Identification of the Best Practices for Design, Construction, and Repair of Bridge Approches, 2005

Bridge approach settlement and the formation of the bump is a common problem in Iowa that draws upon considerable resources for maintenance and creates a negative perception in the minds of transportation users. This research study was undertaken to investigate bridge approach problems and develop new concepts for design, construction, and maintenance that will reduce this costly problem. As a result of the research described in this report, the following changes are suggested for implementation on a pilot test basis: • Use porous backfill behind the abutment and/or geocomposite drainage systems to improve drainage capacity and reduce erosion around the abutment. • On a pilot basis, connect the approach slab to the bridge abutment. Change the expansion joint at the bridge to a construction joint of 2 inch. Use a more effective joint sealing system at the CF joint. Change the abutment wall rebar from #5 to #7 for non-integral abutments. • For bridges with soft foundation or embankment soils, implement practices of better compaction, preloading, ground improvement, soil removal and replacement, or soil reinforcement that reduce time-dependent post construction settlements.

Identification of the Best Practices for Design, Construction, and Repair of Bridge Approaches, January 2005

Bridge approach settlement and the formation of the bump is a common problem in Iowa that draws upon considerable resources for maintenance and creates a negative perception in the minds of transportation users. This research study was undertaken to investigate bridge approach problems and develop new concepts for design, construction, and maintenance that will reduce this costly problem. As a result of the research described in this report, the following changes are suggested for implementation on a pilot test basis: • Use porous backfill behind the abutment and/or geocomposite drainage systems to improve drainage capacity and reduce erosion around the abutment. • On a pilot basis, connect the approach slab to the bridge abutment. Change the expansion joint at the bridge to a construction joint of 2 inch. Use a more effective joint sealing system at the CF joint. Change the abutment wall rebar from #5 to #7 for non-integral abutments. • For bridges with soft foundation or embankment soils, implement practices of better compaction, preloading, ground improvement, soil removal and replacement, or soil reinforcement that reduce time-dependent post construction settlements.

Identification of cancer stem cells in Ewing's sarcoma.

Cancer stem cells that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been shown to date. Here, we identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESFT), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in nonobese diabetic/severe combined immunodeficiency mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic, and chondrogenic lineages. Quantitative real-time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133- counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells and demonstration of their MSC properties, a critical step towards a better biological understanding and rational therapeutic targeting of these tumors.

Forensic identification of urine samples: a comparison between nuclear and mitochondrial DNA markers.

Urine samples from 20 male volunteers of European Caucasian origin were stored at 4 degrees C over a 4-month period in order to compare the identification potential of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) markers. The amount of nDNA recovered from urines dramatically declined over time. Consequently, nDNA likelihood ratios (LRs) greater than 1,000 were obtained for 100, 70 and 55% of the urines analysed after 6, 60 and 120 days, respectively. For the mtDNA, HVI and HVII sequences were obtained for all samples tested, whatever the period considered. Nevertheless, the highest mtDNA LR of 435 was relatively low compared to its nDNA equivalent. Indeed, LRs obtained with only three nDNA loci could easily exceed this value and are quite easier to obtain. Overall, the joint use of nDNA and mtDNA markers enabled the 20 urine samples to be identified, even after the 4-month period.

Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Tumor necrosis factor (TNF) ligand and receptor superfamily members play critical roles in diverse developmental and pathological settings. In search for novel TNF superfamily members, we identified a murine chromosomal locus that contains three new TNF receptor-related genes. Sequence alignments suggest that the ligand binding regions of these murine TNF receptor homologues, mTNFRH1, -2 and -3, are most homologous to those of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors. By using a number of in vitro ligand-receptor binding assays, we demonstrate that mTNFRH1 and -2, but not mTNFRH3, bind murine TRAIL, suggesting that they are indeed TRAIL receptors. This notion is further supported by our demonstration that both mTNFRH1:Fc and mTNFRH2:Fc fusion proteins inhibited mTRAIL-induced apoptosis of Jurkat cells. Unlike the only other known murine TRAIL receptor mTRAILR2, however, neither mTNFRH2 nor mTNFRH3 has a cytoplasmic region containing the well characterized death domain motif. Coupled with our observation that overexpression of mTNFRH1 and -2 in 293T cells neither induces apoptosis nor triggers NFkappaB activation, we propose that the mTnfrh1 and mTnfrh2 genes encode the first described murine decoy receptors for TRAIL, and we renamed them mDcTrailr1 and -r2, respectively. Interestingly, the overall sequence structures of mDcTRAILR1 and -R2 are quite distinct from those of the known human decoy TRAIL receptors, suggesting that the presence of TRAIL decoy receptors represents a more recent evolutionary event.

Identification of an RP1 Prevalent Founder Mutation and Related Phenotype in Spanish Patients with Early-Onset Autosomal Recessive Retinitis.

