Notes sur la pathologie spontanée du chien de laboratoire. 1re note : Léiomyosarcome du mésentère chez une Chienne

Description d’un cas de léiomyosarcome du mésentère chez une Chienne et discussion des problèmes soulevés : avenir expérimental de l’animal ; diagnostic et traitement en chirurgie canine. Nous tenons à remercier très vivement Monsieur le Maître-Assis tant Agrégé G. Van Haverbeke, du Laboratoire d’Anatomie Pathologique de l’Ecole Nationale Vétérinaire de Lyon, qui a bien voulu assurer l’analyse des prélèvements histologiques

Cell therapy for ischemic stroke

Stroke is the second, and in some countries the third cause of mortality in the population and one of the causes of disability in the adult population. According to statistics, in 2018, 15 million cases of stroke and 6 million deaths were diagnosed,The only currently approved treatments for acute stroke are intravenous tissue plasminogen activator (rtPA) and intra-arterial thrombectomy, which are used in less than 10% and 1% of patients, respectively.The literature review is devoted to the pathophysiology and molecular mechanisms of damage in cerebral ischemia. The modern concept of two strategies of cell therapy is discussed: neuroprotection and remodeling; the role of stem cells in reducing local and systemic inflammation, neurogenesis and angiogenesis, increasing neuronal plasticity, and protecting the blood-brain barrier, the role of paracrine factors and extracellular vesicles is shown.Methods of stem cell delivery are described: direct intracerebral transplantation, intraventricular and intrathecal, intravenous and intraarterial; the number of cells, their type and optimal delivery time depending on the acute, subacute and chronic periods of stroke. We also described recently designed the radially branched deployment (RBD) device and Cleveland multiport catheter for convection-enhanced delivery in which a cell-delivery catheter can be deployed at various angles and depths from a single longitudinal cannula. Finally, data on the completed 15 clinical trials from 2015 to the present, in which 513 patients took part, are presented. A detailed analysis of the efficacy and safety of cell therapy has been carried out

Piecewise polynomial approximation of probability density functions with application to uncertainty quantification for stochastic PDEs

The probability density function (PDF) associated with a given set of samples is approximated by a piecewise-linear polynomial constructed with respect to a binning of the sample space. The kernel functions are a compactly supported basis for the space of such polynomials, i.e. finite element hat functions, that are centered at the bin nodes rather than at the samples, as is the case for the standard kernel density estimation approach. This feature naturally provides an approximation that is scalable with respect to the sample size. On the other hand, unlike other strategies that use a finite element approach, the proposed approximation does not require the solution of a linear system. In addition, a simple rule that relates the bin size to the sample size eliminates the need for bandwidth selection procedures. The proposed density estimator has unitary integral, does not require a constraint to enforce positivity, and is consistent. The proposed approach is validated through numerical examples in which samples are drawn from known PDFs. The approach is also used to determine approximations of (unknown) PDFs associated with outputs of interest that depend on the solution of a stochastic partial differential equation

Исправление к статье «Бифункциональные хелаторы к катиону галлия»

Page 126, in Acknowledgments instead ofНа странице 126 в разделе Благодарности вмест

Sampling QCD field configurations with gauge-equivariant flow models

Machine learning methods based on normalizing flows have been shown to address important challenges, such as critical slowing-down and topological freezing, in the sampling of gauge field configurations in simple lattice field theories. A critical question is whether this success will translate to studies of QCD. This Proceedings presents a status update on advances in this area. In particular, it is illustrated how recently developed algorithmic components may be combined to construct flow-based sampling algorithms for QCD in four dimensions. The prospects and challenges for future use of this approach in at-scale applications are summarized

