Wind-induced vibration analysis of the Hong Kong Ting Kau Bridge

Because of their high flexibility and relatively low structural damping, long-span bridges are prone to wind-induced vibration. An efficient wind field simulation technique for wind-induced vibration analysis of long-span bridges is first introduced in this paper. The time-domain expressions for the buffeting and self-excited forces acting on long-span bridges can then be found from the wind velocities. Based on the above theory and the aerodynamic parameters obtained by wind tunnel tests, a study of the wind fluctuations and aerodynamic forces is carried out on the Hong Kong Ting Kau Bridge, which is a cable-stayed bridge comprising two main spans and two side spans. The buffeting response of the bridge is analysed in the time domain by using step-by-step numerical integration techniques. The aerodynamic behaviour of the bridge can therefore be obtained, and the safety performance of the bridge against strong wind can further be evaluated. Numerical results basically agree with the experimental data, indicating that the theory presented in this paper is applicable to engineering practice.published_or_final_versio

Preconception Brief: Occupational/Environmental Exposures

In the last decade, more than half of U.S. children were born to working mothers and 65% of working men and women were of reproductive age. In 2004 more than 28 million women age 18–44 were employed full time. This implies the need for clinicians to possess an awareness about the impact of work on the health of their patients and their future offspring. Most chemicals in the workplace have not been evaluated for reproductive toxicity, and where exposure limits do exist, they were generally not designed to mitigate reproductive risk. Therefore, many toxicants with unambiguous reproductive and developmental effects are still in regular commercial or therapeutic use and thus present exposure potential to workers. Examples of these include heavy metals, (lead, cadmium), organic solvents (glycol ethers, percholoroethylene), pesticides and herbicides (ethylene dibromide) and sterilants, anesthetic gases and anti-cancer drugs used in healthcare. Surprisingly, many of these reproductive toxicants are well represented in traditional employment sectors of women, such as healthcare and cosmetology. Environmental exposures also figure prominently in evaluating a woman’s health risk and that to a pregnancy. Food and water quality and pesticide and solvent usage are increasingly topics raised by women and men contemplating pregnancy. The microenvironment of a woman, such as her choices of hobbies and leisure time activities also come into play. Caregivers must be aware of their patients’ potential environmental and workplace exposures and weigh any risk of exposure in the context of the time-dependent window of reproductive susceptibility. This will allow informed decision-making about the need for changes in behavior, diet, hobbies or the need for added protections on the job or alternative duty assignment. Examples of such environmental and occupational history elements will be presented together with counseling strategies for the clinician

A Novel Recombinant Peste des Petits Ruminants-Canine Adenovirus Vaccine Elicits Long-Lasting Neutralizing Antibody Response against PPR in Goats

BACKGROUND: Peste des petits ruminants (PPR) is a highly contagious infectious disease of goats, sheep and small wild ruminant species with high morbidity and mortality rates. The Peste des petits ruminants virus (PPRV) expresses a hemagglutinin (H) glycoprotein on its outer envelope that is crucial for viral attachment to host cells and represents a key antigen for inducing the host immune response. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether H can be exploited to generate an effective PPRV vaccine, a replication-competent recombinant canine adenovirus type-2 (CAV-2) expressing the H gene of PPRV (China/Tibet strain) was constructed by the in vitro ligation method. The H expression cassette, including the human cytomegalovirus (hCMV) promoter/enhancer and the BGH early mRNA polyadenylation signal, was inserted into the SspI site of the E3 region, which is not essential for proliferation of CAV-2. Infectious recombinant rCAV-2-PPRV-H virus was generated in transfected MDCK cells and used to immunize goats. All vaccinated animals produced antibodies upon primary injection that were effective in neutralizing PPRV in vitro. Higher antibody titer was obtained following booster inoculation, and the antibody was detectable in goats for at least seven months. No serious recombinant virus-related adverse effect was observed in immunized animals and no adenovirus could be isolated from the urine or feces of vaccinated animals. Results showed that the recombinant virus was safe and could stimulate a long-lasting immune response in goats. CONCLUSIONS/SIGNIFICANCE: This strategy not only provides an effective PPR vaccine candidate for goats but may be a valuable mean by which to differentiate infected from vaccinated animals (the so-called DIVA approach)

