Low molecular weight heparin-induced skin necrosis—a systematic review

Background: Low molecular weight heparins (LMWHs) are currently used as a standard for anti-thrombotic therapy. Skin necrosis caused by LMWH is a rare and probably under-reported complication. The aim of our systematic review is to analyse the present literature for cases of LMWH-induced skin necrosis, emphasising the pathogenesis, clinical pattern, and management of this rare side effect. Methods: We performed a Medline literature search (PubMed database) and manual cross-referencing to identify all articles related to LMWH-induced skin necrosis. Data were analysed for type of LMWH used, time until skin necrosis occurred, localisation, size, laboratory findings, switch anticoagulant, complications, and outcome. Additionally, the case of a patient from our hospital is presented. Results: We included a total of 20 articles (21 cases) reporting on LMWH-induced skin necrosis. Skin necrosis occurred locally and distant from the injection site. Heparin-induced antibodies were frequently observed (positive 9/11 articles, negative 2/11). However, severe thrombocytopenia (platelet count <100,000cells/ml) occurred in only four cases, while platelet count remained normal in 50% of the cases. After patients had been switched to other anti-thrombotic drugs, the clinical course was usually benign; however, reconstructive surgery was necessary in two cases. Conclusion: LMWH-induced skin necrosis may occur as part of the heparin-induced thrombocytopenia (HIT) syndrome, but other pathomechanisms, including allergic reactions and local trauma, may also be involved. When HIT is excluded, unfractionated heparin is a safe switch anticoagulant. Otherwise, non-heparin preparations such as hirudin or fondaparinux should be preferre

Hybrid PSO Algorithm with Iterated Local Search Operator for Equality Constraints Problems

This paper presents a hybrid PSO algorithm (Par-ticle Swarm Optimization) with an ILS (Iterated Local Search) operator for handling equality constraints problems in mono-objective optimization problems. The ILS can be used to locally search around the best solutions in some generations, exploring the attraction basins in small portions of the feasible set. This process can compensate the difficulty of the evolutionary algorithm to generate good solutions in zero-volume regions. The greatest advantage of the operator is the simple implementation. Experiments performed on benchmark problems shows improvement in accuracy, reducing the gap for the tested problems

Desenvolvimento de um Algoritmo de Decomposição Híbrido Bioinspirado Baseado em Baleias e Estratégias de Evolução Diferencial para Otimização Multiobjetivo

