BACKGROUND & AIMS: :Priority setting of health interventions is often ad-hoc and resources are not used to an optimal extent. Underlying problem is that multiple criteria play a role and decisions are complex. Interventions may be chosen to maximize general population health, to reduce health inequalities of disadvantaged or vulnerable groups, ad/or to respond to life-threatening situations, all with respect to practical and budgetary constraints. This is the type of problem that policy makers are typically bad at solving rationally, unaided. They tend to use heuristic or intuitive approaches to simplify complexity, and in the process, important information is ignored. Next, policy makers may select interventions for only political motives. This indicates the need for rational and transparent approaches to priority setting. Over the past decades, a number of approaches have been developed, including evidence-based medicine, burden of disease analyses, cost-effectiveness analyses, and equity analyses. However, these approaches concentrate on single criteria only, whereas in reality, policy makers need to make choices taking into account multiple criteria simultaneously. Moreover, they do not cover all criteria that are relevant to policy makers. Therefore, the development of a multi-criteria approach to priority setting is necessary, and this has indeed recently been identified as one of the most important issues in health system research. In other scientific disciplines, multi-criteria decision analysis is well developed, has gained widespread acceptance and is routinely used. This paper presents the main principles of multi-criteria decision analysis. There are only a very few applications to guide resource allocation decisions in health. We call for a shift away from present priority setting tools in health--that tend to focus on single criteria--towards transparent and systematic approaches that take into account all relevant criteria simultaneously.

背景与目标： : 卫生干预措施的优先级设定通常是临时性的，资源的使用没有达到最佳程度。潜在的问题是，多个标准发挥作用，决策很复杂。可以选择干预措施，以最大程度地提高总体人口健康水平，减少弱势或弱势群体的健康不平等，ad/或应对威胁生命的情况，所有这些都涉及实际和预算方面的限制。这是政策制定者通常不善于理性地、没有帮助地解决的问题。他们倾向于使用启发式或直观的方法来简化复杂性，在此过程中，重要的信息被忽略。接下来，政策制定者可能只出于政治动机选择干预措施。这表明需要合理和透明的方法来确定优先级。在过去的几十年中，已经开发了许多方法，包括循证医学，疾病负担分析，成本效益分析和公平性分析。但是，这些方法仅集中在单个标准上，而实际上，决策者需要同时考虑多个标准来做出选择。此外，它们并未涵盖与决策者相关的所有标准。因此，有必要开发一种多标准方法来确定优先级，并且最近确实已将其确定为卫生系统研究中最重要的问题之一。在其他科学学科中，多准则决策分析得到了很好的发展，得到了广泛的认可，并被常规使用。本文介绍了多准则决策分析的主要原理。只有很少的应用程序来指导健康中的资源分配决策。我们呼吁从目前的卫生优先事项设定工具 (往往侧重于单一标准) 转向透明和系统的方法，同时考虑到所有相关标准。

BACKGROUND & AIMS: UNLABELLED:Decreased left ventricular ejection fraction (LVEF) is a relative contraindication for the use of potentially cardiotoxic chemotherapy. A resting LVEF of 50% is usually used as the lower limit of normal values. The decision to change chemotherapy, however, is complex and is affected by many factors, including ejection fraction.

METHODS:To determine how LVEF data were used by clinical oncologists in clinical decision making, we performed a retrospective analysis of patients referred for ejection fraction measurements from the hematology/oncology divisionS of Stanford University from March 1992 through March 1995. The records of 565 patients treated with potentially cardiotoxic chemotherapy were evaluated.

RESULTS:LVEFs < 50% were found in 153 patients. The charts of patients with reduced ejection fractions were reviewed to determine if the radionuclide measurement resulted in either discontinuation of the cardiotoxic agent or substitution of a less cardiotoxic drug or mode of administration. These specific changes in therapy occurred in only 43 of the 153 (28%) patients with ejection fractions below 50%; 24 of the 43 (57%) had ejection fractions < or = 40%. Patients with lower ejection fraction values were more likely to have their therapy changed than those with LVEFs close to normal. Patients with ejection fractions < or = 30 generally had cardiotoxic agents discontinued. Of patients who had a resting LVEF < 50% and whose therapy was not changed, 81% had a normal increase in LVEF with exercise.

