术前MELD评分和术后CD14^＋／HLA—DR测定在肝移植术后感染预测中的意义

目的：探讨原位肝移植术前终末期肝病模型（MELD）评分和术后CD14^＋单核细胞人自细胞DR抗原（CD14^＋／HLA-DR）表达率的变化在术后感染预测中的临床意义。方法：按美国胸科医师协会／危重病医学会的定义,将83例肝移植术后患者分为非感染组、感染组、感染性休克组,分别测定3组患者术前血胆红素、凝血酶原时间国际标准化比值（INR）、血肌酐,计算MELD评分,并动态检测术后CD14^＋／HLA—DR表达率,分析其在感染监测中的价值。结果：感染组和感染休克组术前血胆红素、INR、血肌酐和MELD评分均显著高于非感染组（P〈0．01）,CD14^＋／HLA-DR表达率均显著低于非感染组（P〈0．01）。感染组和感染休克组之间比较,上述指标均无显著性差异（P〉0．05）。感染发生后,感染组、感染性休克组的CD14^＋／HLA—DR值显著下降,与非感染组比较,差异具有显著性（P〈0．05或P〈0．01）;感染最重时两组的CD14^＋／HLA—DR值均降到最低值,与非感染组比较,差异具有显著性（P〈0．01）。结论：术前MELD评分和术后CD14^＋／HLA—DR表达率是监测肝移植术后感染发生及判断预后的良好指标。对术前高MELD评分或术后可疑感染的患者,动态监测CD14^＋／HLA-DR表达率对病情判断和治疗调整均有较好的指导意义。     

Bioactive nutrients - Time for tolerable upper intake levels to address safety

There is increasing interest by consumers, researchers, and regulators into the roles that certain bioactive compounds, derived from plants and other natural sources, can play in health maintenance and promotion, and even prolonging a productive quality of life. Research has rapidly emerged suggesting that a wide range of compounds and mixtures in and from plants (such as fruits and vegetables, tea and cocoa) and animals (such as fish and probiotics) may exert substantial health benefits. There is interest in exploring the possibility of establishing recommended intakes or dietary guidance for certain bioactive substances to help educate consumers. A key aspect of establishing dietary guidance is the assessment of safety/toxicity of these substances. Toxicologists need to be involved in both the development of the safety framework and in the evaluation of the science to establish maximum intake/upper limits.     

A New Approach to Study the Physical Stability of Monoclonal Antibody Formulations—Dilution From a Denaturant

The early-stage assessment of the physical stability of new monoclonal antibodies in different formulations is often based on high-throughput techniques that suffer from various drawbacks. Accordingly, new approaches that facilitate the protein formulation development can be of high value to the industry. In this study, a dynamic light scattering plate reader is used to measure the aggregation (by means of the increase in the hydrodynamic radius [R_h]) of monoclonal antibody samples that were subject to incubation and subsequent dilution from different concentrations of a denaturing agent, that is, guanidine hydrochloride. The increase in the R_h of the protein samples is dependent not only on the denaturant concentration used but also on the buffer in which the incubation/dilution was performed. We also compare the aggregation after dilution from a denaturant with other high-throughput stability-indicating methods and find good agreement between the techniques. The proposed approach to probe the physical stability of monoclonal antibodies in different formulation conditions offers a unique combination of features—it is isothermal, probes both the resistance to denaturant-induced unfolding and the colloidal protein stability, it is entirely label-free, does not rely on complex data evaluation, and requires very short instrument measurement time on standard equipment.     

From a Social Issue to Policy

Summary

This paper outlines a 22 year campaign to introduce openness into the arena of donor conception in the UK. It identifies key aspects of the development of an advocacy based approach to such work and argues that social work values and principles can prove key to identifying structural inequalities which are not necessarily based in socio-economic disadvantage. Donor conceived people may find themselves in families which enjoy material privilege but whose exposure to a legislative framework and dominant professional cultures within the treatment centres encourages secrecy around genetic origins. Social workers' experience of adoption and family work leads them to recognise the danger of such secrets within families. Turning such social issues into policy changes requires vision, strategic long term advocacy and partnership with those directly affected.     