A genome-wide association study of corneal astigmatism: The CREAM Consortium

PURPOSE: To identify genes and genetic markers associated with corneal astigmatism. METHODS: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. RESULTS: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). CONCLUSIONS: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism

A genome-wide association study for corneal astigmatism: The CREAM Consortium

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis was performed of genome-wide association studies (GWAS) of corneal astigmatism undertaken for 14 European ancestry (N = 22,250) and 8 Asian ancestry (N = 9,120) cohorts by the CREAM Consortium. Cases were defined as having >0.75 D of corneal astigmatism. For the meta-analysed results of European ancestry cohorts, subsequent gene-based and gene-set analyses were performed using VEGAS2 and MAGMA software. Additionally, estimates of SNP-based heritability for corneal and refractive astigmatism and spherical equivalent were calculated for Europeans using LD score regression. Results: Meta-analysis of all cohorts identified a genome-wide significant locus near the gene PDGFRA (platelet derived growth factor receptor alpha): top SNP: rs7673984, odds ratio = 1.12 (95% CI: 1.08-1.16), P = 5.55 x 10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified 3 novel candidate genes for corneal astigmatism in Europeans: CLDN7 (claudin-7), ACP2 (acid phosphatase 2, lysosomal) and TNFAIP8L3 (TNF alpha induced protein 8 like 3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified 3 novel candidate genes CLDN7, ACP2 and TNFAIP8L3 that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors to the development of astigmatism

In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/146540/1/12951_2018_Article_425.pd

Deprescribing interventions and their impact on medication adherence in community-dwelling older adults with polypharmacy: a systematic review

Background: Polypharmacy, and the associated adverse drug events such as non-adherence to prescriptions, is a common problem for elderly people living with multiple comorbidities. Deprescribing, i.e. the gradual withdrawal from medications with supervision by a healthcare professional, is regarded as a means of reducing adverse effects of multiple medications including non-adherence. This systematic review examines the evidence of deprescribing as an effective strategy for improving medication adherence amongst older, community dwelling adults. Methods: A mixed methods review was undertaken. Eight bibliographic database and two clinical trials registers were searched between May and December 2017. Results were double screened in accordance with pre-defined inclusion/exclusion criteria related to polypharmacy, deprescribing and adherence in older, community dwelling populations. The Mixed Methods Appraisal Tool (MMAT) was used for quality appraisal and an a priori data collection instrument was used. For the quantitative studies, a narrative synthesis approach was taken. The qualitative data was analysed using framework analysis. Findings were integrated using a mixed methods technique. The review was performed in accordance with the PRISMA reporting statement. Results: A total of 22 original studies were included, of which 12 were RCTs. Deprescribing with adherence as an outcome measure was identified in randomised controlled trials (RCTs), observational and cohort studies from 13 countries between 1996 and 2017. There were 17 pharmacy-led interventions; others were led by General Practitioners (GP) and nurses. Four studies demonstrated an overall reduction in medications of which all studies corresponded with improved adherence. A total of thirteen studies reported improved adherence of which 5 were RCTs. Adherence was reported as a secondary outcome in all but one study. Conclusions: There is insufficient evidence to show that deprescribing improves medication adherence. Only 13 studies (of 22) reported adherence of which only 5 were randomised controlled trials. Older people are particularly susceptible to non-adherence due to multi-morbidity associated with polypharmacy. Bio-psycho-social factors including health literacy and multi-disciplinary team interventions influence adherence. The authors recommend further study into the efficacy and outcomes of medicines management interventions. A consensus on priority outcome measurements for prescribed medications is indicated