3,772 research outputs found
Duffy genotype and clinical manifestations severity in sickle cell anemia
No full textINTRODUÇÃO: Anemia falciforme (AF) apresenta grande variabilidade clínica e estudos prévios sugerem que polimorfismos genéticos podem atuar como preditores de complicações. O antígeno Duffy parece ter importante papel na retirada de quimiocinas inflamatórias da circulação, sugerindo que indivíduos Duffy-Negativo apresentariam menor clearance de citocinas e maior lesão endotelial. OBJETIVOS: Em um grupo de indivíduos com diagnóstico de AF, tivemos por objetivos: determinar a frequência dos fenótipos do sistema Duffy, determinar a frequência alélica do gene DUFFY, correlacionar os achados fenotípicos com os genotípicos, determinar a importância dos fenótipos Duffy em alterações clínico-laboratoriais selecionadas. CASUÍSTICA: 90 pacientes com AF em acompanhamento regular no ambulatório de hemoglobinopatias da Disciplina de Hematologia e Hemoterapia da Universidade Federal de São Paulo (UNIFESP/EPM). MÉTODOS: A fenotipagem eritrocitária foi realizada pela técnica de hemaglutinação em gel. A pesquisa molecular do gene DUFFY foi feita com primers específicos através da técnica de PCR seguida de digestão com enzimas específicas. Foram analisados o polimorfismo rs12075 (125 G>A) que identifica os alelos FY*A e FY*B; as mutações: rs2814778 (-33 T>C) que caracteriza o alelo FY*B-33; e rs34599082 (265 C>T) e rs13962 (298G>A) que identificam o alelo FY*Bfraco. Esses indivíduos foram estratificados, de acordo com os fenótipos, em Duffy-Positivo [Fy(a+b-),. Fy(a+b+) e Fy (a-b+)] e Duffy-Negativo [Fy(a-b-)]. Através de revisão de prontuários, foram avaliados: hemoglobina basal (Hb), hemoglobina fetal (HbF), hemoglobina S (HbS), reticulócitos e dosagem de desidrogenase lática (DHL), úlceras de membros inferiores (UMI), priapismo, episódios de síndrome torácica aguda (STA), osteonecrose (ON), elevação da pressão da artéria pulmonar (PAP = 30mmHg), acidente vascular encefálico (AVE: história e exames de imagem alterados) e indicação de uso de hidroxiuréia (HU). A análise estatística foi realizada com os seguintes testes: Mann-Whitney e Fisher, com nível descritivo de 5%. RESULTADOS: Dos 90 pacientes estudados, 40% eram do gênero masculino, a mediana de idade foi de 30,04 ± 10,15 anos. A análise fenotípica mostrou que 73,3% dos indivíduos eram Duffy-Positivo e 26,7% eram Duffy-Negativo. Observamos maior prevalência do alelo FY*B (71%), sendo que o alelo FY*B-33 foi encontrado em 43% dos alelos FY*B analisados. Os pacientes Duffy-Negativo apresentaram média de Hb de8, 32g/dL, enquanto o grupo Duffy-Positivo mostrava 9,01g/dL (p=0,039). As análises de reticulócitos, HbS, HbF não mostraram significância. O DHL, por sua vez, apresentou média de 634,59U/L nos indivíduos Duffy-Negativo e,506,42U/L (p=0,045). 63,6% dos indivíduos Duffy-Negativo e 31,5% do outrogrupo apresentaram elevação de PAP (p=0,0118; Razão de Chances: 3,792; 95% Intervalo de Confiança: 1,350- 10,652). Não houve diferença significativana frequência de priapismo, ON, STA e UMI entre os grupos. A manifestaçãode AVE foi observada apenas nos pacientes Duffy-Positivo (p=0,0049; Razãode Chances: 0,0625; 95% Intervalo de Confiança: 0,0035-1,089). A indicaçãode uso de HU foi maior nos indivíduos Duffy-Positivo (p=0,0528; Razão de Chances: 0,3524; 95% Intervalo de Confiança: 0,1278-0,9717). CONCLUSÃO:Diante os resultados apresentados, podemos inferir que a presença dasmutações estudadas está fortemente associada à expressão do Sistema Duffy.Do ponto de vista dos dados clínico-laboratoriais associados ao Sistema Duffy,embora os indivíduos Duffy-Negativo apresentem maior frequência de PAPelevada, seu índice de utilização de HU é menor e, portanto, não conseguimos afirmar que apresentam pior evolução clínica. Com isso, mais estudos, de preferência multicêntricos, são necessários para esclarecer esta questão.INTRODUCTION: Sickle cell anemia (SCA) presents with large clinical variability and previous studies suggest that genetic polymorphisms may act as complications predictors. The Duffy antigen appears to play an important role in the removal of inflammatory chemokines from the circulation, suggesting that Duffy-Negative individuals have lower clearance of cytokines and increased endothelial injury. OBJECTIVES: To determine the frequency of Duffy phenotype, determine the allelic frequency of gene DUFFY, correlate the phenotypic findings with the genotype and determine the importance of the Duffy phenotype in clinical and laboratory data from a group of SCA patients. PATIENTS: 90 AF patients regularly followed in the outpatient clinic of Hemoglobinophaties of the Department of Hematology, Federal University of Sao Paulo (UNIFESP / EPM). METHODS: Erytrocyte phenotyping of Duffy blood group was performed by hemagglutination in gel and molecular analysis of DUFFY gene was performed with specific PCR primers followed by digestion with restrition enzymes. We analyzed the rs12075 polymorphism (125 G> A) that identifies the alleles FY*A and FY*B; mutations: rs2814778 (-33 T>C) that characterizes the allele FY*B-33, and rs34599082 (265 C>T) and rs13962 (298G>A) that identify the alleles FY*Bweak. These individuals were stratified according to the phenotype, in Duffy-Positive [Fy (a+b-), Fy (a+b+) and Fy (a-b+)] and Duffy-Negative [Fy(ab-)]. Through medical records review, we evaluated baseline hemoglobin (Hb), fetal hemoglobin (HbF), S hemoglobin (HbS), reticulocytes count, serum lactate dehydrogenase (LDH), ulcers of the lower limbs (UMI), priapism, acute chest syndrome episodes (STA), osteonecrosis (ON), elevated pulmonary arterial pressure (PAP . 