Quasi-binomial zero-inflated regression model suitable for variables with bounded support.

In recent years, a variety of regression models, including zero-inflated and hurdle versions, have been proposed to explain the case of a dependent variable with respect to exogenous covariates. Apart from the classical Poisson, negative binomial and generalised Poisson distributions, many proposals have appeared in the statistical literature, perhaps in response to the new possibilities offered by advanced software that now enables researchers to implement numerous special functions in a relatively simple way. However, we believe that a significant research gap remains, since very little attention has been paid to the quasi-binomial distribution, which was first proposed over fifty years ago. We believe this distribution might constitute a valid alternative to existing regression models, in situations in which the variable has bounded support. Therefore, in this paper we present a zero-inflated regression model based on the quasi-binomial distribution, taking into account the moments and maximum likelihood estimators, and perform a score test to compare the zero-inflated quasi-binomial distribution with the zero-inflated binomial distribution, and the zero-inflated model with the homogeneous model (the model in which covariates are not considered). This analysis is illustrated with two data sets that are well known in the statistical literature and which contain a large number of zeros.

Burkholderia tropica as a Potential Microalgal Growth-Promoting Bacterium in the Biosorption of Mercury from Aqueous Solutions.

The use of microalgal biomass is an interesting technology for the removal of heavy metals from aqueous solutions owing to its high metal-binding capacity, but the interactions with bacteria as a strategy for the removal of toxic metals have been poorly studied. The goal of the current research was to investigate the potential of Burkholderia tropica co-immobilized with Chlorella sp. in polyurethane discs for the biosorption of Hg(II) from aqueous solutions and to evaluate the influence of different Hg(II) concentrations (0.041, 1.0, and 10 mg/l) and their exposure to different contact times corresponding to intervals of 1, 2, 4, 8, 16, and 32 h. As expected, microalgal bacterial biomass adhered and grew to form a biofilm on the support. The biosorption data followed pseudo-second-order kinetics, and the adsorption equilibrium was well described by either Langmuir or Freundlich adsorption isotherm, reaching equilibrium from 1 h. In both bacterial and microalgal immobilization systems in the coimmobilization of Chlorella sp. and B. tropica to different concentrations of Hg(II), the kinetics of biosorption of Hg(II) was significantly higher before 60 min of contact time. The highest percentage of biosorption of Hg(II) achieved in the co-immobilization system was 95% at pH 6.4, at 3.6 g of biosorbent, 30 ± 1°C, and a mercury concentration of 1 mg/l before 60 min of contact time. This study showed that co-immobilization with B. tropica has synergistic effects on biosorption of Hg(II) ions and merits consideration in the design of future strategies for the removal of toxic metals.

Efecto de sobrecargas ligeras sobre el rendimiento del salto vertical con contramovimiento / Effect of light overloads on countermovement vertical jump performance

El propósito de este estudio ha sido determinar el efecto de diferentes sobrecargas ligeras sobre el impulso vertical, la velocidad del centro de masas y el máximo pico de potencia, durante la realización de dos saltos verticales máximos consecutivos. Han participado 28 deportistas practicantes de modalidades deportivas donde el salto vertical constituye una habilidad básica. Se ha utilizado una plataforma de fuerza, operando a 500 Hz, sincronizada temporalmente a una cámara de vídeo, que registraba a 210 Hz el plano sagital de los saltos realizados sobre la plataforma. Los resultados indican que, cuando se utilizan sobrecargas del 7,5% del peso corporal, el tiempo utilizado durante la fase de contramovimiento se incrementa. El impulso vertical y el pico de potencia no varían con el uso de los diferentes niveles de las sobrecargas utilizadas, sin embargo, la velocidad de despegue se reduce un porcentaje similar al incremento de la carga (AU)

The purpose of this study was to determine the effect of different light overloads on the vertical impulse, velocity of center of mass and peak power during two consecutive maximum vertical jumps. 28 athletes practicing different sports where vertical jump is a basic skill have participated. A force platform, operating at 500 Hz, temporally synchronized to a video camera, which recorded at 210 Hz the sagittal plane of the jumps were used for the analysis. The results have shown that when overloads of 7,5% of body weight were used , the time used for the counter- phase increased. The vertical impulse and peak power did not vary with the use of different levels of light overloads used in this study, however, the take-off velocity the CM was reduced with a similar percentage that increased the overload (AU)

UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation.

Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03-4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Malestar psicológico en familiares de pacientes con daño neurológico durante la fase subaguda de NeuroRehabilitación / Psychological distress in relatives of patients with neurological damage during the subacute phase of NeuroRehabilitation

Durante la última década la Neurorehabilitación ha comenzado a prestar mayor atención a las familias de personas que adquieren un daño neurológico. Este giro parece responder a un creciente número de estudios describiendo importantes niveles de malestar psicólogico en dichas familias y advirtiendo de su impacto en el proceso de rehabilitación. En Chile, lamentablemente, no contamos con estudios que exploren el estado emocional de familiares en ninguna de las etapas de rehabilitación, esto, a pesar de existir guías clínicas que sugieren el abordaje familiar como meta central. Dicha falta de información limita tanto la capacidad diagnóstica como interventiva de los equipos de rehabilitación. El objetivo de este artículo es describir, y comparar, el perfil de malestar psicológico en familiares de personas con lesión cerebral y medular en etapa subaguda de rehabilitación. Método. 89 familiares de personas con daño neurológico (Lesión Cerebral Adquirida = 50; Trauma Raquimedular = 39) respondieron el General Health Questionnaire-28 como medida de malestar psicológico. Este instrumento que se compone de cuatro subescalas: síntomas somáticos, ansiedad e insomnio, disfunción social y depresión grave. Resultados. En ambas poblaciones el puntaje total del GHQ-28 se observó por encima de los estándares poblacionales, sugiriendo niveles clínicos de malestar psicológico en 90 por ciento de la muestra. No se observaron diferencias entre ambas poblaciones en términos de puntaje total o puntaje de subescalas, sugiriendo similares perfiles de malestar psicólogico. Dicho perfil se caracterizó por altos niveles de ansiedad e insomnio, seguido en menor grado de síntomas somáticos...

During the last decade NeuroRehabilitation has begun to pay more attention to the families of people with neurological damage. This shift seems to respond to a growing number of studies describing significant levels of psychological distress in families, and warning professionals of its potential impact in the process of rehabilitation. In Chile, unfortunately, we have no studies that explore the emotional state of families in any stage of the rehabilitation process, this, despite the existence of clinical guidelines suggesting to address family needs as a central goal. This lack of information limits rehabilitation teams’ ability as well as their capacity to develop interventions. The aim of this article is to describe, and compare, the profile of psychological distress in relatives of people with brain damage and spinal cord injuries, during the sub-acute phase of rehabilitation. Method. 89 relatives of people with neurological damage (Acquired Brain Injury = 50; Spinal Cord Injury = 39) completed the General Health Questionnaire-28, a self-report measure of psychological distress. This instrument has four subscales, each of them screening for different types of symptoms: somatic, anxiety/insomnia, social dysfunction and severe depression. Results. Both neurological groups presented GHQ-28 total scored above population standards, thus suggesting clinical levels of psychological distress in 90 percent of the sample. No differences were observed between the two groups in terms of GHQ-28 total score or subscale score, thus, suggesting similar profiles of psychological distress. High levels of anxiety and insomnia, followed to a lesser degree by somatic symptoms, characterized this profile...

Associations between pig adiponectin (ADIPOQ) genotype and serum lipid levels are modulated by age-specific modifiers.

The adiponectin (ADIPOQ) locus is a positional and functional candidate gene for 2 porcine chromosome 13 (SSC13) QTL influencing cholesterol (CHOL) and low-density lipoprotein (LDL) concentrations in 190-d-old pigs. By sequencing 2.37 kb of the pig ADIPOQ cDNA, we have identified 1 c.*1512G>T 3' untranslated region polymorphism that has been genotyped in a Duroc pig commercial population with records for serum lipid levels at 45 and 190 d of age. Statistical analysis of the data have revealed significant associations between the ADIPOQ genotype and CHOL (P=0.0040) and LDL (P=0.0011) concentrations at 190 d but not at 45 d. In family 3, most of the SSC13 QTL effects on LDL levels at 190 d were explained by the ADIPOQ genotype. We also found an association with triglyceride levels at 45 d (P=0.0060) but not at 190 d. Measurement of allelic mRNA imbalance demonstrated that the G and T alleles are expressed at very similar levels in muscle and fat tissues, indicating that the c.*1512G>T polymorphism does not affect transcript abundance. As a whole, results obtained in the current work as well as previous data gathered in humans and pigs provide evidence that the magnitude of associations between blood lipid phenotypes and candidate loci genotypes may vary depending on the age of the individual, therefore suggesting the existence of dynamic genotype×environment interactions changing on a temporal scale.

DECR1 and ME1 genotypes are associated with lipid composition traits in Duroc pigs.

