Incidence and management of pulmonary embolism following spinal surgery occurring while under chemical thromboprophylaxis.

Patients undergoing spinal surgery are at risk of developing thromboembolic complications even though lower incidences have been reported as compared to joint arthroplasty surgery. Deep vein thrombosis (DVT) has been studied extensively in the context of spinal surgery but symptomatic pulmonary embolism (PE) has engaged less attention. We prospectively followed a consecutive cohort of 270 patients undergoing spinal surgery at a single institution. From these patients, only 26 were simple discectomies, while the largest proportion (226) was fusions. All patients received both low molecular weight heparin (LMWH) initiated after surgery and compressive stockings. PE was diagnosed with spiral chest CT. Six patients developed symptomatic PE, five during their hospital stay. In three of the six patients the embolic event occurred during the first 3 postoperative days. They were managed by the temporary insertion of an inferior vena cava (IVC) filter thus allowing for a delay in full-dose anticoagulation until removal of the filter. None of the PE patients suffered any bleeding complication as a result of the introduction of full anticoagulation. Two patients suffered postoperative haematomas, without development of neurological symptoms or signs, requiring emergency evacuation. The overall incidence of PE was 2.2% rising to 2.5% after exclusion of microdiscectomy cases. The incidence of PE was highest in anterior or combined thoracolumbar/lumbar procedures (4.2%). There is a large variation in the reported incidence of PE in the spinal literature. Results from the only study found in the literature specifically monitoring PE suggest an incidence of PE as high as 2.5%. Our study shows a similar incidence despite the use of LMWH. In the absence of randomized controlled trials (RCT) it is uncertain if this type of prophylaxis lowers the incidence of PE. However, other studies show that the morbidity of LMWH is very low. Since PE can be a life-threatening complication, LMWH may be a worthwhile option to consider for prophylaxis. RCTs are necessary in assessing the efficacy of DVT and PE prophylaxis in spinal patients.

Determination of the components of the gyration tensor of quartz by oblique incidence transmission two-modulator generalized ellipsometry

The two independent components of the gyration tensor of quartz, g11 and g33, have been spectroscopically measured using a transmission two-modulator generalized ellipsometer. The method is used to determine the optical activity in crystals in directions other than the optic axis, where the linear birefringence is much larger than the optical activity.

Incidence of Garlic common latent virus in Argentina, and phylogenetic and recombination analyses of isolates

The objective of this work was to estimate the incidence and prevalence of Garlic common latent virus (GarCLV) in the main production regions of garlic (Allium sativum) in Argentina, and to perform phylogenetic and recombination analyses in isolates from these regions. Leaf samples (3,050) were taken from four garlic commercial types, in 13 departments of the four main garlic-producing provinces of Argentina, in a 1,175-ha sampling area. Virus infection was evaluated with DAS-Elisa test using specific antiserum, and the phylogenetic and recombination analyses were done with capsid protein (CP) nucleotide sequence of seven GarCLV isolates from the provinces. The incidence of GarCLV in the evaluated provinces varied between 6.7 and 22% of the samples, whereas the prevalence varied between 52.6 and 70%. In the analysis of garlic commercial types, Morado showed the highest incidence of the virus, in the province of San Juan, whereas Rosado Paraguayo had the lowest incidence, in the province of Cordoba. Nucleotide identity in the CP sequences ranged between 80.3 and 97.6%. The phylogenetic analysis shows the presence of two main groups of GarCLV and of a possible third group that would include only a German isolate. The recombination analysis between isolates from different parts of the world evidences the presence of recombinant isolates from Poland and Australia.

The incidence and selection of multiple mating in plants.