Systematic Searching and Selection of Health State Utility Values from the Literature

Health state utility values (HSUVs) are important parameters in decision models in health technology assessment submissions. Reimbursement agencies, such as the National Institute for Health and Clinical Excellence, recognize that such values are obtainable from the published literature. However, to use published values in health technology assessment submissions, it should be demonstrated that HSUVs have been identified and selected systematically to avoid using biased HSUVs resulting in cost-effectiveness analyses. This article presents guidance on how to conduct a systematic literature review to identify and select HSUVs from the published literature based on the authors’ experience. A case study is used to demonstrate some of the features of a systematic HSUV review. Methods are discussed in relation to identifying and selecting the evidence, performing quality and relevance assessment, and undertaking data extraction. It has been developed from a Technical Support Document produced for the National Institute for Health and Clinical Excellence by the Decision Support Unit at the School of Health and Related Research, University of Sheffield.     

Threshold and non-threshold chemical carcinogens: A survey of the present regulatory landscape

For the proper regulation of a carcinogenic material it is necessary to fully understand its mode of action, and in particular whether it demonstrates a threshold of effect. This paper explores our present understanding of carcinogenicity and the mechanisms underlying the carcinogenic response. The concepts of genotoxic and non-genotoxic and threshold and non-threshold carcinogens are fully described. We provide summary tables of the types of cancer considered to be associated with exposure to a number of carcinogens and the available evidence relating to whether carcinogenicity occurs through a threshold or non-threshold mechanism. In light of these observations we consider how different regulatory bodies approach the question of chemical carcinogenesis, looking in particular at the definitions and methodologies used to derive Occupational Exposure Levels (OELs) for carcinogens. We conclude that unless proper differentiation is made between threshold and non-threshold carcinogens, inappropriate risk management measures may be put in place - and lead also to difficulties in translating carcinogenicity research findings into appropriate health policies. We recommend that clear differentiation between threshold and non-threshold carcinogens should be made by all expert groups and regulatory bodies dealing with carcinogen classification and risk assessment.     

Gender and distribution of educational values among the staff in kindergartens

The article reports and reflects on a study of kindergarten staff member’s gendered attitudes. The empirical part consists of answers to a questionnaire from some 700 staff members of all 80 kindergartens in two Danish municipalities. The theoretical approach is informed by the framework of Pierre Bourdieu and the Mary Douglas’ Grid Group Cultural Theory. The common strong point of view is that men are an exceptional educational resource in kindergartens and for the sake of gender equality on the labour market, one is to promote a higher proportion of male workers in kindergartens and in several other sectors, where women commonly are in the majority. We examine these premises in respect of Denmark and Norway and then confront the notion of kindergartens to be gender-segregated in pedagogical and professional terms. In conclusion, it is proposed a renewal of the starting point of the educational gender research.     

Value-based design for the elderly: An application in the field of mobility aids

In the aging society, the need for the elderly to remain mobile and independent is higher than ever. However, many aids supporting mobility often fail to target real needs and lack acceptance. The aim of this study is to demonstrate how value-based design can contribute to the design of mobility aids that address real needs and thus, lead to high acceptance. We elicited values, facilitators, and barriers of mobility of older adults via ten in-depth interviews. Next, we held co-creation sessions, resulting in several designs of innovative mobility aids, which were evaluated for acceptance via nine in-depth interviews. The interviews resulted in a myriad of key values, such as “independence from family” and “doing their own groceries.” Design sessions resulted in three designs for a wheeled walker. Their acceptance was rather low. Current mobility device users were more eager to accept the designs than non-users. The value-based approach offers designers a close look into the lives of the elderly, thereby opening up a wide range of innovation possibilities that better fit their actual needs. Product service systems seem to be a promising focus for targeting human needs in mobility device design.