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1.
BMC Anesthesiol ; 22(1): 122, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473580

RESUMO

BACKGROUND: Increased life expectancy and improved medical technology allow increasing numbers of elderly patients to undergo cardiac surgery. Elderly patients may be at greater risk of postoperative morbidity and mortality. Complications can lead to worsened quality of life, shortened life expectancy and higher healthcare costs. Reducing perioperative complications, especially severe adverse events, is key to improving outcomes in patients undergoing cardiac surgery. The objective of this study is to determine whether perioperative lipid-lowering medication use is associated with a reduced risk of complications and mortality after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: After IRB approval, we reviewed charts of 9,518 patients who underwent cardiac surgery with CPB at three medical centers between July 2001 and June 2015. The relationship between perioperative lipid-lowering treatment and postoperative outcome was investigated. 3,988 patients who underwent CABG met inclusion criteria and were analyzed. Patients were divided into lipid-lowering or non-lipid-lowering treatment groups. RESULTS: A total of 3,988 patients were included in the final analysis. Compared to the patients without lipid-lowering medications, the patients with lipid-lowering medications had lower postoperative neurologic complications and overall mortality (P < 0.05). Propensity weighted risk-adjustment showed that lipid-lowering medication reduced in-hospital total complications (odds ratio (OR) = 0.856; 95% CI 0.781-0.938; P < 0.001); all neurologic complications (OR = 0.572; 95% CI 0.441-0.739; P < 0.001) including stroke (OR = 0.481; 95% CI 0.349-0.654; P < 0.001); in-hospital mortality (OR = 0.616; 95% CI 0.432-0.869; P = 0.006; P < 0.001); and overall mortality (OR = 0.723; 95% CI 0.634-0.824; P < 0.001). In addition, the results indicated postoperative lipid-lowering medication use was associated with improved long-term survival in this patient population. CONCLUSIONS: Perioperative lipid-lowering medication use was associated with significantly reduced postoperative adverse events and improved overall outcome in elderly patients undergoing CABG surgery with CPB.


Assuntos
Ponte de Artéria Coronária , Qualidade de Vida , Idoso , Ponte Cardiopulmonar/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Humanos , Lipídeos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos
2.
Br J Anaesth ; 127(2): 215-223, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34082896

RESUMO

BACKGROUND: Dexmedetomidine sedation has been associated with favourable outcomes after surgery. We aimed to assess whether perioperative dexmedetomidine use is associated with improved survival after cardiac surgery. METHODS: This retrospective cohort study included 2068 patients undergoing on-pump coronary artery bypass grafting and/or valve surgery. Among them, 1029 patients received dexmedetomidine, and 1039 patients did not. Intravenous dexmedetomidine infusion of 0.007 µg kg-1 min-1 was initiated before or immediately after cardiopulmonary bypass and lasted for < 24 h. The primary outcome was 5-year survival after cardiac surgery. The propensity scores matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting approaches were used to minimise bias. Survival analyses were performed with Cox proportional-hazard models. RESULTS: The median age was 63 yr old and the male to female ratio was 71:29 in both groups. Baseline covariates were balanced between groups after adjustment using PSM, IPTW, or overlap weighting. Patients receiving dexmedetomidine in cardiac surgical procedures had higher survival during postoperative 5 yr in unadjusted analysis (hazard ratio [HR]=0.63; 95% confidence interval [CI], 0.51-0.78; P<0.001), and after adjustment with PSM (HR=0.63; 95% CI, 0.45-0.89; P=0.009), IPTW (HR=0.70; 95% CI, 0.51-0.95; P=0.023), or overlap weighting (HR=0.67; 95% CI, 0.51-0.89; P=0.006). The 5-yr mortality rate after cardiac surgery was 13% and 20% in the dexmedetomidine and non-dexmedetomidine groups, respectively (PSM adjusted odds ratio=0.61; 95% CI, 0.42-0.89; P=0.010). CONCLUSION: Perioperative dexmedetomidine infusion was associated with improved 5-yr survival in patients undergoing cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Estudos de Coortes , Ponte de Artéria Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
3.
Mol Cell ; 50(1): 16-28, 2013 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-23434374

RESUMO

Autophagy constitutes a major cell-protective mechanism that eliminates damaged components and maintains energy homeostasis via recycling nutrients under normal/stressed conditions. Although the core components of autophagy have been well studied, regulation of autophagy at the transcriptional level is poorly understood. Herein, we establish ZKSCAN3, a zinc finger family DNA-binding protein, as a transcriptional repressor of autophagy. Silencing of ZKSCAN3 induced autophagy and increased lysosome biogenesis. Importantly, we show that ZKSCAN3 represses transcription of a large gene set (>60) integral to, or regulatory for, autophagy and lysosome biogenesis/function and that a subset of these genes, including Map1lC3b and Wipi2, represent direct targets. Interestingly, ZKSCAN3 and TFEB are oppositely regulated by starvation and in turn oppositely regulate lysosomal biogenesis and autophagy, suggesting that they act in conjunction. Altogether, our study uncovers an autophagy master switch regulating the expression of a transcriptional network of genes integral to autophagy and lysosome biogenesis/function.


