923 resultados para medicamento similar
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Gradient-based approaches to direct policy search in reinforcement learning have received much recent attention as a means to solve problems of partial observability and to avoid some of the problems associated with policy degradation in value-function methods. In this paper we introduce GPOMDP, a simulation-based algorithm for generating a biased estimate of the gradient of the average reward in Partially Observable Markov Decision Processes (POMDPs) controlled by parameterized stochastic policies. A similar algorithm was proposed by Kimura, Yamamura, and Kobayashi (1995). The algorithm's chief advantages are that it requires storage of only twice the number of policy parameters, uses one free parameter β ∈ [0,1) (which has a natural interpretation in terms of bias-variance trade-off), and requires no knowledge of the underlying state. We prove convergence of GPOMDP, and show how the correct choice of the parameter β is related to the mixing time of the controlled POMDP. We briefly describe extensions of GPOMDP to controlled Markov chains, continuous state, observation and control spaces, multiple-agents, higher-order derivatives, and a version for training stochastic policies with internal states. In a companion paper (Baxter, Bartlett, & Weaver, 2001) we show how the gradient estimates generated by GPOMDP can be used in both a traditional stochastic gradient algorithm and a conjugate-gradient procedure to find local optima of the average reward. ©2001 AI Access Foundation and Morgan Kaufmann Publishers. All rights reserved.
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In this paper, laminar natural convection flow from a permeable and isothermal vertical surface placed in non-isothermal surroundings is considered. Introducing appropriate transformations into the boundary layer equations governing the flow derives non-similar boundary layer equations. Results of both the analytical and numerical solutions are then presented in the form of skin-friction and Nusselt number. Numerical solutions of the transformed non-similar boundary layer equations are obtained by three distinct solution methods, (i) the perturbation solutions for small � (ii) the asymptotic solution for large � (iii) the implicit finite difference method for all � where � is the transpiration parameter. Perturbation solutions for small and large values of � are compared with the finite difference solutions for different values of pertinent parameters, namely, the Prandtl number Pr, and the ambient temperature gradient n.
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Background: Treatment-related symptoms continue to place a significant burden on many cancer patients. Many side effects require patients to engage in a range of self-management actions. While some studies have explored self-management of treatment-related side effects in Western settings, very few studies were identified that described the self-management practices of cancer patients in China. Objective: The purposes of this study are to: (1) Investigate Chinese cancer patients. self-management behaviours in dealing with the fatigue, nausea/vomiting and oral mucositis that result from treatment, as well as the perceived effectiveness of these behaviours and related self-efficacy in performing them. (2) Explore factors influencing symptom self-management behaviours using the Cancer Symptom Self-management Framework based on Grey, Knafl and McCorkle.s (2006) self-management framework as a guide. Methods: This study was divided into two phases. Phase One consisted of the translation and modification of two instruments. The adaptation of these instruments to ensure applicability in the Chinese context was achieved through semi-structured interviews with six cancer patients, and content evaluation with eight experienced oncology nurses. A pilot study was conducted with nine cancer patients to trial the questionnaire set in the Chinese context. Based on the results of Phase One, Phase Two involved a cross-sectional survey of Chinese cancer patients undergoing cancer treatment using these instruments. A total of 277 chemotherapy patients with fatigue and/or nausea and vomiting, and 100 radiotherapy patients with oral mucositis were surveyed. Results: Participants in this study reported a variety of self-management behaviours to cope with fatigue, nausea, vomiting and oral mucositis. There are some consistencies as well disparities between strategies that are frequently used and those rated as effective. For fatigue self-management, participants were more likely to use strategies related to rest and sleep, while activity enhancement strategies were rated as achieving higher relief. For nausea and vomiting self-management, dietary modification and taking medication were most frequently used and rated as moderately effective. Psychological strategies were used by more than a third of participants and were rated as mildly effective. Some other infrequently used strategies, such as distraction by keeping busy and