On the Relation Between the Velocity and the Resistance Encountered by Bodies Moving in Fluids.

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Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease

© 2014 John Wiley & Sons Ltd. Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P  <  0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI]  = 11·6-106·4) and this was preserved in early-stage disease patients (P  <  0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL

Telomere length predicts progression and overall survival in chronic lymphocytic leukemia: data from the UK LRF CLL4 trial

Telomere erosion and fusion play an important role in the pathology of many common human malignancies including CLL.1,2 Previous studies in CLL have shown that short telomeres defined on the basis of the median value or receiver operating characteristic (ROC) analysis are associated with unmutated IGHV genes, poor risk genomic abnormalities, genomic complexity and high expression of CD38, CD49d, and ZAP70 whereas long telomeres are associated with increasing IGHV mutational load, isolated deletion of 13q and low CD49d expression. In addition, in predominantly diagnostic or mixed patient cohorts, telomere length (TL) predicts time to first treatment and/or overall survival (OS) in multivariate analyses of models incorporating established biomarkers. 3-7 However uncertainties about the most clinically relevant measure of telomere length, the optimal choice of assay, the need for assay standardisation and the lack of published data on the prognostic value of TL in patients entered into randomised trials have hindered the implementation of TL measurement into routine clinical practice. We have attempted to address these issues by measuring telomere length using monochrome multiplex Q-PCR (MMQ-PCR) in 384 patients at randomisation into the UK LRF CLL4 phase 3 chemotherapy trial (Table S1), of whom 111 samples were also screened by single telomer

Brain Food Recipes

Much is said about nutrition, and for a relatively short time we have been talking about the importance of nutrition on the brain and, therefore, on cognitive performance. A correct diet in sports performance is a priority, but will it guarantee success in competitions? Obviously not, but a wrong diet, almost certainly, will lead us to a sporting and health disaster. The same premise applies to cognitive performance. Will eating properly guarantee academic results? No, but it will facilitate better neuronal connections, more fluid information, and better oxygenation of the brain, which in the end will allow us to obtain better cognitive results. And these behaviours should be avoided in conditions where students are confined for long periods of study during exams, due to illness or any other academic activity. This is why the importance of sociodemographic factors in the dietary preferences of children at an early age is vital. We could even go further by echoing the findings of some studies that suggest that poor food choices, rich in saturated fat, salt and sugar, in preschool age are associated with reduced verbal and cognitive ability scores. Sometimes opinions emerge as to whether breakfast is appropriate or not, in which case the balance strongly shifts more toward “ adequate” breakfast. We wanted to go a bit further by analysing the different ingredients that influence the various brain functions and/or connections, for their integration into students’ daily diets. But to integrate this model it is not enough to tell the students what is right and what is not, but in this case, we have intended that they are the ones who discover them; and use them to develop different recipes so that the message reaches the rest of their classmates better. We hope that this initiative will continue over time, passing the baton to the next generations.Brain food ProjectIntertational School SEKCatergestFundación Felipe Segovi

The Fukushima Daiichi Accident

The Fukushima Daiichi Accident consists of a Report by the IAEA Director General and five technical volumes. It is the result of an extensive international collaborative effort involving five working groups with about 180 experts from 42 Member States with and without nuclear power programmes and several international bodies. It provides a description of the accident and its causes, evolution and consequences, based on the evaluation of data and information from a large number of sources available at the time of writing. The set contains six printed parts and five supplementary CD-ROMs. Contents: Report by the Director General; Technical Volume 1/5, Description and Context of the Accident; Technical Volume 2/5, Safety Assessment; Technical Volume 3/5, Emergency Preparedness and Response; Technical Volume 4/5, Radiological Consequences; Technical Volume 5/5, Post-accident Recovery; Annexes. The JRC contributed to volumes 1,2 and 3, which are attached.JRC.F.5-Nuclear Reactor Safety Assessmen

A proposal for calculating the no-observed-adverse-effect level (NOAEL) for organic compounds responsible for liver toxicity based on their physicochemical properties

Objectives: Both environmental and occupational exposure limits are based on the no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL) or benchmark dose (BMD) deriving from epidemiological and experimental studies. The aim of this study is to investigate to what extent the NOAEL values for organic compounds responsible for liver toxicity calculated based on their physicochemical properties could be used for calculating occupational exposure limits. Material and Methods: The distribution coefficients from air to the liver (log Kliver) were calculated according to the Abraham solvation equation. NOAEL and LOAEL values for early effects in the liver were obtained from the literature data. The descriptors for Abraham's equation were found for 59 compounds, which were divided into 2 groups: "non-reactive" (alcohols, ketones, esters, ethers, aromatic and aliphatic hydrocarbons, amides) and "possibly reactive" (aldehydes, allyl compounds, amines, benzyl halides, halogenated hydrocarbons, acrylates). Results: The correlation coefficients between log-log K and log NOAEL for non-reactive and reactive compounds amounted to r = -0.8123 and r = -0.8045, respectively, and were statistically significant. It appears that the Abraham equation could be used to predict the NOAEL values for compounds lacking information concerning their liver toxicity. Conclusions: In view of the tendency to limit animal testing procedures, the method proposed in this paper can improve the practice of setting exposure guidelines for the unstudied compounds