Assuntos
Autofagia , Lisossomos/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica , Autofagia/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Proteínas de Transporte/metabolismo , Forma Celular , Senescência Celular , Metabolismo Energético , Regulação da Expressão Gênica , Células HeLa , Humanos , Lisossomos/patologia , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas de Ligação a Fosfato , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Fatores de Transcrição/genética , Transfecção
4.
J Card Surg ; 36(9): 3040-3051, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34118080

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons' perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.


Assuntos
COVID-19 , Cirurgiões , Adulto , Descontaminação , Humanos , Pandemias , Percepção , SARS-CoV-2
5.
J Cardiothorac Vasc Anesth ; 30(6): 1502-1508, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27435836

RESUMO

OBJECTIVE: The goal of this retrospective study was to investigate the effects of perioperative use of dexmedetomidine (Dex) on outcomes for older patients undergoing cardiac surgery. DESIGN: Retrospective investigation. SETTING: Patients from a single tertiary medical center. PARTICIPANTS: A total of 505 patients (≥65 years old) who underwent coronary artery bypass graft (CABG) or valve surgery. CABG and/or valve surgery plus other procedures were divided into 2 groups: 283 received intravenous Dex infusion (Dex group) and 222 did not (Non-Dex group). INTERVENTIONS: Perioperative Dex intravenous infusion (0.24 to 0.6 µg/kg/h) initiated after cardiopulmonary bypass and continued for<24 hours postoperatively in the ICU. MEASUREMENTS AND MAIN RESULTS: Data were risk adjusted, propensity score weighted, and multivariate logistic regression was used. The primary outcome was mortality. Secondary outcomes included postoperative stroke, coma, myocardial infarction, heart block, cardiac arrest, delirium, renal failure, and sepsis. Perioperative Dex infusion significantly decreased in-hospital mortality (0.90% v 2.83%; adjusted odds ratio (OR), 0.099; 95% confidence interval (CI), 0.030-0.324; p = 0.004) and operative mortality (1.35% v 3.18%; adjusted OR, 0.251; 95% CI, 0.077-0.813; p = 0.021). Perioperative Dex treatment also reduced the risk of stroke (0.90% v 1.77%; adjusted OR, 0.15; 95% CI, 0.038-0.590; p = 0.007), and delirium (7.21% v 10.95%; adjusted OR, 0.35; 95% CI, 0.212-0.578; p < 0.0001). CONCLUSIONS: Results from this study (ClinicalTrials.gov identifier: NCT01683448) suggested perioperative use of dexmedetomidine was associated with decreases in in-hospital and operative mortality in elderly patients following cardiac surgery. It also reduced incidences of postoperative stroke and delirium in elderly patients.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/métodos , Dexmedetomidina/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Delírio/etiologia , Delírio/prevenção & controle , Dexmedetomidina/administração & dosagem , Feminino , Valvas Cardíacas/cirurgia , Mortalidade Hospitalar , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
6.
J Cardiothorac Vasc Anesth ; 30(5): 1308-16, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27461794

RESUMO

OBJECTIVES: Body mass index (BMI) commonly is used in obesity classification as a surrogate measure, and obesity is associated with a cluster of risk factors for cardiovascular disease. The aim of this study was to investigate the impact of BMI on short-term outcomes after cardiac surgery. DESIGN: A retrospective cohort study. SETTING: University teaching hospital, 2 centers. PARTICIPANTS: The study comprised 4,740 patients who underwent cardiac surgery at 2 hospitals-from July 1, 2001, to June 30, 2013, in 1 hospital and from September 1, 2003, to August 31, 2014, in a second hospital. INTERVENTIONS: No changes to standard practice were required. MEASUREMENTS AND MAIN RESULTS: Patients were assigned into 6 BMI groups as follows: underweight (BMI<18.5 kg/m(2)), normal weight (≥18.5 to<25 kg/m(2)), overweight (≥25 to<30 kg/m(2)), class I obese (≥30 to<35 kg/m(2)), class II obese (≥35 to<40 kg/m(2)), and class III obese (BMI≥40 kg/m(2)). Short-term major postoperative complications (postoperative stroke, cardiac arrest, new atrial fibrillation/flutter, permanent rhythm device insertion, deep sternal infection, sepsis, prolonged ventilation, pneumonia, renal dialysis, renal failure, intensive care unit readmission, total intensive care unit hours, and readmission in 30 days, and mortalities (in-hospital mortality, 30-day mortality, surgical mortality) were compared among various BMI groups after cardiac surgery. Age, sex, surgery type, family history of coronary artery disease, diabetes, hypertension, heart failure, and lipid-lowering medication were the risk factors for early outcomes. Multiple logistic regression analysis indicated that the underweight and class III obese BMI groups demonstrated significant, adverse differences in some short-term outcomes, including deep sternal infection, prolonged ventilation, new atrial fibrillation/flutter, and renal failure. However, being in the overweight or class I obese group demonstrated a positive effect on discharge and surgical mortality. CONCLUSIONS: The results of this study demonstrated that extreme obesity and underweight were significantly associated with early major adverse clinical outcomes. However, there was an "obese paradox" in short-term mortality after cardiac surgery.


