Modeling repeated ordinal responses using a family of power transformations: application to neonatal hypothermia data

BACKGROUND: For analyzing a repeated ordinal response, it is common to use a multivariate cumulative logit model. This model may fit poorly, especially when a nonsymmetric response is available. In these cases, alternative strategies should be utilized. METHODS: In this paper, we present a family of power transformations for the cumulative probabilities to model asymmetric departures from the random-intercept cumulative logit model. To illustrate this method, we analyze the data from an epidemiologic study to identify risk factors of hypothermia among newly born infants in some referral university hospitals in Tehran, Iran. RESULTS: For hypothermia data, using this family of transformations and comparing the goodness-of-fit statistics showed that a model with the cumulative complementary log-log link gives us a better fit compared to a model with the cumulative logit link. CONCLUSION: In some areas, using the ordinary cumulative logit link function does not lead to the best fit. So, other link functions should be evaluated to discover the best transformation for the cumulative probabilities

A Deletion in Exon 9 of the LIPH Gene Is Responsible for the Rex Hair Coat Phenotype in Rabbits (Oryctolagus cuniculus)

The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the “r1” mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Z = 78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits

A Deletion in Exon 9 of the LIPH Gene Is Responsible for the Rex Hair Coat Phenotype in Rabbits (Oryctolagus cuniculus)

The fur of common rabbits is constituted of 3 types of hair differing in length and diameter while that of rex animals is essentially made up of amazingly soft down-hair. Rex short hair coat phenotypes in rabbits were shown to be controlled by three distinct loci. We focused on the “r1” mutation which segregates at a simple autosomal-recessive locus in our rabbit strains. A positional candidate gene approach was used to identify the rex gene and the corresponding mutation. The gene was primo-localized within a 40 cM region on rabbit chromosome 14 by genome scanning families of 187 rabbits in an experimental mating scheme. Then, fine mapping refined the region to 0.5 cM (Z = 78) by genotyping an additional 359 offspring for 94 microsatellites present or newly generated within the first defined interval. Comparative mapping pointed out a candidate gene in this 700 kb region, namely LIPH (Lipase Member H). In humans, several mutations in this major gene cause alopecia, hair loss phenotypes. The rabbit gene structure was established and a deletion of a single nucleotide was found in LIPH exon 9 of rex rabbits (1362delA). This mutation results in a frameshift and introduces a premature stop codon potentially shortening the protein by 19 amino acids. The association between this deletion and the rex phenotype was complete, as determined by its presence in our rabbit families and among a panel of 60 rex and its absence in all 60 non-rex rabbits. This strongly suggests that this deletion, in a homozygous state, is responsible for the rex phenotype in rabbits

Influence of Uranium on Bacterial Communities: A Comparison of Natural Uranium-Rich Soils with Controls

This study investigated the influence of uranium on the indigenous bacterial community structure in natural soils with high uranium content. Radioactive soil samples exhibiting 0.26% - 25.5% U in mass were analyzed and compared with nearby control soils containing trace uranium. EXAFS and XRD analyses of soils revealed the presence of U(VI) and uranium-phosphate mineral phases, identified as sabugalite and meta-autunite. A comparative analysis of bacterial community fingerprints using denaturing gradient gel electrophoresis (DGGE) revealed the presence of a complex population in both control and uranium-rich samples. However, bacterial communities inhabiting uraniferous soils exhibited specific fingerprints that were remarkably stable over time, in contrast to populations from nearby control samples. Representatives of Acidobacteria, Proteobacteria, and seven others phyla were detected in DGGE bands specific to uraniferous samples. In particular, sequences related to iron-reducing bacteria such as Geobacter and Geothrix were identified concomitantly with iron-oxidizing species such as Gallionella and Sideroxydans. All together, our results demonstrate that uranium exerts a permanent high pressure on soil bacterial communities and suggest the existence of a uranium redox cycle mediated by bacteria in the soil

Meeting the home-care needs of disabled older persons living in the community: does integrated services delivery make a difference?

