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Notizen: Objective To establish reference ranges for the levels of alpha-fetoprotein, albumin, prealbumin (transthyretin) alpha-1-antitrypsin, transferrin, ceruloplasmin and total protein in the plasma of normal human fetuses and newborn babies.Design Prospective study of individual normal cases to fulfil objectives.Setting Pathology laboratories of the University of Edinburgh and the biochemistry laboratories of the University of Keele.Subjects Twenty-two normal fetuses 13 to 22 weeks of gestation and 66 babies born between 24 and 41 weeks gestation.Results Albumin is the predominant plasma protein throughout gestation. The levels of alpha-fetoprotein and prealbumin fell significantly with increasing gestation, whereas the concentrations of the other proteins studied increased. The ratios of individual proteins to total protein demonstrated similar trends.Conclusions This study provides developmental profiles of normal human fetal plasma proteins to serve as possible reference data for abnormal fetuses. Declining levels of prealbumin (transthyretin) were unexpected and suggest a functional role for this protein in early pregnancy.

Notizen: Abstract: Metabolism of [U-13C5]glutamine was studied in primary cultures of cerebral cortical astrocytes in the presence or absence of extracellular glutamate. Perchloric acid extracts of the cells as well as redissolved lyophilized media were subjected to nuclear magnetic resonance and mass spectrometry to identify 13C-labeled metabolites. Label from glutamine was found in glutamate and to a lesser extent in lactate and alanine. In the presence of unlabeled glutamate, label was also observed in aspartate. It could be clearly demonstrated that some [U-13C5]glutamine is metabolized through the tricarboxylic acid cycle, although to a much smaller extent than previously shown for [U-13C5]glutamate. Lactate formation from tricarboxylic acid cycle intermediates has previously been demonstrated. It has, however, not been demonstrated that pyruvate, formed from glutamate or glutamine, may reenter the tricarboxylic acid cycle after conversion to acetyl-CoA. The present work demonstrates that this pathway is active, because [4,5-13C2]glutamate was observed in astrocytes incubated with [U-13C5]glutamine in the additional presence of unlabeled glutamate. Furthermore, using mass spectrometry, mono-labeled alanine, glutamate, and glutamine were detected. This isotopomer could be derived via the action of pyruvate carboxylase using 13CO2 produced within the mitochondria or from labeled intermediates that had stayed in the tricarboxylic acid cycle for more than one turn.

Notizen: AbstractThe paper reviews the work done and conclusions reached on resource allocation to R&D in the public sector in the last twenty years, and examines what changes have been made in the field of R&D assessment. The paper is based mainly on the author's experience with the UK government's Programmes Analysis Unit (PAU) which was set up in the early 1960s.The Unit's main remit was to examine and disseminate techniques by the use of which the benefit to the nation from possible R&D strategies, programmes and projects might be calculated. It was also called in to help review policy and carry out long-range forecasting. In the course of its existence — it was wound up in 1977 — it analysed many new techniques of analysis which have now passed into common use and took part in studies to support decisions at all levels from the macro-economic sector down to the individual project.The author lists the benefits derivable from such analyses — helping to identify objectives, assemble total programmes, evaluate efficiency of technological transfer, carry out technology assessment and so on. But he warns of their limitations.As for the present day, the author is unhappy about the importance given by the UK Government to the market as a test of value in decision-making about R&D, in so far as it leads to neglect of long-term issues and relies on uncertain causal relationships among critical inputs. Cost-benefit is adequate for dealing with short-term, small-scale projects. For larger projects with controversial long-term implications he advocates broader-based techniques such as multi-attribute analysis, which bring the interests of many parties into the judgment and take into account considerations such as the environment, finite resources and social

Notizen: In this article the author, using case study material, considers the motives which induce individuals either to join associations or to free-ride. In particular, he concludes that analysis and thinking on the free-rider problem needs to be pursued in a specific, well defined manner.

Notizen: Objective To analyse biopsies of large loop excision of the transformation zone of the cervix; to identify factors associated with negative histology; and to develop predictive models in order to reduce the number of negative loop excisions.Design Retrospective analysis of patient notes and audit database.Setting Colposcopy clinic of a large district general hospital in North Staffordshire.Population Four hundred and fifty-two women who underwent a large loop excision of the transformation zone (LLETZ) procedure for suspected cervical intraepithelial neoplasia.Methods Women who underwent a LLETZ procedure were placed in two different groups, one positive for cervical intra epithelial neoplasia and the other negative for cervical intra epithelial neoplasia. Information was obtained on a number of clinical and colposcopic variables. Analysis was undertaken to determine if there were any differences between the two groups. These factors were then identified and three predictive models generated. Receiver-operator characteristic curves were used to assess and test these models.Main outcomes measures To identify factors associated with negative histology on a LLETZ specimen. To predict how to reduce the number of negative LLETZ specimens.Results Four hundred and fifty-two women underwent a LLETZ procedure, 88 were negative (19%) and 364 were positive (81%). In women who were treated at their first visit, 56/316 (18%) had negative histology. There were significant associations between negative histology in the LLETZ and negative or low grade cytological atypia, negative colposcopic findings and years of age 〉 50 in both bivariate analysis and stepwise logistic regression. In the predictive models, the sensitivity ranged between 72% and 80%, the specificity 59%–72%, and the area under the receiver-operator characteristic was 0.75–0.77. If we had used the predictor models and managed women with negative or low grade cervical atypia and negative colposcopy findings conservatively, we would have reduced the negative biopsy rate from 19% to 14%, but five cases of high grade disease and 25 cases of low grade disease would have been missed. If we had also included women aged 〉 50 years in this model, the negative biopsy rate would have dropped from 19% to 15%, with only one case of high grade disease and 11 cases of low grade disease missed. All these women would require continued cytological and colposcopic surveillance. Importantly, no cases of invasion would have been missed.Conclusion Using a predictive model can reduce the number of negative LLETZ specimens, but at the expense of continued cytological and colposcopic surveillance and cannot be recommended in normal practice. This raises the question whether current standards for negative histology in LLETZ specimens are set unrealistically high.