LC-MS/MS法测定人血浆中布康唑浓度的不确定度评定

目的：评定LC-MS/MS法测定人血浆中布康唑浓度的不确定度。方法：分析测定过程中不确定度的来源，包括对照品的称量、仪器误差、标准溶液的配制、含药血浆样品的配制、血浆样品的处理、标准曲线的拟合、基质效应、重复性等，评定各来源分量的不确定度，计算合成不确定度和扩展不确定度。结果：人血浆中低（60.0 pg·mL^-1）、中（600.0 pg·mL^-1）、高（6 400.0 pg·mL^-1）浓度布康唑的扩展不确定度分别为5.62，63.90，626.26 pg·mL^-1（k=2，P=95%）。结论：LC-MS/MS法测定人血浆中布康唑浓度的不确定度主要由基质效应、血浆样品的处理（提取回收率），仪器误差、重复性（精密度）引入。     

Risk communication in a patient decision aid for radiotherapy in breast cancer: How to deal with uncertainty?

Background and aimPatient decision aids for oncological treatment options, provide information on the effect on recurrence rates and/or survival benefit, and on side-effects and/or burden of different treatment options. However, often uncertainty exists around the probability estimates for recurrence/survival and side-effects which is too relevant to be ignored. Evidence is lacking on the best way to communicate these uncertainties. The aim of this study is to develop a method to incorporate uncertainties in a patient decision aid for breast cancer patients to support their decision on radiotherapy.MethodsFirstly, qualitative interviews were held with patients and health care professionals. Secondly, in the development phase, thinking aloud sessions were organized with four patients and 12 health care professionals, individual and group-wise.ResultsConsensus was reached on a pictograph illustrating the whole range of uncertainty for local recurrence risks, in combination with textual explanation that a more exact personalized risk would be given by their own physician. The pictograph consisted of 100 female icons in a 10 x 10 array. Icons with a stepwise gradient color indicated the uncertainty margin. The prevalence and severity of possible side-effects were explained using verbal labels.ConclusionsWe developed a novel way of visualizing uncertainties in recurrence rates in a patient decision aid. The effect of this way of communicating risk uncertainty is currently being tested in the BRASA study (NCT03375801).     

Health technology assessment with risk aversion in health

Standard cost-effectiveness models compare incremental cost increases to incremental average gains in health, commonly expressed in Quality-Adjusted Life Years (QALYs). Our research generalizes earlier models in several ways. We introduce risk aversion in Quality of Life (QoL), which leads to “willingness-to-pay” thresholds that rise with illness severity, potentially by an order of magnitude. Unlike traditional CEA analyses, which discriminate against persons with disabilities, our analysis implies that the marginal value of improving QoL rises for disabled individuals. Our model can also value the uncertain benefits of medical interventions by employing well-established analytic methods from finance. Finally, we show that traditional QALYs no longer serve as a single index of health, when consumers are risk-averse. To address this problem, we derive a generalized single-index of health outcomes—the Generalized Risk-Adjusted QALY (GRA-QALY). Earlier models of CEA that abstract from risk-aversion nest as special cases of our more general model.     

Mixed h2 and h∞ optimal robust control design

This paper introduces a design methodology for a dynamic compensator that simultaneously minimizes the upper bound of a quadratic performance index and the H_∞-norm of a disturbance transfer function matrix of a multiple-input/multiple-output system whose model contains parameter uncertainty in the state and input matrices. The real parameter uncertainty is modelled as additional measurement outputs and as additional weights on the existing noise inputs and measurement outputs of the system. The compensator equations are derived by taking the dual of a system with parameter variation in the state and output matrices, for which the compensator equations have previously been derived, and then taking the dual of the compensator equations. An algorithm for applying this theory is given and an example is shown.     

Establishing the Cost-Effectiveness of New Pharmaceuticals under Conditions of Uncertainty—When Is There Sufficient Evidence?

Decisions about which health-care interventions represent adequate value to collectively funded health-care systems are as widespread as they are unavoidable. In the case of new pharmaceuticals, many countries now require formal cost-effectiveness analysis to inform this decision-making process. This requires evidence on parameters associated with health-related utilities, treatment effects, resource use, and costs, for which data from available regulatory trials are invariably absent or highly uncertain. This uncertainty results from a number of factors including the predominance of intermediate end points in the clinical evidence-base and the limited period of follow-up of patients in clinical studies. Despite these imperfections in the evidence base, decisions about whether new pharmaceuticals are sufficiently cost-effective for reimbursement cannot be side-stepped. Data limitations do, however, require the use of rigorous analytical methods to support decision making. Probabilistic decision models and value of information analysis offer a means of structuring decision problems, synthesizing all available data, characterizing the uncertainty in the decision, quantifying the cost of uncertainty, and establishing the expected value of perfect information. This analytical framework is important because it addresses two fundamental questions about new pharmaceuticals. First, is the product expected to be cost-effective on the basis of existing evidence? Second, is additional research concerning the product itself cost-effective? In addressing these questions, the analytical framework can establish when sufficient evidence exists to sustain a claim for a new pharmaceutical to be cost-effective.     