<p>Abstract</p> <p>Background</p> <p>The PRISMA Model is an innovative coordination-type integrated-service-delivery (ISD) network designed to manage and better match resources to the complex and evolving needs of elders. The goal of this study was to examine the impact of this ISD network on unmet needs among disabled older persons living in the community.</p> <p>Methods</p> <p>Using data from the PRISMA study, we compared unmet needs of elders living in the community in areas with or without an ISD network. Disabilities and unmet needs were assessed with the Functional Autonomy Measurement System (SMAF). We used growth-curve analysis to examine changes in unmet needs over time and the variables associated with initial status and change. Sociodemographic characteristics, level of disability, self-perceived health status, cognitive functioning, level of empowerment, and the hours of care received were investigated as covariates. Lastly, we report the prevalence of needs and unmet needs for 29 activities in both areas at the end of the study.</p> <p>Results</p> <p>On average, participants were 83 years old; 62% were women. They had a moderate level of disability and mild cognitive problems. On average, they received 2.07 hours/day (SD = 1.08) of disability-related care, mostly provided by family. The findings from growth-curve analysis suggest that elders living in the area where ISD was implemented and those with higher levels of disability experience better fulfillment of their needs over time. Besides the area, being a woman, living alone, having a higher level of disability, more cognitive impairments, and a lower level of empowerment were linked to initial unmet needs (r²= 0.25; p < 0.001). At the end of the study, 35% (95% CI: 31% to 40%) of elders with needs living in the ISD area had at least one unmet need, compared to 67% (95% CI: 62% to 71%) in the other area. In general, unmet needs were highest for bathing, grooming, urinary incontinence, walking outside, seeing, hearing, preparing meals, and taking medications.</p> <p>Conclusions</p> <p>In spite of more than 30 years of home-care services in the province of Quebec, disabled older adults living in the community still have unmet needs. ISD networks such as the PRISMA Model, however, appear to offer an effective response to the long-term-care needs of the elderly.</p

Functional Redundancy of Two Pax-Like Proteins in Transcriptional Activation of Cyst Wall Protein Genes in Giardia lamblia

The protozoan Giardia lamblia differentiates from a pathogenic trophozoite into an infectious cyst to survive outside of the host. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately induced. Pax family transcription factors are involved in a variety of developmental processes in animals. Nine Pax proteins have been found to play an important role in tissue and organ development in humans. To understand the progression from primitive to more complex eukaryotic cells, we tried to identify putative pax genes in the G. lamblia genome and found two genes, pax1 and pax2, with limited similarity. We found that Pax1 may transactivate the encystation-induced cwp genes and interact with AT-rich initiatior elements that are essential for promoter activity and transcription start site selection. In this study, we further characterized Pax2 and found that, like Pax1, Pax2 was present in Giardia nuclei and it may specifically bind to the AT-rich initiator elements of the encystation-induced cwp1-3 and myb2 genes. Interestingly, overexpression of Pax2 increased the cwp1-3 and myb2 gene expression and cyst formation. Deletion of the C-terminal paired domain or mutation of the basic amino acids of the paired domain resulted in a decrease of nuclear localization, DNA-binding activity, and transactivation activity of Pax2. These results are similar to those found in the previous Pax1 study. In addition, the profiles of gene expression in the Pax2 and Pax1 overexpressing cells significantly overlap in the same direction and ERK1 associated complexes may phosphorylate Pax2 and Pax1, suggesting that Pax2 and Pax1 may be downstream components of a MAPK/ERK1 signaling pathway. Our results reveal functional redundancy between Pax2 and Pax1 in up-regulation of the key encystation-induced genes. These results illustrate functional redundancy of a gene family can occur in order to increase maintenance of important gene function in the protozoan organism G. lamblia

Tumor-induced stromal reprogramming drives lymph node transformation.

Lymph node (LN) stromal cells, particularly fibroblastic reticular cells (FRCs), provide critical structural support and regulate immunity, tolerance and the transport properties of LNs. For many tumors, metastasis to the LNs is predictive of poor prognosis. However, the stromal contribution to the evolving microenvironment of tumor-draining LNs (TDLNs) remains poorly understood. Here we found that FRCs specifically of TDLNs proliferated in response to tumor-derived cues and that the network they formed was remodeled. Comparative transcriptional analysis of FRCs from non-draining LNs and TDLNs demonstrated reprogramming of key pathways, including matrix remodeling, chemokine and/or cytokine signaling, and immunological functions such as the recruitment, migration and activation of leukocytes. In particular, downregulation of the expression of FRC-derived chemokine CCL21 and cytokine IL-7 were accompanied by altered composition and aberrant localization of immune-cell populations. Our data indicate that following exposure to tumor-derived factors, the stroma of TDLNs adapts on multiple levels to exhibit features typically associated with immunosuppression.This research was supported by the CIMR Flow Cytometry Core Facility. We wish to thank all FCCF staff members for their advice and support in flow cytometry and cell sorting applications. Work was supported by Medical Research Council funding. BAH is supported by the Royal Society (University Research Fellowship).This is the author accepted manuscript