Impact of urban form on concentration of air pollutants within street canyons at pedestrian level

Recent estimates published by WHO reported that in 2018 air pollution caused eight million premature deaths worldwide. The same report highlighted that outdoor air pollution was responsible for 4.2 million deaths. This implies that further efforts and mitigations are needed to reduce individuals’ exposure to harmful air pollutants. In this respect, governments around the world developed and published a number of air quality plans and frameworks. However, they either ignored or paid less attention to microclimate and urban form attributes and their impact on air pollution concentrations or dispersion in urban spaces, particularly within urban street canyons. Considering the above, this study postulates that there is a correlation between urban form and air quality. Therefore, the core focus of this thesis is to investigate this relationship in greater depth and to propose a set of recommendations that can create a desirable microclimate within various urban street canyons capable of mitigating air pollution concentrations and thereby reducing its negative impact on human health. This thesis employs a variety of methods, including fieldwork, computational modelling, and correlation analysis, to measure the influence of various street canyon configurations on the concentration of air pollution. The findings of this study confirmed several correlations between air pollution concentrations and urban form within street canyons. This study generated new knowledge on air pollution and microclimate behaviour within various street canyons. It provided recommendations for 30 distinct urban street canyon configurations in order to increase dispersion and protect pedestrians from harmful levels of air pollution. It also offered much needed knowledge and recommendations for urban designers and planners to consider to make informed design decisions to encourage greater dispersion of air pollution within various urban street canyons, particularly in areas with high pedestrian traffic to reduce and limit public exposure to harmful air pollution

Fibrocytes and the pathogenesis of diffuse parenchymal lung disease

Fibrosis is fundamental to the pathogenesis of many chronic lung diseases, including some lung infections, airway diseases such as bronchiectasis and asthma, and most of the diffuse parenchymal lung diseases. Idiopathic pulmonary fibrosis, the prototypical fibrotic lung disease, is amongst the most common diffuse parenchymal lung diseases and is characterized by progressive decline in lung function and premature death from respiratory failure. The clinical management of patients with this illness is hampered by our current inability to predict clinical deterioration and lack of an effective therapy. Fibrocytes are a population of bone marrow-derived circulating progenitor cells that home to injured tissues and differentiate into fibroblasts and myofibroblasts, thus contributing to scar formation. We summarize the evidence supporting the role of these cells in the pathogenesis of fibrotic lung diseases

The role of fibrocytes in fibrotic diseases of the lungs and heart

Fibrosis is the end result of a complex series of events that follow tissue injury and inflammation. Pathophysiologic fibrosis results in permanent scar formation, and can impair organ function. Fibrocytes are circulating, bone-marrow-derived progenitor cells that traffic from the bone marrow to the injured organ via the bloodstream, where they differentiate into fibroblasts and myofibroblasts, and play a pivotal role in both physiologic and aberrant fibrosis. In this review, we focus on the contribution of fibrocytes to fibrotic diseases of the lungs and the heart, including interstitial lung diseases, asthma, pulmonary hypertension, atherosclerosis and ischemic cardiomyopathy

The Relationship between resistance exercise induced testosterone and cortisol responses and steroid receptor phosphorylation