A Multiobjective Optimization Problem (MOP) requires the optimization of several objective functions simultaneously, usually in conflict with each other. One of the most efficient algorithms for solving MOPs is MOEA/D (Multiobjective Evolutionary Algorithm Based on Decomposition), which decomposes a MOP into single-objective optimization subproblems and solves them using information from neighboring subproblems. MOEA/D variants with other evolutionary operators have emerged over the years, improving their efficiency in various MOPs. Recently, the IWOA (Improved Whale Optimization Algorithm) was proposed, an optimization algorithm bioinspired by the whale hunting method hybridized with Differential Evolution, which presented excellent results in single-objective optimization problems. This work proposes the MOEA/D-IWOA algorithm, which associates characteristics of the evolutionary operators of the IWOA to MOEA/D. Computational experiments were accomplished to analyze the performance of the MOEA/D-IWOA in benchmark MOPs suites. The results were compared with those obtained by the MOEA/D, Non-dominated Sorting Genetic Algorithm II (NSGA-II), Third Evolution Step of Generalized Differential Evolution (GDE3), Improving the Strength Pareto Evolutionary Algorithm (SPEA2), and Indicator-Based Evolutionary Algorithm (IBEA) algorithms in the Hypervolume and Inverted Generational Distance Plus (IGD+) indicators. The MOEA/D-IWOA proved to be competitive, with a good performance profile, in addition to presenting the best results in some POMs.Um Problema de Otimização Multiobjetivo (POM) requer a otimização de várias funções objetivo simultaneamente, geralmente conflitantes entre si. Um dos algoritmos mais eficientes para resolver POMs é o MOEA/D (Multiobjective Evolutionary Algorithm Based on Decomposition), que decompõe um POM em subproblemas de otimização monobjetivo, isto é, com uma única função objetivo a ser minimizada, e os resolve usando informações de subproblemas vizinhos. Variantes do MOEA/D com outros operadores evolutivos surgiram ao longo dos anos, melhorando sua eficiência em diversos POMs. Recentemente foi proposto o IWOA (Improved Whale Optimization Algorithm), um algoritmo de otimização bioinspirado no método de caça das baleias hibridizado com Evolução Diferencial que apresentou ótimos resultados em problemas de otimização monobjetivo. Esse trabalho propõe o algoritmo MOEA/D-IWOA, que extende o IWOA para resolver POMs associando características dos seus operadores evolutivos ao MOEA/D. Experimentos computacionais para analisar o desempenho do MOEA/D-IWOA em POMs benchmark foram realizados e os resultados comparados aos obtidos pelos algoritmos bem conhecidos da literatura, a saber, MOEA/D, Non-dominated Sorting Genetic Algorithm II (NSGA-II), Third Evolution Step of Generalized Differential Evolution (GDE3), Improving the Strength Pareto Evolutionary Algorithm (SPEA2) e Indicator-Based Evolutionary Algorithm (IBEA) nos indicadores Hypervolume e Inverted Generational Distance Plus (IGD+). O MOEA/D-IWOA se mostrou competitivo, com bom perfil de desempenho, além de apresentar os melhores resultados em alguns POMs

Hydrodynamic dispersion within porous biofilms

Many microorganisms live within surface-associated consortia, termed biofilms, that can form intricate porous structures interspersed with a network of fluid channels. In such systems, transport phenomena, including flow and advection, regulate various aspects of cell behavior by controlling nutrient supply, evacuation of waste products, and permeation of antimicrobial agents. This study presents multiscale analysis of solute transport in these porous biofilms. We start our analysis with a channel-scale description of mass transport and use the method of volume averaging to derive a set of homogenized equations at the biofilm-scale in the case where the width of the channels is significantly smaller than the thickness of the biofilm. We show that solute transport may be described via two coupled partial differential equations or telegrapher's equations for the averaged concentrations. These models are particularly relevant for chemicals, such as some antimicrobial agents, that penetrate cell clusters very slowly. In most cases, especially for nutrients, solute penetration is faster, and transport can be described via an advection-dispersion equation. In this simpler case, the effective diffusion is characterized by a second-order tensor whose components depend on (1) the topology of the channels' network; (2) the solute's diffusion coefficients in the fluid and the cell clusters; (3) hydrodynamic dispersion effects; and (4) an additional dispersion term intrinsic to the two-phase configuration. Although solute transport in biofilms is commonly thought to be diffusion dominated, this analysis shows that hydrodynamic dispersion effects may significantly contribute to transport

Characterisation of the mycobacterial NER system reveals novel functions of uvrD1 helicase

In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair. Mycobacterium smegmatis lacking the NER excinuclease component uvrB, the helicase uvrD1 and a double knock-out lacking both proteins were constructed and their sensitivity to a series of DNA damaging agents wa analysed. As anticipated, the mycobacterial NER system was shown to be involved in the processing of bulky DNA adducts and inter-strand cross-links. In addition, it could be shown to exert a protective effect against oxidising and nitrosating agents. Interestingly, inactivation of uvrB and uvrD1 significantly increased marker integration frequencies in gene conversion assays. This implies that in mycobacteria, which lack the postreplicative mismatch repair system, NER, and particularly the UvrD1 helicase, is involved in the processing of a subset of recombination-associated mismatches

The origin of the "European Medieval Warm Period"

