RESUMO
Subjective belief elicitation about uncertain events has a long lineage in the economics and statistics literatures. Recent developments in the experimental elicitation and statistical estimation of subjective belief distributions allow inferences about whether these beliefs are biased relative to expert opinion, and the confidence with which they are held. Beliefs about COVID-19 prevalence and mortality interact with risk management efforts, so it is important to understand relationships between these beliefs and publicly disseminated statistics, particularly those based on evolving epidemiological models. The pandemic provides a unique setting over which to bracket the range of possible COVID-19 prevalence and mortality outcomes given the proliferation of estimates from epidemiological models. We rely on the epidemiological model produced by the Institute for Health Metrics and Evaluation together with the set of epidemiological models summarised by FiveThirtyEight to bound prevalence and mortality outcomes for one-month, and December 1, 2020 time horizons. We develop a new method to partition these bounds into intervals, and ask subjects to place bets on these intervals, thereby revealing their beliefs. The intervals are constructed such that if beliefs are consistent with epidemiological models, subjects are best off betting the same amount on every interval. We use an incentivised experiment to elicit beliefs about COVID-19 prevalence and mortality from 598 students at Georgia State University, using six temporally-spaced waves between May and November 2020. We find that beliefs differ markedly from epidemiological models, which has implications for public health communication about the risks posed by the virus.
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COVID-19/mortalidade , COVID-19/psicologia , Cultura , Tomada de Decisões , Modelo de Crenças de Saúde , Inquéritos e Questionários/normas , COVID-19/epidemiologia , Tomada de Decisões/fisiologia , Humanos , Mortalidade/tendências , PrevalênciaRESUMO
There is widespread concern in developing countries with the expansion of formal insurance products to help manage significant risks. These concerns arise primarily from a lack of understanding of insurance products, general failures of financial literacy and the need to use relatively exotic products in order to keep costs down for poor households. We investigate the importance of incentivized measures for general understanding, as well as domain-specific knowledge of the decision context on the purchase and the quality of index insurance decisions. We evaluate the quality of financial decisions by comparing the individual expected welfare outcomes of a number of decisions each individual makes to purchase index insurance or not. We find that excess purchase is an important driver of welfare losses, and that our incentivized measure of domain-specific literacy plays a critical role in bringing about better quality index insurance decisions. Supplementary Information: The online version contains supplementary material available at 10.1057/s10713-020-00060-1.
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We examine the manner in which the population prevalence of disordered gambling has usually been estimated, on the basis of surveys that suffer from a potential sample selection bias. General population surveys screen respondents using seemingly innocuous "trigger," "gateway" or "diagnostic stem" questions, applied before they ask the actual questions about gambling behavior and attitudes. Modeling the latent sample selection behavior generated by these trigger questions using up-to-date econometrics for sample selection bias correction leads to dramatically different inferences about population prevalence and comorbidities with other psychiatric disorders. The population prevalence of problem or pathological gambling in the United States is inferred to be 7.7%, rather than 1.3% when this behavioral response is ignored. Comorbidities are inferred to be much smaller than the received wisdom, particularly when considering the marginal association with other mental health problems rather than the total association. The issues identified here apply, in principle, to every psychiatric disorder covered by standard mental health surveys, and not just gambling disorder. We discuss ways in which these behavioral biases can be mitigated in future surveys.
