Large-scale Nonlinear Variable Selection via Kernel Random Features

We propose a new method for input variable selection in nonlinear regression. The method is embedded into a kernel regression machine that can model general nonlinear functions, not being a priori limited to additive models. This is the first kernel-based variable selection method applicable to large datasets. It sidesteps the typical poor scaling properties of kernel methods by mapping the inputs into a relatively low-dimensional space of random features. The algorithm discovers the variables relevant for the regression task together with learning the prediction model through learning the appropriate nonlinear random feature maps. We demonstrate the outstanding performance of our method on a set of large-scale synthetic and real datasets.Comment: Final version for proceedings of ECML/PKDD 201

An increase in nitric oxide produced by rat peritoneal neutrophils is not involved in cell apoptosis

Polymorphonuclear neutrophils (PMN) obtained from carrageenin-stimulated peritoneal cavities of rats, but not blood PMN, spontaneously produced nitric oxide (NO) when incubated in vitro. Incubation of the cells with the NO synthase inhibitors, L-imino-ethyl-L-ornithine (L-NIO) or NG-monomethyl-L-arginine (L-NMMA), inhibited NO production. This inhibition could be reversed by L-arginine. Incubation of PMN with lipopolysaccharide (LPS) failed to enhance NO production. Pretreatment of the rats with dexamethasone (DEXA) prior to carrageenin injection or incubation of PMN with the glucocorticoid in vitro partially inhibited the spontaneous release of NO. On the other hand, when PMN obtained from DEXA pretreated rats were incubated in vitro with DEXA, NO synthase activity and hence NO generation were almost abolished. A similar inhibition was also observed following the addition of L-NIO or cycloheximide to cultures of carrageenin-elicited PMN. The NO production by PMN did not appear to be related to cell viability or apoptosis. Indeed, neither the blockade of NO generation by L-NIO nor the incubation of the neutrophils with a NO donor, S-nitroso-acetylpenicillamine (SNAP) modified the pattern of LDH release or DNA fragmentation. In summary, it appears that PMN migration triggers a continuous NO synthesis, and that NO produced by these cells is not related to their apoptosis

A community-based oral health self-care intervention for Hispanic families

Objectives A community-based intervention is described that targets oral health self-care practices among Hispanic children in the United States and is being tested in an ongoing trial. Descriptive results of baseline oral health variables are presented. Methods As of January 2013, 284 Hispanic children of ages 5–7 enrolled in the Healthy Families Study in Nashville, TN, USA. Families are randomized to one of two culturally appropriate interventions. Results At baseline, 69.6 % of children brushed at least twice daily, and 40.6 % brushed before bed daily. One-third of parents did not know if their children’s toothpaste contained fluoride. Conclusions This intervention fills the need for community-based interventions to improve oral health self-care practices that are culturally appropriate in Hispanic families

Association between functional EGF+61polymorphism and glioma risk

Epidermal growthf actor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61in glioma susceptibility and prognosis. Experimental Design:A case-control study involving197 glioma patients and 570 controlswas done. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). False-positive report probability was also assessed.The luciferase reporter gene assay was used to ascertain the functional consequences of this polymorphism. Results: Corroborating the univariate analysis, the multivariate model showed that the G allele conferred higher risks for gliomas (OR,1.32; 95% CI,1.04-1.67), glioblastomas (OR,1.47; 95% CI, 1.02-2.10), and oligodendrogliomas (OR,1.55; 95% CI,1.07-2.23).TheGG genotypeswere associatedwithincreased risk for gliomas (OR,1.71; 95%CI,1.07-2.73), glioblastomas (OR, 2.03; 95% CI, 1.02-4.05), and oligodendrogliomas (OR, 2.72; 95% CI, 1.18-6.28). In addition, the AG+GG genotypes were associated withhigher risk for gliomas (OR,1.52; 95% CI,1.03-2.23) and oligodendrogliomas (OR, 2.80; 95% CI,1.35-5.79). No significant associationwas observed between the EGF+61polymorphism and glioblastoma or oligodendroglioma patients’overall survival. The luciferase reporter gene assay exhibited a significant increased promoter activity for the G variant compared withthe referenceA allele. Conclusions: These findings support the role of the EGF+61polymorphism as a susceptibility factor for development of gliomas and show its implication on EGF promoter activity.Sixth Research Framework Programme of the European Union, Project INCA (LSHC-CT-2005-018704

