新颖性推定方式及举证责任分配原则的探讨 ——医药生物领域专利新颖性评判热点问题分析

结合具体案例分析医药生物领域专利新颖性评判的热点问题之一 —— 新颖性推定的审查方式的主要类型和基本思路,并探讨相 应的举证责任分配原则。在此基础上提出,新颖性推定方式作为一种事实推定,实际上体现了高度盖然性的评判标准,应当在推定基础、 推定主体、推定过程、考量因素以及推定结论把握等方面加以规范,同时合理分配举证责任,避免主观性的干扰。     

举证责任倒置对医生影响的调查分析

目的:了解举证责任倒置实施以来,该政策对医生的影响及实施中存在的问题。方法:应用自制问卷,对青岛、西安两地9家三甲综合性医院共256名医生进行问卷调查,运用spss16.0进行统计分析。结果:举证责任倒置一方面给医生的医疗行为带来了积极影响,另一方面也给医生带来了较大的心理压力,尤其是发生过纠纷、被起诉的医生,对其以后的行为产生了消极影响。结论:医院除应加强对医生医疗技术、法律知识培训外,还应成立专门的机构来缓解医生的心理压力,解除其心理问题。     

矩阵的加号逆理论在参数估计中的应用

本文从矩阵的加号逆理论出发,根据求矛盾线性方程组最佳逼近解的方法,建立起一种新的参数估计方法,同时给出了显著性检验方法,这种方法更简单更精确．     

Technocratic precautionary principle: Korean risk governance of genetically modified organisms

Regulations for genetically modified organisms (GMOs) in Korea fluctuate between technocracy and the precautionary principle (PP). Technocratic PP denotes the coexistence, or coproduction, of technocracy with PP – a complex ensemble of technocratic, precautionary policies, and hybrids of the two. This paper analyzes four types of PP-based policies linked to Korean GMO regulations: foresight and monitoring of risk; reverse burden of proof; public participation; and the public's right to know. Korean GMO regulations are consistent with the Cartagena Protocol on Biosafety, a type of PP, but lack long-term risk assessment as well as public participation. Technocracy is embedded both in advance informed agreements as a reverse burden of proof and in proof-based GMO labeling as a right-to-know policy. Technocratic PP results in inconsistencies between PP and technocratic epistemology and the gap between PP-based institutions and technocratic practices. Technocratic PP is therefore a typical phenomenon that occurs in the “glocalization” of risk regulation.     

Challenges to Consensus in Preparing the Supplement to the Surgeon General's Report on Mental Health

Preparing the Supplement to the Surgeon General's Report on Mental Health proved controversial because the assignment, by its nature, challenged several forms of consensus that typically remain unexamined. They included disciplinary assumptions about theory and methods, sociopolitical assumptions about the relevance of history to contemporary circumstances of ethnic minority groups in America, the rigor and usefulness of cultural formulation, and whether the burden of proof rested with those who took for granted that sociocultural differences exist in theories of behavior, or those who took for granted the existence of universals. Preparation of the Supplement illustrates the uncertainty and tension that arise when unexamined boundaries and perspectives lose their capacity to serve as guides to scientific judgment and discourse.     

A kinematic theory of rapid human movement. Part IV: a formal mathematical proof and new insights

A few years ago a kinematic theory was proposed to study and analyze rapid human movements. The theory relies on a model of a synergy made up of two neuromuscular systems, one agonist and the other antagonist to the movement. Representing these systems with lognormal impulse responses, it is predicted that the velocity profile of a fast movement will be described by a delta-lognormal equation. So far, many studies have been conducted to test and empirically validate the theory. This paper presents an extended mathematical proof of the model. The proof is based on the Central Limit Theorem under the assumption that a law of proportionate effect governs the cumulative time delays of a sequence of dependent subprocesses constituting a neuromuscular system. Furthermore, a detailed interpretation of the parameters of the delta-lognormal equation, in terms of movement time and amplitude, response time and time delays, is discussed, providing new insights into the properties of the model with respect to neuromuscular system activity and movement generation.     

Passive Membrane Potentials: A Generalization of the Theory of Electrotonus

The theory of electrotonus, which has been well developed for small cylinders, is extended: the fundamental potential equations for a membrane of arbitrary shape are derived, and solutions are found for cylindrical and spherical geometries. If two purely conductive media are separated by a resistance-capacitance membrane, then Laplace's equation describes the potential in either medium, and two boundary equations relate the transmembrane potential to applied currents and to currents flowing into the membrane from each medium. The core conductor model, on which most previous work on cylindrical electrotonus has been based, gives rise to a one dimensional diffusion equation, the cable equation, for the transmembrane potential in a small cylinder. Under the assumptions of the core conductor model the more general equations developed here are shown to reduce to the cable equation. The two theories agree well in predicting the transmembrane potential in a small cylinder owing to an applied current step, and the extracellular potential for this cylinder is estimated numerically from the general theory. A detailed proof is given for the isopotentiality of a spherical soma membrane.     