CONCLUSION:In clinical practice at our institution, ejection fraction < 50% is not used as an absolute contraindication to cardiotoxic chemotherapy. When the LVEF is less than 40%, potentially cardiotoxic therapy is most often discontinued or omitted. Radionuclide evidence of cardiac reserve may account for decisions to continue cardiotoxic agents despite ejection fractions < 50% in the majority of patients. Further study will be needed to establish standard criteria. Reserve function, as measured by the change in ejection fraction from rest to stress may be an important parameter used by oncologists to help select patients for continued therapy in spite of a reduced ejection fraction. Our results argue that use of fixed criteria may be too restrictive.

背景与目标： 未标记 : 左心室射血分数 (LVEF) 降低是使用潜在心脏毒性化学疗法的相对禁忌症。50% 的静息LVEF通常用作正常值的下限。然而，改变化疗的决定是复杂的，并且受到许多因素的影响，包括射血分数。
方法 : 为了确定临床肿瘤学家如何在临床决策中使用LVEF数据，我们对1992年3月至1995年3月期间接受斯坦福大学血液学/肿瘤学部门射血分数测量的患者进行了回顾性分析。评估了565例接受潜在心脏毒性化学疗法治疗的患者的记录。
结果 : 在153例患者中发现LVEFs <50%。回顾了射血分数降低的患者的图表，以确定放射性核素测量是否导致停用心脏毒性药物或替代心脏毒性较小的药物或给药方式。这些特定的治疗变化仅发生在射血分数低于50% 的153 (28%) 患者中; 43 (57%) 中的24的射血分数 <或 = 40%。射血分数值较低的患者比LVEFs接近正常的患者更有可能改变治疗。射血分数 <或 = 30的患者通常停用心脏毒性药物。在静息LVEF <50% 且治疗未改变的患者中，81% 的LVEF随运动而正常增加。
结论 : 在我们机构的临床实践中，射血分数 <50% 不作为心脏毒性化疗的绝对禁忌症。当LVEF小于40% 时，潜在的心脏毒性治疗通常被停止或省略。尽管大多数患者的射血分数 <50%，但心脏储备的放射性核素证据可能解释了继续服用心脏毒性药物的决定。需要进一步研究以建立标准。储备功能 (通过从静息到压力的射血分数变化来衡量) 可能是肿瘤学家使用的重要参数，尽管射血分数降低，但可以帮助选择患者继续治疗。我们的结果认为，使用固定标准可能过于严格。

BACKGROUND & AIMS: BACKGROUND:Abnormal respiratory rates are one of the first indicators of clinical deterioration in emergency department(ED) patients. Despite the importance of respiratory rate observations, this vital sign is often inaccurately recorded on ED observation charts, compromising patient safety. Concurrently, there is a paucity of research reporting why this phenomenon occurs. OBJECTIVE:To develop a substantive theory explaining ED registered nurses' reasoning when they miss or misreport respiratory rate observations. DESIGN:This research project employed a classic grounded theory analysis of qualitative data. PARTICIPANTS:Seventy-nine registered nurses currently working in EDs within Australia. Data collected included detailed responses from individual interviews and open-ended responses from an online questionnaire. METHODS:Classic grounded theory (CGT) research methods were utilised, therefore coding was central to the abstraction of data and its reintegration as theory. Constant comparison synonymous with CGT methods were employed to code data. This approach facilitated the identification of the main concern of the participants and aided in the generation of theory explaining how the participants processed this issue. RESULTS:The main concern identified is that ED registered nurses do not believe that collecting an accurate respiratory rate for ALL patients at EVERY round of observations is a requirement, and yet organizational requirements often dictate that a value for the respiratory rate be included each time vital signs are collected. The theory 'Rationalising Transgression', explains how participants continually resolve this problem. The study found that despite feeling professionally conflicted, nurses often erroneously record respiratory rate observations, and then rationalise this behaviour by employing strategies that adjust the significance of the organisational requirement. These strategies include; Compensating, when nurses believe they are compensating for errant behaviour by enhancing the patient's outcome; Minimalizing, when nurses believe that the patient's outcome would be no different if they recorded an accurate respiratory rate or not and; Trivialising, a strategy that sanctions negligent behaviour and occurs when nurses 'cut corners' to get the job done. Nurses' use these strategies to titrate the level ofemotional discomfort associated with erroneous behaviour, thereby rationalising transgression CONCLUSION: This research reveals that despite continuing education regarding gold standard guidelines for respiratory rate collection, suboptimal practice continues. Ideally, to combat this transgression, a culture shift must occur regarding nurses' understanding of acceptable practice methods. Nurses must receive education in a way that permeates their understanding of the relationship between the regular collection of accurate respiratory rate observations and optimal patient outcomes.