ANEURISMAS DA ARTÉRIA ESPLÉNICA — SEGUIMENTO DE 2 CASOS TRATADOS COM RECURSO A ENDOPRÓTESE VASCULAR RECOBERTA

Os aneurismas da artéria esplénica são raros, mas constituem cerca de 60% de todos os aneurismas arteriais viscerais. A grande maioria dos doentes (80%) é assintomática sendo o diagnóstico realizado através de um achado em exames de imagem. O risco de rotura estimado é de 3% a 10%, com uma taxa de mortalidade associada à rotura de 25 a 70%. Critérios para tratamento eletivo incluem aneurismas sintomáticos, aneurismas com dimensões superiores a 20 mm ou com o aumento rápido do diâmetro. Adicionalmente, aneurismas diagnosticados em pacientes com hipertensão portal ou mulheres em idade fértil também têm indicação para tratamento, independentemente do diâmetro. O tratamento endovascular é a primeira linha em doentes com aneurismas da artéria esplenica, e inclui várias opções, como embolização com coils, oclusão com recurso a balões destacáveis e colocação de endoprótese vascular. Esta última é mais adequada para aneurismas localizados proximalmente e sua principal vantagem consiste no potencial para preservar o fluxo arterial esplénico e a função esplénica. É de salientar que a colocação de endoprótese para o tratamento de aneurismas da artéria esplénica está pouco descrita na literatura, consistindo sobretudo em pequenas séries de casos, todas com menos de 10 doentes. Trata-se de um procedimento que pode ser tecnicamente desafiante devido à tortuosidade da artéria esplênica. Não há resultados de follow-up a longo prazo na literatura. Neste artigo descrevemos dois casos de reparação de aneurisma da artéria utilizando stent grafts, com um follow-up máximo de 8 anos. Atingiu-se sucesso técnico em ambos os casos, sem crescimento pós-procedimento, endoleak, kinking, migração, re-intervenções ou outras complicações. Como conclusão, os dados na literatura sobre o uso de stents recobertos em aneurismas da artéria esplénica são escassos. Os resultados destes dois casos no nosso centro são encorajadores com um período de seguimento exceciona

Genetic variants identified by target next-generation sequencing in heart transplant patients with dilated cardiomyopathy

Introduction and Objectives: Dilated cardiomyopathy (DCM) is a myocardial disease that can progress to a terminal stage, requiring heart transplantation. In this work we aim to contribute to knowledge of genetic variants in adult patients undergoing heart transplantation due to end-stage DCM, reporting the results obtained in our single-center tertiary hospital series using target next-generation sequencing (NGS). Methods and Results: Genetic variants were screened in 15 genes, preselected based on variants previously identified in DCM patients. Thirteen unrelated patients were included, nine (69%) male, mean age at diagnosis 33±13 years, eight (62%) with familial DCM. Nine genetic variants were identified in six (46%) patients: five in LMNA, two in LBD3, one in TNNT2 and one in TCAP. These variants were new in most patients. The majority were classified as of uncertain significance. Two patients were double and triple heterozygotes in the LBD3 and LMNA genes, respectively. Conclusion: Our results highlight the potential of NGS in the genetic characterization of DCM patients. LMNA is one of the most frequently mutated genes and should be included in all target gene assessments of end-stage DCM patients until more data are available.This study received a research grant from Fundação para a Ciência e Tecnologia ( FCT-PTDC/BIM-MEC/0650/2012 )

Analysis of bovine blastocysts indicates ovarian stimulation does not induce chromosome errors, nor discordance between inner-cell mass and trophectoderm lineages

Contemporary systems for oocyte retrieval and culture of both cattle and human embryos are suboptimal with respect to pregnancy outcomes following transfer. In humans, chromosome abnormalities are the leading cause of early pregnancy loss in assisted reproduction. Consequently, pre-implantation genetic testing for aneuploidy (PGT-A) is widespread and there is considerable interest in its application to identify suitable cattle IVP embryos for transfer. Here we report on the nature and extent of chromosomal abnormalities following transvaginal follicular aspiration (OPU) and IVP in cattle. Nine sexually mature Holstein heifers underwent nine sequential cycles of OPU-IVP (six non-stimulated and three stimulated cycles), generating 459 blastocysts from 783 oocytes. We adopted a SNP-array approach normally employed in genomic evaluations but reanalysed (Turner et al., 2019; Theriogenology 125: 249) to detect levels of meiotic aneuploidy. Specifically, we asked whether ovarian stimulation increased the level of aneuploidy in either trophectoderm (TE) or inner-cell mass (ICM) lineages of blastocysts generated from OPU-IVP cycles. The proportion of Day 8 blastocysts of inseminated was greater (P < 0.001) for stimulated than non-stimulated cycles (0.712 ± 0.0288 vs. 0.466 ± 0.0360), but the overall proportion aneuploidy was similar for both groups (0.241 ± 0.0231). Most abnormalities consisted of meiotic trisomies. Twenty in vivo derived blastocysts recovered from the same donors were all euploid, thus indicating that 24 h of maturation is primarily responsible for aneuploidy induction. Chromosomal errors in OPU-IVP blastocysts decreased (P < 0.001) proportionately as stage/grade improved (from 0.373 for expanded Grade 2 to 0.128 for hatching Grade 1 blastocysts). Importantly, there was a high degree of concordance in the incidence of aneuploidy between TE and ICM lineages. Proportionately, 0.94 were “perfectly concordant” (i.e. identical result in both); 0.01 were imperfectly concordant (differing abnormalities detected); 0.05 were discordant; of which 0.03 detected a potentially lethal TE abnormality (false positives), leaving only 0.02 false negatives. These data support the use of TE biopsies for PGT-A in embryos undergoing genomic evaluation in cattle breeding. Finally, we report chromosome-specific errors and a high degree of variability in the incidence of aneuploidy between donors, suggesting a genetic contribution that merits further investigation