The δ-function counterion condensate around a line charge derived from the Fuoss,Katchalsky, and Lifson polyelectrolyte theory

It has recently been proven that the counterion condensate around an isolated line charge in an electrolyte, as characterized by nonlinear Poisson-Boltzmann theory, is an encapsulating δ-function. Here the identical result is shown to hold in the framework of the polyelectrolyte theory of Fuoss, Katchalsky, and Lifson. The proof fully exploits analytic solutions to the differential equation which are not available for the nonlinear, cylindrical Poisson-Boltzmann equation.     

The precautionary approach in fisheries management: the devil is in the details

The William and Lenore Mote International Symposium 'Targets, thresholds and the burden of proof in fishery management' was held at the Mote Marine Laboratory, Sarasota, FL, USA, from 30 October to 2 November 2000.     

Suffering at the end of life

In the end‐of‐life context, alleviation of the suffering of a distressed patient is usually seen as a, if not the, central goal for the medical personnel treating her. Yet it has also been argued that suffering should be seen as a part of good dying. More precisely, it has been maintained that alleviating a dying patient’s suffering can make her unable to take care of practical end‐of‐life matters, deprive her of an opportunity to ask questions about and find meaning in and for her existence, and detach her from reality. In this article, I argue that the aims referred to either do not support suffering or are better served by alleviating it. When the aims would be equally well served by enduring suffering and relieving it, the latter appears to be the preferable option, given that the distress a patient experiences has no positive intrinsic value. Indeed, as the suffering can be very distressing, it may not be worth bearing even if that was the best way to achieve the aims: the distress can sometimes be bad enough to outbalance the worth of achieving the goals. Having considered an objection to the effect that a patient can have a self‐regarding moral duty to endure the distress she faces at the end of life, I conclude that the burden of proof is on the side of those who maintain that the suffering experienced at the end of life ought to be endured as a part of dying well.     

Increased permeability of gut mucosa in rats infected with Nippostrongylus brasiliensis.

The permeability of the gut mucosa to macromolecules has been examined in 4 different strains of rats infected with Nippostrongylus brasiliensis (N. brasiliensis). There is a marked increase in mucosal permeability during the infection. In addition, a considerable strain difference is observed in both worm burden kinetics and the kinetics of intestinal permeability. The dose-response and drug treatment experiments in outbred Wistar rats suggest that increased mueosal permeability is a function of the worm burden. However, the increased permeability is related neither to the rapid phase of worm expulsion nor to the rise in intestinal mast cell numbers.     

General continuum analysis of transport through pores. I. Proof of Onsager's reciprocity postulate for uniform pore.

The nonelectrolyte (Js) and volume (Jv) flux across a membrane is usually described in terms of two equations derived from the theory of irreversible thermodynamics: (see article) where delta c and delta P are the concentration and pressure difference; omega and Lp are the diffuse and hydraulic permeability; and sigma s and sigma v are the reflection coefficients. If Onsager's reciprocity postulate is assumed, it can be shown that signa s and sigma v are equal. This is an important assumption because it allows one to apply the continuum theory relationship between sigma s and the pore radius to experimental measurements of sigma v. In this paper, general continuum expressions for both the Jv (a new result) and Js equation will be derived and the equality of sigma s and sigma v proved. The proof uses only general hydrodynamic results and does not require explicit solutions for the drag coefficients or, for example, the assumption that the solute is in the center of the pore. The proof applys to arbitrarily shaped solutes and any pore whose shape is independent of axial position (uniform). In addition, new expressions for the functional dependence of omega and sigma on the pore radius are derived (including the effect of the particle lying off the pore axis). These expressions differ slightly from earlier results and are probably more accurate.     

Relationships and burden: An empirical‐ethical investigation of lived experience in home nursing arrangements

Quantitative research has called attention to the burden associated with informal caregiving in home nursing arrangements. Less emphasis has been placed, however, on care recipients’ subjective feelings of being a burden and on caregivers’ willingness to carry the burden in home care. This article uses empirical material from semi‐structured interviews conducted with older people affected by multiple chronic conditions and in need of long‐term home care, and with informal and professional caregivers, as two groups of relevant others. The high burden of home‐care arrangements is unanimously stressed by all three groups involved in the triangle of care. An empirical‐ethical investigation of what can be legitimately expected from family members and informal caregivers, informed by Frith's symbiotic empirical ethics approach, was undertaken. Key tenets from the special goods theory and nursing professionalism are used as analytical tools. The study concludes that the current situation may hinder professional development and can reinforce feelings of being a burden to relevant others.     