30 mmHg), stroke (history and neuroimaging) and indication of use of hydroxyurea (HU). Statistical analysis was performed with Mann-Whitney and Fisher tests, with a significance level of 5%. RESULTS: 40% of the patients were male, median age was 30.04 } 10.15 years. Phenotypic analysis revealed 73.3% Duffy-Positive and 26.7% Duffy-Negative individuals. The allele FY*B was found in 71% of the patients, and the FY*B-33 allele was found in 43% of the FY*B alleles. Duffy-Negative patients had a mean Hb of 8.32 g/dL, while Duffy-Positive the mean Hb was 9.01 g/dL (p = 0.039). There were no differences in the reticulocyte count, Hb, HbF withing the groups. However, the mean DHL was 634.59 U/L in Duffy-Negative individuals and 506.42 U/L in Duffy-Positive (p=0.045). 63.6% of Duffy-Negative individuals and 31.5% in Duffy-Positive showed elevated PAP (p = 0.0118, odds ratio: 3.792, 95% confidence interval: 1.350 to 10.652). There were no statistical differences in priapism, ON, STA and UMI frequencies of amoung groups. Stroke was observed only in Duffy-Positive patients (p=0.0049, odds ratio: 0.0625, 95% Confidence Interval: 0.0035 to 1.089). Indications of HU use was higher in Duffy-Positive subjects (p=0.0528, odds ratio: 0.3524, 95% Confidence Interval: 0.1278 to 0.9717). CONCLUSION: Given the results above, we can infer that the presence of the studied mutations is strongly associated with expression of the Duffy antigens. From clinical and laboratory data viewpoint, although Duffy-Negative individuals had a greater frequency of PAP, its rate of use of HU is smaller and therefore one can not say that they had a worse clinical outcome. Thus, further studies, preferably multicenter, are needed to clarify this issue.TEDEBV UNIFESP: Teses e dissertaçõesFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP - 05/55237
Analysis of Cultured Human Melanocytes Based on Polymorphisms within the SLC45A2/MATP, SLC24A5/NCKX5, and OCA2/P Loci.
No full textDIRECTION OF CAUSATION - REPLY TO COMMENTARIES
No full textWe reply to the commentaries on the lead papers by Neale et al. [1994a] and Duffy and Martin [1994]. Topics covered include power calculations, cross-sectional measurement vs. lifetime reports, the appropriateness of the direction of causation (DOG) model, extensions to study causation between the latent variables, sampling of subjects, and heterogeneity. We consider the potential of combining genetically informative research designs with multivariate longitudinal and experimental methods. (C) 1994 Wiley-Liss, Inc
Utilising Deep Learning Models for the Surface Registration Problem in HoloNav
No full textSurface Registration is a registration problem that handles the registration of two similar surfaces. In most research that utilises Deep Learning (DL) models to handle surface registration two theories are investigated; the first being whether surfaces sampled from the same origin can be registered together, and the second theory being whether the models can register Point Clouds with low overlapping data for utilisation in Simultaneous Localisation and Mapping (SLAM) applications. However, the surface registration to be utilised in the HoloNav Augmented Reality (AR) navigation system will utilise Point Clouds sampled from different origins with a high overlap ratio. This research, therefore, aims to determine the viability of DL methods for surface registration in HoloNav data. To determine the viability, rotation and translation errors in the match were used, with the aforementioned metrics later being evaluated manually with the utilisation of a visualiser. The results indicate that the models can generalise on the navigator data for an initial Euler angle difference of 45 degrees, but due to the difference in sampling density on the utilised point clouds can not provide accurate matches. Therefore, the utilisation of DL models can be considered to be viable if the navigator data has a sampling density similar to the pre-operative model.https://github.com/alpcicimen/holonav-dl-registration The link to the github repository containing the utilised dataset, scripts, as well as the modified DL models RPMNet and PREDATOR.CSE3000 Research ProjectComputer Science and Engineerin
The Scent of a Smell: An Extensive Comparison between Textual and Structural Smells
No full textCode smells are symptoms of poor design or implementation choices that have a negative effect on several aspects of software maintenance and evolution, such as program comprehension or change- and fault-proneness. This is why researchers have spent a lot of effort on devising methods that help developers to automatically detect them in source code. Almost all the techniques presented in literature are based on the analysis of structural properties extracted from source code, although alternative sources of information (e.g., textual analysis) for code smell detection have also been recently investigated. Nevertheless, some studies have indicated that code smells detected by existing tools based on the analysis of structural properties are generally ignored (and thus not refactored) by the developers. In this paper, we aim at understanding whether code smells