Бифункциональные хелаторы к катиону галлия

Objectives. The chemistry of 67Ga and 68Ga radionuclides plays a key role in nuclear medicine for applications in radiopharmaceuticals, in particular, in noninvasive in vivo molecular imaging techniques. The use of radiometals for labeling biomolecules typically requires the use of bifunctional chelators, which contain a functional group for covalent bonding with the targeting vector in addition to the polydentate fragment coordinating the metal. The aim of the present review article is to analyze the currently accumulated experimental material on the development and application of bifunctional chelators of gallium cations in medical research, as well as to identify the main requirements for the structure of the chelator and its complexes with 68Ga, which are used to create effective Gabased pharmaceutical preparations.Results. The review analyzed macrocyclic bifunctional chelators forming stable in vivo complexes with 68Ga and acyclic chelators, whose main advantage is faster complexation kinetics due to the short half-life of 68Ga. The advantages and disadvantages of both types of ligands were evaluated. In addition, a critical analysis of the binding constants and the conditions for the formation of complexes was presented. Examples of the influence of the geometry, lipophilicity, and total charge of the metal complex on the biodistribution of target radiopharmaceuticals were also given.Conclusions. Despite the progress made in the considered areas of bifunctional chelators, the problem of correlating the chemical structure of a metal-based radiopharmaceutical with its behavior in vivo remains important. Comparative studies of drugs having an identical targeting vector but containing different bifunctional chelating agents could help further elucidate the effectof metal chelate moiety on pharmacokinetics. In order to create effective bifunctional chelating agents, it is necessary to take into account such factors as the stability and inertness of the chelator and its complexes under physiological conditions, lipophilicity, complexation kinetics, chelation selectivity, combinatoriality of the basic structure, along with economic aspects, e.g., the availability of raw materials and the complexity of the synthesis scheme.Цели. Химия радионуклидов 67Ga и 68Ga играет одну из ключевых ролей в ядерной медици­не для применения в радиофармпрепаратах, в частности, в неинвазивных методах мо­лекулярной визуализации in vivo. Использование радиометаллов для мечения биомолекул обычно требует использования бифункциональных хелаторов, которые, кроме полиден­татного фрагмента, координирующего металл, содержат функциональную группу для ковалентного связывания с вектором-мишенью. Цели данного обзора – проанализировать накопленный к настоящему времени экспериментальный материал, касающийся разра­ботки и применения в медицинских исследованиях бифункциональных хелаторов к кати­ону галлия, а также выявить и проанализировать основные требования, предъявляемые к структуре хелатора и его комплексов с 68Ga, необходимые для создания эффективных фармакологических препаратов на его основе.Результаты. Рассмотрены макроциклические бифункциональные хелаторы, образую­щие стабильные in vivo комплексы с 68Ga, а также ациклические хелаторы, преимуще­ство которых заключается в более быстрой кинетике комплексообразования, что явля­ется ключевым фактором, учитывающим короткий период полураспада 68Ga. Проведена оценка достоинств и недостатков обоих типов лигандов. Кроме того, осуществлен кри­тический анализ констант связывания и условий образования комплексов. Рассмотрены примеры влияния природы металлического комплекса (геометрия, липофильность, об­щий заряд) на биораспределение целевых радиофармацевтических препаратов.Выводы. Несмотря на достигнутые успехи в рассмотренных направлениях создания би­фунциональных хелаторов, по-прежнему важной остается проблема корреляции хими­ческой структуры радиофармпрепаратов на основе металлов с их поведением in vivo. В этом отношении сравнительные исследования препаратов, имеющих идентичный вектор нацеливания, но включающих разные бифункциональные хелатируюшие агенты, могут помочь в дальнейшем выявлении влияния металл-хелатного фрагмента на фар­макокинетику. В целом можно отметить, что для создания эффективного бифункци­онального хелатирующего агента нужно принимать во внимание целую совокупность факторов, включающую стабильность и инертность хелатора и его комплексов в физиологических условиях, липофильность, кинетику комплексообразования, селективность хеланирования, комбинаторность базовой структуры, а также экономические аспекты: доступность сырья, сложность схемы синтеза

learning and adaptation to detect changes and anomalies in high dimensional data

The problem of monitoring a datastream and detecting whether the data generating process changes from normal to novel and possibly anomalous conditions has relevant applications in many real scenarios, such as health monitoring and quality inspection of industrial processes. A general approach often adopted in the literature is to learn a model to describe normal data and detect as anomalous those data that do not conform to the learned model. However, several challenges have to be addressed to make this approach effective in real world scenarios, where acquired data are often characterized by high dimension and feature complex structures (such as signals and images). We address this problem from two perspectives corresponding to different modeling assumptions on the data-generating process. At first, we model data as realization of random vectors, as it is customary in the statistical literature. In this settings we focus on the change detection problem, where the goal is to detect whether the datastream permanently departs from normal conditions. We theoretically prove the intrinsic difficulty of this problem when the data dimension increases and propose a novel non-parametric and multivariate change-detection algorithm. In the second part, we focus on data having complex structure and we adopt dictionaries yielding sparse representations to model normal data. We propose novel algorithms to detect anomalies in such datastreams and to adapt the learned model when the process generating normal data changes