背景与目标：

BACKGROUND & AIMS: Decay of fluorescence polarization after an impulsive excitation is correlated with wobbling motion of fluorescent molecules in membranes. The motion is characterized by two parameters, a "wobbling diffusion constant" and a "degree of orientational constraint" both of which can be determined directly from experimentally obtained decay. Detailed discussion, including theoretically calculated time-courses of polarization decay, is given for several types of molecules embedded in lipid bilayers; these types cover a large part of fluorescent probes available at present. The theory is useful for the analysis of fluorescence polarization decay in any system where the orientation of fluorophore is restricted by the surrounding structure.

背景与目标： 脉冲激发后荧光偏振的衰减与膜中荧光分子的摆动运动有关。运动的特征在于两个参数，即 “摆动扩散常数” 和 “定向约束度”，这两个参数都可以直接从实验获得的衰减中确定。针对脂质双层中嵌入的几种类型的分子，进行了详细的讨论，包括理论上计算的极化衰减的时间过程; 这些类型涵盖了目前可用的大部分荧光探针。该理论对于分析荧光团的取向受周围结构限制的任何系统中的荧光偏振衰减都很有用。

BACKGROUND & AIMS: STUDY QUESTION:How good is fertility knowledge and what are treatment beliefs in an international sample of men and women currently trying to conceive? SUMMARY ANSWER:The study population had a modest level of fertility knowledge and held positive and negative views of treatment. WHAT IS KNOWN ALREADY:Few studies have examined general fertility treatment attitudes but studies of specific interventions show that attitudes are related to characteristics of the patient, doctor and context. Further, research shows that fertility knowledge is poor. However, the majority of these studies have examined the prevalence of infertility, the optimal fertile period and/or age-related infertility in women, in university students and/or people from high-resource countries making it difficult to generalize findings. STUDY DESIGN, SIZE, DURATION:A cross-sectional sample completed the International Fertility Decision-making Study (IFDMS) over a 9-month period, online or via social research panels and in fertility clinics. PARTICIPANTS/MATERIALS, SETTING, METHODS:Participants were 10 045 people (8355 women, 1690 men) who were on average 31.8 years old, had been trying to conceive for 2.8 years with 53.9% university educated. From a total of 79 countries, sample size was >100 in 18 countries. All 79 countries were assigned to either a very high Human Development Index (VH HDI) or a not very high HDI (NVH HDI). The IFDMS was a 45-min, 64-item English survey translated into 12 languages. The inclusion criteria were the age between 18 and 50 years and currently trying to conceive for at least 6 months. Fertility knowledge was assessed using a 13-item correct/incorrect scale concerned with risk factors, misconceptions and basic fertility facts (range: 0-100% correct). Treatment beliefs were assessed with positive and negative statements about fertility treatment rated on a five-point agree/disagree response scale. MAIN RESULTS AND THE ROLE OF CHANCE:Average correct score for Fertility Knowledge was 56.9%, with greater knowledge significantly related to female gender, university education, paid employment, VH HDI and prior medical consultation for infertility (all P < 0.001). The mean agreement scores for treatment beliefs showed that agreement for positive items (safety, efficacy) was correlated with agreement for negative items (short/long-term physical/emotional effects) (P > 0.001). People who had given birth/fathered a child, been trying to conceive for less than 12 months, who had never consulted for a fertility problem and who lived in a country with an NVH HDI agreed less with negative beliefs. HDI, duration of trying to conceive and help-seeking were also correlates of higher positive beliefs, alongside younger age, living in an urban area and having stepchildren. Greater fertility knowledge was associated with stronger agreement on negative treatment beliefs items (P < 0.001) but was unrelated to positive treatment beliefs items. LIMITATIONS, REASONS FOR CAUTION:There was volunteer bias insofar as more women, people of higher education and people with fertility problems (i.e. met criteria for infertility, had consulted a medical doctor, had conceived with fertility treatment) participated and this was true in VH and NVH HDI countries. The bias may mean that people in this sample had better fertility knowledge and less favourable treatment beliefs than is the case in the general population. WIDER IMPLICATIONS OF THE FINDINGS:Educational interventions should be directed at improving knowledge of fertility health. Future prospective research should be aimed at investigating how fertility knowledge and treatment beliefs affect childbearing and help-seeking decision-making.

