Modelos nulos de redes complejas

"En esta Tesis se proponen modelos nulos, basados en ensambles de matrices aleatorias, para las matrices de adyacencia de redes complejas. Entre las redes complejas estudiadas están: (i) grafos aleatorios de tipo Erdös-Rényi (ii) redes bipartitas, (iii) redes mutualistas, (iv) grafos geométricos aleatorios no uniformes y (v) grafos con pérdidas y ganancias. Se realizó análisis de escalamiento para identificar el parámetro universal de cada modelo nulo. Para ello se caracterizaron cantidades topológicas y espectrales de la red. Para las cantidades topológicas se calcularon algunos índices topológicos basados en los grados de los vértices. Mientras que para cantidades espectrales se calcularon cantidades comúnmente utilizadas en estudios de Teoría de Matrices Aleatorias, tales como: (i) la entropía de Shannon (o entropía de información) de los autovectores, (ii) el promedio de la razón de espaciamientos entre autovalores consecutivos y (iii) la distribución de las razones de espaciamientos entre autovalores consecutivos. En todos los casos se identificó la fase conectada, la fase aislada, así como el régimen de transición entre ambas fases. Esta Tesis pretende sistematizar la definición y el estudio de modelos nulos de redes complejas. Cuando fue posible comparamos nuestros resultados con datos de redes del mundo real"

Comments on Hynes et al. Prevalence of Marijuana Use among University Students in Bolivia, Colombia, Ecuador and Peru.

We have read and analyzed the article entitled “Prevalence of marijuana use among university students in Bolivia, Colombia, Ecuador and Peru”. We propose some objective points which could enhance the internal validity of the study (i.e., we suggest to report participation proportions).Revisión por pare

Comparison of appendicular functions released trough sight of pre-term newly born infants and to a term in the first 3 months of life

OBJETIVO: caracterizar e comparar o desenvolvimento de funções apendiculares entre dois grupos de lactentes a termo e pré-termo e verificar se a fixação visual pode ser considerada como um pré-requisito para as ações dos membros superiores. MÉTODO: estudo realizado no Centro de Estudos e Pesquisas em Reabilitação"Prof. Dr. Gabriel Porto", da Universidade Estadual de Campinas em dois grupos: 1) pré-termo, constituído de 21 lactentes, com idade corrigida entre 1 e 3 meses e 2) 21 recém-nascido a termo. Para avaliação utilizou-se o Método de Avaliação da Conduta Visual de Lactentes. Na análise estatística utilizou-se o teste "Q"de Cochran e o teste de Yates. RESULTADOS: verificou-se que, embora, no primeiro mês de vida a fixação visual tenha sido mais frequente no grupo a termo, não se observaram valores de significância estatística para cada grupo e entre eles. Verificou-se diferença estatística mês a mês para o grupo pré-termo e a termo em ambas as funções apendiculares, observando-se o mesmo valor de significância estatística (p = 0,000). Na comparação entre os grupos, tais funções não mostraram diferença significativa, embora tenha sido observado menores frequências nos pré-termo. Apesar da sequência das aquisições apendiculares desencadeadas pela visão ser semelhante nos grupos, o ritmo e o padrão de desenvolvimento apendicular dos lactentes pré-termo, com a idade corrigida, foram diferentes dos a termo, nos aspectos de frequência e qualidade.OBJECTIVE: to characterize and compare the appendicular functions released trough the sight from a pre-term infant group and to a term at the Centro de Estudos e Pesquisas em Reabilitação "Prof. Dr. Gabriel Porto" (Center of Studies and Rehabilitation "Professor Dr. Gabriel Porto", from the State University from Campinas. METHOD: 21 pre-term with gestational age under 37 completed weeks of gestation, suitable weight for the gestational age and corrected age between 1 and 3 months and, 21 to a term with gestational age between 39 to 41 gestational weeks, suitable weight to the gestational age and chronological age between 1 and 3 months. To evaluate it was used the Conduct Visual Infant Method of Evaluation. In the statistic analysis it was used the "Q" test from Cochran and the Test from Yates. RESULTS: although in the first month of life, the visual fixation was more frequent to the terms, it wasn't noticed significant values for each group and between them. In the pre-term and to a term it was noticed a statistic difference in both, the appendicular functions, observing the same value of significant statistic(p=0,000). Between the groups comparison, those functions do not show significant difference, though minor frequency have been observed in the pre-terms. CONCLUSION: the rhythm and the development pattern of appendicular functions released through the sight in the pre-term infants, with corrected age, differ from the term in terms of frequency and quality