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Jogo de Azar/epidemiologia , Transtornos Mentais/epidemiologia , Adulto , Idoso , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Risco , Viés de Seleção , Inquéritos e Questionários , Estados Unidos/epidemiologiaRESUMO
We study Danish adult gambling behavior with an emphasis on discovering patterns relevant to public health forecasting and economic welfare assessment of policy. Methodological innovations include measurement of formative in addition to reflective constructs, estimation of prospective risk for developing gambling disorder rather than risk of being falsely negatively diagnosed, analysis with attention to sample weights and correction for sample selection bias, estimation of the impact of trigger questions on prevalence estimates and sample characteristics, and distinguishing between total and marginal effects of risk-indicating factors. The most significant novelty in our design is that nobody was excluded on the basis of their response to a 'trigger' or 'gateway' question about previous gambling history. Our sample consists of 8405 adult Danes. We administered the Focal Adult Gambling Screen to all subjects and estimate prospective risk for disordered gambling. We find that 87.6% of the population is indicated for no detectable risk, 5.4% is indicated for early risk, 1.7% is indicated for intermediate risk, 2.6% is indicated for advanced risk, and 2.6% is indicated for disordered gambling. Correcting for sample weights and controlling for sample selection has a significant effect on prevalence rates. Although these estimates of the 'at risk' fraction of the population are significantly higher than conventionally reported, we infer a significant decrease in overall prevalence rates of detectable risk with these corrections, since gambling behavior is positively correlated with the decision to participate in gambling surveys. We also find that imposing a threshold gambling history leads to underestimation of the prevalence of gambling problems.
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Comportamento Aditivo/epidemiologia , Jogo de Azar/epidemiologia , Adulto , Comportamento Aditivo/psicologia , Dinamarca/epidemiologia , Feminino , Jogo de Azar/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Saúde Pública , Inquéritos e QuestionáriosRESUMO
Behavioral responses to surveys can significantly affect inferences about population prevalence unless correctly modeled statistically. An important case study is the prevalence of nicotine dependence, a formal psychiatric disorder satisfying clinical criteria. Data from the National Epidemiologic Survey on Alcohol and Related Conditions in the United States are used, along with a flexible semi-nonparametric sample selection model. Corrections for sample selection responses to "gateway" survey questions lead to significantly higher estimates of the prevalence of nicotine dependence among current daily smokers. These corrections also imply even higher levels of the decades-long and lifetime-long persistence of nicotine dependence after the onset of smoking.
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Economia Comportamental/estatística & dados numéricos , Inquéritos Epidemiológicos , Vigilância da População/métodos , Viés de Seleção , Tabagismo/epidemiologia , Adolescente , Adulto , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Fatores de Risco , Estados UnidosRESUMO
The COVID-19 pandemic presents a remarkable opportunity to put to work all of the research that has been undertaken in past decades on the elicitation and structural estimation of subjective belief distributions as well as preferences over atemporal risk, patience, and intertemporal risk. As contributors to elements of that research in laboratories and the field, we drew together those methods and applied them to an online, incentivized experiment in the United States. We have two major findings. First, the atemporal risk premium during the COVID-19 pandemic appeared to change significantly compared to before the pandemic, consistent with theoretical results of the effect of increased background risk on foreground risk attitudes. Second, subjective beliefs about the cumulative level of deaths evolved dramatically over the period between May and November 2020, a volatile one in terms of the background evolution of the pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s10683-021-09738-3.
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OBJECTIVE: Aboriginal and Torres Strait Islander patients are overrepresented in Australian EDs. The present study aimed to assess their characteristics in utilising ED services at a national level. METHODS: This exploratory, quantitative study used 2016-2017 de-identified data from the National Non-admitted Patient Emergency Department Care Database to assess the proportions (with 95% confidence interval) of Indigenous and non-Indigenous Australians across various aspects of ED presentations, including mode of arrival, triage scale, diagnosis information, episode end status and ED length of stay. Episode level ED data were compared by Indigenous status and geographical remoteness of EDs. RESULTS: Of 7.4 million presentations, 6.58% were Indigenous presentations, with over two-thirds occurring in regional and remote EDs. Indigenous patients were more likely than non-Indigenous patients to arrive to EDs by ambulance and police/correctional services vehicle across all remoteness areas. Additionally, they were more likely to present with respiratory system illness, illness of the skin/subcutaneous tissue/breast and mental/behavioural disorders. Indigenous Australians were more likely to leave EDs before being seen or care complete (odds ratio 1.73, 95% confidence interval 1.71-1.74), and this was observed for patients classified across all levels of triage scale. CONCLUSIONS: This is the first national study looking at the characteristics of and reasons for presenting to Australian EDs for Indigenous and non-Indigenous patients. Our findings provide important insight into the potential factors affecting Indigenous patient care, and an impetus for ongoing research and advocacy work to improve the quality of emergency care provided to Indigenous Australians.