背景与目标：

BACKGROUND & AIMS: Despite numerous legal interventions, minors continue to purchase and consume alcohol. Prior research had suggested that the decision to request identification to prove legal age was susceptible to various judgement and decision heuristics. This research examined whether the physical attractiveness of the potential consumer and the presence or absence of others were significant predictors of alcohol accessibility. Bartenders (n = 130) rated a target individual who was either high or low in attractiveness. Results indicated that attractiveness was a significant predictor of "proofing likelihood". High levels of attractiveness were associated with a decrease in the likelihood of being asked to provide proof of legal age for the purchase of alcohol. Individuals presented alone were seen as significantly older than when grouped with others. Implications of these findings for the restriction of alcohol availability among minors are considered.

背景与目标： 尽管有许多法律干预，未成年人仍继续购买和消费酒精。先前的研究表明，要求证明合法年龄的决定容易受到各种判断和决策启发式的影响。这项研究检查了潜在消费者的身体吸引力以及其他人的存在与否是否是酒精可及性的重要预测因素。调酒师 (n = 130) 对吸引力高或低的目标个体进行了评分。结果表明，吸引力是 “打样可能性” 的重要预测指标。高吸引力与被要求提供购买酒精的法定年龄证明的可能性降低有关。单独出现的人被认为比与他人分组时要大得多。考虑了这些发现对限制未成年人饮酒的影响。

BACKGROUND & AIMS: BACKGROUND:Low utilization of effective coronary heart disease (CHD) prevention strategies may be due to many factors, but chief among them is the lack of patient involvement in prevention decisions. We undertook this study to test the effectiveness of an individually-tailored, computerized decision aid about CHD on patients' discussions with their doctor and their plans for CHD prevention. METHODS:We conducted a pilot randomized trial in a convenience sample of adults with no previous history of cardiovascular disease to test the effectiveness of an individually-tailored, computerized decision aid about CHD prevention against a risk factor list that patients could present to their doctor. RESULTS:We enrolled 75 adults. Mean age was 53. 59% were female, 73% white, and 23% African-American. 66% had some college education. 43% had a 10-year CHD risk of 0-5%, 25% a risk of 6-10%, 24% a risk of 11-20%, and 5% a risk of > 20%. 78% had at least one option to reduce their CHD risk, but only 45% accurately identified the strategies best supported by evidence. 41 patients received the decision aid, 34 received usual care. In unadjusted analysis, the decision aid increased the proportion of patients who discussed CHD risk reduction with their doctor from 24% to 40% (absolute difference 16%; 95% CI -4% to +37%) and increased the proportion who had a specific plan to reduce their risk from 24% to 37% (absolute difference 13%; 95% CI -7% to +34%). In pre-post testing, the decision aid also appeared to increase the proportion of patients with plans to intervene on their CHD risk (absolute increase ranging from 21% to 47% for planned medication use and 5% to 16% for planned behavioral interventions). CONCLUSION:Our study confirms patients' limited knowledge about their CHD risk and effective risk reduction options and provides preliminary evidence that an individually-tailored decision aid about CHD prevention might be expected to increase patients' discussions about CHD prevention with their doctor and their plans for CHD risk reduction. These findings should be replicated in studies with a larger sample size and patients at overall higher risk of CHD.

