56 research outputs found

    Analysis of Pavement Riding Quality: A Triaxial Evaluation of Pavement Roughness

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    For the last twenty-five years considerable research has been directed toward developing reliable equipment for evaluating pavement roughness. Since roughness inhibits passenger riding comfort and safety, as well as inducing vehicle deterioration, the determination of the features that cause roughness would indicate possible improvements in pavement design, materials, construction practices and equipment. For example, certain types of base design might be found to produce smoother surfaces than others; and a construction practice such as a blade-spread leveling course might result in more uniform pavements. Then too, evaluation of pavement roughness would permit relative comparison of pavements as one of several factors in determining the most needed of possible improvements, with the normally limited finances available. This could appear in a tabulation of sufficiency ratings such as those used by the Kentucky Department of Highway

    Triaxial Acceleration Analysis Applied to the Evaluation of Pavement Riding Qualities

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    Traditionally the riding qualities of a pavement are expressed as some function of localized irregularities in the contour of the pavement surface. This is predicated on the fact that the portion of passenger comfort or discomfort imparted by all features of the pavement surface can not be isolated and determined separately from other influences such as vehicle characteristics or psychological and physiological aspects of the passenger himself. Measurements of riding qualities have dealt almost exclusively with vehicle displacements in the vertical direction only, these having been and still being the most prominent and most amenable to measurement. By this procedure displacements in other directions have been ignored, although their relative influence on riding comfort as determined by comfort research is known to be great. During the past few years certain features of highway construction and use have emphasized surface irregularities that cause significant amounts of combined transverse and longitudinal motion. In response to this developing need for determination of riding qualities on the basis of component motions, an instrument for measuring and recording induced accelerations in the three principal directions was developed and adapted to a passenger vehicle. This paper describes the equipment and its use in evaluating riding qualities of various pavements in Kentucky

    A low-carbohydrate, ketogenic diet to treat type 2 diabetes

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    BACKGROUND: The low-carbohydrate, ketogenic diet (LCKD) may be effective for improving glycemia and reducing medications in patients with type 2 diabetes. METHODS: From an outpatient clinic, we recruited 28 overweight participants with type 2 diabetes for a 16-week single-arm pilot diet intervention trial. We provided LCKD counseling, with an initial goal of <20 g carbohydrate/day, while reducing diabetes medication dosages at diet initiation. Participants returned every other week for measurements, counseling, and further medication adjustment. The primary outcome was hemoglobin A(1c). RESULTS: Twenty-one of the 28 participants who were enrolled completed the study. Twenty participants were men; 13 were White, 8 were African-American. The mean [± SD] age was 56.0 ± 7.9 years and BMI was 42.2 ± 5.8 kg/m(2). Hemoglobin A(1c )decreased by 16% from 7.5 ± 1.4% to 6.3 ± 1.0% (p < 0.001) from baseline to week 16. Diabetes medications were discontinued in 7 participants, reduced in 10 participants, and unchanged in 4 participants. The mean body weight decreased by 6.6% from 131.4 ± 18.3 kg to 122.7 ± 18.9 kg (p < 0.001). In linear regression analyses, weight change at 16 weeks did not predict change in hemoglobin A(1c). Fasting serum triglyceride decreased 42% from 2.69 ± 2.87 mmol/L to 1.57 ± 1.38 mmol/L (p = 0.001) while other serum lipid measurements did not change significantly. CONCLUSION: The LCKD improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication

    Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

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    The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines

    Barriers and facilitators to recruitment of physicians and practices for primary care health services research at one centre

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    <p>Abstract</p> <p>Background</p> <p>While some research has been conducted examining recruitment methods to engage physicians and practices in primary care research, further research is needed on recruitment methodology as it remains a recurrent challenge and plays a crucial role in primary care research. This paper reviews recruitment strategies, common challenges, and innovative practices from five recent primary care health services research studies in Ontario, Canada.</p> <p>Methods</p> <p>We used mixed qualitative and quantitative methods to gather data from investigators and/or project staff from five research teams. Team members were interviewed and asked to fill out a brief survey on recruitment methods, results, and challenges encountered during a recent or ongoing project involving primary care practices or physicians. Data analysis included qualitative analysis of interview notes and descriptive statistics generated for each study.</p> <p>Results</p> <p>Recruitment rates varied markedly across the projects despite similar initial strategies. Common challenges and creative solutions were reported by many of the research teams, including building a sampling frame, developing front-office rapport, adapting recruitment strategies, promoting buy-in and interest in the research question, and training a staff recruiter.</p> <p>Conclusions</p> <p>Investigators must continue to find effective ways of reaching and involving diverse and representative samples of primary care providers and practices by building personal connections with, and buy-in from, potential participants. Flexible recruitment strategies and an understanding of the needs and interests of potential participants may also facilitate recruitment.</p