acupressure, were rated as moderately effective. For oral mucositis self-management, having soft, bland food and keeping the mouth moisturised were most frequently reported and they were rated as achieving moderate relief. A prescribed mouthwash was used by most but not all participants and brought moderate relief. In general, patients had low-to-moderate self-efficacy in nausea and vomiting self-management behaviours, moderate self-efficacy in fatigue self-management behaviours, and low-to-moderate self-efficacy in oral mucositis self-management behaviours. In terms of the factors influencing symptom self-management, different predictors were identified affecting engagement in fatigue, nausea/vomiting and oral mucositis self-management behaviours. Self-efficacy scores of different behaviours were consistently found to be a positive predictor of the relief level from corresponding behaviours, after controlling for other variables. Perceived social support from health care professionals was identified as an important factor influencing nausea and vomiting self-management behaviours, while neighbourhood support was important for fatigue self-management. In addition, symptom distress was identified as an important factor influencing nausea and vomiting self-management. Conclusion: Similar to reports from overseas, Chinese cancer patients initiate a wide range of self-management behaviours in response to treatment-related side effects. While some behaviours were reported to provide relief, many did not. Given these results, this study has a number of practical implications for health care professionals, particularly in relation to developing tailored self-management programs for fatigue, nausea, vomiting and oral mucositis. Additionally, this study suggests a number of theoretical implications and directions for future research. It is envisaged that these recommendations may pave the way for further studies understanding and promoting cancer symptom self-management in Chinese people affected by cancer.
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Facial expression recognition (FER) algorithms mainly focus on classification into a small discrete set of emotions or representation of emotions using facial action units (AUs). Dimensional representation of emotions as continuous values in an arousal-valence space is relatively less investigated. It is not fully known whether fusion of geometric and texture features will result in better dimensional representation of spontaneous emotions. Moreover, the performance of many previously proposed approaches to dimensional representation has not been evaluated thoroughly on publicly available databases. To address these limitations, this paper presents an evaluation framework for dimensional representation of spontaneous facial expressions using texture and geometric features. SIFT, Gabor and LBP features are extracted around facial fiducial points and fused with FAP distance features. The CFS algorithm is adopted for discriminative texture feature selection. Experimental results evaluated on the publicly accessible NVIE database demonstrate that fusion of texture and geometry does not lead to a much better performance than using texture alone, but does result in a significant performance improvement over geometry alone. LBP features perform the best when fused with geometric features. Distributions of arousal and valence for different emotions obtained via the feature extraction process are compared with those obtained from subjective ground truth values assigned by viewers. Predicted valence is found to have a more similar distribution to ground truth than arousal in terms of covariance or Bhattacharya distance, but it shows a greater distance between the means.
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Raman spectroscopy has been used to study vanadates in the solid state. The molecular structure of the vanadate minerals vésigniéite [BaCu3(VO4)2(OH)2] and volborthite [Cu3V2O7(OH)2·2H2O] have been studied by Raman spectroscopy and infrared spectroscopy. The spectra are related to the structure of the two minerals. The Raman spectrum of vésigniéite is characterized by two intense bands at 821 and 856 cm−1 assigned to ν1 (VO4)3− symmetric stretching modes. A series of infrared bands at 755, 787 and 899 cm−1 are assigned to the ν3 (VO4)3− antisymmetric stretching vibrational mode. Raman bands at 307 and 332 cm−1 and at 466 and 511 cm−1 are assigned to the ν2 and ν4 (VO4)3− bending modes. The Raman spectrum of volborthite is characterized by the strong band at 888 cm−1, assigned to the ν1 (VO3) symmetric stretching vibrations. Raman bands at 858 and 749 cm−1 are assigned to the ν3 (VO3) antisymmetric stretching vibrations; those at 814 cm−1 to the ν3 (VOV) antisymmetric vibrations; that at 508 cm−1 to the ν1 (VOV) symmetric stretching vibration and those at 442 and 476 cm−1 and 347 and 308 cm−1 to the ν4 (VO3) and ν2 (VO3) bending vibrations, respectively. The spectra of vésigniéite and volborthite are similar, especially in the region of skeletal vibrations, even though their crystal structures differ.