Proxy records and results of a three dimensional climate model show that European summer temperatures roughly a millennium ago were comparable to those of the last 25 years of the 20th century, supporting the existence of a summer "Medieval Warm Period" in Europe. Those two relatively mild periods were separated by a rather cold era, often referred to as the "Little Ice Age". Our modelling results suggest that the warm summer conditions during the early second millennium compared to the climate background state of the 13th–18th century are due to a large extent to the long term cooling induced by changes in land-use in Europe. During the last 200 years, the effect of increasing greenhouse gas concentrations, which was partly levelled off by that of sulphate aerosols, has dominated the climate history over Europe in summer. This induces a clear warming during the last 200 years, allowing summer temperature during the last 25 years to reach back the values simulated for the early second millennium. Volcanic and solar forcing plays a weaker role in this comparison between the last 25 years of the 20th century and the early second millennium. Our hypothesis appears consistent with proxy records but modelling results have to be weighted against the existing uncertainties in the external forcing factors, in particular related to land-use changes, and against the uncertainty of the regional climate sensitivity. Evidence for winter is more equivocal than for summer. The forced response in the model displays a clear temperature maximum at the end of the 20th century. However, the uncertainties are too large to state that this period is the warmest of the past millennium in Europe during winter

The Application and Performance of Single Nucleotide Polymorphism Markers for Population Genetic Analyses of Lepidoptera

Microsatellite markers are difficult to apply within lepidopteran studies due to the lack of locus-specific PCR amplification and the high proportion of “null” alleles, such that erroneous estimations of population genetic parameters often result. Herein single nucleotide polymorphism (SNP) markers are developed from Ostrinia nubilalis (Lepidoptera: Crambidae) using next generation expressed sequence tag (EST) data. A total of 2742 SNPs were predicted within a reference assembly of 7414 EST contigs, and a subset of 763 were incorporated into 24 multiplex PCR reactions. To validate this pipeline, 5 European and North American sample sites were genotyped at 178 SNP loci, which indicated 84 (47.2%) were in Hardy–Weinberg equilibrium. Locus-by-locus FST, analysis of molecular variance, and STRUCTURE analyses indicate significant genetic differentiation may exist between European and North American O. nubilalis. The observed genetic diversity was significantly lower among European sites, which may result from genetic drift, natural selection, a genetic bottleneck, or ascertainment bias due to North American origin of EST sequence data. SNPs are an abundant source of mutation data for molecular genetic marker development in non-model species, with shared ancestral SNPs showing application within closely related species. These markers offer advantages over microsatellite markers for genetic and genomic analyses of Lepidoptera, but the source of mutation data may affect the estimation of population parameters and likely need to be considered in the interpretation of empirical data

Smooth stable and unstable manifolds for stochastic partial differential equations

Invariant manifolds are fundamental tools for describing and understanding nonlinear dynamics. In this paper, we present a theory of stable and unstable manifolds for infinite dimensional random dynamical systems generated by a class of stochastic partial differential equations. We first show the existence of Lipschitz continuous stable and unstable manifolds by the Lyapunov-Perron's method. Then, we prove the smoothness of these invariant manifolds

Report from the CVOT Summit 2020: new cardiovascular and renal outcomes

The 6th Cardiovascular Outcome Trial (CVOT) Summit “Cardiovascular and Renal Outcomes 2020” was the first to be held virtually on October 29–30, 2020. As in previous years, this summit served as reference meeting for in-depth discussions on the topic of recently completed and presented major outcome trials. This year, focus was placed on the outcomes of VERTIS-CV, EMPEROR-Reduced, DAPA-CKD, and FIDELIO-DKD. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussion evolved from major outcome trials using SGLT-2 inhibitors for treatment and prevention of heart failure and chronic kidney disease in people with and without diabetes, to additional therapy options for chronic kidney disease with a novel mineralocorticoid receptor antagonist. Furthermore, challenges in diabetes management like COVID-19 and obesity, as well as novel treatment strategies and guidelines, were discussed. The 7th Cardiovascular Outcome Trial Summit will be held virtually on November, 18–19, 2021 (http://www.cvot.org)