背景与目标：

BACKGROUND & AIMS: Systematic reviews can be a very useful decision-making tool because they objectively summarize large amounts of information, identify gaps in medical research, and identify beneficial or harmful interventions. Consumers can use systematic reviews to help them make health care decisions. Policymakers can use systematic reviews to help them make decisions about what types of health care to provide. Despite the potential value of systematic reviews, little evidence of their direct impact on the decisions made by consumers and policymakers is available. We discuss strategies for optimizing the use of systematic reviews by increasing the awareness and identification of reviews, learning to critically evaluate the findings of reviews, and overcoming barriers to the incorporation of reviews into the decision-making process. In addition, the participation of consumers and policymakers in the design, conduct, and reporting of systematic reviews can help to produce reviews that are relevant and understandable to target audiences. Because decisions that involve health care policies and issues are complex processes in which information (such as that provided by systematic reviews) plays only a part, strategies for increasing the use of systematic reviews should be evaluated for their usefulness in the decision-making process.

背景与目标： 系统评价可以是一个非常有用的决策工具，因为它们客观地总结了大量信息，确定了医学研究中的差距，并确定了有益或有害的干预措施。消费者可以使用系统的评论来帮助他们做出医疗保健决策。政策制定者可以使用系统的审查来帮助他们决定提供哪些类型的医疗保健。尽管系统审查具有潜在的价值，但几乎没有证据表明它们对消费者和政策制定者做出的决定有直接影响。我们讨论了通过提高对评论的认识和识别，学会批判性地评估评论的结果以及克服将评论纳入决策过程的障碍来优化系统评论使用的策略。此外，消费者和政策制定者参与系统审查的设计，进行和报告可以帮助产生与目标受众相关且易于理解的评论。由于涉及医疗保健政策和问题的决策是复杂的过程，其中信息 (例如由系统审查提供的信息) 仅起一部分作用，因此应评估增加使用系统审查的策略在决策过程中的有用性。

BACKGROUND & AIMS: BACKGROUND:Reverse engineering cellular networks is currently one of the most challenging problems in systems biology. Dynamic Bayesian networks (DBNs) seem to be particularly suitable for inferring relationships between cellular variables from the analysis of time series measurements of mRNA or protein concentrations. As evaluating inference results on a real dataset is controversial, the use of simulated data has been proposed. However, DBN approaches that use continuous variables, thus avoiding the information loss associated with discretization, have not yet been extensively assessed, and most of the proposed approaches have dealt with linear Gaussian models. RESULTS:We propose a generalization of dynamic Gaussian networks to accommodate nonlinear dependencies between variables. As a benchmark dataset to test the new approach, we used data from a mathematical model of cell cycle control in budding yeast that realistically reproduces the complexity of a cellular system. We evaluated the ability of the networks to describe the dynamics of cellular systems and their precision in reconstructing the true underlying causal relationships between variables. We also tested the robustness of the results by analyzing the effect of noise on the data, and the impact of a different sampling time. CONCLUSION:The results confirmed that DBNs with Gaussian models can be effectively exploited for a first level analysis of data from complex cellular systems. The inferred models are parsimonious and have a satisfying goodness of fit. Furthermore, the networks not only offer a phenomenological description of the dynamics of cellular systems, but are also able to suggest hypotheses concerning the causal interactions between variables. The proposed nonlinear generalization of Gaussian models yielded models characterized by a slightly lower goodness of fit than the linear model, but a better ability to recover the true underlying connections between variables.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:In recent years, decision makers in Canada and elsewhere have expressed a desire for more explicit, evidence-based approaches to priority setting. To achieve this aim within health care organizations, knowledge of both the organizational context and stakeholder attitudes towards priority setting are required. The current work adds to a limited yet growing body of international literature describing priority setting practices in health organizations. METHODS:A qualitative study was conducted using in-depth, face-to-face interviews with 25 key decision makers of the Provincial Health Services Authority (PHSA) of British Columbia. Major themes and sub-themes were identified through content analysis. RESULTS:Priorities were described by decision makers as being set in an ad hoc manner, with resources generally allocated along historical lines. Participants identified the Strategic Plan and a strong research base as strengths of the organization. The main areas for improvement were a desire to have a more transparent process for priority setting, a need to develop a culture which supports explicit priority setting, and a focus on fairness in decision making. Barriers to an explicit allocation process included the challenge of providing specialized services for disparate patient groups, and a lack of formal training in priority setting amongst decision makers. CONCLUSION:This study identified factors important to understanding organizational context and informed next steps for explicit priority setting for a provincial health authority. While the PHSA is unique in its organizational structure in Canada, lessons about priority setting should be transferable to other contexts.

背景与目标：

BACKGROUND & AIMS: :The problem of inferring haplotypes from genotypes of single nucleotide polymorphisms (SNPs) is essential for the understanding of genetic variation within and among populations, with important applications to the genetic analysis of disease propensities and other complex traits. The problem can be formulated as a mixture model, where the mixture components correspond to the pool of haplotypes in the population. The size of this pool is unknown; indeed, knowing the size of the pool would correspond to knowing something significant about the genome and its history. Thus methods for fitting the genotype mixture must crucially address the problem of estimating a mixture with an unknown number of mixture components. In this paper we present a Bayesian approach to this problem based on a nonparametric prior known as the Dirichlet process. The model also incorporates a likelihood that captures statistical errors in the haplotype/genotype relationship trading off these errors against the size of the pool of haplotypes. We describe an algorithm based on Markov chain Monte Carlo for posterior inference in our model. The overall result is a flexible Bayesian method, referred to as DP-Haplotyper, that is reminiscent of parsimony methods in its preference for small haplotype pools. We further generalize the model to treat pedigree relationships (e.g., trios) between the population's genotypes. We apply DP-Haplotyper to the analysis of both simulated and real genotype data, and compare to extant methods.

背景与目标： : 从单核苷酸多态性 (snp) 的基因型推断单倍型的问题对于理解种群内部和种群之间的遗传变异至关重要，对于疾病倾向和其他复杂性状的遗传分析具有重要应用。可以将问题表述为混合模型，其中混合成分对应于种群中的单倍型库。这个池的大小是未知的; 实际上，知道池的大小将对应于了解基因组及其历史的重要信息。因此，用于拟合基因型混合物的方法必须至关重要地解决估计具有未知数量的混合物成分的混合物的问题。在本文中，我们基于称为Dirichlet过程的非参数先验，提出了一种解决此问题的贝叶斯方法。该模型还结合了一种可能性，该可能性捕获了单倍型/基因型关系中的统计误差，将这些误差与单倍型池的大小进行了权衡。我们在模型中描述了一种基于马尔可夫链蒙特卡罗的后验推理算法。总体结果是一种灵活的贝叶斯方法，称为DP-Haplotyper，它使人想起了对小型单体型池的偏爱。我们进一步推广了该模型，以处理人群基因型之间的血统关系 (例如三重奏)。我们将DP-Haplotyper应用于模拟和真实基因型数据的分析，并与现有方法进行比较。

BACKGROUND & AIMS: :Millions of people worldwide use over-the-counter analgesics on a regular basis; yet little is known about how decisions to self-medicate are made. This study used the theory of planned behavior to explore the influence of beliefs about medicines (Beliefs about Medicines Questionnaire) and individual pain experience as predictors of intent to self-medicate. Both emerged as significant predictors of intent to self-medicate. Furthermore, intent to self-medicate significantly predicted reported use of analgesics. These findings indicate that use of over-the-counter pain medication is more likely when the value of the pain relief is greater than concerns about harm.

背景与目标： : 全世界有数百万人定期使用非处方止痛药; 然而，对于如何做出自我药物的决定知之甚少。这项研究使用计划行为理论来探索对药物的信念 (关于药物的信念问卷) 和个人疼痛体验的影响，以此作为自我治疗意图的预测指标。两者都成为自我治疗意图的重要预测指标。此外，自我药物治疗的意图显著预测了镇痛药的使用。这些发现表明，当缓解疼痛的价值大于对伤害的担忧时，使用非处方止痛药的可能性更大。

BACKGROUND & AIMS: :Water plays an active role in many fundamental phenomena in cellular systems such as molecular recognition, folding and conformational equilibria, reaction kinetics and phase partitioning. Hence, our ability to account for the energetics of these processes is highly dependent on the models we use for calculating solvation effects. For example, theoretical prediction of protein-ligand binding modes (i.e., docking) and binding affinities (i.e., scoring) requires an accurate description of the change in hydration that accompanies solute binding. In this review, we discuss the challenges of constructing solvation models that capture these effects, with an emphasis on continuum models and on more recent developments in the field. In our discussion of methods, relatively greater attention will be given to boundary element solutions to the Poisson equation and to nonpolar solvation models, two areas that have become increasingly important but are likely to be less familiar to many readers. The other focus will be upon the trending efforts for evaluating solvation models in order to uncover limitations, biases, and potentially attractive directions for their improvement and applicability. The prospective and retrospective performance of a variety of solvation models in the SAMPL blind challenges will be discussed in detail. After just a few years, these benchmarking exercises have already had a tangible effect in guiding the improvement of solvation models.