Changes in EEG order in neuroleptically treated normal volunteers during a voluntary movement task

Summary 15 normal volunteers were treated over three weeks with haloperidol (HAL) and in the third week additionally with biperidene (BIP). The order of the EEG spectra at different topographical locations and in different frequency bands during a movement task was analyzed using uncertainty analysis (UA), a multivariate analysis technique based on informationtheoretical methods. Different patterns of drug-induced changes were found. HAL decreases the theta and alpha band order at the fronto-central lateral areas but increases it at the fronto-central midline in the theta band and at the parietal areas in the alpha band. With the exception of the fronto-central midline locations, BIP more or less counterbalances the effect of HAL. Volunteers felt unwell and had motor disturbances during HAL and felt well again during HAL + BIP. Reaction time values were increased during HAL and normalized during HAL + BIP.     

时滞系统鲁棒稳定性的新判据

基于Ｌｙａｐｎｕｏｖ泛函方法，研究了满足匹配条件的不确定性时滞系统的鲁棒稳定性及具有稳定度β〉０鲁棒稳定性，给出了已有结果不能推出的新判据。这些新判据对已有结果难以使用的情况下也可有是有效的，或有时减少了已有结果的保守性。     

Neurosis of acquired helplessness and role of hypoxia in the formation of this disorder in rats

Acquisition of instrumental defense response with pain reinforcement uncertainty (25% reinforcement) induced the development of acquired helplessness in 50% rats. Acquired helplessness is characterized by the absence of responses to conditioned (light) and unconditioned stimuli (pain), minor response of plasma corticosterone to learning, gas markers of circulatory cerebral hypoxia (DA/V pO₂ carotid artery/jugular vein), low sensitivity to severe hypobaric conditions, and high resistance of Purkinje cells in the cerebellum. Piracetam improved learning and prevented the development of acquired helplessness. Local changes in cerebral blood flow and energy deficit in neurons responsible for emotional stress during acquired helplessness impair adaptive capacity, but reduce energy consumption and protect neuronal structures.     

The Orienting Response as Novelty and Significance Detector: Reply to O''Gorman

O'Goiman's (1979) criticisms of the orienting response (OR) significance hypothesis are not well-founded. The hypothesis is not based solely on electrodermal data—studies reporting significance effects for heart rate and pupillary OR are cited. The hypothesis does not discard novelty but suggests that an interaction between uncertainty and significance triggers OR. Differential reactivity across OR components reflects stimulus- and individual-response factors, and does not require separate “significance registers.” Since the hypothesis specifically maintains that appraisals of stimulus significance affect the OR, not the mere fact of cognitive appraisal per se, no general “cognitive appraisal effect” was ever expected. O'Gorman confuses the difficulty of estimating the subject's spontaneous judgments of significance with the relative ease of manipulating significance in the laboratory. He considers classic OR theory more “objective” only because he fails to look closely enough at the complex judgmental processes involved in stimulus intake, model building, and matching functions. O'Gorman's contentions of different initial- and test-ORs, and of a simple additive relationship between significance and OR, lack supportive data and are challenged by available evidence. Literature is cited suggesting that: a) scanning is continuously biased toward the detection of significant stimuli; b) detection of a sgnificant stimulus feature triggers increased information scanning, increasing the possibility that previously unrecognized uncertainty will be detected, and c) lowers the criterion level of the OR “threshold,” increasing the likelihood of OR if uncertainty is detected. Evidence is cited suggesting that the significance-OR, and perhaps attention in general, is mediated by neocortical-limbic interaction, the limbic' “motivational” evaluator of stimulus input steering and switching neocortical “intellectual” analyzers of stimulus pattern.     

Reproductive planning after genetic counselling: a perspective from the last decade

Studies from the last decade on factors influencing reproductive planning after genetic counselling were reviewed. Increased possibilities of DNA-analysis and prenatal diagnosis might have brought about a shift in the paramountcy of factors influencing reproductive planning after genetic counselling. In contrast to the literature in the seventies, the magnitude of the genetic risk was no longer found to be one of the decisive factors in postcounselling reproductive planning. Instead, the interpretation of the risk as high or low and the desire to have children appeared to be paramount. The impact of new developments in DNA-analysis in prenatal diagnosis and presymptomatic testing will be an important subject for future studies on factors influencing reproductive planning.