Why only few are so successful ?

In many professons employees are rewarded according to their relative performance. Corresponding economy can be modeled by taking $N$ independent agents who gain from the market with a rate which depends on their current gain. We argue that this simple realistic rate generates a scale free distribution even though intrinsic ability of agents are marginally different from each other. As an evidence we provide distribution of scores for two different systems (a) the global stock game where players invest in real stock market and (b) the international cricket.Comment: 8 pages, 3 eps figures, elsart.cls (included), accepted in Physica

Non-Negative Matrix Factorization for the Analysis of Complex Gene Expression Data: Identification of Clinically Relevant Tumor Subtypes

Non-negative matrix factorization (NMF) is a relatively new approach to analyze gene expression data that models data by additive combinations of non-negative basis vectors (metagenes). The non-negativity constraint makes sense biologically as genes may either be expressed or not, but never show negative expression. We applied NMF to five different microarray data sets. We estimated the appropriate number metagens by comparing the residual error of NMF reconstruction of data to that of NMF reconstruction of permutated data, thus finding when a given solution contained more information than noise. This analysis also revealed that NMF could not factorize one of the data sets in a meaningful way. We used GO categories and pre defined gene sets to evaluate the biological significance of the obtained metagenes. By analyses of metagenes specific for the same GO-categories we could show that individual metagenes activated different aspects of the same biological processes. Several of the obtained metagenes correlated with tumor subtypes and tumors with characteristic chromosomal translocations, indicating that metagenes may correspond to specific disease entities. Hence, NMF extracts biological relevant structures of microarray expression data and may thus contribute to a deeper understanding of tumor behavior

Effects of High Dose Fibrinogen on in vitro Haemodilution with Different Therapeutic Fluids

Background: Therapeutic fluids used in intensive care can have profound effects on coagulation, not only by dilution itself but also by other more complicated interactions. The aim of this in vitro study was to monitor the extent of dilutive coagulopathy induced by the most common therapeutic fluids and to attempt normalization of haemostasis by fibrinogen addition. Methods: 8 patients were recruited from the intensive care unit. Native whole blood was drawn, diluted by 50% with 9 different fluids, and run through a Sonoclot Analyzer. This was then repeated with high dose fibrinogen (corresponding to an in vivo dose of 8g/70kg) added to the dilutions. The fluids used were Voluven, Venofundin, Volulyte, Tetraspan, Albumin 5%, Macrodex, Gelofusine, Ringer’s acetate and NaCl. This covers the entire spectrum of fluids available in Sweden. Results: A significant in vitro dilutive response compared to undiluted blood was seen for all synthetic colloid fluids but not for albumin or crystalloids. Dextran and Gelofusine’s impact on coagulation parameters was greater than both NaCl and Ringer’s acetate. The individual patient’s response showed a high variability, which was reflected in high standard deviations. No significant improvement from fibrinogen addition could be seen on Sonoclot parameters. Conclusion: The dilutive effects of resuscitation fluids at 50% dilution are more severe for synthetic colloids compared to alternative therapies. Fibrinogen addition did not affect the induced coagulopathy as measured by the Sonoclot

Independent component analysis reveals new and biologically significant structures in micro array data

BACKGROUND: An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS) problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes. RESULTS: We applied independent component analysis (ICA) to three different microarray data sets; two tumor data sets and one time series experiment. To obtain reliable components we used iterated ICA to estimate component centrotypes. We found that many of the low ranking components indeed may show a strong biological coherence and hence be of biological significance. Generally ICA achieved a higher resolution when compared with results based on correlated expression and a larger number of gene clusters with significantly enriched for gene ontology (GO) categories. In addition, components characteristic for molecular subtypes and for tumors with specific chromosomal translocations were identified. ICA also identified more than one gene clusters significant for the same GO categories and hence disclosed a higher level of biological heterogeneity, even within coherent groups of genes. CONCLUSION: Although the ICA approach primarily detects hidden variables, these surfaced as highly correlated genes in time series data and in one instance in the tumor data. This further strengthens the biological relevance of latent variables detected by ICA

Robust assignment of cancer subtypes from expression data using a uni-variate gene expression average as classifier

<p>Abstract</p> <p>Background</p> <p>Genome wide gene expression data is a rich source for the identification of gene signatures suitable for clinical purposes and a number of statistical algorithms have been described for both identification and evaluation of such signatures. Some employed algorithms are fairly complex and hence sensitive to over-fitting whereas others are more simple and straight forward. Here we present a new type of simple algorithm based on ROC analysis and the use of metagenes that we believe will be a good complement to existing algorithms.</p> <p>Results</p> <p>The basis for the proposed approach is the use of metagenes, instead of collections of individual genes, and a feature selection using AUC values obtained by ROC analysis. Each gene in a data set is assigned an AUC value relative to the tumor class under investigation and the genes are ranked according to these values. Metagenes are then formed by calculating the mean expression level for an increasing number of ranked genes, and the metagene expression value that optimally discriminates tumor classes in the training set is used for classification of new samples. The performance of the metagene is then evaluated using LOOCV and balanced accuracies.</p> <p>Conclusions</p> <p>We show that the simple uni-variate gene expression average algorithm performs as well as several alternative algorithms such as discriminant analysis and the more complex approaches such as SVM and neural networks. The R package <it>rocc </it>is freely available at <url>http://cran.r-project.org/web/packages/rocc/index.html</url>.</p

