numerical simulation of ultrafine particle dispersion in urban street canyons with the spalart allmaras turbulence model

The increased traffic emissions and reduced ventilation of urban street canyons lead to the formation of high particle concentrations as a function of the related flow field and geometry. In this context, the use of advanced modelling tools, able to evaluate particle concentration under different traffic and meteorological conditions, may be helpful. In this work, a numerical scheme based on the non-commercial fully explicit AC-CBS algorithm, and the one-equation Spalart-Allmaras turbulence model, was developed to perform numerical simulations of fluid flow and ultrafine particle dispersion in different street canyon configurations and under different wind speed and traffic conditions. The proposed non-commercial numerical tool was validated through a comparison with data drawn from the scientific literature. The results obtained from ultrafine particle concentration simulations show that as the building height increases the dispersion of particles in the canyon becomes weaker, due to the restricted interaction between the flow field in the street canyon and the undisturbed flow. Higher values of approaching wind speed facilitate the dispersion of the particles. The traffic effect has been evaluated by imposing different values of particles emission, depending on the vehicles type, with the lowest concentration values obtained for the Euro 6 vehicles, and the highest for High Duty Vehicles. A parametric analysis was also performed concerning the exposure to particles of pedestrians in different positions at the road level as a function of street canyon geometry, traffic mode, and wind speed. The worst exposure (1.25 × 10 6 part./cm 3 ) was found at the leeward side for an aspect ratio H/W = 1, wind speed of 5 m/s when High Duty Vehicles traffic was considered

Tucatinib's Journey from Clinical Development to Clinical Practice: New Horizons for HER2-Positive Metastatic Disease and Promising Prospects for Brain Metastatic Spread

: Approximately 20% of breast cancers (BCs) overexpress human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein with tyrosine kinase activity, encoded by ERBB2 gene. Historically, HER2 overexpression has been linked with increased disease recurrence and a worse prognosis. However, the increasing availability of different anti-HER2 compounds and combinations is progressively improving HER2-positive BC outcome, thus requiring expertise to prioritize both overall survival (OS) prolongation and quality of life, without neglecting the accessibility to further treatment lines with a low attrition rate. In this context, tucatinib, an oral tyrosine kinase inhibitor, has recently been granted approval by regulatory agencies based on evidence from the HER2CLIMB, a clinical trial which randomized patients with metastatic BC to receive trastuzumab and capecitabine with either tucatinib or placebo. A distinctive feature of this study was the inclusion of patients with new or active brain metastases (BMs) at study entry, a population traditionally excluded from clinical trials. Thus, HER2CLIMB provides the first solid evidence of an OS benefit in patients with BC and BMs, addressing a long standing unmet medical need, especially given the high incidence of central nervous system metastatic spread in patients with HER2-positive disease. This review provides an overview of the molecular and clinical landscape of tucatinib for the treatment of advanced BC. It focuses on the technological journey that drove the development of this therapeutic innovation, from preclinical data to clinical practice

Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively.In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatini

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Implementing propensity score matching with network data: The effect of GATT on bilateral trade

Motivated by the evaluation of the effect of GATT, we investigate the role of network information in propensity score matching. Under the assumption of strong ignorability, propensity score matching (PSM) is a widely used technique in causal inference studies to adjust for bias arising from an unbalanced distribution of observed confounders between a treatment and a control group. Both theoretical and applied works has recently considered the PSM for structured data, but the analysis of interlinked data is still missing. In this paper we consider the implementation of PSM in the context of network data. In our application, together with individual unit characteristics, also features of the social network in which units are embedded are considered as confounders (i.e., variables that impact on both the probability of receiving the treatment and the outcome). We study the sensibility of causal inference with respect to the presence of characteristics of the network in the set of confounders conditional on which strong ignorability is assumed to hold. We find that estimates of the average causal effect are sensitive to the presence of network information in the set of confounders, therefore we argue that estimates may suffer from omitted variable bias when network data are ignored, at least in our application

Airborne particle emission of a commercial 3D printer: The effect of filament material and printing temperature

The knowledge of exposure to the airborne particle emitted from three-dimensional (3D) printing activities is becoming a crucial issue due to the relevant spreading of such devices in recent years. To this end, a low-cost desktop 3D printer based on fused deposition modeling (FDM) principle was used. Particle number, alveolar-deposited surface area, and mass concentrations were measured continuously during printing processes to evaluate particle emission rates (ERs) and factors. Particle number distribution measurements were also performed to characterize the size of the emitted particles. Ten different materials and different extrusion temperatures were considered in the survey. Results showed that all the investigated materials emit particles in the ultrafine range (with a mode in the 10–30-nm range), whereas no emission of super-micron particles was detected for all the materials under investigation. The emission was affected strongly by the extrusion temperature. In fact, the ERs increase as the extrusion temperature increases. Emission rates up to 1×1012 particles min−1were calculated. Such high ERs were estimated to cause large alveolar surface area dose in workers when 3D activities run. In fact, a 40-min-long 3D printing was found to cause doses up to 200 mm2