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Serviço Hospitalar de Emergência , Havaiano Nativo ou Outro Ilhéu do Pacífico , Austrália/epidemiologia , Humanos , TriagemRESUMO
OBJECTIVE: Presently, no objective quality control mechanism exists for monitoring procedural skills among Australasian College for Emergency Medicine trainees. The present study examined trainee and fellow procedural experience and perceived competency, participation in accredited training courses and support for a procedural logbook. METHODS: A cross-sectional mail survey of Australasian College for Emergency Medicine advanced trainees and fellows was performed. Experience and perceived competency in 23 common and important ED procedures were examined. RESULTS: In total, 202 fellows and 264 trainees responded (overall response rate 39.0%). Overall, fellow procedural experience and perceived competency were reasonable. However, some fellows had never performed a number of procedures including some common procedures (e.g. nasal packing, fracture reduction) and there were reports of 'very poor' competency for 17 (73.9%) procedures. Trainee experience and perceived competency were less than the fellows but showed similar patterns. Perceived numbers of each procedure required to achieve competency varied considerably between the procedures and among the respondents. However, there were no significant differences in the perceived numbers reported by the trainees and the fellows (P > 0.05). Variable proportions of trainees and fellows had undertaken courses that incorporated procedural skills training. More fellows (75.7%, 95% confidence interval 69.1-81.4) than trainees (59.9%, 95% confidence interval 53.6-65.8) supported the use of a procedural logbook (P = 0.003). CONCLUSIONS: Lack of experience in some procedures among some fellows, especially commonly performed procedures, might represent a deficiency in existing quality assurance mechanisms for procedural skills training. Greater participation in skills courses, to improve experience in difficult and uncommonly encountered procedures, is recommended. Improved quality assurance mechanisms, including a procedural logbook, should be considered.
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Competência Clínica , Medicina de Emergência/educação , Garantia da Qualidade dos Cuidados de Saúde , Austrália , Estudos Transversais , Avaliação Educacional , HumanosRESUMO
OBJECTIVES: To characterize effects of A(3) adenosine receptor (A(3)AR) activation and gene knock-out on responses to ischemia-reperfusion in mouse heart. METHODS: Perfused hearts from wild-type and A(3)AR gene knock-out (A(3)AR KO) mice were subjected to 20 min ischemia and 30 min reperfusion. Functional responses were assessed and changes in energy metabolism and cytosolic pH monitored via 31P-NMR spectroscopy. RESULTS: Selective A(3)AR agonism with 100 nM 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (chloro-IB-MECA) enhanced post-ischemic contractile recovery without altering contracture development in wild-type hearts, an effect unrelated to non-selective activation of A(1) or A(2) adenosine receptors. Chloro-IB-MECA also improved recovery in hearts overexpressing A(1)ARs. Paradoxically, post-ischemic recovery was enhanced by A(3)AR KO. Developed pressure, +dP/dt, and -dP/dt all recovered to higher levels in A(3)AR KO (70-80% of pre-ischemia) vs. wild-type hearts (45-50% of pre-ischemia) (P<0.05). Enhanced recovery was unrelated to recoveries of ATP, phosphocreatine (PCr), inorganic phosphate (P(i)), energy state ([ATP]/[ADP] x [P(i)], DeltaG(ATP)) or cytosolic pH. CONCLUSIONS: Selective A(3)AR activation is cardioprotective in wild-type hearts and hearts overexpressing A(1)ARs, yet A(3)AR gene deletion generates an ischemia-tolerant phenotype without altering energy metabolism or pH. This may be due to compensatory changes or undefined genotypic differences in A(3)AR KO vs. wild-type hearts.