Variation at the porcine DECR1 and ME1 genes has been associated with meat quality traits and backfat thickness in Landrace pigs, respectively. However, it has not been investigated yet whether DECR1 and ME1 genotypes influence lipid composition. With this aim, we have genotyped two missense DECR1 substitutions (c.160G>C and c.437G>C) and one silent ME1 (c.576C>T) polymorphism in 361 Duroc barrows distributed in five half-sib families and phenotyped for serum lipid concentrations and intramuscular fat content and composition traits. At the whole-population level, relevant associations, that is, with a posterior probability of the allele substitution effect to be over or below zero (PPN0) > 0.90, were observed between DECR1 genotype and serum cholesterol (CHOL) (PPN0 = 0.932) and LDL concentrations (PPN0 = 0.945) at 190 days, as well as between ME1 genotype and longissimus dorsi saturated fatty acid content (PPN0 = 0.924). At the within-family level, we found relevant associations between DECR1 and ME1 genotypes and diverse lipid composition traits, but most of them were family-specific. Discrepancies in allele substitution effects estimated in half-sib families might be produced by many factors such as number of individuals, marker allele frequencies and informativeness in each family, unaccounted random genetic and environmental effects, epistasis and family-specific differences in the linkage phase or amount of linkage disequilibrium between causal and marker mutations. This lack of consistency across families, combined with the fact that the ME1 mutation is synonymous and that the two DECR1 polymorphisms are conservative, suggests that the associations found are not causative.

Application of the microarray technology to the transcriptional analysis of muscle phenotypes in pigs.

The transcriptome refers to the collection of all transcripts present in a cell. Gene expression has a very dynamic nature; it acts as a bridge between epigenetic marks, DNA sequence and proteins and changes to accommodate the requirements of the cell at each given time. Recent technological advances have created new opportunities to study complex phenotypes from a global point of view. From an animal production perspective, muscle transcriptomics has been investigated in relation to muscle growth, carcass fattening and meat quality traits. In this review, we discuss the impact of nutritional, anatomical and genetic factors on muscle gene expression and meat quality of pigs assessed by microarray technologies. Altogether, several common themes have been revealed by the in-depth analysis of the current body of knowledge, for instance, the involvement of genes related to energy balance and substrate turnover in the oxidative/glycolytic phenotype of red/white muscle fibre types and in the storage of intramuscular fat. The review also covers recent advances in the discovery of expression QTL and regulatory RNAs in porcine breeds as well as technical developments in the field of deep-sequencing technologies that are expected to substantially increase our knowledge about the genetic architecture of meat quality and production traits.

MicroRNA expression at diagnosis adds relevant prognostic information to molecular categorization in patients with intermediate-risk cytogenetic acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease, and optimal treatment varies according to cytogenetic risk factors and molecular markers. Several studies have demonstrated the prognostic importance of microRNAs (miRNAs) in AML. Here we report a potential association between miRNA expression and clinical outcome in 238 intermediate-risk cytogenetic AML (IR-AML) patients from 16 institutions in the CETLAM cooperative group. We first profiled 670 miRNAs in a subset of 85 IR-AML patients from a single institution and identified 10 outcome-related miRNAs. We then validated these 10 miRNAs by individual assays in the total cohort and confirmed the prognostic impact of 4 miRNAs. High levels of miR-196b and miR-644 were independently associated with shorter overall survival, and low levels of miR-135a and miR-409-3p with a higher risk of relapse. Interestingly, miR-135a and miR-409-3p maintained their independent prognostic value within the unfavorable molecular subcategory (wild-type NPM1 and CEBPA and/or FLT3-ITD), and miR-644 retained its value within the favorable molecular subcategory. miR-409-3p, miR-135a, miR-196b and mir-644 arose as prognostic markers for IR-AML, both overall and within specific molecular subgroups.

Genetics of serum and muscle lipids in pigs.

Pork meat is one of the most important sources of animal protein in the human diet. Its nutritional properties are partly determined by intramuscular fat content and composition, with existing general consensus about the detrimental effects of cholesterol and saturated fat on cardiovascular health in humans. Because of their physiological resemblance, pigs can be also used as a valuable animal model to study the genetics of human diseases such as atherosclerosis, obesity and dyslipidaemias. Heritability estimates and QTL maps of porcine muscle and serum lipid traits evidence that a considerable amount of genetic variance determining these phenotypes exists, but its molecular basis remains mostly unknown. The recent advent of high-throughput genotyping and sequencing technologies has revolutionised the field of animal genomics. With these powerful tools, finding needles in the genomic haystack has become increasingly feasible. However, these methodological advances should not be deemed as magic bullets. The goal of identifying the many polymorphisms that shape the variability of lipid phenotypes is so challenging that success can be achieved only under the scope of large international consortia.

