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Fundamental Requirement (fundamental + requirement)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Combining adenoviral oncolysis with temozolomide improves cell killing of melanoma cells

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2007
Christina Quirin
Abstract Oncolytic Adenoviruses are emerging agents for treatment of cancer by tumor-restricted virus replication, cell lysis and virus spread. Clinical studies with first generation oncolytic adenoviruses have revealed that an increased potency is warranted in order to achieve therapeutic efficacy. One approach towards this end is to combine adenoviral oncolysis with chemotherapy. Here, a fundamental requirement is that chemotherapy does not interfere with adenovirus replication in cancer cells. We have previously developed a melanoma-targeted oncolytic adenovirus, Ad5/3.2xTyr, which features tyrosinase promoter regulated replication and enhanced cell entry into melanoma cells. In this study, we investigated a combination treatment of melanoma cells with Ad5/3.2xTyr and temozolomide (TMZ), which produces the same active metabolite as Dacarbazine/DTIC, the standard chemotherapy for advanced melanoma. We report that TMZ does not inhibit adenovirus replication in melanoma cells. Additive or synergistic cell killing of melanoma cells, dependent on the cell line used, was observed. Enhanced cell binding was not responsible for synergism of adenoviral oncolysis and TMZ treatment. We rather observed that higher numbers of virus genomes are produced in TMZ-treated cells, which also showed a cell cycle arrest in the G2 phase. Our results have important implications for the clinical implementation of adenoviral oncolysis for treatment of malignant melanoma. It suggests that such studies are feasible in the presence of TMZ or DTIC chemotherapy and recommends the investigation of a viro-chemo combination therapy. © 2007 Wiley-Liss, Inc. [source]

Capitation funding in the public sector

JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 2 2001
Peter C. Smith
A fundamental requirement of government at all levels,national and local,is to distribute the limited funds that it wishes to spend on particular public services between geographical areas or institutions, which are effectively competitors for such funds. Increasing use is now being made of capitation methods for such purposes, in which a standard estimate of expected expenditure is attached to a citizen with given characteristics. Statistical methods are playing an important role in determining such capitations, but they give rise to profound methodological problems. This paper examines the rationale for capitation and discusses the associated methodological issues. It illustrates the issues raised with two examples taken from the UK public sector: in personal social services and hospital care. Severe limitations of the data mean that small area data are used as the unit of observation, giving rise to considerable complexity in the model to be estimated. As a result, a range of methodologies including two-stage least squares and multilevel modelling methods are deployed. The paper concludes with a suggestion for an approach which would represent an improvement on current capitation methods, but which would require data on individuals rather than on small areas. [source]

Know your client's business

PERFORMANCE IMPROVEMENT, Issue 10 2009
Geary Rummler CPT
A fundamental requirement of effective performance consulting is that the performance consultant know his or her client's business. Easier said than done? Not necessarily. With a good framework and the right tools, you can efficiently and effectively "profile" a client's organization. This article is reprinted from Performance Improvement 43(3), pages 21,27 [10.1002/pfi.4140430306]. [source]

Inductive reasoning in medicine: lessons from Carl Gustav Hempel's ,inductive-statistical' model

JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 2 2003
Afschin Gandjour MD PhD
Abstract The purpose of this paper is to discuss both the fundamental requirements of sound scientific explanations and predictions and common fallacies that occur in explaining and predicting medical problems. To this end, the paper presents Carl Gustav Hempel's ,covering-law' model (1948 and 1962) and reviews some of the criticism of the model. The strength of Hempel's model is that it shows that inductive arguments, when applied with the requirement of maximal specificity, can serve as explanations as well as predictions. The major weakness of the ,covering-law' model, its inability to portray causal relatedness, has been addressed by philosophers such as Wesley Salmon. While few philosophers today agree with the ,covering-law' model in its original formulation, there is widespread consensus that the law has made a central contribution to describing the fundamental requirements of sound scientific explanations. Applying this model and its revisions in the medical context may help uncover potentially undetected fallacies in reasoning when explaining and predicting medical problems. [source]