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.     

睾丸旁促结缔组织增生性小圆细胞肿瘤1例报告及文献复习

目的:探讨睾丸旁促结缔组织增生性小圆细胞肿瘤的临床、病理特征、诊断及治疗。方法:回顾分析1例睾丸旁促结缔组织增生性小圆细胞肿瘤的诊治及随访资料,并复习相关文献。患者,男,27岁,因阴囊内无痛性肿块4个月就诊。体检于左侧阴囊内可扪及囊性肿块,同侧睾丸不能扪及。行左侧睾丸根治性切除术,术后辅以化疗。结果:术中见左侧睾丸旁多发结节状隆起肿块,质偏硬;术后病理检查肿瘤细胞呈巢状或梁索状结构并埋没在增生的纤维结缔组织中;免疫组化显示瘤细胞具有上皮源性、间质性和神经源性等多向分化的特点。术后已随访3年无瘤生存,预后良好。结论:促结缔组织增生性小圆细胞肿瘤有特异的临床病理特征,好发于年轻男性,手术切除肿瘤联合化疗是治疗的主要方法,睾丸旁促结缔组织增生性小圆细胞肿瘤比腹腔型预后相对好。     

金地鼠颊囊癌前病变的细胞增殖动力学研究

目的研究口腔上皮组织癌和癌前病变的细胞动力学变化特征。方法采用Ｓａｌｅｙ的ＤＭＢＡ涂布诱导法，建立金地鼠颊囊癌前病变模型，并用溴脱氧尿苷流式细胞动力学检测方法，对３０只叙利亚种金地鼠进行分组对照研究。结果涂药组光镜下的细胞病变程度随涂药时间延长而逐渐加重，而空白对照组无变化；ＦＣＭ检测显示涂药组与对照组在Ｓ期阳性细胞检出率存在显著差异。即使在光镜下表现为轻度不典型增生时，ＦＣＭ检测结果也有显著差别。结论金地鼠颊囊癌前病变具有细胞异常增殖的细胞动力学特征     

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.     

聋幼儿情绪状态对认知发展的影响

为促进聋幼儿各方面的正常发展，使其早日回归主流社会，我们对聋幼儿进行了认知和情绪表现的研究。通过问卷调查、观察和实验研究得知，聋幼儿的认知发展和良好情绪的培养是分不开的，认知内容适中有利于聋幼儿良好情绪的培养，而良好积极的情绪又可促进聋幼儿认知的发展。对此，我们实验并总结了培养聋幼儿积极情绪和促进认知发展的方法。     

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.     

Improved intracranial lesion characterization by tissue segmentation based on a 3D feature map

Our aim was to develop an accurate multispectral tissue segmentation method based on 3D feature maps. We utilized proton density (PD), T₂-weighted fast spin-echo (FSE), and T₁-weighted spin-echo images as inputs for segmentation. Phantom constructs, cadaver brains, an animal brain tumor model and both normal human brains and those from patients with either multiple sclerosis (MS) or primary brain tumors were analyzed with this technique. Initially, misregistration, RF inhomogeneity and image noise problems were addressed. Next, a qualified observer identified samples representing the tissues of interest. Finally, k-nearest neighbor algorithm (k-NN) was utilized to create a stack of color-coded segmented images. The inclusion of T₁ based images, as a third input, produced significant improvement in the delineation of tissues. In MS, our 3D technique was found to be far superior to that based on any combination of 2D feature maps (P < 0.001). We identified at least two distinctly different classes of lesions within the same MS plaque, representing different stages of the disease process. Further, we obtained the regional distribution of MS lesion burden and followed its changes over time. Neuropsychological aberrations were the clinical counterpart of the structural changes detected in segmentation. We could also delineate the margins of benign brain tumors. In malignant tumors, up to four abnormal tissues were identified: 1) a solid tumor core, 2) a cystic component, 3) edema in the white matter, and 4) areas of necrosis and hemorrhage. Subsequent neurosurgical exploration confirmed the distribution of tissues as predicted by this analysis.     

多发性颅骨内血管瘤一例报告并文献复习

目的探讨多发性颅骨内血管瘤的临床特征和预后。方法报告1例多发性颅骨内血管瘤病例,结合相关文献分析该疾病的X线、CT、MRI和DSA等临床特征,探讨治疗效果和预后。结果多发性颅骨内血管瘤临床上极为罕见,大约占所有骨肿瘤的0.2%。X线平片检查见整个颅骨内蜂窝状改变,CT、MRI显示颅骨溶骨性病变或糜烂并向颅内外发展,DSA造影病变无染色,病理显示大小不等的异常血管,骨结构异常以及出血征象。外科治疗效果不佳。结论多发性颅骨血管瘤为颅骨内破坏性病变,涉及整个颅骨的多发性颅骨血管瘤,外科治疗效果不佳。