Assuntos
Índice de Massa Corporal , Procedimentos Cirúrgicos Cardíacos , Obesidade/complicações , Complicações Pós-Operatórias , Magreza/complicações , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
7.
Air Med J ; 34(4): 188-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26206543

RESUMO

OBJECTIVE: Fixed wing medical transportation crashes operating under 14 CFR Part 91 show higher fatal outcomes than nonmedical Part 91 flights. Advanced certification may translate into increased safety, yet we know of no charity air medical transportation requiring such certification. Herein, in a retrospective study, we determined whether commercial certification is associated with a reduced fatality rate compared with the less stringent private pilot certificate and accident causes. METHODS: The National Transportation Safety Board accident database was queried for fatal accidents in single-engine aircraft occurring between 2002 and 2012. Poisson and proportion tests were used in statistical analyses. RESULTS: For the period spanning 2002-2012, commercial pilots showed a lower fatality rate. Under visual meteorologic conditions, aerodynamic stall was a frequent cause for fatal accidents affecting both airman cohorts equally. For operations in instrument meteorologic conditions, fatal accidents were most commonly attributed to instrument approach deficiency and spatial disorientation. At night, failure to maintain obstacle/terrain clearance was the most prevalent cause of fatal crashes. CONCLUSION: Our data suggest that charity air medical transportation organizations should encourage their pilots to acquire commercial certification. Furthermore, our study indicates areas in which general aviation training/currency should be directed to reduce fatal accidents.


Assuntos
Acidentes Aeronáuticos/estatística & dados numéricos , Certificação , Instituições de Caridade , Pilotos/normas , Resgate Aéreo , Humanos , Pilotos/educação , Estudos Retrospectivos , Estados Unidos
8.
Nucleic Acids Res ; 40(2): 600-13, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21937508

RESUMO

The urokinase receptor (u-PAR) which is largely regulated at the transcriptional level has been implicated in tumor progression. In this study, we explored the epigenetic regulation of u-PAR and showed that the histone variant H2A.Z negatively regulates its expression in multiple cell lines. Chromatin immunoprecipitation assays revealed that H2A.Z was enriched at previously characterized u-PAR-regulatory regions (promoter and a downstream enhancer) and dissociates upon activation of gene expression by phorbol ester (PMA). Using specific chemical and dominant negative expression constructs, we show that the MEK-ERK signaling pathway terminating at AP-1 transcription factors intersects with the epigenetic control of u-PAR expression by H2A.Z. Furthermore, we demonstrate that two other AP-1 targets (MMP9 gene and miR-21 microRNA) are also H2A.Z regulated. In conclusion, our work demonstrates that (i) the expression of two genes and a microRNA all implicated in tumor progression are directly regulated by H2A.Z and (ii) MEK-ERK signaling terminating at AP-1 intersects with the epigenetic control of target gene expression by H2A.Z.


Assuntos
Epigênese Genética , Histonas/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Fator de Transcrição AP-1/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Elementos Facilitadores Genéticos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Genes ras , Humanos , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , MicroRNAs/biossíntese , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mutação , Regiões Promotoras Genéticas , Receptores de Ativador de Plasminogênio Tipo Uroquinase/biossíntese , Fatores de Transcrição/metabolismo , Ativação Transcricional , Regulação para Cima
9.
Aviat Space Environ Med ; 85(6): 631-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24919384