The precise contribution of hormones to resistance training adaptations remains unclear. Recently, resistance exercise (RE) has been shown to change phosphorylation of androgen (pAR) & glucocorticoid receptors (pGR). Examining the relationships between the hormonal responses & steroid receptor phosphorylation may elucidate the role of acute hormonal responses to training adaptations. PURPOSE: The purpose of this study was to examine relationships between exercise-induced hormonal responses and pGR & pAR. METHODS: Resistance trained (RT) (n = 10; age = 21.3±1.7yrs, ht = 175.8±6.8cm, bodymass = 84.5±13.5kg) & untrained (UT) (n = 9; age = 20.8±3.1yrs, ht = 178.7±8.9cm, bodymass = 81.0±14.0kg) men completed an acute RE session of 6 sets of 10 reps, & 4 sets of 10 reps at 75% 1RM of barbell back squats, & knee extension, respectively. Muscle biopsies were obtained at rest, 10+, 30+, 60+, & 180+ minutes post-exercise & analyzed for total AR, pAR at ser81, ser213, ser515, ser650, total GR, and pGR at ser134, ser211, ser226. Testosterone & cortisol samples were obtained before, & up to 45 minutes post-exercise. Pearson correlations were performed to determine relationships between endocrine responses (area-under-curve [AUC]) & changes in total & phosphorylated AR & GR. Significance was determined at p≤0.05. RESULTS: The change in total AR at 180+ was correlated with cortisol (Pooled: r = -0.668, p = 0.002) & was strongest in RT subjects (RT: r = -0.767, p = 0.010). Cortisol was correlated with pARser81 at 60+ (r = 0.601, p = 0.006) & 180+ (r = 0.537, p = 0.018). Cortisol was correlated with the change in pARser650 at 180+ (r = 0.724, p = 0.018) in RT subjects. In UT the changes in pGRser134 & pGRser226 were correlated at 10+ (r = 0.987, p = 0.001) & 30+ (r = 0.943, p = 0.001). CONCLUSION: Cortisol responses were related to AR content, & changes in phosphorylation at sites regulating AR ligand sensitivity, & AR localization. There was a training status-specific relationship in UT subjects between pGR sites that regulate receptor localization, & GR sensitivity to cellular stress. Individualized cortisol responses are strongly related to AR activity and may explain the discrepancy in studies that solely investigated anabolic hormones & training adaptations, since these relationships also appear to be specific to different training statuses

The efficacy of aripiprazole versus risperidone as augmentation therapy in treatment-resistant obsessive-compulsive disorder: A double blind clinical trial

Background: Obsessive-compulsive disorder (OCD) is the fourth common psychiatric disorder. Among the anxiety disorders, OCD has the least therapeutic response and 40-60 of OCD patients do not satisfactorily respond to the first-line standard treatment known as treatment-resistant OCD. One of the best therapeutic strategies is the augmentation therapy, which is adding antipsychotics to the standard treatment (SSRIs). Objectives: In this study, the efficacy of risperidone and aripiprazole was compared as an augmentation therapy. Methods: In this double blind randomized clinical trial, 100 patients with treatment-resistant OCD were diagnosed based on the DSM-IV-TR and were followed for twelve weeks. The patients were randomly divided into two groups of aripiprazole and risperidone and received an average daily dose of 5 mg and 1.5 mg for twelve weeks, respectively. The efficacy of treatment was measured and compared by the Yale-brown obsessive compulsive scale (Y-BOCS) at 4, 8 and 12 weeks. Results: The mean Y-BOCS score of patients in risperidone and aripiprazole groups were 25.26 ± 4.17 and 25.02 ± 4.46; respectively and had no significant difference (P = 0.79) at the beginning of the trial. At the end of the study (12th week) it was changed for the risperidone and aripiprazole groups to 20.00 ± 4.45 and 16.24 ± 4.41, respectively (P < 0.001). Furthermore, there was a significant decreasing trend of Y-BOCS scores in both groups, which was demonstrated by the repeated measurement analysis (P < 00.1). Conclusions: It was found that both aripiprazole and risperidone could be effective in treatment of treatment-resistant OCD patients. However, aripiprazole showed a higher efficacy compared to risperidone. © 2016, Author(s)

Laser interactions with bundle fiber structures

Laser damages of materials are in research focus during the last decade. These terms can be understood as useful in the treatment of materials or in theoretical modeling of interactions of laser beams with the material. Also, they can be destructive when it comes to high power density where the nonlinear effects are present, too. In addition to the theory, many detailed experimental work is required for new optical components applications. The experiments with Nd 3+ : YAG laser (1.064 µm) with defined working regime and power densities and specifically developed optical fiber bundles are the subject of this paper. The fibers are developed in laboratory conditions for specific purposes. Also, commercial optical fiber bundle for dental use are presented and discussed as comparison with the same laser types

A.R.G! Augmented Reality and Gait: Analyzing the Influence of Cues on Gait Patterns in Augmented Reality

