (p > 0.05). After adjusting for relevant biological factors, peak oxygen consumption, leg muscle mass, and gait velocity remained positively associated with tibial BSI on both sides (R (2) change = 6.9-14.2%), whereas spasticity of the paretic leg was negatively associated with tibial BSI on the same side (R (2) change = 4.8%). CONCLUSIONS: Cardiovascular function, muscle atrophy, mobility, and spasticity are independently associated with BSI of the distal tibia epiphysis among chronic stroke patients.


Assuntos
Sistema Cardiovascular/fisiopatologia , Atrofia Muscular/fisiopatologia , Paresia/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Tíbia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Força Compressiva/fisiologia , Epífises/fisiopatologia , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Atrofia Muscular/etiologia , Paresia/etiologia , Acidente Vascular Cerebral/complicações , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X
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