    Deregulated expression of CD40 ligand in HTLV-I infection: Distinct mechanisms of downregulation in HTLV-I-transformed cell lines and ATL patients

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    AbstractHTLV-I infection is associated with the development of adult T cell leukemia (ATL) and the neuroinflammatory disease HAM/TSP. There are quantitative and qualitative differences in the antiviral cytotoxic T cell (CTL) response in ATL and HAM/TSP although the underlying mechanisms are unclear. Here, we demonstrate that the HTLV-I Tax trans-activating protein is a transcriptional activator of CD40 ligand (CD40L), a critical regulator of dendritic cell maturation and adaptive immunity. Tax activates CD40L expression via a cyclosporin A insensitive pathway that is also independent of NF-κB. Although Tax upregulates CD40L gene expression, CD40L expression is absent in Tax-expressing HTLV-I-transformed cell lines via an epigenetic mechanism involving methylation. T lymphocytes cultured ex vivo from ATL patients, but not HAM/TSP or normal controls, exhibit a potent block in the induction of CD40L, but not CD69. However, the CD40L gene is not silenced by methylation in ATL patients, thus CD40L is downregulated by distinct mechanisms in HTLV-I-transformed cell lines and ATL patients

    Comparative genomics of small RNA regulatory pathway components in vector mosquitoes

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    <p>Abstract</p> <p>Background</p> <p>Small RNA regulatory pathways (SRRPs) control key aspects of development and anti-viral defense in metazoans. Members of the Argonaute family of catalytic enzymes degrade target RNAs in each of these pathways. SRRPs include the microRNA, small interfering RNA (siRNA) and PIWI-type gene silencing pathways. Mosquitoes generate viral siRNAs when infected with RNA arboviruses. However, in some mosquitoes, arboviruses survive antiviral RNA interference (RNAi) and are transmitted via mosquito bite to a subsequent host. Increased knowledge of these pathways and functional components should increase understanding of the limitations of anti-viral defense in vector mosquitoes. To do this, we compared the genomic structure of SRRP components across three mosquito species and three major small RNA pathways.</p> <p>Results</p> <p>The <it>Ae. aegypti, An. gambiae </it>and <it>Cx. pipiens </it>genomes encode putative orthologs for all major components of the miRNA, siRNA, and piRNA pathways. <it>Ae. aegypti </it>and <it>Cx. pipiens </it>have undergone expansion of Argonaute and PIWI subfamily genes. Phylogenetic analyses were performed for these protein families. In addition, sequence pattern recognition algorithms MEME, MDScan and Weeder were used to identify upstream regulatory motifs for all SRRP components. Statistical analyses confirmed enrichment of species-specific and pathway-specific cis-elements over the rest of the genome.</p> <p>Conclusion</p> <p>Analysis of Argonaute and PIWI subfamily genes suggests that the small regulatory RNA pathways of the major arbovirus vectors, <it>Ae. aegypti and Cx. pipiens</it>, are evolving faster than those of the malaria vector <it>An. gambiae </it>and <it>D. melanogaster</it>. Further, protein and genomic features suggest functional differences between subclasses of PIWI proteins and provide a basis for future analyses. Common UCR elements among SRRP components indicate that 1) key components from the miRNA, siRNA, and piRNA pathways contain NF-kappaB-related and Broad complex transcription factor binding sites, 2) purifying selection has occurred to maintain common pathway-specific elements across mosquito species and 3) species-specific differences in upstream elements suggest that there may be differences in regulatory control among mosquito species. Implications for arbovirus vector competence in mosquitoes are discussed.</p
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