Gene regulatory networks reused to build novel traits: co-option of an eye-related gene regulatory network in eye-like organs and red wing patches on insect wings is suggested by optix expression

Co-option of the eye developmental gene regulatory network may have led to the appearance of novel functional traits on the wings of flies and butterflies. The first trait is a recently described wing organ in a species of extinct midge resembling the outer layers of the midge's own compound eye. The second trait is red pigment patches on Heliconius butterfly wings connected to the expression of an eye selector gene, optix. These examples, as well as others, are discussed regarding the type of empirical evidence and burden of proof that have been used to infer gene network co-option underlying the origin of novel traits. A conceptual framework describing increasing confidence in inference of network co-option is proposed. Novel research directions to facilitate inference of network co-option are also highlighted, especially in cases where the pre-existent and novel traits do not resemble each other.     

Motion sickness and otolith asymmetry.

There is a highly scattered inter-individual susceptibility in man to motion sickness. It is discussed whether different masses of otoconias between right and left sides are responsible for a high susceptibility. In order to proof this theory, we measured the otoliths of fish (salmons, trouts, Xiphophorus Helleri; Sumatra barbes) and found big differences in the utricular stones up to 140%. The mass differences of the saccular stones were much smaller. In fish, showing abnormal swimming behavior during off-vertical axis rotation we found big mass differences compared to that of normal swimmers. This difference was only seen in the utricular and not in the saccular stones. We therefore assume, that a big mass difference is one of the factors to trigger motion sickness especially for the high susceptibility to it. The macula utriculi seem to be much more integrated in the vestibular sense than the macula sacculi.     

Ancestral maximum likelihood of evolutionary trees is hard

Maximum likelihood (ML) (Neyman, 1971) is an increasingly popular optimality criterion for selecting evolutionary trees. Finding optimal ML trees appears to be a very hard computational task--in particular, algorithms and heuristics for ML take longer to run than algorithms and heuristics for maximum parsimony (MP). However, while MP has been known to be NP-complete for over 20 years, no such hardness result has been obtained so far for ML. In this work we make a first step in this direction by proving that ancestral maximum likelihood (AML) is NP-complete. The input to this problem is a set of aligned sequences of equal length and the goal is to find a tree and an assignment of ancestral sequences for all of that tree's internal vertices such that the likelihood of generating both the ancestral and contemporary sequences is maximized. Our NP-hardness proof follows that for MP given in (Day, Johnson and Sankoff, 1986) in that we use the same reduction from Vertex Cover; however, the proof of correctness for this reduction relative to AML is different and substantially more involved.     

Some pitfalls in curve-fitting and how to avoid them: A case in point

When curve-fitting is used to support a complex nonlinear model containing several exponential terms, some of which have closely-spaced time constants, a particular burden of proof must be assumed. Most important, the uniqueness of the solution must be explored and discussed. Statistical tests for the degree of error and independence of the parameters should be provided, as well as information relating to the steps actually used in the fitting procedures. As an example of the need for the procedures we recommend in this communication, we have chosen an important case in point that has been published recently, and which deals with the kinetics of electron transfer from fully-reduced cytochrome oxidase to O₂, analyzed by the method of SVD-based least squares. The problems we deal with in this case are applicable to a wide variety of other cases that involve curve-fitting to mathematical models.     

Validation of statistical models for estimating hospitalization associated with influenza and other respiratory viruses

Background

Reliable estimates of disease burden associated with respiratory viruses are keys to deployment of preventive strategies such as vaccination and resource allocation. Such estimates are particularly needed in tropical and subtropical regions where some methods commonly used in temperate regions are not applicable. While a number of alternative approaches to assess the influenza associated disease burden have been recently reported, none of these models have been validated with virologically confirmed data. Even fewer methods have been developed for other common respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza and adenovirus.

Methods and Findings

We had recently conducted a prospective population-based study of virologically confirmed hospitalization for acute respiratory illnesses in persons <18 years residing in Hong Kong Island. Here we used this dataset to validate two commonly used models for estimation of influenza disease burden, namely the rate difference model and Poisson regression model, and also explored the applicability of these models to estimate the disease burden of other respiratory viruses. The Poisson regression models with different link functions all yielded estimates well correlated with the virologically confirmed influenza associated hospitalization, especially in children older than two years. The disease burden estimates for RSV, parainfluenza and adenovirus were less reliable with wide confidence intervals. The rate difference model was not applicable to RSV, parainfluenza and adenovirus and grossly underestimated the true burden of influenza associated hospitalization.

Conclusion

The Poisson regression model generally produced satisfactory estimates in calculating the disease burden of respiratory viruses in a subtropical region such as Hong Kong.     

解剖学工作者的职业病在工作环境中举证责任倒置的探讨

甲醛可引起机体一系列异常反应,针对解剖工作者所处的工作环境,可以通过改善工作环境、使用检测仪器和定期进行体检来预防甲醛对机体的危害,在防治职业病的发生的基础上,认识到职业病在工作环境中的举证责任倒置问题,可以对疾病进行早发现和早治疗,并对职业病的法律维权有所帮助。