背景与目标： : 水在细胞系统中的许多基本现象中起着积极作用，例如分子识别，折叠和构象平衡，反应动力学和相分配。因此，我们解释这些过程的能量学的能力在很大程度上取决于我们用于计算溶剂化效应的模型。例如，蛋白质-配体结合模式 (即对接) 和结合亲和力 (即评分) 的理论预测需要准确描述伴随溶质结合的水合变化。在这篇综述中，我们讨论了构建捕获这些影响的溶剂化模型的挑战，重点是连续模型和该领域的最新发展。在我们对方法的讨论中，将相对更多地关注泊松方程的边界元解和非极性溶剂化模型，这两个领域已变得越来越重要，但许多读者可能不太熟悉。另一个重点将放在评估溶剂化模型的趋势上，以发现局限性，偏见以及其改进和适用性的潜在吸引力方向。将详细讨论SAMPL盲挑战中各种溶剂化模型的前瞻性和回顾性表现。短短几年后，这些基准测试工作已经在指导溶剂化模型的改进方面产生了切实的效果。

BACKGROUND & AIMS: :Possible options in a decision often organize as a hierarchy of subdecisions. A recent study concluded that perceptual processes in primates mimic this hierarchical structure and perform subdecisions in parallel. We argue that a flat model that directly selects between final choices accounts more parsimoniously for the reported behavioral and neural data. Critically, a flat model is characterized by decision signals integrating evidence at different hierarchical levels, in agreement with neural recordings showing this integration in localized neural populations. Our results point to the role of experience for building integrated perceptual categories where sensory evidence is merged prior to decision.

背景与目标： : 决策中的可能选项通常组织为子决策的层次结构。最近的一项研究得出的结论是，灵长类动物的感知过程模仿了这种层次结构，并并行执行子决策。我们认为，直接在最终选择之间进行选择的平面模型对报告的行为和神经数据更为宽容。至关重要的是，扁平模型的特征是决策信号在不同的层次级别上集成了证据，与神经记录一致，表明这种集成在局部神经种群中。我们的结果指出了经验在建立综合感知类别中的作用，在这些类别中，感官证据在做出决定之前就已合并。

BACKGROUND & AIMS: PURPOSE:To assess how different diagnostic decision aids perform in terms of sensitivity, specificity, and harm. METHODS:Four diagnostic decision aids were compared, as applied to a simulated patient population: a findings-based algorithm following a linear or branched pathway, a serial threshold-based strategy, and a parallel threshold-based strategy. Headache in immune-compromised HIV patients in a developing country was used as an example. Diagnoses included cryptococcal meningitis, cerebral toxoplasmosis, tuberculous meningitis, bacterial meningitis, and malaria. Data were derived from literature and expert opinion. Diagnostic strategies' validity was assessed in terms of sensitivity, specificity, and harm related to mortality and morbidity. Sensitivity analyses and Monte Carlo simulation were performed. RESULTS:The parallel threshold-based approach led to a sensitivity of 92% and a specificity of 65%. Sensitivities of the serial threshold-based approach and the branched and linear algorithms were 47%, 47%, and 74%, respectively, and the specificities were 85%, 95%, and 96%. The parallel threshold-based approach resulted in the least harm, with the serial threshold-based approach, the branched algorithm, and the linear algorithm being associated with 1.56-, 1.44-, and 1.17-times higher harm, respectively. Findings were corroborated by sensitivity and Monte Carlo analyses. CONCLUSION:A threshold-based diagnostic approach is designed to find the optimal trade-off that minimizes expected harm, enhancing sensitivity and lowering specificity when appropriate, as in the given example of a symptom pointing to several life-threatening diseases. Findings-based algorithms, in contrast, solely consider clinical observations. A parallel workup, as opposed to a serial workup, additionally allows for all potential diseases to be reviewed, further reducing false negatives. The parallel threshold-based approach might, however, not be as good in other disease settings.

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