Mating with more than one pollen donor, or polyandry, is common in land plants. In flowering plants, polyandry occurs when the pollen from different potential sires is distributed among the fruits of a single individual, or when pollen from more than one donor is deposited on the same stigma. Because polyandry typically leads to multiple paternity among or within fruits, it can be indirectly inferred on the basis of paternity analysis using molecular markers. A review of the literature indicates that polyandry is probably ubiquitous in plants except those that habitually self-fertilize, or that disperse their pollen in pollen packages, such as polyads or pollinia. Multiple mating may increase plants' female component by alleviating pollen limitation or by promoting competition among pollen grains from different potential sires. Accordingly, a number of traits have evolved that should promote polyandry at the flower level from the female's point of view, e.g. the prolongation of stigma receptivity or increases in stigma size. However, many floral traits, such as attractiveness, the physical manipulation of pollinators and pollen-dispensing mechanisms that lead to polyandrous pollination, have probably evolved in response to selection to promote male siring success in general, so that polyandry might often best be seen as a by-product of selection to enhance outcross siring success. In this sense, polyandry in plants is similar to geitonogamy (selfing caused by pollen transfer among flowers of the same plant), because both polyandry and geitonogamy probably result from selection to promote outcross siring success, although geitonogamy is almost always deleterious while polyandry in plants will seldom be so.

RiskDiff: A web tool for the analysis of the difference due to risk and demographic factors for incidence or mortality data.

Background Analysing the observed differences for incidence or mortality of a particular disease between two different situations (such as time points, geographical areas, gender or other social characteristics) can be useful both for scientific or administrative purposes. From an epidemiological and public health point of view, it is of great interest to assess the effect of demographic factors in these observed differences in order to elucidate the effect of the risk of developing a disease or dying from it. The method proposed by Bashir and Estève, which splits the observed variation into three components: risk, population structure and population size is a common choice at practice. Results A web-based application, called RiskDiff has been implemented (available at http://rht.iconcologia.net/riskdiff.htm webcite), to perform this kind of statistical analyses, providing text and graphical summaries. Code from the implemented functions in R is also provided. An application to cancer mortality data from Catalonia is used for illustration. Conclusions Combining epidemiological with demographical factors is crucial for analysing incidence or mortality from a disease, especially if the population pyramids show substantial differences. The tool implemented may serve to promote and divulgate the use of this method to give advice for epidemiologic interpretation and decision making in public health.

Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells.

Gene transfer in eukaryotic cells and organisms suffers from epigenetic effects that result in low or unstable transgene expression and high clonal variability. Use of epigenetic regulators such as matrix attachment regions (MARs) is a promising approach to alleviate such unwanted effects. Dissection of a known MAR allowed the identification of sequence motifs that mediate elevated transgene expression. Bioinformatics analysis implied that these motifs adopt a curved DNA structure that positions nucleosomes and binds specific transcription factors. From these observations, we computed putative MARs from the human genome. Cloning of several predicted MARs indicated that they are much more potent than the previously known element, boosting the expression of recombinant proteins from cultured cells as well as mediating high and sustained expression in mice. Thus we computationally identified potent epigenetic regulators, opening new strategies toward high and stable transgene expression for research, therapeutic production or gene-based therapies.

Développement et validation d'une méthode de calcul indépendant des unités moniteur basée sur les simulations Monte Carlo pour la vérification des traitements IMRT