Achillotenotomiák hosszú távú eredményei spasticus cerebralis paresisben szenvedő betegekben = Long-term follow-up of achillotenotomy in patients with cerebral palsy

Absztrakt: Bevezetés: A spasticus cerebralis paresisben szenvedő betegek kezelésének egyik legfontosabb faktora az állást és a járásképességet befolyásoló equinuscontractura műtéti megoldása. Klinikánkon nyílt Z-achillotenotomia mellett az Achilles-ín percutan tripla hemisectióját végezzük rutinszerűen. Célkitűzés: Munkánk célja volt, hogy a klinikánkon spasticus cerebralis paresises betegeken végzett achillotenotomiák hosszú távú eredményeit elemezzük, keressük a fő komplikációk prediszponáló faktorait, illetve összehasonlítsuk a nyílt és percutan végzett műtétek hosszú távú kimenetelét. Módszer: Klinikánkon 1990 és 2006 között 211 betegnél, összesen 347 esetben végeztük el az Achilles-ín megnyújtását. 261 esetben percutan, 86 esetben pedig nyílt feltárásból történtek a műtétek. Munkánk során a betegek átlagosan 15 éves utánkövetésének retrospektív analízisét végeztük el. Az egyes esetek hosszú távú eredményeit a műtéti életkor, az alapbetegség topográfiai megjelenési formája és a cerebralis paresis súlyossága alapján elemeztük. A betegek járóképességét, illetve annak változását a kezelés során az úgynevezett ’Physician Rating Scale’ pontrendszer szerint értékeltük. Eredmények: Recidív equinuscontractura miatt 74 esetben végeztünk reachillotenotomiát (21,3%); 14 esetben (4%) a reachillotenotomiát második alkalommal is el kellett végezni. Túlkorrekcióval 12 esetben (3,5%) találkoztunk. Fiatalabb életkorban (<7 év) operált, illetve súlyosabb paresis (GMFCS II–III.) esetén bizonyult a recidívaráta a legmagasabbnak (~26%). A recidíva 9 és 14 éves kor között jelentős halmozódást mutatott. Következtetés: A műtétet követő legfontosabb komplikáció a recidíva volt. Recidíva a legnagyobb arányban a fiatalabb korban operált, az alapbetegség súlyosabb formájában szenvedő betegeknél jelentkezett. Megfigyeltük, hogy a recidíva szoros összefüggést mutat a testnövekedéssel, illetve halmozódást mutat serdülőkorban. Orv Hetil. 2020; 161(8): 306–312. | Abstract: Introduction: The surgical solution of equinus deformity is one of the most important factors in the treatment of patients with cerebral palsy. We perform open Z achillotenotomy and percutaneus triple hemisection routinely in our department. Aim: The goal of our work was to analyze the long-term results of achillotenotomies in patients with cerebral palsy, to look for predisposing factors of major complications, and to compare the results of the performed operative methods. Method: Between 1990 and 2006, we performed 347 surgical Achilles tendon lengthenings. In 261 cases, the operations were performed percutaneusly, and in 86 cases we performed open Z achillotenotomy. The average follow-up time was 15 years. The long-term outcomes were analyzed based on the age at surgery, the topographic appearance and the severity of cerebral palsy. Analysis regarding functional outcome was based on the widely known Physician Rating Scale system. Results: Due to recurrent equinus deformity, re-achillotenotomy was performed in 74 cases (21.3%), and in 14 cases (4%) the re-achillotenotomy needed to be performed a second time. We encountered overcorrection and calcaneus deformity in 12 cases (3.5%). Recurrence rate was higher in patients operated at a younger age (<7 years) and in patients with a more severe cerebral palsy (GMFCS II–III, ~26%). Recurrence showed accumulation in patients 9–14 years old. Conclusion: The major complication we encountered was recurrence of the equinus deformity. The majority of relapses occured in patients who were operated at a younger age and suffered from a more severe form of cerebral palsy. We observed that recurrence showed an association with growth and accumulated in aldolescence. Orv Hetil. 2020; 161(8): 306–312

Behavioral interactions between opiate and antiepileptic drugs in the mouse

Morphine and related opioid compounds are known to possess proconvulsant activity based upon both electroencephalographic and behavioral criteria. The present authors previously suggested that opiate-related seizures were behaviorally inhibitory, and this was further investigated in the present study. The effects of pretreatment with three pharmacologically distinct compounds (sodium valproic acid, trimethadione, taurine) upon normal behavioral activation to systemic morphine were examined in the mouse. Morphine consistently increased activity levels in comparison with vehicle. Each of the three experimental compounds itself was behaviorally inhibitory; nonetheless both sodium valproate and trimethadione facilitated behavioral responses to morphine. The effects of the same drugs upon activation produced by central administration of a long-lasting enkephalin analog (-ala2-leu-enkephalinamide) were investigated, with similar results. These findings confirm a behavioral interaction between opiate and anticonvulsant drugs, although it may be selective for certain classes of anticonvulsant compounds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24414/1/0000684.pd