Estimated research and development costs of rotavirus vaccines

Diseases like rotavirus afflict both upper- and lower-income countries, but most serious illnesses and deaths occur among the latter. It is a vital public health issue that vaccines for these types of global diseases can recover research and development (R&D) costs from high-priced markets quickly so that manufacturers can offer affordable prices to lower-income nations. Cost recovery depends on how high R&D costs are, and this study attempts to replace high, unverified estimates with lower, more verifiable estimates for two new vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline or GSK), based on detailed searches of public information and follow-up interviews with senior informants. We also offer a new perspective on “cost of capital” as a claim for recovery from public bodies. Our estimates suggest that companies can recover all fixed costs quickly from affluent markets and thus can offer these vaccines to lower-income countries at prices they can afford. Better vaccines are a shared project between companies and public health agencies; greater transparency and consistency in reporting of R&D costs is needed so that fair prices can be established.     

Simultaneous versus sequential optimal design for pharmacokinetic-pharmacodynamic models with FO and FOCE considerations

We consider nested multiple response models which are used extensively in the area of pharmacometrics. Given the conditional nature of such models, differences in predicted responses are a consequence of different assumptions about how the models interact. As such, sequential versus simultaneous and First Order (FO) versus First Order Conditional Estimation (FOCE) techniques have been explored in the literature where it was found that the sequential and FO approaches can produce biased results. It is therefore of interest to determine any design consequences between the various methods and approximations. As optimal design for nonlinear mixed effects models is dependent upon initial parameter estimates and an approximation to the expected Fisher information matrix, it is necessary to incorporate any influence of nonlinearity (or parameter-effects curvature) into our exploration. Hence, sequential versus simultaneous design with FO and FOCE considerations are compared under low, typical and high degrees of nonlinearity. Additionally, predicted standard errors of parameters are also compared to empirical estimates formed via a simulation/estimation study in NONMEM. Initially, design theory for nested multiple response models is developed and approaches mentioned above are investigated by considering a pharmacokinetic–pharmacodynamic model found in the literature. We consider design for situations where all responses are continuous and extend this methodology to the case where a response may be a discrete random variable. In particular, for a binary response pharmacodynamic model, it is conjectured that such responses will offer little information about all parameters and hence a sequential optimization, in the form of product design optimality, may yield near optimal designs.     

Perugia urodynamic method of analysis (PUMA): a new advanced method of urodynamic analysis applied clinically and compared with other advanced methods.

AIMS: The aim of this study is to compare PUMA curves with different pathologic conditions causing bladder dysfunction in 158 men and 83 women. METHODS: PUMA results in terms of bladder outlet obstruction and detrusor contractility were compared in 92 men with benign prostatic hypertrophy (BPH) and p(ves) congruent with p(det) (i.e., p(abd) congruent with 0) with the results of the urodynamics operator's opinion, the provisional International Continence Society method, Abrams and Griffith's diagram, urethral resistence factor (URA), Sch?fer's diagram, and Watt factor. PUMA curves correlated reliably with different pathologic conditions such as obstructive BPH, orthotopic bladder, cystocele, the neurological bladder, and bladder diverticulum. Statistical analysis indicated excellent agreement between PUMA and URA; agreement with other methods was good in cases of obstruction and nonobstruction. In doubtful cases, as diagnosed by standard methods, PUMA agreed only with the Abrams and Griffith's diagram. PUMA and Wmax were in good agreement on detrusor con traction force. Agreement between PUMA and Sch?fer's diagram was excellent for patients with detrusor hypercontractility and good for patients with detrusor hypocontractility and normocontractility. PUMA is the only method applicable to women. It is easy to perform. When integrated with other diagnostic tests, it provides realistic data for diagnosis, medical or surgical therapy, and outcome.     

病理技术质量控制的探讨

病理技术是病理学诊断不可分割的一部分,正确的染色结果是病理诊断的重要依据之一.病理技术的规范与否,制片质量的好坏很大程度上影响病理医生作出正确的病理诊断.     

Fat and water separation in balanced steady-state free precession using the Dixon method.

In this work the feasibility of separating fat and water signals using the balanced steady-state free precession (SSFP) technique is demonstrated. The technique is based on the observation (Scheffler and Hennig, Magnetic Resonance in Medicine 2003;49:395-397) that at the nominal values of TE = TR/2 in SSFP imaging, phase coherence can be achieved at essentially only two orientations (0 degrees and 180 degrees ) relative to the RF pulses in the rotating frame, under the assumption of TR < T2, and independently of the SSFP angle. This property allows in-phase and out-of-phase SSFP images to be obtained by proper choices of the center frequency offset, and thus allows the Dixon subtraction method to be utilized for effective fat-water separation. The TR and frequency offset for optimal fat-water separation are derived from theories. Experimental results from healthy subjects, using a 3.0 Tesla system, show that nearly complete fat suppression can be accomplished.     

中风毒邪论与神经保护治疗的研究

中风毒邪论是一种与传统中医中风病理有所不同的理论 ,在中风毒邪论指导下形成解毒通络方是较为理想的神经保护剂 ,可解决目前神经保护治疗的主要障碍 ,有望成为提高中医治疗中风急性期疗效的关键     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

大学新生心理健康状况的调查研究

目的　了解大学新生的心理健康状况 ,探讨提高其心理健康水平的措施。方法　采用大学生人格问卷(UPI) ,以班级为单位 ,在新生正式上课两周以后进行测试。结果　学生一类筛选率 9.2 4 %。UPI关键题选择中 ,以常常失眠占的比例最高 ,想轻生的比例最低 (P <0 .0 5 )。UPI附加题选择中 ,以自身健康方面有问题及有健康或心理卫生方面想要咨询的问题较多 (P <0 .0 5 )。选择“想轻生”的男生的比例略高于女生 ,选择“常常失眠”的女生的比例却明显高于男生 (P <0 .0 5 ) ;选择“常常失眠”、“对任何事情都不感兴趣”和“感觉自己的过去及家庭不幸”的农村学生的比例都高于城市学生 (P <0 .0 5 )。选择“想轻生”和“对任何事情都不感兴趣”的独生子女的比例明显高于非独生子女 ,而选择“自己的过去和家庭是不行的”和“常常失眠”的非独生子女的比例又明显高于独生子女 (P <0 .0 5 )。结论　单亲家庭学生、残疾学生、家庭经济困难学生、独生子女学生是心理问题高危人群     

蓬辣滩水电站泄洪闸门及其监控系统改造

介绍了蓬辣滩水电站泄洪闸门的状况、计算机监控系统改造方案的结构和特点及闸门定轮轴承的改造情况,通过上述改造,提高了泄洪设备运行的自动化水平,同时也为其他闸门工程提供参考。     

随机系统的最小熵控制

本文放弃传统的MSE准则,从信息论观点出发,发展了随机系统的一种最小熵(ME)控制方法,并从ME控制的等价性、控制限度、存在性、唯一性及必要条件等方面,研究了ME控制的合理性和实用性。ME方法是一种全局分析法,它不仅包含了MSE和MAP准则,且由于全文在整个推导中并未假定高斯性、线性和非时变等,因而原则上适用于诸如非高斯、非线性、时变等传统方法难以处理的复杂系统;不仅适用于工程系统,将其推广到决策、社会、经济等领域会更为自然和切合实际。