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Purpose: This study provides a simple method for improving precision of x-ray computed tomography (CT) scans of irradiated polymer gel dosimetry. The noise affecting CT scans of irradiated gels has been an impediment to the use of clinical CT scanners for gel dosimetry studies. Method: In this study, it is shown that multiple scans of a single PAGAT gel dosimeter can be used to extrapolate a ‘zero-scan’ image which displays a similar level of precision to an image obtained by averaging multiple CT images, without the compromised dose measurement resulting from the exposure of the gel to radiation from the CT scanner. Results: When extrapolating the zero-scan image, it is shown that exponential and simple linear fits to the relationship between Hounsfield unit and scan number, for each pixel in the image, provides an accurate indication of gel density. Conclusions: It is expected that this work will be utilised in the analysis of three-dimensional gel volumes irradiated using complex radiotherapy treatments.
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Insulated rail joints (IRJs) possess lower bending stiffness across the gap containing insulating endpost and hence are subjected to wheel impact. IRJs are either square cut or inclined cut to the longitudinal axis of the rails in a vertical plane. It is generally claimed that the inclined cut IRJs outperformed the square cut IRJs; however, there is a paucity of literature with regard to the relative structural merits of these two designs. This article presents comparative studies of the structural response of these two IRJs to the passage of wheels based on continuously acquired field data from joints strain-gauged closer to the source of impact. Strain signatures are presented in time, frequency, and avelet domains and the peak vertical and shear strains are systematically employed to examine the relative structural merits of the two IRJs subjected to similar real-life loading. It is shown that the inclined IRJs resist the wheel load with higher peak shear strains and lower peak vertical strains than that of the square IRJs.
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The Upper Roper River is one of the Australia’s unique tropical rivers which have been largely untouched by development. The Upper Roper River catchment comprises the sub-catchments of the Waterhouse River and Roper Creek, the two tributaries of the Roper River. There is a complex geological setting with different aquifer types. In this seasonal system, close interaction between surface water and groundwater contributes to both streamflow and sustaining ecosystems. The interaction is highly variable between seasons. A conceptual hydrogeological model was developed to investigate the different hydrological processes and geochemical parameters, and determine the baseline characteristics of water resources of this pristine catchment. In the catchment, long term average rainfall is around 850 mm and is summer dominant which significantly influences the total hydrological system. The difference between seasons is pronounced, with high rainfall up to 600 mm/month in the wet season, and negligible rainfall in the dry season. Canopy interception significantly reduces the amount of effective rainfall because of the native vegetation cover in the pristine catchment. Evaporation exceeds rainfall the majority of the year. Due to elevated evaporation and high temperature in the tropics, at least 600 mm of annual rainfall is required to generate potential recharge. Analysis of 120 years of rainfall data trend helped define “wet” and “dry periods”: decreasing trend corresponds to dry periods, and increasing trend to wet periods. The period from 1900 to 1970 was considered as Dry period 1, when there were years with no effective rainfall, and if there was, the intensity of rainfall was around 300 mm. The period 1970 – 1985 was identified as the Wet period 2, when positive effective rainfall occurred in almost every year, and the intensity reached up to 700 mm. The period 1985 – 1995 was the Dry period 2, with similar characteristics as Dry period 1. Finally, the last decade was the Wet period 2, with effective rainfall intensity up to 800 mm. This variability in rainfall over decades increased/decreased recharge and discharge, improving/reducing surface water and groundwater quantity and quality in different wet and dry periods. The stream discharge follows the rainfall pattern. In the wet season, the aquifer is replenished, groundwater levels and groundwater discharge are high, and surface runoff is the dominant component of streamflow. Waterhouse River contributes two thirds and Roper Creek one third to Roper River flow. As the dry season progresses, surface runoff depletes, and groundwater becomes the main component of stream flow. Flow in Waterhouse River is negligible, the Roper Creek dries up, but the Roper River maintains its flow throughout the year. This is due to the groundwater and spring discharge from the highly permeable Tindall Limestone and tufa aquifers. Rainfall seasonality and lithology of both the