Ocular antisense oligonucleotide delivery by cationic nanoemulsion for improved treatment of ocular neovascularization: an in-vivo study in rats and mice.

The efficacy of an antisense oligonucleotide (ODN17) cationic nanoemulsion directed at VEGF-R2 to reduce neovascularization was evaluated using rat corneal neovascularization and retinopathy of prematurity (ROP) mouse models. Application of saline solution or scrambled ODN17 solution on eyes of rats led to the highest extent of corneal neovascularization. The groups treated with blank nanoemulsion or scrambled ODN17 nanoemulsion showed moderate inhibition in corneal neovascularization with no significant difference with the saline and scrambled ODN17 control solution groups, while the groups treated with ODN17 solution or Avastin® (positive ODN17 control) clearly elicited marked significant inhibition in corneal neovascularization confirming the results reported in the literature. The highest significant corneal neovascularization inhibition efficiency was noted in the groups treated with ODN17 nanoemulsion (topical and subconjunctivally). However, in the ROP mouse model, the ODN17 in PBS induced a 34% inhibition of retinal neovascularization when compared to the aqueous-vehicle-injected eyes. A significantly higher inhibition of vitreal neovascularization (64%) was observed in the group of eyes treated with ODN17 nanoemulsion. No difference in extent of neovascularization was observed between blank nanoemulsion, scrambled ODN17 nanoemulsion, vehicle or non-treated eyes. The overall results indicate that cationic nanoemulsion can be considered a promising potential ocular delivery system and an effective therapeutic tool of high clinical significance in the prevention and forthcoming treatment of ocular neovascular diseases.

A Transportation Safety Planning Tool for the City of Ames, August 2011

The historically-reactive approach to identifying safety problems and mitigating them involves selecting black spots or hot spots by ranking locations based on crash frequency and severity. The approach focuses mainly on the corridor level without taking the exposure rate (vehicle miles traveled) and socio-demographics information of the study area, which are very important in the transportation planning process, into consideration. A larger study analysis unit at the Transportation Analysis Zone (TAZ) level or the network planning level should be used to address the needs of development of the community in the future and incorporate safety into the long-range transportation planning process. In this study, existing planning tools (such as the PLANSAFE models presented in NCHRP Report 546) were evaluated for forecasting safety in small and medium-sized communities, particularly as related to changes in socio-demographics characteristics, traffic demand, road network, and countermeasures. The research also evaluated the applicability of the Empirical Bayes (EB) method to network-level analysis. In addition, application of the United States Road Assessment Program (usRAP) protocols at the local urban road network level was investigated. This research evaluated the applicability of these three methods for the City of Ames, Iowa. The outcome of this research is a systematic process and framework for considering road safety issues explicitly in the small and medium-sized community transportation planning process and for quantifying the safety impacts of new developments and policy programs. More specifically, quantitative safety may be incorporated into the planning process, through effective visualization and increased awareness of safety issues (usRAP), the identification of high-risk locations with potential for improvement, (usRAP maps and EB), countermeasures for high-risk locations (EB before and after study and PLANSAFE), and socio-economic and demographic induced changes at the planning-level (PLANSAFE).

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.

Controlled expression of recombinant proteins in Physcomitrella patens by a conditional heat-shock promoter: a tool for plant research and biotechnology.

The ability to express tightly controlled amounts of endogenous and recombinant proteins in plant cells is an essential tool for research and biotechnology. Here, the inducibility of the soybean heat-shock Gmhsp17.3B promoter was addressed in the moss Physcomitrella patens, using beta-glucuronidase (GUS) and an F-actin marker (GFP-talin) as reporter proteins. In stably transformed moss lines, Gmhsp17.3B-driven GUS expression was extremely low at 25 degrees C. In contrast, a short non-damaging heat-treatment at 38 degrees C rapidly induced reporter expression over three orders of magnitude, enabling GUS accumulation and the labelling of F-actin cytoskeleton in all cell types and tissues. Induction levels were tightly proportional to the temperature and duration of the heat treatment, allowing fine-tuning of protein expression. Repeated heating/cooling cycles led to the massive GUS accumulation, up to 2.3% of the total soluble proteins. The anti-inflammatory drug acetyl salicylic acid (ASA) and the membrane-fluidiser benzyl alcohol (BA) also induced GUS expression at 25 degrees C, allowing the production of recombinant proteins without heat-treatment. The Gmhsp17.3B promoter thus provides a reliable versatile conditional promoter for the controlled expression of recombinant proteins in the moss P. patens.

Physiopathologie et prévention des infections liées aux accès vasculaires [Pathophysiology and prevention of intravascular catheter-related infection]

Les infections liées aux accès vasculaires sont à l'origine d'une proportion importante des infections nosocomiales. Elles comprennent leur colonisation par des micro-organismes, les infections du site d'insertion et les bactériémies et fongémies qui leur sont associées ou attribuées. Une bactériémie complique l'insertion de 3 à 5 % des voies veineuses, correspondant à une incidence de 2 à 14 épisodes pour 1000 jourcathéters. Cette proportion ne représente toutefois que la partie visible de l'iceberg puisque la plupart des épisodes de sepsis clinique sans foyer infectieux associé sont également considérés comme liés aux accès vasculaires. Après un rappel de leur physiopathologie, cet article passe en revue les éléments importants pour leur prévention, y compris ceux concernant l'utilisation de cathéters imprégnés de désinfectants ou d'antibiotiques. Pour terminer, nous discutons en détail les stratégies préventives globales. Fondées sur la prise en compte d'un ensemble d'éléments spécifiques, ces approches sont centrées sur l'éducation du personnel au respect des règles d'hygiène de base et sur l'introduction de recommandations précises pour l'insertion et l'utilisation des accès vasculaires.