detected using textual analysis are perceived and refactored by developers in the same or different way than code smells detected through structural analysis. To this aim, we set up two different experiments. We have first carried out a software repository mining study to analyze how developers act on textually or structurally detected code smells. Subsequently, we have conducted a user study with industrial developers and quality experts in order to qualitatively analyze how they perceive code smells identified using the two different sources of information. Results indicate that textually detected code smells are easier to identify and for this reason they are considered easier to refactor with respect to code smells detected using structural properties. On the other hand, the latter are often perceived as more severe, but more difficult to exactly identify and remove.Accepted Author ManuscriptSoftware Engineerin
Questions about Chemokine and Chemokine Receptor Antagonism in Renal Inflammation
No full textChemokines remain attractive therapeutic targets for modulating inflammatory diseases in all areas of medicine including acute and chronic kidney disease. Industry has launched huge programs for the development of chemokine antagonists, and clinical trials with chemokine and chemokine receptor antagonists are ongoing. However, chemokine biology remains an area of unexpected discoveries. Here we discuss a number of questions which need to be addressed to further explore the potential of chemokine antagonism in renal inflammation: Why does renal expression of chemokines and chemokine receptors not always correlate with their functional significance? Why does chemokine antagonism only partially reduce renal leukocyte counts? Will antagonist combinations be more effective in reducing renal inflammation? What are the functional roles of homeostatic chemokines and atypical, nonsignaling chemokine receptors in renal inflammation? And finally, what classes of chemokine antagonists are available to address these questions experimentally? Copyright (C) 2009 S. Karger AG, Base
Experimental evaluation of policies for sequencing the presentation of associations
No full textTwo policies for sequencing the presentation of associations are compared to the standard policy of randomly cycling through the list of associations. According to the modified-dropout policy, on each trial an association is presented that has not been presented on the two most recent trials and on which the observed number of correct responses since the last error is minimum. The second policy is based on a Markov state model of learning: on each trial, an association is presented that maximizes an arithmetic function of Bayesian estimates of residence in model states, a function that approximately indexes how unlearned associations are. Retention is improved relative to the standard policy only for the model-based policy.</p
March dl: Adding Adaptive Heuristics and a New Branching Strategy
No full textWe introduce the march dl satisability (SAT) solver, a successor of march eq. The latter was awarded state-of-the-art in two categories during the Sat 2004 competition. The focus lies on presenting those features that are new in march dl. Besides a description, each of these features is illustrated with some experimental results. By extending the pre-processor, using adaptive heuristics, and by using a new branching strategy, march dl is able to solve nearly all benchmarks faster than its predecessor. Moreover, various instances which were beyond the reach of march eq, can now be solved - relatively easily - due to these new features.Software TechnologyElectrical Engineering, Mathematics and Computer Scienc
Crash Reproduction Using Helper Objectives
No full textEvolutionary-based crash reproduction techniques aid developers in their debugging practices by generating a test case that reproduces a crash given its stack trace. In these techniques, the search process is typically guided by a single search objective called Crash Distance. Previous studies have shown that current approaches could only reproduce a limited number of crashes due to a lack of diversity in the population during the search. In this study, we address this issue by applying Multi-Objectivization using Helper-Objectives (MO-HO) on crash reproduction. In particular, we add two helper-objectives to the Crash Distance to improve the diversity of the generated test cases and consequently enhance the guidance of the search process. We assessed MO-HO against the single-objective crash reproduction. Our results show that MO-HO can reproduce two additional crashes that were not previously reproducible by the single-objective approach.Virtual/online event due to COVID-19 Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Software EngineeringSoftware Technolog
A General Formulation to Describe Empirical Rainfall Thresholds for Landslides
No full textAbstractIn this paper, a brief description of the Generalized FLaIR Model (GFM, De Luca and Versace, 2016) is provided, that is able to reproduce all the empirical thresholds proposed in literature, aimed to forecast landslides triggered by rainfall. In particular, this paper focuses on Antecedent Precipitation (AP) schemes. The paper demonstrates that these are particular solutions of the GFM and will exemplify this using AP schemes for NE Italy1, Seattle2 and Nicaragua - El Salvador3
- …