Molecular characterization of multidrug resistant Enterobacterales strains isolated from liver and kidney transplant recipients in Spain

The objective of this study was to analyse the mechanisms of resistance to carbapenems and other extended-spectrum-?-lactams and to determine the genetic relatedness of multidrug-resistant Enterobacterales (MDR-E) causing colonization or infection in solid-organ transplantation (SOT) recipients. Prospective cohort study in kidney (n= 142), liver (n= 98) or kidney/pancreas (n= 7) transplant recipients between 2014 and 2018 in seven Spanish hospitals. We included 531 MDR-E isolates from rectal swabs obtained before transplantation and weekly for 4?6 weeks after the procedure and 10 MDR-E from clinical samples related to an infection. Overall, 46.2% Escherichia coli, 35.3% Klebsiella pneumoniae, 6.5% Enterobacter cloacae, 6.3% Citrobacter freundii and 5.7% other species were isolated. The number of patients with MDR-E colonization post-transplantation (176; 71.3%) was 2.5-fold the number of patients colonized pre-transplantation (71; 28.7%). Extended spectrum ?-lactamases (ESBLs) and carbapenemases were detected in 78.0% and 21.1% of MDR-E isolates respectively. In nine of the 247 (3.6%) transplant patients, the microorganism causing an infection was the same strain previously cultured from surveillance rectal swabs. In our study we have observed a low rate of MDR-E infection in colonized patients 4?6 weeks post-transplantation. E. coli producing blaCTX-M-G1 and K. pneumoniae harbouring blaOXA-48 alone or with blaCTX-M-G1 were the most prevalent MDR-E colonization strains in SOT recipients.Acknowledgements The authors thank Mª Jesús Lecea and Laura Álvarez for technical assistance. Tis research was supported by ‘Plan Nacional de I+D+i and Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias 13/01191), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, and the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0007, RD16/0016/0010, RD16/0016/0012, RD16/0016/0011, RD16/0016/0008, RD16/0016/0002). Te study was co-fnanced by the European Development Regional Fund “A way to achieve Europe” and the Operative Program Intelligent Growth 2014‐2020

WORKSHOP TO REVIEW AND UPDATE OSPAR STATUS ASSESSMENTS FOR STOCKS OF LISTED SHARK, SKATES AND RAYS IN SUPPORT OF OSPAR (WKSTATUS)