Résumé : La radiothérapie par modulation d'intensité (IMRT) est une technique de traitement qui utilise des faisceaux dont la fluence de rayonnement est modulée. L'IMRT, largement utilisée dans les pays industrialisés, permet d'atteindre une meilleure homogénéité de la dose à l'intérieur du volume cible et de réduire la dose aux organes à risque. Une méthode usuelle pour réaliser pratiquement la modulation des faisceaux est de sommer de petits faisceaux (segments) qui ont la même incidence. Cette technique est appelée IMRT step-and-shoot. Dans le contexte clinique, il est nécessaire de vérifier les plans de traitement des patients avant la première irradiation. Cette question n'est toujours pas résolue de manière satisfaisante. En effet, un calcul indépendant des unités moniteur (représentatif de la pondération des chaque segment) ne peut pas être réalisé pour les traitements IMRT step-and-shoot, car les poids des segments ne sont pas connus à priori, mais calculés au moment de la planification inverse. Par ailleurs, la vérification des plans de traitement par comparaison avec des mesures prend du temps et ne restitue pas la géométrie exacte du traitement. Dans ce travail, une méthode indépendante de calcul des plans de traitement IMRT step-and-shoot est décrite. Cette méthode est basée sur le code Monte Carlo EGSnrc/BEAMnrc, dont la modélisation de la tête de l'accélérateur linéaire a été validée dans une large gamme de situations. Les segments d'un plan de traitement IMRT sont simulés individuellement dans la géométrie exacte du traitement. Ensuite, les distributions de dose sont converties en dose absorbée dans l'eau par unité moniteur. La dose totale du traitement dans chaque élément de volume du patient (voxel) peut être exprimée comme une équation matricielle linéaire des unités moniteur et de la dose par unité moniteur de chacun des faisceaux. La résolution de cette équation est effectuée par l'inversion d'une matrice à l'aide de l'algorithme dit Non-Negative Least Square fit (NNLS). L'ensemble des voxels contenus dans le volume patient ne pouvant être utilisés dans le calcul pour des raisons de limitations informatiques, plusieurs possibilités de sélection ont été testées. Le meilleur choix consiste à utiliser les voxels contenus dans le Volume Cible de Planification (PTV). La méthode proposée dans ce travail a été testée avec huit cas cliniques représentatifs des traitements habituels de radiothérapie. Les unités moniteur obtenues conduisent à des distributions de dose globale cliniquement équivalentes à celles issues du logiciel de planification des traitements. Ainsi, cette méthode indépendante de calcul des unités moniteur pour l'IMRT step-andshootest validée pour une utilisation clinique. Par analogie, il serait possible d'envisager d'appliquer une méthode similaire pour d'autres modalités de traitement comme par exemple la tomothérapie. Abstract : Intensity Modulated RadioTherapy (IMRT) is a treatment technique that uses modulated beam fluence. IMRT is now widespread in more advanced countries, due to its improvement of dose conformation around target volume, and its ability to lower doses to organs at risk in complex clinical cases. One way to carry out beam modulation is to sum smaller beams (beamlets) with the same incidence. This technique is called step-and-shoot IMRT. In a clinical context, it is necessary to verify treatment plans before the first irradiation. IMRT Plan verification is still an issue for this technique. Independent monitor unit calculation (representative of the weight of each beamlet) can indeed not be performed for IMRT step-and-shoot, because beamlet weights are not known a priori, but calculated by inverse planning. Besides, treatment plan verification by comparison with measured data is time consuming and performed in a simple geometry, usually in a cubic water phantom with all machine angles set to zero. In this work, an independent method for monitor unit calculation for step-and-shoot IMRT is described. This method is based on the Monte Carlo code EGSnrc/BEAMnrc. The Monte Carlo model of the head of the linear accelerator is validated by comparison of simulated and measured dose distributions in a large range of situations. The beamlets of an IMRT treatment plan are calculated individually by Monte Carlo, in the exact geometry of the treatment. Then, the dose distributions of the beamlets are converted in absorbed dose to water per monitor unit. The dose of the whole treatment in each volume element (voxel) can be expressed through a linear matrix equation of the monitor units and dose per monitor unit of every beamlets. This equation is solved by a Non-Negative Least Sqvare fif algorithm (NNLS). However, not every voxels inside the patient volume can be used in order to solve this equation, because of computer limitations. Several ways of voxel selection have been tested and the best choice consists in using voxels inside the Planning Target Volume (PTV). The method presented in this work was tested with eight clinical cases, which were representative of usual radiotherapy treatments. The monitor units obtained lead to clinically equivalent global dose distributions. Thus, this independent monitor unit calculation method for step-and-shoot IMRT is validated and can therefore be used in a clinical routine. It would be possible to consider applying a similar method for other treatment modalities, such as for instance tomotherapy or volumetric modulated arc therapy.