Bone marrow WT1 levels at diagnosis, post-induction and post-intensification in adult de novo AML.

We retrospectively assessed whether normalized bone marrow WT1 levels could be used for risk stratification in a consecutive series of 584 acute myeloid leukemia (AML) patients. A cutoff value of 5065 copies at diagnosis identified two prognostic groups (overall survival (OS): 44 ± 3 vs 36 ± 3%, P=0.023; leukemia-free survival (LFS): 47 ± 3 vs 36 ± 4%, P=0.038; and cumulative incidence of relapse (CIR): 37 ± 3 vs 47 ± 4%, P=:0.043). Three groups were identified on the basis of WT1 levels post-induction: Group 0 (WT1 between 0 and 17.5 copies, 134 patients, OS: 59 ± 4%, LFS:59 ± 4% and CIR: 26 ± 4%); Group 1 (WT1 between 17.6 and 170.5 copies, 160 patients, OS: 48 ± 5%, LFS:41 ± 4% and CIR: 45 ± 4%); and Group 2 (WT1 >170.5 copies, 71 patients, OS: 23 ± 6%, LFS: 19 ± 7% and CIR: 68 ± 8%) (P<0.001). Post-intensification samples distinguished three groups: patients with WT1 >100 copies (47 patients, 16%); an intermediate group of patients with WT1 between 10 and 100 copies (148 patients, 52%); and a third group with WT1 <10 copies (92 patients, 32%). Outcomes differed significantly in terms of OS (30 ± 7%, 59 ± 4%, 72 ± 5%), LFS (24 ± 7%, 46 ± 4%, 65 ± 5%) and relapse probability (CIR 72 ± 7%, 45 ± 4%, 25 ± 5%), all P<0.001. WT1 levels in bone marrow assayed using the standardized ELN method provide relevant prognostic information in de novo AML.

Newly diagnosed adult AML and MPAL patients frequently show clonal residual hematopoiesis.

Adult acute myeloid leukemia (AML) is a highly heterogeneous stem cell malignancy characterized by the clonal expansion of immature myeloid precursors. AML may emerge de novo, following other hematopoietic malignancies or after cytotoxic therapy for other disorders. Here, we investigated the clonal vs reactive nature of residual maturing bone marrow cells in 59 newly diagnosed adult AML and mixed phenotype acute leukemia (MPAL) patients as assessed by interphase fluorescence in situ hybridization analysis of AML and myelodysplastic syndrome-associated cytogenetic alterations and/or the pattern of chromosome X inactivation, in females. In addition, we investigated the potential association between the degree of molecular/genetic involvement of hematopoiesis and coexistence of altered immunophenotypes by flow cytometry. Our results indicate that residual maturing neutrophils, monocytes and nucleated red cell precursors from the great majority of newly diagnosed AML and MPAL cases show a clonal pattern of involvement of residual maturing hematopoietic cells, in association with a greater number of altered immunophenotypes. These findings are consistent with the replacement of normal/reactive hematopoiesis by clonal myelopoiesis and/or erythropoiesis in most newly diagnosed AML and MPAL cases, supporting the notion that in most adults presenting with de novo AML, accumulation of blast cells could occur over a pre-existing clonal hematopoiesis.

A variant in IRF3 impacts on the clinical outcome of AML patients submitted to Allo-SCT.

Allo-SCT has a strong curative potential for AML patients mainly due to a GVL effect. Unfortunately, GvL and GVHD are intimately linked. IFN regulatory factor-3 (IRF3), by modulating innate immune reactions, could impact on the incidence and intensity of GVL and GVHD. We analyzed two gene variants in IRF3 (rs7251 and rs2304205) on the clinical outcome of 249 AML patients submitted to HLA-identical sibling allo-SCT. Patients with a donor carrying the dominant GG gene variant in rs7251 had, as compared with GC and CC variants, a lower acute GVHD (aGVHD) III-IV incidence (4% vs 11% vs 27%; P=0.0078), a higher relapse incidence (49% vs 35% vs 26%; P=0.018), and lower TRM (7% vs 24% vs 18%; P=0.0065). In functional studies, the GG variant was associated with lower production of IFN-γ, decreased lymphocyte proliferation after antigen presentation by DCs, and lower cytotoxic response of mature natural killer cells. Patients carrying the AA dominant variant in rs2304205 had higher relapse incidence (50% vs 39% vs 18%, P=0.0068). The presence of both variants (GG in rs7251 and AA in rs2304205) in donors and patients resulted in a stronger clinical impact.