catchment and aquifers are shown to influence water chemistry. In the wet season, dilution of water bodies by rainwater is the main process. In the dry season, when groundwater provides baseflow to the streams, their chemical composition reflects lithology of the aquifers, in particular the karstic areas. Water chemistry distinguishes four types of aquifer materials described as alluvium, sandstone, limestone and tufa. Surface water in the headwaters of the Waterhouse River, the Roper Creek and their tributaries are freshwater, and reflect the alluvium and sandstone aquifers. At and downstream of the confluence of the Roper River, river water chemistry indicates the influence of rainfall dilution in the wet season, and the signature of the Tindall Limestone and tufa aquifers in the dry. Rainbow Spring on the Waterhouse River and Bitter Spring on the Little Roper River (known as Roper Creek at the headwaters) discharge from the Tindall Limestone. Botanic Walk Spring and Fig Tree Spring discharge into the Roper River from tufa. The source of water was defined based on water chemical composition of the springs, surface and groundwater. The mechanisms controlling surface water chemistry were examined to define the dominance of precipitation, evaporation or rock weathering on the water chemical composition. Simple water balance models for the catchment have been developed. The important aspects to be considered in water resource planning of this total system are the naturally high salinity in the region, especially the downstream sections, and how unpredictable climate variation may impact on the natural seasonal variability of water volumes and surface-subsurface interaction.
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Many drivers in highly motorised countries believe that aggressive driving is increasing. While the prevalence of the behaviour is difficult to reliably identify, the consequences of on-road aggression can be severe, with extreme cases resulting in property damage, injury and even death. This research program was undertaken to explore the nature of aggressive driving from within the framework of relevant psychological theory in order to enhance our understanding of the behaviour and to inform the development of relevant interventions. To guide the research a provisional ‘working’ definition of aggressive driving was proposed encapsulating the recurrent characteristics of the behaviour cited in the literature. The definition was: “aggressive driving is any on-road behaviour adopted by a driver that is intended to cause physical or psychological harm to another road user and is associated with feelings of frustration, anger or threat”. Two main theoretical perspectives informed the program of research. The first was Shinar’s (1998) frustration-aggression model, which identifies both the person-related and situational characteristics that contribute to aggressive driving, as well as proposing that aggressive behaviours can serve either an ‘instrumental’ or ‘hostile’ function. The second main perspective was Anderson and Bushman’s (2002) General Aggression Model. In contrast to Shinar’s model, the General Aggression Model reflects a broader perspective on human aggression that facilitates a more comprehensive examination of the emotional and cognitive aspects of aggressive behaviour. Study One (n = 48) examined aggressive driving behaviour from the perspective of young drivers as an at-risk group and involved conducting six focus groups, with eight participants in each. Qualitative analyses identified multiple situational and person-related factors that contribute to on-road aggression. Consistent with human aggression theory, examination of self-reported experiences of aggressive driving identified key psychological elements and processes that are experienced during on-road aggression. Participants cited several emotions experienced during an on-road incident: annoyance, frustration, anger, threat and excitement. Findings also suggest that off-road generated stress may transfer to the on-road environment, at times having severe consequences including crash involvement. Young drivers also appeared quick to experience negative attributions about the other driver, some having additional thoughts of taking action. Additionally, the results showed little difference between males and females in the severity of behavioural responses they were prepared to adopt, although females appeared more likely to displace their negative emotions. Following the self-reported on-road incident, evidence was also found of a post-event influence, with females being more likely to experience ongoing emotional effects after the event. This finding was evidenced by ruminating thoughts or distraction from tasks. However, the impact of such a post-event influence on later behaviours or interpersonal interactions appears to be minimal. Study Two involved the quantitative analysis of n = 926 surveys completed by a wide age range of drivers from across Queensland. The study aimed to explore the relationships between the theoretical components of aggressive driving that were identified in the literature review, and refined based on the findings of Study One. Regression analyses were used to examine participant emotional, cognitive and behavioural responses to two differing on-road scenarios whilst exploring the proposed theoretical framework. A number of socio-demographic, state and trait person-related variables such as age, pre-study emotions, trait aggression and problem-solving style were found to predict the likelihood of a negative emotional response such as frustration, anger, perceived threat, negative attributions and the likelihood of adopting either an instrumental or hostile behaviour in response to Scenarios One and Two. Complex relationships were found to exist between the variables, however, they were interpretable based on the literature review findings. Factor analysis revealed evidence supporting Shinar’s (1998) dichotomous description of on-road aggressive behaviours as being instrumental or hostile. The second stage of Study Two used logistic regression to examine the factors that predicted the potentially hostile aggressive drivers (n = 88) within the sample. These drivers were those who indicated a preparedness to engage in direct acts of interpersonal aggression on the road. Young, male drivers 17–24 years of age were more likely to be classified as potentially hostile aggressive drivers. Young drivers (17–24 years) also scored significantly higher than other drivers on all subscales of the Aggression Questionnaire (Buss & Perry, 1992) and on the ‘negative problem orientation’ and ‘impulsive careless style’ subscales of the Social Problem Solving Inventory – Revised (D’Zurilla, Nezu & Maydeu-Olivares, 2002). The potentially hostile aggressive drivers were also significantly more likely to engage in speeding and drink/drug driving behaviour. With regard to the emotional, cognitive and behavioural variables examined, the potentially hostile aggressive driver group also scored significantly higher than the ‘other driver’ group on most variables examined in the proposed theoretical framework. The variables contained in the framework of aggressive driving reliably distinguished potentially hostile aggressive drivers from other drivers (Nagalkerke R2 = .39). Study Three used a case study approach to conduct an in-depth examination of the psychosocial characteristics of n = 10 (9 males and 1 female) self-confessed hostile aggressive drivers. The self-confessed hostile aggressive drivers were aged 24–55 years of age. A large proportion of these drivers reported a Year 10 education or better and average–above average incomes. As a group, the drivers reported committing a number of speeding and unlicensed driving offences in the past three years and extensive histories of violations outside of this period. Considerable evidence was also found of exposure to a range of developmental risk factors for aggression that may have contributed to the driver’s on-road expression of aggression. These drivers scored significantly higher on the Aggression Questionnaire subscales and Social Problem Solving Inventory Revised subscales, ‘negative problem orientation’ and ‘impulsive/careless style’, than the general sample of drivers included in Study Two. The hostile aggressive driver also scored significantly higher on the Barrett Impulsivity Scale – 11 (Patton, Stanford & Barratt, 1995) measure of impulsivity than a male ‘inmate’, or female ‘general psychiatric’ comparison group. Using the Carlson Psychological Survey (Carlson, 1982), the self-confessed hostile aggressive drivers scored equal or higher scores than the comparison group of incarcerated individuals on the subscale measures of chemical abuse, thought disturbance, anti-social tendencies and self-depreciation. Using the Carlson Psychological Survey personality profiles, seven participants were profiled ‘markedly anti-social’, two were profiled ‘negative-explosive’ and one was profiled as ‘self-centred’. Qualitative analysis of the ten case study self-reports of on-road hostile aggression revealed a similar range of on-road situational factors to those identified in the literature review and Study One. Six of the case studies reported off-road generated stress that they believed contributed to the episodes of aggressive driving they recalled. Intense ‘anger’ or ‘rage’ were most frequently used to describe the emotions experienced in response to the perceived provocation. Less frequently ‘excitement’ and ‘fear’ were cited as relevant emotions. Notably, five of the case studies experienced difficulty articulating their emotions, suggesting emotional difficulties. Consistent with Study Two, these drivers reported negative attributions and most had thoughts of aggressive actions they would like to take. Similarly, these drivers adopted both instrumental and hostile aggressive behaviours during the self-reported incident. Nine participants showed little or no remorse for their behaviour and these drivers also appeared to exhibit low levels of personal insight. Interestingly, few incidents were brought to the attention of the authorities. Further, examination of the person-related characteristics of these drivers indicated that they may be more likely to have come from difficult or dysfunctional backgrounds and to have a history of anti-social behaviours on and off the road. The research program has several key theoretical implications. While many of the findings supported Shinar’s (1998) frustration-aggression model, two key areas of difference emerged. Firstly, aggressive driving behaviour does not always appear to be frustration driven, but can also be driven by feelings of excitation (consistent with the tenets of the General Aggression Model). Secondly, while the findings supported a distinction being made between instrumental and hostile aggressive behaviours, the characteristics of these two types of behaviours require more examination. For example, Shinar (1998) proposes that a driver will adopt an instrumental aggressive behaviour when their progress is impeded if it allows them to achieve their immediate goals (e.g. reaching their destination as quickly as possible); whereas they will engage in hostile aggressive behaviour if their path to their goal is blocked. However, the current results question this assertion, since many of the hostile aggressive drivers studied appeared prepared to engage in hostile acts irrespective of whether their goal was blocked or not. In fact, their behaviour appeared to be characterised by a preparedness to abandon their immediate goals (even if for a short period of time) in order to express their aggression. The use of the General Aggression Model enabled an examination of the three components of the ‘present internal state’ comprising emotions, cognitions and arousal and how these influence the likelihood of a person responding aggressively to an on-road situation. This provided a detailed insight into both the cognitive and emotional aspects of aggressive driving that have important implications for the design of relevant countermeasures. For example, the findings highlighted the potential value of utilising Cognitive Behavioural Therapy with aggressive drivers, particularly the more hostile offenders. Similarly, educational efforts need to be mindful of the way that person-related factors appear to influence one’s perception of another driver’s behaviour as aggressive or benign. Those drivers with a predisposition for aggression were more likely to perceive aggression or ‘wrong doing’ in an ambiguous on-road situation and respond with instrumental and/or hostile behaviour, highlighting the importance of perceptual processes in aggressive driving behaviour.
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Purpose – The paper aims to argue that there has been a privileging of the private (social mobility) and economic (social efficiency) purposes of schooling at the expense of the public (democratic equality) purposes of schooling. Design/methodology/approach – The paper employs a literature review, policy and document analysis. Findings – Since the late 1980s, the schooling agenda in Australia has been narrowed to one that gives primacy to purposes of schooling that highlight economic orientations (social efficiency) and private purposes (social mobility). Practical implications – The findings have wider relevance beyond Australia, as similar policy agendas are evident in many other countries raising the question as to how the shift in purposes of education in those countries might mirror those in Australia. Originality/value – While earlier writers have examined schooling policies in Australia and noted the implications of managerialism in relation to these policies, no study has analysed these policies from the perspective of the purposes of schooling. Conceptualising schooling, and its purposes in particular, in this way refocuses attention on how societies use their educational systems to promote (or otherwise) the public good.
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Background Prevention and control of ovine enzootic abortion (OEA) can be achieved by application of a live vaccine. In this study, five sheep flocks with different vaccination and infection status were serologically tested using a competitive enzyme-linked immunosorbent assay (cELISA) specific for Chlamydophila (Cp.) abortus over a two-year time period. Results Sheep in Flock A with recent OEA history had high antibody values after vaccination similar to Flock C with natural Cp. abortus infections. In contrast, OEA serology negative sheep (Flock E) showed individual animal-specific immunoreactions after vaccination. Antibody levels of vaccinated ewes in Flock B ranged from negative to positive two and three years after vaccination, respectively. Positive antibody values in the negative control Flock D (without OEA or vaccination) are probably due to asymptomatic intestinal infections with Cp. abortus. Excretion of the attenuated strain of Cp. abortus used in the live vaccine through the eye was not observed in vaccinated animals of Flock E. Conclusion The findings of our study indicate that, using serology, no distinction can be made between vaccinated and naturally infected sheep. As a result, confirmation of a negative OEA status in vaccinated animals by serology cannot be determined.