Prévention quaternaire: agir est-il toujours justifié en médecine de famille [Quaternary prevention: is acting always justified in family medicine?].

Quaternary prevention aims to protect the patient or population against overmedicalisation. Quaternary prevention influences all the activities of family medicine by questioning the utility of primary prevention and early diagnosis, identifying the risks of creating new pathological entities and practicing a maximalist medicine. Family doctors can support quaternary prevention by focusing on their patients' priorities and the local resources of an efficient health system.

MADAP, a flexible clustering tool for the interpretation of one-dimensional genome annotation data.

A recurring task in the analysis of mass genome annotation data from high-throughput technologies is the identification of peaks or clusters in a noisy signal profile. Examples of such applications are the definition of promoters on the basis of transcription start site profiles, the mapping of transcription factor binding sites based on ChIP-chip data and the identification of quantitative trait loci (QTL) from whole genome SNP profiles. Input to such an analysis is a set of genome coordinates associated with counts or intensities. The output consists of a discrete number of peaks with respective volumes, extensions and center positions. We have developed for this purpose a flexible one-dimensional clustering tool, called MADAP, which we make available as a web server and as standalone program. A set of parameters enables the user to customize the procedure to a specific problem. The web server, which returns results in textual and graphical form, is useful for small to medium-scale applications, as well as for evaluation and parameter tuning in view of large-scale applications, requiring a local installation. The program written in C++ can be freely downloaded from ftp://ftp.epd.unil.ch/pub/software/unix/madap. The MADAP web server can be accessed at http://www.isrec.isb-sib.ch/madap/.

2 Iowa Safety Efforts: Analyst Tool & Location Aggregation Project, July 8, 2003

Report produced by the Iowa Department of Transportation about Iowa Safety with Tools and Aggregation.

Prescription footwear for severe injuries of foot and ankle: effect on regularity and symmetry of the gait assessed by trunk accelerometry.

After foot and/or ankle fracture, the restoration of optimal gait symmetry is one of the criteria of recovery. Orthotic insoles and orthopaedic shoes improve gait symmetry and regularity by controlling joint motion and improving alignment. The aim of the present study was to assess the effect of prescription footwear on gait quality by using accelerometers attached to the lower back. Sixteen adult patients with persistent disability after ankle and/or foot fractures performed two 30-s walking trials with and without prescription footwear (insoles and stabilizing shoes). Sixteen control subjects were also tested for comparison. The autocorrelation function was computed from the acceleration signal and the first two dominant periods were assessed (d1 and d2). Two parameters were used: (1) Stride Regularity (SR) which expresses the similarity between strides over time (d2), and (2) Stride Symmetry (SS) a ratio (d1/d2) which expresses the left/right similarity of gait independently of repeatability in the successive movements of each limb. In control subjects, SR and SS were 0.86+/-0.05 (correlation coefficient) and 81+/-10%, respectively. In the patient group, the effect of footwear was significant (SR: 0.88+/-0.06 vs. 0.90+/-0.05, SS: 38+/-23% vs. 46+/-27%). Pain was also significantly reduced (-34%). By using a rapid and low-cost method, we objectively quantified gait quality improvement after footwear intervention, concomitant to pain reduction. Substantial inter-patient variability in the footwear outcome was observed. In conclusion, we believe that trunk accelerometry can be a useful tool in the field of gait rehabilitation.

High-precision satellite positioning system as a new tool to study the biomechanics of human locomotion.

New Global Positioning System (GPS) receivers allow now to measure a location on earth at high frequency (5Hz) with a centimetric precision using phase differential positioning method. We studied whether such technique was accurate enough to retrieve basic parameters of human locomotion. Eight subjects walked on an athletics track at four different imposed step frequencies (70-130steps/min) plus a run at free pace. Differential carrier phase localization between a fixed base station and the mobile antenna mounted on the walking person was calculated. In parallel, a triaxial accelerometer, attached to the low back, recorded body accelerations. The different parameters were averaged for 150 consecutive steps of each run for each subject (total of 6000 steps analyzed). We observed a perfect correlation between average step duration measured by accelerometer and by GPS (r=0.9998, N=40). Two important parameters for the calculation of the external work of walking were also analyzed, namely the vertical lift of the trunk and the velocity variation per step. For an average walking speed of 4.0km/h, average vertical lift and velocity variation were, respectively, 4.8cm and 0.60km/h. The average intra-individual step-to-step variability at a constant speed, which includes GPS errors and the biological gait style variation, were found to be 24. 5% (coefficient of variation) for vertical lift and 44.5% for velocity variation. It is concluded that GPS technique can provide useful biomechanical parameters for the analysis of an unlimited number of strides in an unconstrained free-living environment.