Assuntos
Adenosina/análogos & derivados , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina/análise , Adenosina/farmacologia , Aminoácidos/farmacologia , Animais , Creatina/análise , Frequência Cardíaca/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Contração Miocárdica/efeitos dos fármacos , Miocárdio/química , Perfusão , Fenetilaminas/farmacologia , Ácidos Pipecólicos/farmacologia , Antagonistas de Receptores Purinérgicos P1 , Quinazolinas/farmacologia , Receptor A3 de Adenosina , Receptores Purinérgicos P1/genética , Triazóis/farmacologia , Xantinas/farmacologiaRESUMO
Adenosine is an important cardioprotective agent that works via several adenosine receptor (ADOR) subtypes to regulate cardiovascular activity. It is well established that functional responses to adenosine decline with age. What is unclear, though, is whether these changes occur at the receptor, second messenger or translational level. In this study we determined the effect of age on cardiac adenosine receptor expression using the housekeeping gene 18S rRNA versus the adenosine A(2B) receptor gene as internal controls. Absolute quantification showed that no age-related changes occurred in the expression of 18S rRNA or adenosine A(2B) receptor internal control genes. Subsequently, relative analysis of the adenosine receptor subtypes using 18S rRNA found a significant age-related reduction in the expression of the adenosine A(1) receptor (5.5-fold), with no changes in the expression of the adenosine A(2A), A(2B) and A(3) receptors. When using the expression of the adenosine A(2B) receptor as the internal control gene, a significant down regulation of both the adenosine A(1) (5.4-fold) and A(2A) (2.2-fold) receptors with no change in the expression of adenosine A(3) receptor was found. Therefore, the high level of expression of the 18S rRNA housekeeping gene was found to mask a significant change in expression of the adenosine A(2A) receptor with age. Ultimately, these findings show an age-related reduction in adenosine A(1) and A(2A) receptor expression in rat heart.
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Envelhecimento/fisiologia , Coração/fisiologia , Receptores Purinérgicos P1/genética , Animais , Expressão Gênica , Masculino , RNA Mensageiro/análise , RNA Ribossômico 18S/genética , Ratos , Ratos Wistar , Receptor A1 de Adenosina/genética , Receptor A2A de Adenosina/genética , Receptor A2B de Adenosina/genética , Receptor A3 de Adenosina/genéticaRESUMO
In this study, we investigated the effect of noradrenaline depletion on contractile recovery in rat isolated heart following myocardial ischaemia. Groups tested included control tissues and hearts from reserpinised rats. Reserpine 1 mg/kg s.c. was injected into rats 18 to 24 h prior to experiments. Hearts underwent 15 min global normothermic ischaemia followed by 30 min reperfusion. Functional data (end diastolic pressure (EDP), heart rate (HR), left ventricular developed pressure (LVDP), dP/dt(max), dP/dt(min)) showed that contractile function following ischaemia-reperfusion is unaffected by reserpinisation. However, pre- and post-ischaemic coronary flow rates (CFR) were increased by 16 to 38% in hearts from reserpinised rats versus control hearts. Pre-ischaemic CFRs in control hearts (11.17+/-0.67 ml/in(-1) x g tissue(-1), n=9) were significantly lower then CFRs derived from reserpinised rat hearts (14.57+/-0.72 ml/min(-1)/g tissue(-1), n=10). Post-ischaemic reactive hyperaemia was evident in all groups. CFRs in reserpinised hearts remained elevated when compared to pre-ischaemic values through reperfusion (P<0.05). Reserpine treatment did not significantly alter pre- or post-ischaemic adenosine efflux. The A(2B) adenosine receptor antagonist alloxazine (10 microM) attenuated pre- and post-ischaemic CFRs in both control and reserpinised hearts (P<0.05) without altering the hyperaemic response while the A(2A) adenosine receptor antagonist 8-(3-chlorostyryl) caffeine (1 microM) did not alter CFRs in both groups. The A(3) adenosine receptor antagonist MRS1191 (0.1 microM) increased CFR in control and reserpinised hearts (P<0.05). Catecholamine depletion with reserpinisation enhances the responsiveness of the coronary resistance vessels to endogenous adenosine through activation of the A(2B) adenosine receptor.