Factors affecting glomerular filtration rate, as measured by iohexol disappearance, in men with or at risk for HIV infection

Objective: Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD). Design: Cross-sectional measurement of iohexol-based GFR (iGFR) in HIV(+) men (n = 455) receiving antiretroviral therapy, and HIV-uninfected (HIV(-)) men (n = 258) in the Multicenter AIDS Cohort Study. Methods: iGFR was calculated from disappearance of infused iohexol from plasma. Determinants of GFR and the presence of CKD were compared using iGFR and GFR estimated by the CKD-Epi equation (eGFR). Results: Median iGFR was higher among HIV(+) than HIV(-) men (109 vs. 106 ml/min/1.73 m2, respectively, p = .046), and was 7 ml/min higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR (≤90 ml/min/1.73 m2) was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. CKD was more common in HIV(+) than HIV(-) men; predictors of CKD were similar using iGFR and eGFR. Conclusions: iGFR was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men. Presence of CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR. © 2014 Margolick et al

Novel Methods for Analysing Bacterial Tracks Reveal Persistence in Rhodobacter sphaeroides

Tracking bacteria using video microscopy is a powerful experimental approach to probe their motile behaviour. The trajectories obtained contain much information relating to the complex patterns of bacterial motility. However, methods for the quantitative analysis of such data are limited. Most swimming bacteria move in approximately straight lines, interspersed with random reorientation phases. It is therefore necessary to segment observed tracks into swimming and reorientation phases to extract useful statistics. We present novel robust analysis tools to discern these two phases in tracks. Our methods comprise a simple and effective protocol for removing spurious tracks from tracking datasets, followed by analysis based on a two-state hidden Markov model, taking advantage of the availability of mutant strains that exhibit swimming-only or reorientating-only motion to generate an empirical prior distribution. Using simulated tracks with varying levels of added noise, we validate our methods and compare them with an existing heuristic method. To our knowledge this is the first example of a systematic assessment of analysis methods in this field. The new methods are substantially more robust to noise and introduce less systematic bias than the heuristic method. We apply our methods to tracks obtained from the bacterial species Rhodobacter sphaeroides and Escherichia coli. Our results demonstrate that R. sphaeroides exhibits persistence over the course of a tumbling event, which is a novel result with important implications in the study of this and similar species

Statistics for Fission-Track Thermochronology

This chapter introduces statistical tools to extract geologically meaningful information from fission-track (FT) data using both the external detector and LA-ICP-MS methods. The spontaneous fission of 238U is a Poisson process resulting in large single-grain age uncertainties. To overcome this imprecision, it is nearly always necessary to analyse multiple grains per sample. The degree to which the analytical uncertainties can explain the observed scatter of the single-grain data can be visually assessed on a radial plot and objectively quantified by a chi-square test. For sufficiently low values of the chi-square statistic (or sufficiently high p values), the pooled age of all the grains gives a suitable description of the underlying ‘true’ age population. Samples may fail the chi-square test for several reasons. A first possibility is that the true age population does not consist of a single discrete age component, but is characterised by a continuous range of ages. In this case, a ‘random effects’ model can constrain the true age distribution using two parameters: the ‘central age’ and the ‘(over)dispersion’. A second reason why FT data sets might fail the chi-square test is if they are underlain by multimodal age distributions. Such distributions may consist of discrete age components, continuous age distributions, or a combination of the two. Formalised statistical tests such as chi-square can be useful in preventing overfitting of relatively small data sets. However, they should be used with caution when applied to large data sets (including length measurements) which generate sufficient statistical ‘power’ to reject any simple yet geologically plausible hypothesis