Use of Augmented Reality (AR) technology for rehabilitation has drastically increased in recent years. While theoretically AR can be used to cue gait adaptations such as changes to step length and cadence through visual and auditory cues, it is still unknown how people respond to the technology. PURPOSE: To assess the feasibility of external visual and auditory cues delivered through AR on spatiotemporal gait outcomes in a healthy, young population. METHODS: 20 healthy participants between age 18 and 35 were screened and recruited to perform randomized gait trials consisting of four different cueing conditions. The participants wore a Magic Leap One AR headset with a custom-designed cueing application. Participants were instructed to walk 10 steps under one of four cueing conditions provided by the AR application: No Cues (NC) (i.e., natural gait), Visual (V), Auditory (A), and Visual and Auditory (VA). Each condition was completed three times in a randomized order for a total of 12 trials per participant. An Inertial Measurement Unit (IMU) system was used to collect spatiotemporal gait data. A System Usability Survey (SUS) was administered after each participant completed their trials to determine the usability of our novel application and to determine whether the reported usability of the system was related to changes in gait variability. RESULTS: Preliminary results indicate all cueing conditions exhibited a significantly faster cadence compared to NC trials. Surprisingly, the cadence variability increased across all A trials. Increased system usability SUS results were significantly correlated with increased percent stance variability across A trials. V trials exhibited significantly decreased stride lengths compared to NC. Combined (AV) cues had no effect on gait outcomes. CONCLUSION: Our findings reinforced that certain visual and auditory cues affect gait parameters, albeit in a direction opposite of what was expected (e.g., greater cadence variability with auditory cues). These results provide insight into how healthy populations respond to cues delivered through AR, as well as provide a foundation for future studies to implement this technology with clinical populations such as those with Parkinson’s disease

Using (1,3)-β-D-glucan concentrations in serum to monitor the response of azole therapy in patients with eumycetoma caused by Madurella mycetomatis

Introduction: (1,3)-β-D-glucan is a panfungal biomarker secreted by many fungi, including Madurella mycetomatis, the main causative agent of eumycetoma. Previously we demonstrated that (1,3)-β-D-glucan was present in serum of patients with eumycetoma. However, the use of (1,3)-β-D-glucan to monitor treatment responses in patients with eumycetoma has not been evaluated. Materials and Methods: In this study, we measured (1,3)-β-D-glucan concentrations in serum with the WAKO (1,3)-β-D-glucan assay in 104 patients with eumycetoma treated with either 400 mg itraconazole daily, or 200 mg or 300 mg fosravuconazole weekly. Serial serum (1,3)-β-D-glucan concentrations were measured at seven different timepoints. Any correlation between initial and final (1,3)-β-D-glucan concentrations and clinical outcome was evaluated. Results: The concentration of (1,3)-β-D-glucan was obtained in a total of 654 serum samples. Before treatment, the average (1,3)-β-D-glucan concentration was 22.86 pg/mL. During the first 6 months of treatment, this concentration remained stable. (1,3)-β-D-glucan concentrations significantly dropped after surgery to 8.56 pg/mL. After treatment was stopped, there was clinical evidence of recurrence in 18 patients. Seven of these 18 patients had a (1,3)-β-D-glucan concentration above the 5.5 pg/mL cut-off value for positivity, while in the remaining 11 patients, (1,3)-β-D-glucan concentrations were below the cut-off value. This resulted in a sensitivity of 38.9% and specificity of 75.0%. A correlation between lesion size and (1,3)-β-D-glucan concentration was noted. Conclusion: Although in general (1,3)-β-D-glucan concentrations can be measured in the serum of patients with eumycetoma during treatment, a sharp decrease in β-glucan concentration was only noted after surgery and not during or after antimicrobial treatment. (1,3)-β-D-glucan concentrations were not predictive for recurrence and seem to have no value in determining treatment response to azoles in patients with eumycetoma.</p

Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains

The design of compounds that can discriminate between closely related target proteins remains a central challenge in drug discovery. Specific therapeutics targeting the highly conserved myosin motor family are urgently needed as mutations in at least six of its members cause numerous diseases. Allosteric modulators, like the myosin-II inhibitor blebbistatin, are a promising means to achieve specificity. However, it remains unclear why blebbistatin inhibits myosin-II motors with different potencies given that it binds at a highly conserved pocket that is always closed in blebbistatin-free experimental structures. We hypothesized that the probability of pocket opening is an important determinant of the potency of compounds like blebbistatin. To test this hypothesis, we used Markov state models (MSMs) built from over 2 ms of aggregate molecular dynamics simulations with explicit solvent. We find that blebbistatin\u27s binding pocket readily opens in simulations of blebbistatin-sensitive myosin isoforms. Comparing these conformational ensembles reveals that the probability of pocket opening correctly identifies which isoforms are most sensitive to blebbistatin inhibition and that docking against MSMs quantitatively predicts blebbistatin binding affinities (