Assuntos
Antagonistas do Receptor A2 de Adenosina , Adenosina/análogos & derivados , Inibidores da Captação Adrenérgica/farmacologia , Isquemia Miocárdica/fisiopatologia , Miocárdio/metabolismo , Reserpina/farmacologia , Adenosina/metabolismo , Adenosina/farmacologia , Animais , Flavinas/farmacologia , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/metabolismo , Norepinefrina/metabolismo , Purinas/metabolismo , Ratos , Ratos Wistar , Reperfusão , Fatores de Tempo , Tiramina/metabolismo , Vasodilatadores/farmacologiaRESUMO
In our laboratory we have developed a quantitative-polymerase chain reaction (Q-PCR) strategy to examine the differential expression of adenosine receptor (ADOR), A(1), A(2A), A(2B) and A(3), and estrogen receptors (ER) alpha and beta. Brain and uterine mRNA were first used to optimise specific amplification conditions prior to SYBR Green I real time analysis of receptor subtype expression. SYBR Green I provided a convenient and sensitive means of examining specific PCR amplification product in real time, and allowed the generation of standard curves from which relative receptor abundance could be determined. Real time Q-PCR analysis was then performed, to examine changes in receptor expression levels in brains of adult female Wistar rats 3-month post ovariectomy. Comparison with sham-operated age-matched control rats demonstrated both comparative and absolute-copy number changes in receptor levels. Evaluation of both analytical methods investigated 18S rRNA as an internal reference for comparative gene expression analysis in the brain. The results of this study revealed preferential repression of ADORA(2A) (>4-fold down) and consistent (>2-fold) down-regulation of ADORA(1), ADORA(3), and ER-beta, following ovariectomy. No change was found in ADORA(2B) or ER-alpha. Analysis of absolute copy number in this study revealed a correlation between receptor expression in response to ovariectomy, and relative receptor subtype abundance in the brain.
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Encéfalo/metabolismo , Regulação para Baixo/genética , Estrogênios/deficiência , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/análise , Receptores de Estrogênio/genética , Receptores Purinérgicos P1/genética , Animais , Receptor beta de Estrogênio , Feminino , Regulação da Expressão Gênica/genética , Ovariectomia , RNA Mensageiro/metabolismo , RNA Ribossômico 18S/análise , RNA Ribossômico 18S/genética , Ratos , Ratos Wistar , Receptor A2A de Adenosina , Receptor A3 de AdenosinaRESUMO
Cardiac ischemia--reperfusion injury results in oxidative stress and poor physiological recovery. This study examined the amount of lipid and protein oxidation during ischemia-reperfusion to assess the degree of oxidative stress. Selenium supplementation was used to alter the antioxidant status of rats and the recovery of myocardial function post ischemia-reperfusion was investigated. Male Wistar rats were fed diets containing 0, 50, and 1000 microg/kg sodium selenite for 5 weeks, whilst controls received normal rat food containing 240 microg/kg selenium. Langendorff-perfused hearts were subjected to 22.5 min global ischemia and 45 min reperfusion, with functional recovery assessed. Heart tissues were assayed for the presence of lipid peroxides and protein carbonyls and correlated to cardiac recovery. Following ischemia and reperfusion there was a significant increase in both protein oxidation and lipid peroxidation. Hearts from selenium-deficient animals demonstrated higher levels of both protein carbonyls and lipid peroxides and were more susceptible to ischemia-reperfusion injury when compared to controls (38% versus 47% recovery of rate pressure product (RPP)). Selenium supplementation lowered the levels of protein carbonyls and lipid peroxides and resulted in improved recovery of cardiac function post ischemia-reperfusion (57% recovery of RPP). These data suggest that selenium supplementation may provide an effective method for reducing oxidative damage post cardiac ischemia-reperfusion.
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Dieta , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Selênio/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Coração/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Oxirredução , Proteínas/metabolismo , Ratos , Selênio/deficiênciaRESUMO
Glutathione peroxidase and thioredoxin reductase are selenocysteine-dependent enzymes that protect against oxidative injury. This study examined the effects of dietary selenium on the activity of these two enzymes in rats, and investigated the ability of selenium to modulate myocardial function post ischemia-reperfusion. Male wistar rats were fed diets containing 0, 50, 240 and 1000 microg/kg sodium selenite for 5 weeks. Langendorff perfused hearts isolated from these rats were subjected to 22.5 min global ischemia and 45 min reperfusion, with functional recovery assessed. Liver samples were collected at the time of sacrifice, and heart and liver tissues assayed for thioredoxin reductase and glutathione peroxidase activity. Selenium deficiency reduced the activity of both glutathione peroxidase and thioredoxin reductase systemically. Hearts from selenium deficient animals were more susceptible to ischemia-reperfusion injury when compared to normal controls (38% recovery of rate pressure product (RPP) vs. 47% recovery of RPP). Selenium supplementation increased the endogenous activity of thioredoxin reductase and glutathione peroxidase and resulted in improved recovery of cardiac function post ischemia reperfusion (57% recovery of RPP). Endogenous activity of glutathione peroxidase and thioredoxin reductase is dependent on an adequate supply of the micronutrient selenium. Reduced activity of these antioxidant enzymes is associated with significant reductions in myocardial function post ischemia-reperfusion.
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Dieta , Glutationa Peroxidase/metabolismo , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica , Miocárdio/metabolismo , Selênio , Tiorredoxina Dissulfeto Redutase/metabolismo , Animais , Peso Corporal , Suplementos Nutricionais , Técnicas In Vitro , Fígado/enzimologia , Masculino , Contração Miocárdica/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Selênio/administração & dosagem , Selênio/metabolismo , Selênio/farmacologiaRESUMO
We examine the subjective risks of driving behavior using a controlled virtual reality experiment. Use of a driving simulator allows us to observe choices over risky alternatives that are presented to the individual in a naturalistic manner, with many of the cues one would find in the field. However, the use of a simulator allows us the type of controls one expects from a laboratory environment. The subject was tasked with making a left-hand turn into incoming traffic, and the experimenter controlled the headways of oncoming traffic. Subjects were rewarded for making a successful turn, and lost income if they crashed. The experimental design provided opportunities for subjects to develop subjective beliefs about when it would be safe to turn, and it also elicited their attitudes towards risk. A simple structural model explains behavior, and showed evidence of heterogeneity in both the subjective beliefs that subjects formed and their risk attitudes. We find that subjective beliefs change with experience in the task and the driver's skill. A significant difference was observed in the perceived probability to successfully turn among the inexperienced drivers who did and did not crash even though there was no significant difference in drivers' risk attitudes among the two groups. We use experimental economics to design controlled, incentive compatible tasks that provide an opportunity to evaluate the impact on driver safety of subject's subjective beliefs about when it would be safe to turn as well as their attitudes towards risk. This method could be used to help insurance companies determine risk premia associated with risk attitudes or beliefs of crashing, to better incentivize safe driving.
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Acidentes de Trânsito , Atitude , Condução de Veículo/psicologia , Motivação , Assunção de Riscos , Interface Usuário-Computador , Simulação por Computador , Humanos , SegurançaRESUMO
We elicit measures of individual discount rates from a representative sample of the Danish population and test two substantive hypotheses. The first hypothesis is that smokers have higher individual discount rates than non-smokers. The second hypothesis is that smokers are more likely to have time inconsistent preferences than non-smokers, where time inconsistency is indicated by a hyperbolic discounting function. We control for the concavity of the utility function in our estimates of individual discount rates and find that male smokers have significantly higher discount rates than male non-smokers. However, smoking has no significant association with discount rates among women. This result is robust across exponential and hyperbolic discounting functions. We consider the sensitivity of our conclusions to a statistical specification that allows each observation to potentially be generated by more than one latent data-generating process.
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Comportamento de Escolha , Individualidade , Fumar/psicologia , Dinamarca , Feminino , Humanos , Masculino , Risco , Fatores de TempoRESUMO
L-Arginine increases myocardial nitric oxide production. Nitric oxide mediates many of the cardiovascular actions of adenosine and modulates adenosine metabolism. In this study, we examined the effect of chronic L-arginine (5%) intake on cardiac nitric oxide synthase (NOS) and adenosine receptor expression and cardiac function in rat Langendorff-isolated perfused hearts. Our results show that 4-week chronic l-arginine ingestion increases the weight of rat hearts by 17.6% (P < 0.05). L-Arginine treatment decreased the expression of all the cardiac adenosine receptors, with reductions in adenosine A(1) (20-fold), A(2A) (7.7-fold), A(2B) (76-fold) and A(3) (25.6-fold) mRNA (P < 0.05). NOS expression was variably affected with no change in the expression of NOS(1) and 4.2-fold down-regulation of NOS(3) expression with chronic L-arginine treatment (P < 0.05). NOS(2) was expressed in control tissues; however, in L-arginine-treated hearts the amount of NOS(2) mRNA was reduced to non-detectable levels. Following chronic L-arginine treatment, an increase in coronary perfusion pressure was observed (P < 0.05). Purine efflux was used as an indicator of metabolic efficiency. L-Arginine did not alter catecholamine-induced purine efflux (P > 0.05); however, noradrenaline-mediated increases in contractility and myocardial oxygen consumption were reduced. Vasodilator responses to 5'-N-ethylcarboxamidoadenosine (NECA) were reduced in hearts from l-arginine-treated rats and the NOS inhibitor N omega-nitro-L-arginine methyl ester (3 microM) did not inhibit responses to NECA. In conclusion, 4-week dietary supplementation of L-arginine reduced the expression of cardiac adenosine receptors and NOSs with a subsequent decrease in noradrenaline-stimulated cardiac function and adenosine receptor-mediated coronary vasodilation.
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Arginina/farmacologia , Miocárdio/metabolismo , Óxido Nítrico Sintase/biossíntese , Receptores Purinérgicos P1/biossíntese , Animais , Arginina/administração & dosagem , Suplementos Nutricionais , Regulação para Baixo , Masculino , Ratos , Ratos WistarRESUMO
Nitric oxide (NO) is essential for normal function of the cardiovascular system. This study has determined whether chronic administration of l-arginine, the biological precursor of NO, attenuates the development of structural and functional changes in hearts and blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Uninephrectomized rats treated with DOCA (25 mg every 4th day sc) and 1% NaCl in the drinking water for 4 wk were treated with l-arginine (5% in food, 3.4 +/- 0.3 g x kg body wt(-1) x day(-1)). Changes in cardiovascular structure and function were determined by echocardiography, microelectrode studies, histology, and studies in isolated hearts and thoracic aortic rings. DOCA-salt hypertensive rats developed hypertension, left ventricular hypertrophy with increased left ventricular wall thickness and decreased ventricular internal diameter, increased inflammatory cell infiltration, increased ventricular interstitial and perivascular collagen deposition, increased passive diastolic stiffness, prolonged action potential duration, increased oxidative stress, and inability to increase purine efflux in response to an increased workload. l-Arginine markedly attenuated or prevented these changes and also normalized the reduced efficacy of norepinephrine and acetylcholine in isolated thoracic aortic rings of DOCA-salt hypertensive rats. This study suggests that a functional NO deficit in blood vessels and heart due to decreased NO synthase activity or increased release of reactive oxygen species such as superoxide may be a key change initiating many aspects of the cardiovascular impairment observed in DOCA-salt hypertensive rats. These changes can be prevented or attenuated by administration of l-arginine.