Self-Organising Maps and Correlation Analysis as a Tool to Explore Patterns in Excitation-Emission Matrix Data Sets and to Discriminate Dissolved Organic Matter Fluorescence Components

Dissolved organic matter (DOM) is a complex mixture of organic compounds, ubiquitous in marine and freshwater systems. Fluorescence spectroscopy, by means of Excitation-Emission Matrices (EEM), has become an indispensable tool to study DOM sources, transport and fate in aquatic ecosystems. However the statistical treatment of large and heterogeneous EEM data sets still represents an important challenge for biogeochemists. Recently, Self-Organising Maps (SOM) has been proposed as a tool to explore patterns in large EEM data sets. SOM is a pattern recognition method which clusterizes and reduces the dimensionality of input EEMs without relying on any assumption about the data structure. In this paper, we show how SOM, coupled with a correlation analysis of the component planes, can be used both to explore patterns among samples, as well as to identify individual fluorescence components. We analysed a large and heterogeneous EEM data set, including samples from a river catchment collected under a range of hydrological conditions, along a 60-km downstream gradient, and under the influence of different degrees of anthropogenic impact. According to our results, chemical industry effluents appeared to have unique and distinctive spectral characteristics. On the other hand, river samples collected under flash flood conditions showed homogeneous EEM shapes. The correlation analysis of the component planes suggested the presence of four fluorescence components, consistent with DOM components previously described in the literature. A remarkable strength of this methodology was that outlier samples appeared naturally integrated in the analysis. We conclude that SOM coupled with a correlation analysis procedure is a promising tool for studying large and heterogeneous EEM data sets.

Covariance Matrix Estimation and Mean-Variance Optimization in application to International Diversification

Tutkimus keskittyy kansainväliseen hajauttamiseen suomalaisen sijoittajan näkökulmasta. Tutkimuksen toinen tavoite on selvittää tehostavatko uudet kovarianssimatriisiestimaattorit minimivarianssiportfolion optimointiprosessia. Tavallisen otoskovarianssimatriisin lisäksi optimoinnissa käytetään kahta kutistusestimaattoria ja joustavaa monimuuttuja-GARCH(1,1)-mallia. Tutkimusaineisto koostuu Dow Jonesin toimialaindekseistä ja OMX-H:n portfolioindeksistä. Kansainvälinen hajautusstrategia on toteutettu käyttäen toimialalähestymistapaa ja portfoliota optimoidaan käyttäen kahtatoista komponenttia. Tutkimusaieisto kattaa vuodet 1996-2005 eli 120 kuukausittaista havaintoa. Muodostettujen portfolioiden suorituskykyä mitataan Sharpen indeksillä. Tutkimustulosten mukaan kansainvälisesti hajautettujen investointien ja kotimaisen portfolion riskikorjattujen tuottojen välillä ei ole tilastollisesti merkitsevää eroa. Myöskään uusien kovarianssimatriisiestimaattoreiden käytöstä ei synnytilastollisesti merkitsevää lisäarvoa verrattuna otoskovarianssimatrisiin perustuvaan portfolion optimointiin.

Different concentrations of Mg++ ions affect nuclear matrix protein distribution during thermal stabilization of isolated nuclei.

The nuclear matrix, a proteinaceous network believed to be a scaffolding structure determining higher-order organization of chromatin, is usually prepared from intact nuclei by a series of extraction steps. In most cell types investigated the nuclear matrix does not spontaneously resist these treatments but must be stabilized before the application of extracting agents. Incubation of isolated nuclei at 37C or 42C in buffers containing Mg++ has been widely employed as stabilizing agent. We have previously demonstrated that heat treatment induces changes in the distribution of three nuclear scaffold proteins in nuclei prepared in the absence of Mg++ ions. We studied whether different concentrations of Mg++ (2.0-5 mM) affect the spatial distribution of nuclear matrix proteins in nuclei isolated from K562 erythroleukemia cells and stabilized by heat at either 37C or 42C. Five proteins were studied, two of which were RNA metabolism-related proteins (a 105-kD component of splicing complexes and an RNP component), one a 126-kD constituent of a class of nuclear bodies, and two were components of the inner matrix network. The localization of proteins was determined by immunofluorescent staining and confocal scanning laser microscope. Mg++ induced significant changes of antigen distribution even at the lowest concentration employed, and these modifications were enhanced in parallel with increase in the concentration of the divalent cation. The different sensitivity to heat stabilization and Mg++ of these nuclear proteins might reflect a different degree of association with the nuclear scaffold and can be closely related to their functional or structural role.

Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100β from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100β from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100β, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Breast cancer incidence and overdiagnosis in Catalonia (Spain)

Introduction: Early detection of breast cancer (BC) with mammography may cause overdiagnosis and overtreatment, detecting tumors which would remain undiagnosed during a lifetime. The aims of this study were: first, to model invasive BC incidence trends in Catalonia (Spain) taking into account reproductive and screening data; and second, to quantify the extent of BC overdiagnosis. Methods: We modeled the incidence of invasive BC using a Poisson regression model. Explanatory variables were: age at diagnosis and cohort characteristics (completed fertility rate, percentage of women that use mammography at age 50, and year of birth). This model also was used to estimate the background incidence in the absence of screening. We used a probabilistic model to estimate the expected BC incidence if women in the population used mammography as reported in health surveys. The difference between the observed and expected cumulative incidences provided an estimate of overdiagnosis. Results: Incidence of invasive BC increased, especially in cohorts born from 1940 to 1955. The biggest increase was observed in these cohorts between the ages of 50 to 65 years, where the final BC incidence rates more than doubled the initial ones. Dissemination of mammography was significantly associated with BC incidence and overdiagnosis. Our estimates of overdiagnosis ranged from 0.4% to 46.6%, for women born around 1935 and 1950, respectively. Conclusions: Our results support the existence of overdiagnosis in Catalonia attributed to mammography usage, and the limited malignant potential of some tumors may play an important role. Women should be better informed about this risk. Research should be oriented towards personalized screening and risk assessment tools.

Recruitment of Matrix Metalloproteinase-9 (MMP-9) to the Fibroblast Cell Surface by Lysyl Hydroxylase 3 (LH3) Triggers Transforming Growth Factor-β (TGF-β) Activation and Fibroblast Differentiation.

Solid tumor growth triggers a wound healing response. Similar to wound healing, fibroblasts in the tumor stroma differentiate into myofibroblasts (also referred to as cancer-associated fibroblasts) primarily, but not exclusively, in response to transforming growth factor-β (TGF-β). Myofibroblasts in turn enhance tumor progression by remodeling the stroma. Among proteases implicated in stroma remodeling, matrix metalloproteinases (MMPs), including MMP-9, play a prominent role. Recent evidence indicates that MMP-9 recruitment to the tumor cell surface enhances tumor growth and invasion. In the present work, we addressed the potential relevance of MMP-9 recruitment to and activity at the surface of fibroblasts. We show that recruitment of MMP-9 to the fibroblast cell surface occurs through its fibronectin-like (FN) domain and that the molecule responsible for the recruitment is lysyl hydroxylase 3 (LH3). Functional assays suggest that both pro- and active MMP-9 trigger α-smooth muscle actin expression in cultured fibroblasts, reflecting myofibroblast differentiation, possibly as a result of TGF-β activation. Moreover, the recombinant FN domain inhibited both MMP-9-induced TGF-β activation and α-smooth muscle actin expression by displacing MMP-9 from the fibroblast cell surface. Together our results uncover LH3 as a new docking receptor of MMP-9 on the fibroblast cell surface and demonstrate that the MMP-9 FN domain is essential for the interaction. They also show that the recombinant FN domain inhibits MMP-9-induced TGF-β activation and fibroblast differentiation, providing a potentially attractive therapeutic reagent toward attenuating tumor progression where MMP-9 activity is strongly implicated.