Association analysis with lipid traits of 2 candidate genes (LRP12 and TRIB1) mapping to a SSC4 QTL for serum triglyceride concentration in pigs.

The performance of a genome scan for serum lipid traits at 45 and 190 d in 5 half-sib families of Duroc pigs allowed us to detect several pig chromosomal regions with significant effects on these phenotypes. In the current work, we aimed to refine the position of 1 chromosome 4 (SSC4) genome-wide significant QTL for serum triglyceride concentration at 190 d. Genotyping of 4 additional microsatellites allowed reduction of the 90% confidence interval of this QTL to the genomic interval between markers SW2409 and SW839. Sequencing experiments were performed to characterize the variability of 2 lipid-related genes, the lipoprotein receptor-related protein 12 (LRP12) and tribbles homolog 1 (TRIB1) loci, that map to this region. In this way, 2 (c.771A > G and c.1101A > G) and 1 (c.*156_157del) polymorphisms were identified at the LRP12 coding region and TRIB1 3' untranslated region, respectively. Association analyses between LRP12 and TRIB1 genotypes did not reveal any significant effect on serum lipid concentrations, suggesting that variation of these two loci does not explain the segregation of the SSC4 QTL. However, highly significant associations were observed for gluteus medius saturated fatty acid content (LRP12 c.1101A > G, P = 0.0006; TRIB1 c.*156_157del, P = 0.0003). In the light of these and other findings, the potential involvement of LRP12 and TRIB1 in muscle lipid metabolism deserves to be further explored.

Appearance, flavor, and texture attributes of pig dry-cured hams have a complex polygenic genomic architecture.

The influence that the genetics of species used as food sources has on the human perception of sensory attributes has been rarely addressed in previous studies. Dry-cured hams are high-quality highly appreciated pork products obtained by salting, curing, drying, and aging processes. We performed a QTL scan for 17 sensory attributes (including appearance, taste, flavor, and texture) and the overall liking evaluated by a panel of trained tasters in both semimembranosus (SM) and biceps femoris (BF) muscles of dry-cured hams from pigs raised in identical nutrition and management conditions. The QTL scan yielded a large array of chromosome- and genomewide QTL, reflecting the complex polygenic architecture of these traits. Among them, 6 QTL affecting SM flavor attributes (aged, matured, sweetness, and umami), 7 QTL associated to SM texture defects (adhesiveness and pastiness), and a single QTL for appearance (BF color intensity) reached the genomewide significant threshold. Discrepancies were observed between the BF and SM QTL maps, probably due to the differential drying and ripening rates determined by the external (SM) vs. internal (BF) location of each muscle. Within muscle, a certain degree of pleiotropy is supported by QTL co-localization for flavor (aged, matured, and sweet) or texture (such as pastiness and adhesiveness defects caused by excessive proteolysis) attributes. On the whole, QTL for overall sensory liking tended to co-localize with aged and matured QTL. Several functional candidate genes involved in the biochemical processes that shape flavor and texture attributes, such as ANPEP, LIPE, LIPA, MEP1B, and MMP28, co-localized with QTL hotspots. These results demonstrate that genetic factors of the pig influence the perception of the sensory attributes generated during dry-cured ham processing and represent a first contribution to elucidate which genetic factors may modulate the sensory properties of dry-cured hams.

Mapping and tissue mRNA expression analysis of the pig solute carrier 27A (SLC27A) multigene family.

Solute-carrier family 27A molecules are integral transmembrane proteins that play a fundamental role in the uptake of long-chain fatty acids into mammalian cells. Our goal was to characterize this multigene family in pigs. Chromosomal location of the six porcine SLC27A genes was determined by radiation hybrid mapping and indicated that the six genes map to six different chromosomal locations. Moreover, we analyzed SLC27A mRNA expression in six pig tissues by quantitative RT-PCR. While SLC27A1, SLC27A3 and SLC27A4 were expressed in most, if not all, analyzed tissues, SLC27A2, SLC27A5 and SLC27A6 were predominantly expressed in the liver. In general, pig and human SLC27A mRNA expression profiles were remarkably concordant, although important differences were observed for SLC27A1 and SLC27A6 mRNAs. Discrepancies between mRNA expression profiles have been observed even in closely related primate species, and they might reflect the acquisition of regulatory changes promoting evolutionary adaptation.