RESUMO

BACKGROUND: The fatality rate for general aviation, 82 times that of air carriers and even higher for those involving aeromedical transportation, has not declined over time. Although noncommercial (private) pilots are increasingly seeking the instrument rating (IFR), which offers safety advantages, there is a paucity of research on causes of fatal crashes for this aviator subset. METHODS: The NTSB accident database was queried for general aviation fatal accidents involving private pilots. Exact two sample proportions, linear regression model outcomes (log-odds), and Poisson rate ratio tests were used for statistical analysis. RESULTS: The fatal accident rate for flights in instrument conditions decreased 55% over 10 yr (2002-2011) although an increased fatality rate was evident for pilots > 65 yr of age. Instrument approach deficiency (lAD), spatial disorientation/failure to maintain control (SD/FMC), and failure to maintain obstacle/terrain clearance (FMOTC) were common causes of fatal accidents in reduced visibility. However a > 55% decline in fatal accidents due to IAD was evident over the decade. Under visual conditions, engine/air-frame malfunction, aerodynamic stall, and FMOTC represented frequent causes. Of these, FMOTC showed a statistically significant decline over 10 yr. Comparing day and night operations, fatal crashes attributed to FMOTC and IAD were more frequent at night. CONCLUSION: For the IFR-rated private pilot, our study argues for an emphasis on training and currency in SD/FMC and aerodynamic stall recovery. Likewise training to remedy IAD, the frequent cause of fatal night accidents, and flying by instrument flight rules to assure obstacle/terrain clearance should be encouraged for pilots undertaking such operations.


Assuntos
Acidentes Aeronáuticos/mortalidade , Acidentes Aeronáuticos/tendências , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aviação/tendências , Humanos , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
10.
Aerosp Med Hum Perform ; 95(5): 254-258, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38715275

RESUMO

INTRODUCTION: Although an unintended aircraft landing on water (referred to as ditching) is a rare event, the potential for occupant injury/fatality increases immediately following the event due to adverse conditions. However, to date, few studies have addressed the subject. Herein, ditching events and post-ditching survival were investigated.METHODS: Ditchings (1982-2022) in the United States were identified from the National Transportation Safety Board database. Occupant injury severity, aircraft type, pilot experience, flight conditions, and number of occupants were extracted. Poisson distribution, the Chi-squared test (2-tailed), Mann-Whitney U test, and Kruskal-Wallis one-way analysis of variance were employed.RESULTS: A total of 96 ditchings were identified. A systematic survey was hampered by the lack of a standardized reporting matrix in the reports. In total, 77 reports were included in the analysis. Across all ditchings, 128 of 169 (76%) occupants survived ditching and were rescued. Importantly, the initial ditching event was survived by 95% of all occupants. However, 32 (19%) occupants died post-ditching by drowning (21/32 cases) or for undetermined reasons. Considering probability per ditching event, in 26 (34%) of all ditchings, one or more occupants was/were fatally injured.DISCUSSION: Initial survival of the emergency ditching is high. Drowning was the leading cause of death after ditching and reduced the overall survival to 76%. Further investigation is needed to identify risk factors for fatal outcomes and/or improve probability of survival after ditching.Schick VC, Boyd DD, Hippler C, Hinkelbein J. Survival after ditching in motorized aircraft, 1989-2022. Aerosp Med Hum Perform. 2024; 95(5):254-258.


Assuntos
Acidentes Aeronáuticos , Aeronaves , Humanos , Acidentes Aeronáuticos/mortalidade , Acidentes Aeronáuticos/estatística & dados numéricos , Estados Unidos/epidemiologia , Afogamento/mortalidade , Masculino , Bases de Dados Factuais , Pilotos/estatística & dados numéricos
11.
BJU Int ; 111(6): 934-40, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23350937

RESUMO

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Little is known as to the potential for over-treatment of young men diagnosed with prostate cancer. We show that for men aged ≤55 years with PSA screen-detected disease, 45% of the tumours are classified as very low risk and 85% of these have favourable pathology, yet most are actively treated. These findings raise the spectre of over-treatment for a group of men likely to be affected by treatment side-effects. OBJECTIVE: To identify a population of young men (aged <55 years at diagnosis) with very-low-risk prostate cancer (stage cT1c, with prostate-specific antigen [PSA] density of <0.15 ng/mL/g, Gleason score ≤6, and ≤2 positive biopsy cores with <50% tumour involvement) that may be candidates for active surveillance (AS). PATIENTS AND METHODS: We queried a Department of Defense tumour registry and hard-copy records for servicemen diagnosed with prostate cancer from 1987 to 2010. Statistical analyses were undertaken using Fisher's exact and chi-square testing. RESULTS: From 1987-1991 and 2007-2010, PSA screen-detected tumours diagnosed in men aged ≤55 years rose >30-fold. Data for a subset of men (174) with PSA screen-detected cancer were evaluable for disease risk assessment. Of the 174 men with screen-detected disease, 81 (47%) had very-low-risk disease. Of that group, 96% (78/81) selected treatment and, of 57 men undergoing radical prostatectomy (RP), the tumours of 49 (86%) carried favourable pathology (organ confined, <10% gland involvement, Gleason ≤6). CONCLUSIONS: Nearly half of young men with PSA screen-detected prostate cancer are AS candidates but the overwhelming majority seek treatment. Considering that many tumours show favourable pathology at RP, there is a possibility that these patients may benefit from AS management.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Vigilância da População , Antígeno Prostático Específico/sangue , Próstata/patologia , Neoplasias da Próstata/imunologia , Adulto , Distribuição por Idade , Humanos , Masculino , Pessoa de Meia-Idade , Militares , Gradação de Tumores , Seleção de Pacientes , Valor Preditivo dos Testes , Neoplasias da Próstata/epidemiologia , Medição de Risco , Estados Unidos/epidemiologia
12.
J Safety Res ; 84: 99-107, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36868678

RESUMO

BACKGROUND: Air carriers, but not general aviation, have long employed in-flight data to identify risks/implement corrective measures for improved safety. Herein, using in-flight data, aircraft (in non-instrument-rated private pilots (PPLs) ownership) operations in two potentially hazardous environments (mountains, degraded visibility) were researched for safety practice deficiencies. Four questions were posed, the first two related to mountainous terrain operations: were aircraft (a) flown with hazardous ridge-level winds, (b) within gliding distance of level terrain? Regarding degraded visibility, did aviators (c) depart with low cloud ceilings (≤3,000 ft.), (d) fly at night away from urban lighting? METHODS: The study cohort comprised: (a) single engine aircraft in sole PPL proprietorship (b) registered in Automatic Dependent Surveillance-Broadcast (ADS-B-Out) equipage-required locations prone to low cloud ceilings in three mountainous states. ADS-B-Out data for cross-country flights (>200 nm) were collected. RESULTS: 250 flights (50 airplanes) were tracked (spring/summer 2021). For aircraft transiting areas subject to mountain winds influences, 65% completed one/multiple flights with potentially hazardous ridge-level winds. Two thirds of airplanes traversing mountainous topography would have, for at least one flight, been unable to glide to level terrain with a powerplant failure. Encouragingly, flight departures for 82% of the aircraft were with >3,000 ft. cloud ceilings. Likewise, flights for >86% of the study cohort were undertaken during daylight. Employing a risk scale, operations for 68% of the study cohort did not exceed low-risk (i.e., ≤1 unsafe practice) and high-risk flight(s) (three concurrent unsafe practices) were rare (4% of airplanes). In log-linear analysis, no interactions were evident between the four unsafe practices (p = 0.602). DISCUSSION: Hazardous winds and inadequate engine failure planning were identified as safety deficiencies for general aviation mountain operations. PRACTICAL APPLICATION: This study advocates for the expanded use of ADS-B-Out in-flight data to inform safety deficiencies/implement corrective measures toward improving general aviation safety.


Assuntos
Aviação , Aeronaves , Ácido Dioctil Sulfossuccínico , Iluminação , Fenolftaleína
13.
Aerosp Med Hum Perform ; 94(11): 807-814, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37853584

RESUMO

INTRODUCTION: General aviation (GA), mainly comprised of light (≤12,500 lb) aircraft, maintains an inferior safety record compared with air carriers. To improve safety, aeronautical decision-making (ADM) practices have been advocated to GA pilots since 1991. Herein, we determined the extent to which GA pilots disregard such practices.METHODS: Fatal accidents (1991-2019) involving private pilots (PPLs) in single-engine airplanes were identified (N = 1481) from the National Transportation Safety Board AccessR database. Of these, deficient go/no-go and in-flight ADM-related mishaps were scored using the PAVE (pilot, aircraft, environment, external pressure)/IMSAFE (illness, medicine, stress, alcohol, fatigue, eating) and PPP (perceive, process, perform) models, respectively. Statistical testing used Poisson distributions, Fisher exact tests, and Mann-Whitney U-tests.RESULTS: Of the 1481 accidents, 846 were identified as deficient ADM-related. Electing to depart into a hazardous environment (PAVE), disregarding wellness (IMSAFE), and poor aircraft familiarity (PAVE) represented the most common categories (54%, 21%, and 20%, respectively) of errant go/no-go ADM. A 64% decline in fatal accidents related to errant go/no-go decisions for the environment category was evident over the 30-yr period, with little decrements in the other domains. Within the errant environment-related category accidents, the decision to depart into forecasted adverse weather (e.g., degraded visibility, icing, thunderstorms) constituted the most prevalent subcategory (56%, N = 195). Surprisingly, of this subcategory, accidents were overrepresented by over nine- and threefold for instrument-rated PPLs disregarding icing and thunderstorm forecasts, respectively.CONCLUSION: With little decrement in ADM-related accidents in the pilot, aircraft, and external pressure domains, new strategies to address such deficiencies for PPLs are warranted.Boyd DD, Scharf MT. Deficient aeronautical decision-making contributions to fatal general aviation accidents. Aerosp Med Hum Perform. 2023; 94(11):807-814.


Assuntos
Acidentes Aeronáuticos , Aviação , Pilotos , Humanos , Fatores de Risco , Aeronaves
14.
Biochem J ; 434(2): 233-42, 2011 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21143195

RESUMO

u-PAR (urokinase-type plasminogen activator receptor), anchored to the cell surface via a glycolipid moiety, drives tumour progression. We previously reported that colon cancer cells (RKO clone 2 FS2), attenuated for in vivo tumorigenicity, are diminished >15-fold for u-PAR display when compared with their tumorigenic isogenic counterparts (RKO clone 2), this disparity not reflecting altered transcription/mRNA stability. FACS, confocal microscopy and Western blotting using a fused u-PAR-EGFP (enhanced green fluorescent protein) cDNA revealed a >14-fold differential in the u-PAR-EGFP signal between the isogenic cells, ruling out alternate splicing as a mechanism. Although metabolic labelling indicated similar synthesis rates, pulse-chase revealed accelerated u-PAR-EGFP turnover in the RKO clone 2 FS2 cells. Expression in RKO clone 2 cells of a u-PAR-EGFP protein unable to accept the glycolipid moiety yielded diminished protein amounts, thus mirroring the low endogenous protein levels evident with RKO clone 2 FS2 cells. Transcript levels for the phosphatidylglycan anchor biosynthesis class B gene required for glycolipid synthesis were reduced by 65% in RKO clone 2 FS2 cells, and forced overexpression in these cells partially restored endogenous u-PAR. Thus attenuated u-PAR levels probably reflects accelerated turnover triggered by inefficient addition of the glycolipid moiety.


Assuntos
Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Processamento Alternativo , Neoplasias do Colo/metabolismo , DNA Complementar/metabolismo , Glicolipídeos/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Transdução de Sinais , Transfecção , Células Tumorais Cultivadas , Ativador de Plasminogênio Tipo Uroquinase/genética
15.
J Biol Chem ; 285(35): 26908-26915, 2010 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-20592017

RESUMO

Activating transcription factor 3 (ATF3) is a common stress sensor, and its rapid induction by cellular stresses (e.g. DNA damage) is crucial for cells to mount appropriate responses (e.g. activating the tumor suppressor p53) and maintain homeostasis. Although emerging evidence suggests that dysregulation of ATF3 contributes to occurrences of human diseases including cancer, the mechanism(s) by which ATF3 expression is regulated is largely unknown. Here, we demonstrate that mouse double minute 2 (MDM2) is a bona fide E3 ubiquitin ligase for ATF3 and regulates ATF3 expression by promoting its degradation. MDM2 via its C-terminal RING finger can bind to the Basic region of ATF3 and mediate the addition of ubiquitin moieties to the ATF3 leucine zipper domain. As a consequence, ATF3, but not a mutant deficient in MDM2 binding (Delta80-100), is degraded by MDM2-mediated proteolysis. Consistent with these results, ablation of MDM2 in cells not only increases basal ATF3 levels, but results in stabilization of ATF3 in late stages of DNA damage responses. Because ATF3 was recently identified as a p53 activator, these results suggest that MDM2 could inactivate p53 through an additional feedback mechanism involving ATF3. Therefore, we provide the first evidence demonstrating that ATF3 is regulated by a posttranslational mechanism.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Regulação da Expressão Gênica/fisiologia , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ubiquitinação/fisiologia , Fator 3 Ativador da Transcrição/genética , Animais , Linhagem Celular , Dano ao DNA/fisiologia , Humanos , Camundongos , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismo , Dedos de Zinco
16.
J Urol ; 185(6): 2137-42, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21496842

RESUMO

PURPOSE: Periodic Health Assessments have been mandated for United States Air Force servicemen since the mid 1990s. Thus, we determined whether United States Air Force prostate cancer incidence rates increased thereafter and how these tumors segregate into low and intermediate/high risk categories. We also identified treatment choices. MATERIALS AND METHODS: We queried the Department of Defense Automated Central Tumor Registry for prostate cancer diagnosed in United States Air Force servicemen between 1991 and 2008 to determine incidence rates, disease risk category and treatments. RESULTS: Age adjusted rates in white active duty servicemen diagnosed for the most recent period of 2005 to 2008 increased 3-fold relative to the rate in the earliest period of 1991 to 1994. A similar trend was evident in black servicemen. Relative to the Surveillance, Epidemiology and End Results population prostate cancer rates in active duty United States Air Force men between 1995 and 2008 were significantly increased for the 2 racial groups. A significantly greater proportion of active duty servicemen than retirees (62% vs 40%) presented with low risk disease, defined as prostate specific antigen less than 10 ng/ml, Gleason sum less than 7 and clinical stage T1a-T2a. Of those with low risk disease significantly more active duty servicemen elected curative surgery than retirees (93% vs 53%). CONCLUSIONS: Prostate cancer incidence rates in United States Air Force servicemen have increased with time, exceeding rates in the Surveillance, Epidemiology and End Results population. While most cases are characterized as low risk, aggressive management is elected.


Assuntos
Militares , Neoplasias da Próstata/epidemiologia , Adulto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/terapia , Fatores de Risco , Estados Unidos/epidemiologia
17.
Aviat Space Environ Med ; 82(11): 1067-70, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22097644

RESUMO

INTRODUCTION: Several studies investigating whether prostate cancer incidence is elevated in aviators both in the civilian and military sectors have yielded inconsistent findings. Most investigations have compared aviators to the general population. Instead, our study compared prostate cancer incidence rates among officer aviators and non-aviators in the U.S. Air Force (USAF) to reduce confounding by socioeconomic status and frequency of medical exams. METHODS: This retrospective analysis ascertained prostate cancer cases using the Automated Cancer Tumor Registry of the Department of Defense linked to personnel records from the USAF Personnel Center to identify aviators and non-aviators. Survival analysis using the Cox Proportional Hazards model allowed comparison of prostate cancer incidence rates in USAF aviators and non-aviators. RESULTS: After adjustment for age and race, the hazards ratio for prostate cancer incidence comparing aviators with non-aviators was 1.15 (95% confidence interval, 0.85-1.44). Neither prostate cancer incidence nor time to diagnosis differed significantly between the two groups. CONCLUSION: Our study compared prostate cancer rates in aviators with a reference group of non-aviators similar in socio-economic level and frequency of exams. When compared to this internal reference group the risk of prostate cancer in USAF officer aviators appeared similar with no significant excess.


Assuntos
Militares/estatística & dados numéricos , Neoplasias da Próstata/epidemiologia , Medicina Aeroespacial , Estudos de Casos e Controles , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Grupos Raciais/estatística & dados numéricos , Análise de Regressão , Estudos Retrospectivos , Estados Unidos/epidemiologia
18.
Aerosp Med Hum Perform ; 92(10): 773-779, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34641997

RESUMO

BACKGROUND/OBJECTIVE: The COVID-19 virus has caused over 582,000 deaths in the United States to date. However, the pandemic has also afflicted the mental health of the population at large in the domains of anxiety and sleep disruption, potentially interfering with cognitive function. From an aviation perspective, safely operating an aircraft requires an airmans cognitive engagement for: 1) situational awareness, 2) spatial orientation, and 3) avionics programming. Since impaired cognitive function could interfere with such tasks, the current study was undertaken to determine if flight safety for a cohort of single engine, piston-powered light airplanes was adversely affected during a period of the pandemic (MarchOctober 2020) prior to U.S. approval of the first COVID-19 vaccine. METHODS: Airplane accidents were per the National Transportation Safety Board Access database. Fleet times were derived using Automatic Dependent Surveillance-Broadcast. Statistics used Poisson distributions, Chi-squared/Fisher, and Mann-Whitney tests. RESULTS: Little difference in accident rate was evident between the pandemic period (MarchOctober 2020) and the preceding (JanuaryFebruary) months (19 and 22 mishaps/100,000 h, respectively). Similarly, a proportional comparison of accidents occurring in 2020 with those for the corresponding months in 2019 failed to show over-representation of mishaps during the pandemic. Although a trend to a higher injury severity (43% vs. 34% serious/fatal injuries) was evident for pandemic-period mishaps, the proportional difference was not statistically significant when referencing the corresponding months in 2019. CONCLUSION: Surprisingly, using accidents as an outcome, the study herein shows little evidence of diminished flight safety for light aircraft operations during the COVID-19 pandemic. Boyd DD. General aviation flight safety during the COVID-19 pandemic. Aerosp Med Hum Perform. 2021; 92(10):773779.


Assuntos
Aviação , COVID-19 , Vacinas contra COVID-19 , Humanos , Pandemias , Fatores de Risco , SARS-CoV-2 , Estados Unidos/epidemiologia
19.
Aerosp Med Hum Perform ; 92(5): 294-302, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875061

RESUMO

INTRODUCTION: Air taxis conduct nonscheduled transport and employ aircraft in various performance categories hereafter referred to as low, medium, and high performance, respectively. No study has yet addressed fixed-wing air taxi safety by performance category. Herein, we compared accident rates/occupant injury across air taxi airplane fleets grouped by performance category and identified human factors contributing to fatal accidents for airplanes in that category with the highest mishap rate.METHODS: Accidents (20042018) in the United States were identified from the National Transportation Safety Board database. General Aviation/Part 135 Activity Surveys provided annual fleet times. Fatal accident contributing factors were per the Human Factors Classification System (HFACS). Statistics utilized Poisson distributions, Chi-Square/Fisher, and Mann-Whitney tests.RESULTS: There were 269 air taxi mishaps (53 fatal) identified. Over the 15 yr, the accident rate (1.10/million flight hours-all categories) declined 50%, largely due to a reduction in medium/high performance category airplane crashes. However, little temporal change was observed for low performance airplanes (1.5/million flight hours) and injury severity trended higher. At the aircrew/physical environment levels, HFACS revealed decision (improper choices), skill-based (stick and rudder) and perceptual (night, instrument conditions) errors contributing to > 60% of fatal accidents involving low performance airplanes. At the organizational level, failing to correct problems, time pressures, and incentive systems contributed to 16% of fatal mishaps.CONCLUSION: Safety deficits remain for the low performance category air taxi fleet warranting increased pilot instrument flight training/utilization of the mandatory 3-axis autopilot in degraded visibility. Safety culture improvements to address issues of personnel/equipment/training deficiencies, failing to correct problems, and time pressures/a safety-compromising incentive system all need to be addressed.Budde D, Hinkelbein J, Boyd DD. Analysis of air taxi accidents (20042018) and associated human factors by aircraft performance class. Aerosp Med Hum Perform. 2021; 92(5):294302.


Assuntos
Acidentes Aeronáuticos , Aviação , Acidentes , Aeronaves , Humanos , Fatores de Risco , Estados Unidos
20.
J Safety Res ; 76: 127-134, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653543

RESUMO

INTRODUCTION: The extremely low accident rate for U.S air carriers relative to that of general aviation (∼1 and ∼60/million flight hours respectively) partly reflects advanced airman certification, more demanding recurrency training and stringent operational regulations. However, whether such skillset/training/regulations translate into improved safety for airline pilots operating in the general aviation environment is unknown and the aim of this study. METHODS: Accidents (1998-2017) involving airline pilots and instrument-rated private pilots (PPL-IFR) operating non-revenue light aircraft were identified from the NTSB accident database. An online survey informed general aviation flight exposure for both pilot cohorts. Statistics used proportion testing and Mann-Whitney U tests. RESULTS: In degraded visibility, 0 and 40% (χ2p = 0.043) of fatal accidents involving airline and PPL-IFR airmen were due to in-flight loss-of-control, respectively. For landing accidents, airline pilots were under-represented for mishaps related to airspeed mismanagement (p = 0.036) relative to PPL-IFR but showed a dis-proportionate count (2X) of ground loss-of-directional control accidents (p = 0.009) the latter likely reflecting a preference for tail-wheel aircraft. The proportion of FAA rule violation-related mishaps by airline pilots was >2X (7 vs. 3%) that for PPL-IFR airmen. Moreover, airline pilots showed a disproportionate (χ2p = 0.021) count of flights below legal minimum altitudes. Not performing an official preflight weather briefing or intentionally operating in instrument conditions without an IFR flight plan represented 43% of airline pilot accidents involving FAA rule infractions. CONCLUSIONS: These findings inform safety deficiencies for: (a) airline pilots, landing/ground operations in tail-wheel aircraft and lack of 14CFR 91 familiarization regulations regarding minimum operating altitudes and (b) PPL-IFR airmen in-flight loss-of-control and poor landing speed management. Practical Applications: For PPL-IFR airmen, training/recurrency should focus on unusual attitude recovery and managing approach speeds. Airline pilots should seek additional instructional time regarding landing tail-wheel aircraft and become familiar with 14CFR 91 rules covering minimum altitudes.


Assuntos
Acidentes Aeronáuticos/estatística & dados numéricos , Aeronaves/classificação , Aviação/estatística & dados numéricos , Pilotos/educação , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Pilotos/classificação , Fatores de Risco , Estados Unidos
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