publishedVersio

Visual behavior of infants in the first and second months of life

Este estudo objetivou avaliar e conhecer o comportamento visual de lactentes no primeiro e segundo meses de vida. Os participantes foram 66 lactentes procedentes da região metropolitana de Campinas, nascidos no Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM/UNICAMP), assintomáticos, com peso ao nascimento variando de 3000g a 4140g, integrantes do Programa de Detecção de Alterações Audiológicas em Neonatos (DAANE), que compareceram ao Centro de Estudos e Pesquisas em Reabilitação "Prof. Dr. Gabriel Porto" da Faculdade de Ciências Médicas (CEPRE/FCM/UNICAMP) para triagem auditiva e cujos pais concordaram em participar do estudo. Para avaliação do comportamento visual utilizou-se o Método de Avaliação da Conduta Visual em Lactentes. A análise dos resultados utilizando-se o SPSS (Statistical Package for Social Sciences, versão 13) revelou, no primeiro mês, um destaque para as provas: fixação visual 97,62%, contato de olho 97,62%, sorriso 52,38%, seguimento visual horizontal 97,62% e seguimento visual vertical 52,38%. No segundo mês obteve-se 100% de resposta para as provas fixação visual, contato de olho, sorriso, seguimento visual horizontal e vertical. Os resultados obtidos no presente estudo estão em concordância com dados de estudos recentes sobre o comportamento visual de lactentes no primeiro trimestre de vida. A possibilidade de detectar oportunamente alterações no desenvolvimento visual está ligada a um diagnóstico oportuno e a um pronto encaminhamento a serviços de habilitação infantil, favorecendo, assim, a qualidade de vida das crianças e suas famílias.The aim of this study was to assess as well as understand the visual behavior of infants in the first and second months of life. The participants were 66 asymptomatic infants from Campinas, São Paulo, Brazil, born at the Integral Attention Center for Women's Health at Campinas State University (CAISM/UNICAMP), with birth weight ranging from 3000g to 4140g. These infants were participants in the Program for Detecting Audiological Alterations in Newborns (DAANE) who attended the Center for Studies and Research on Rehabilitation "Prof. Dr. Gabriel Porto" at the Faculty of Medical Sciences (CEPRE/FCM/UNICAMP) for auditory trial, and whose parents consented to participate in this study. Visual behaviors were assessed through the Method for Assessing Visual Acuity in Infants. The data analysis was performed by using the Statistical Package for Social Sciences (version 13). In the first month, the infants showed: visual fixation (97.62%), eye contact (97.62%), smile (52.38%), horizontal tracking (97.62%), and vertical tracking (52.38%). In the second month, they reached 100% in these same tests. The results are in accordance with recent studies on visual behavior of infants in the first three months of life. The possibility of opportunely detecting alterations in visual development is related to a timely diagnosis and a prompt referral to rehabilitation services for infants. As a consequence, it may improve the quality of life of children and their families

Variability of HIV-1 Genomes among Children and Adolescents from São Paulo, Brazil

Background: Genetic variability is a major feature of the human immunodeficiency virus type 1 (HIV-1) and considered the key factor to frustrating efforts to halt the virus epidemic. in this study, we aimed to investigate the genetic variability of HIV-1 strains among children and adolescents born from 1992 to 2009 in the state of São Paulo, Brazil.Methodology: Plasma and peripheral blood mononuclear cells (PBMC) were collected from 51 HIV-1-positive children and adolescents on ART followed between September 1992 and July 2009. After extraction, the genetic materials were used in a polymerase chain reaction (PCR) to amplify the viral near full length genomes (NFLGs) from 5 overlapped fragments. NFLGs and partial amplicons were directly sequenced and data were phylogenetically inferred.Results: of the 51 samples studied, the NFLGs and partial fragments of HIV-1 from 42 PBMCs and 25 plasma were successfully subtyped. Results based on proviral DNA revealed that 22 (52.4%) patients were infected with subtype B, 16 (38.1%) were infected with BF1 mosaic variants and 4 (9.5%) were infected with sub-subtype F1. All the BF1 recombinants were unique and distinct from any previously identified unique or circulating recombinant forms in South America. Evidence of dual infections was detected in 3 patients coinfected with the same or distinct HIV-1 subtypes. Ten of the 31 (32.2%) and 12 of the 21 (57.1%) subjects with recovered proviral and plasma, respectively, protease sequences were infected with major mutants resistant to protease inhibitors. the V3 sequences of 14 patients with available sequences from PBMC/or plasma were predicted to be R5-tropic virus except for two patients who harbored an X4 strain.Conclusions: the high proportion of HIV-1 BF1 recombinant, coinfection rate and vertical transmission in Brazil merits urgent attention and effective measures to reduce the transmission of HIV among spouses and sex partners.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)National Institutes of HealthUniv São Paulo, Sch Med, Clin & Res Lab LIM 03, São Paulo, BrazilUniv São Paulo, Inst Trop Med, Virol Lab LIM HCFMUSP 52, São Paulo, BrazilUniv Florida, Miller Sch Med, Story Lab 2, Miami, FL USAUniversidade Federal de São Paulo, Paulista Sch Med, Dept Pediat, São Paulo, BrazilUniv São Paulo, Sch Med, Div Clin Immunol & Allergy, São Paulo, BrazilUniv Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA USAUniversidade Federal de São Paulo, Paulista Sch Med, Dept Pediat, São Paulo, BrazilFAPESP: 2011/09983-1FAPESP: 2009/540055-5FAPESP: 2009/52381-2FAPESP: 2010/05845-0 2004/15856-9FAPESP: 2006/50096-0CAPES: 2571/2009National Institutes of Health: R01 AI060379Web of Scienc