OBJECTIVE: To identify the genetic causes underlying early-onset autosomal recessive retinitis pigmentosa (arRP) in the Spanish population and describe the associated phenotype. DESIGN: Case series. PARTICIPANTS: A total of 244 unrelated families affected by early-onset arRP. METHODS: Homozygosity mapping or exome sequencing analysis was performed in 3 families segregating arRP. A mutational screening was performed in 241 additional unrelated families for the p.Ser452Stop mutation. Haplotype analysis also was conducted. Individuals who were homozygotes, double heterozygotes, or carriers of mutations in RP1 underwent an ophthalmic evaluation to establish a genotype-phenotype correlation. MAIN OUTCOME MEASURES: DNA sequence variants, homozygous regions, haplotypes, best-corrected visual acuity, visual field assessments, electroretinogram responses, and optical coherence tomography images. RESULTS: Four novel mutations in RP1 were identified. The new mutation p.Ser542Stop was present in 11 of 244 (4.5%) of the studied families. All chromosomes harboring this mutation shared the same haplotype. All patients presented a common phenotype with an early age of onset and a prompt macular degeneration, whereas the heterozygote carriers did not show any signs of retinitis pigmentosa (RP). CONCLUSIONS: p.Ser542Stop is a single founder mutation and the most prevalent described mutation in the Spanish population. It causes early-onset RP with a rapid macular degeneration and is responsible for 4.5% of all cases. Our data suggest that the implication of RP1 in arRP may be underestimated. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Androgenetic alopecia: identification of four genetic risk loci and evidence for the contribution of WNT signaling to its etiology.

The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are associated with AGA development. However, a significant fraction of the overall heritable risk still awaits identification. Furthermore, the understanding of the pathophysiology of AGA is incomplete, and each newly associated locus may provide novel insights into contributing biological pathways. The aim of this study was to identify unknown AGA risk loci by replicating SNPs at the 12 genomic loci that showed suggestive association (5 × 10(-8)<P<10(-5)) with AGA in a recent meta-analysis. We analyzed a replication set comprising 2,759 cases and 2,661 controls of European descent to confirm the association with AGA at these loci. Combined analysis of the replication and the meta-analysis data identified four genome-wide significant risk loci for AGA on chromosomes 2q35, 3q25.1, 5q33.3, and 12p12.1. The strongest association signal was obtained for rs7349332 (P=3.55 × 10(-15)) on chr2q35, which is located intronically in WNT10A. Expression studies in human hair follicle tissue suggest that WNT10A has a functional role in AGA etiology. Thus, our study provides genetic evidence supporting an involvement of WNT signaling in AGA development.

Identification of novel elements of the Drosophila blisterome sheds light on potential pathological mechanisms of several human diseases.

Main developmental programs are highly conserved among species of the animal kingdom. Improper execution of these programs often leads to progression of various diseases and disorders. Here we focused on Drosophila wing tissue morphogenesis, a fairly complex developmental program, one of the steps of which - apposition of the dorsal and ventral wing sheets during metamorphosis - is mediated by integrins. Disruption of this apposition leads to wing blistering which serves as an easily screenable phenotype for components regulating this process. By means of RNAi-silencing technique and the blister phenotype as readout, we identify numerous novel proteins potentially involved in wing sheet adhesion. Remarkably, our results reveal not only participants of the integrin-mediated machinery, but also components of other cellular processes, e.g. cell cycle, RNA splicing, and vesicular trafficking. With the use of bioinformatics tools, these data are assembled into a large blisterome network. Analysis of human orthologues of the Drosophila blisterome components shows that many disease-related genes may contribute to cell adhesion implementation, providing hints on possible mechanisms of these human pathologies.

Fathers of girls, fathers of boys: influence of child's gender on fathers' experience of, engagement in, and representations of paternity.

The aim of this study was to examine the influence of child's gender on several dimensions-of paternity: the fathers' personal experience of paternity, their involvement in child rearing, and their representations. A total of 147 Swiss fathers of 18-month-old children (65 girls and 82 boys) relationship to the child or relationship with the child's completed questionnaires. The child's gender had little influence on paternal experience, mother. Globally, the fathers took on few responsibilities which were largely devolved to mothers. Fathers of boys were more involved in child care than fathers of girls. Finally, a discrepancy was found between the fathers representations of paternal roles in rearing girls and boys and the actual level of responsibility that fathers adopted in their relationship with their child.

Identification of a key lysine residue in heat shock protein 90 required for azole and echinocandin resistance in Aspergillus fumigatus.

Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. We previously showed that genetic repression of Hsp90 reduced Aspergillus fumigatus virulence and potentiated the effect of the echinocandin caspofungin. In this study, we sought to identify sites of posttranslational modifications (phosphorylation or acetylation) that are important for Hsp90 function in A. fumigatus. Phosphopeptide enrichment and tandem mass spectrometry revealed phosphorylation of three residues in Hsp90 (S49, S288, and T681), but their mutation did not compromise Hsp90 function. Acetylation of lysine residues of Hsp90 was recovered after treatment with deacetylase inhibitors, and acetylation-mimetic mutations (K27A and K271A) resulted in reduced virulence in a murine model of invasive aspergillosis, supporting their role in Hsp90 function. A single deletion of lysine K27 or an acetylation-mimetic mutation (K27A) resulted in increased susceptibility to voriconazole and caspofungin. This effect was attenuated following a deacetylation-mimetic mutation (K27R), suggesting that this site is crucial and should be deacetylated for proper Hsp90 function in antifungal resistance pathways. In contrast to previous reports in Candida albicans, the lysine deacetylase inhibitor trichostatin A (TSA) was active alone against A. fumigatus and potentiated the effect of caspofungin against both the wild type and an echinocandin-resistant strain. Our results indicate that the Hsp90 K27 residue is required for azole and echinocandin resistance in A. fumigatus and that deacetylase inhibition may represent an adjunctive anti-Aspergillus strategy.

Identification of care needs of patients with and without the use of a classification instrument

Objective: To analyze the agreement and disagreement between the assessments by applying or not a patient classification instrument, and to investigate the association between the agreement and personal and professional characteristics of the evaluators. Method: This is a descriptive exploratory study. 105 patients were hospitalized in a teaching hospital in the state of Sao Paulo, using the kappa statistic (weighted) and the Bootstrap method. Results: The agreement between the assessments were​​: kw 0.87 (instrument x internal evaluator), kw 0.78 (instrument x external evaluator) and kw 0.76 (between evaluators) and the influence of some personal and professional characteristics. The assessments conducted through the use of an instrument contemplated a greater number of areas of care in relation to when the instrument was not applied. Conclusion: The use of this instrument is recommended in order to more effectively identify care needs of patients.




Use and records of child health handbook focused on growth and development

Objective To evaluate the use and records of the Child Health Handbook (CHH), especially growth and development. Method Cross-sectional study with 358 mother-child pairs registered in 12 Primary Health Centers (PHCs) of a small municipality. Mothers were interviewed at the PHC from February to April 2013 using a questionnaire. Data analysis was done using WHO Anthro software, Epi InfoTM and Stata. Results Fifty-three percent of the mothers were carrying the CHH at the time of the interview, similar to the proportion of mothers who were instructed to bring the CHH to health appointments. Annotations in the CHH during the visits were reported by 49%. The vaccination schedule was completed in 97% of the CHH, but only 9% and 8% of the CHH, respectively, contained growth charts and properly completed developmental milestones. Conclusion Low rates of use and unsatisfactory record-keeping in the CHH reinforce the need for investment in professional training and community awareness for the CHH to become an effective instrument of promotion of child health.

Structural and Resting State Functional Connectivity of the Subthalamic Nucleus: Identification of Motor STN Parts and the Hyperdirect Pathway.

Deep brain stimulation (DBS) for Parkinson's disease often alleviates the motor symptoms, but causes cognitive and emotional side effects in a substantial number of cases. Identification of the motor part of the subthalamic nucleus (STN) as part of the presurgical workup could minimize these adverse effects. In this study, we assessed the STN's connectivity to motor, associative, and limbic brain areas, based on structural and functional connectivity analysis of volunteer data. For the structural connectivity, we used streamline counts derived from HARDI fiber tracking. The resulting tracks supported the existence of the so-called "hyperdirect" pathway in humans. Furthermore, we determined the connectivity of each STN voxel with the motor cortical areas. Functional connectivity was calculated based on functional MRI, as the correlation of the signal within a given brain voxel with the signal in the STN. Also, the signal per STN voxel was explained in terms of the correlation with motor or limbic brain seed ROI areas. Both right and left STN ROIs appeared to be structurally and functionally connected to brain areas that are part of the motor, associative, and limbic circuit. Furthermore, this study enabled us to assess the level of segregation of the STN motor part, which is relevant for the planning of STN DBS procedures.

In the context of a daycare center: nursing and their representations of child care as an educational act

This study aimed to analyze the social representations in the professionals of technical staff, who work with children at USP daycare centers. Eight professionals of the nursing field underwent a semi-structured interview. The interviews were recorded and transcribed in their entirety and the content of the discourse was subjected to thematic-categorical analysis. The categories were transformed into variables and processed by the software Classification Hiérarchique Classificatoire et Cohésitive (CHIC®) and analyzed by the hierarchical similarity tree. The results indicate that actions to promote health are reported as educational and transformative, in which health care gains new meaning through contextualized conceptions in the field of child education. We conclude that professionals attribute new meanings to their practices in the health care environment of daycare centers as their representations shifts from the logic of the biomedical field to a logic of educational care. In this sense, they perceive themselves as being challenged to establish an interaction with the children in terms of their activities related to the promotion of health and in an educational act.