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Thirty-four elementary school teachers and 32 education students from Canada rated their reactions towards vignettes describing children who met attention-deficit/hyperactivity disorder (ADHD) symptom criteria that included or did not include the label “ADHD.” “ADHD”-labeled vignettes elicited greater perceptions of the child's impairment as well as more negative emotions and less confidence in the participants, although it also increased participants' willingness to implement treatment interventions. Ratings were similar to vignettes of boys versus girls; however, important differences in ratings between teachers and education students emerged and are discussed. Finally, we investigated the degree to which teachers' professional backgrounds influenced bias based on the label “ADHD.” Training specific to ADHD consistently predicted label bias, whereas teachers' experience working with children with ADHD did not.
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We seek numerical methods for second‐order stochastic differential equations that reproduce the stationary density accurately for all values of damping. A complete analysis is possible for scalar linear second‐order equations (damped harmonic oscillators with additive noise), where the statistics are Gaussian and can be calculated exactly in the continuous‐time and discrete‐time cases. A matrix equation is given for the stationary variances and correlation for methods using one Gaussian random variable per timestep. The only Runge–Kutta method with a nonsingular tableau matrix that gives the exact steady state density for all values of damping is the implicit midpoint rule. Numerical experiments, comparing the implicit midpoint rule with Heun and leapfrog methods on nonlinear equations with additive or multiplicative noise, produce behavior similar to the linear case.
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This paper describes a series of double strap shear tests loaded in tension to investigate the bond between CFRP sheets and steel plates. Both normal modulus (240 GPa) and high modulus (640 GPa) CFRPs were used in the test program. Strain gauges were mounted to capture the strain distribution along the CFRP length. Different failure modes were observed for joints with normal modulus CFRP and those with high modulus CFRP. The strain distribution along the CFRP length was found to be similar for the two cases. A shorter effective bond length was obtained for joints with high modulus CFRP whereas larger ultimate load carrying capacity can be achieved for joints with normal modulus CFRP when the bond length is long enough. The Hart-Smith Model was modified to predict the effective bond length and ultimate load carrying capacity of joints between the normal modulus CFRP and steel plates. The Multilayer Distribution Model developed by the authors was modified to predict the load carrying capacity of joints between the high modulus CFRP and steel plates. The predicted values agreed well with experimental ones.
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Abstract Opioid drugs, such as morphine, are among the most effective analgesics available. However, their utility for the treatment of chronic pain is limited by side effects including tolerance and dependence. Morphine acts primarily through the mu-opioid receptor (MOP-R) , which is also a target of endogenous opioids. However, unlike endogenous ligands, morphine fails to promote substantial receptor endocytosis both in vitro, and in vivo. Receptor endocytosis serves at least two important functions in signal transduction. First, desensitization and endocytosis act as an "off" switch by uncoupling receptors from G protein. Second, endocytosis functions as an "on" switch, resensitizing receptors by recycling them to the plasma membrane. Thus, both the off and on function of the MOP-R are altered in response to morphine compared to endogenous ligands. To examine whether the low degree of endocytosis induced by morphine contributes to tolerance and dependence, we generated a knockin mouse that expresses a mutant MOP-R that undergoes morphine-induced endocytosis. Morphine remains an excellent antinociceptive agent in these mice. Importantly, these mice display substantially reduced antinociceptive tolerance and physical dependence. These data suggest that opioid drugs with a pharmacological profile similar to morphine but the ability to promote endocytosis could provide analgesia while having a reduced liability for promoting tolerance and dependence