Lentiviral gene therapy reverts GPIX expression and phenotype in Bernard-Soulier syndrome type C

Bernard-Soulier syndrome (BSS) is a rare congenital disease characterized by macrothrombocytopenia and frequent bleeding. It is caused by pathogenic variants in three genes (GP1BA, GP1BB, or GP9) that encode for the GPIbα, GPIbβ, and GPIX subunits of the GPIb-V-IX complex, the main platelet surface receptor for von Willebrand factor, being essential for platelet adhesion and aggregation. According to the affected gene, we distinguish BSS type A1 (GP1BA), type B (GP1BB), or type C (GP9). Pathogenic variants in these genes cause absent, incomplete, or dysfunctional GPIb-V-IX receptor and, consequently, a hemorrhagic phenotype. Using gene-editing tools, we generated knockout (KO) human cellular models that helped us to better understand GPIb-V-IX complex assembly. Furthermore, we developed novel lentiviral vectors capable of correcting GPIX expression, localization, and functionality in human GP9-KO megakaryoblastic cell lines. Generated GP9-KO induced pluripotent stem cells produced platelets that recapitulated the BSS phenotype: absence of GPIX on the membrane surface and large size. Importantly, gene therapy tools reverted both characteristics. Finally, hematopoietic stem cells from two unrelated BSS type C patients were transduced with the gene therapy vectors and differentiated to produce GPIX-expressing megakaryocytes and platelets with a reduced size. These results demonstrate the potential of lentiviral-based gene therapy to rescue BSS type C

Existence of reprogrammed lymphoma stem cells in a murine ALCL-like model.

Funder: DJCLS (R14/22) MSCA-ITN-2015-ETN AlkatrasFunder: DFG (CRC850)Funder: DFG (CRC850) BMBF (DeCaRe, FKZ 01ZX1409B)Funder: DJCLS (R14/22) MSCA-ITN-2015-ETN Alkatras DFG (FOR 2033 B1)Funder: DJCLS (R14/22) MSCA-ITN-2015-ETN Alkatras Grant from the Government of Baden-Württemberg (BSL)While cancer stem cells are well established in certain hematologic and solid malignancies, their existence in T cell lymphoma is unclear and the origin of disease is not fully understood. To examine the existence of lymphoma stem cells, we utilized a mouse model of anaplastic large cell lymphoma. Established NPM-ALK+ lymphomas contained heterogeneous cell populations ranging from mature T cells to undifferentiated hematopoietic stem cells. Interestingly, CD4-/CD8- double negative (DN) lymphoma cells aberrantly expressed the T cell receptor α/β chain. Serial transplantation of sorted CD4/CD8 and DN lymphoma subpopulations identified lymphoma stem cells within the DN3/DN4 T cell population, whereas all other subpopulations failed to establish serial lymphomas. Moreover, transplanted lymphoma DN3/DN4 T cells were able to differentiate and gave rise to mature lymphoma T cells. Gene expression analyses unmasked stem-cell-like transcriptional regulation of the identified lymphoma stem cell population. Furthermore, these lymphoma stem cells are characterized by low CD30 expression levels, which might contribute to limited long-term therapeutic success in patients treated with anti-CD30-targeted therapies. In summary, our results highlight the existence of a lymphoma stem cell population in a NPM-ALK-driven CD30+ mouse model, thereby giving the opportunity to test innovative treatment strategies developed to eradicate the origin of disease

Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci