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The tunnel industry has started focusing on the maintenance and management challenges of an existing infrastructure. It is an urgent matter in industrialised countries, where the stakeholders’ attention is increasing at a fast pace considering the incidents and the disruptions caused by improper monitoring and maintenance. This paper presents an innovative methodology to survey and inspect existing railway tunnels through multi-dimensional mobile mapping systems. The proposed approach belongs to the digital strategies for infrastructure maintenance. An integrated multidimensional survey system (ARCHITA) allows for collecting information necessary for the diagnostics of a structure with non-destructive tests. Linear cameras, thermographic cameras, and ground-penetrating radars acquire data to be digitalised and manipulated in different IT environments. The results, in terms of the collected data on structural defects, allow for a new approach for the Management and Identification of the Risk for Existing Tunnels (MIRET). The innovative approach aims at a smart integration of information and models for the Facility Management of the transport system. The workflow for the digitalisation and diagnosis from mobile mapping data has been implemented on two 40km-long metro tunnels.

Vitamin C (ascorbic acid) is widely used in skin care products, yet it is a challenging compound due to its physical and chemical instability. Several strategies have been applied to improve the stability of vitamin C, such as the addition of other antioxidants in the system (e.g., Vitamin E, ferulic acid, and sodium metabisulfite). In addition, clay minerals have been used in cosmetic preparations due to their high ion-exchange capacity, thermal stability, softness, the small size of their particles, and their attractive adsorptive properties. In this study, we proposed the association of kaolin clay and well-known antioxidants and chelators to improve the stability of vitamin C. Although the kaolin clay alone did not improve the stability of the vitamin C, the clay mineral in association with certain chelators and/or antioxidants could improve the stability of formulations containing vitamin C.

Ascorbic acid (AA) is a powerful antioxidant capable of acting significantly both in the prevention and treatment of the skin aging process. One way to assess the in vivo efficacy of anti-aging treatments is by using the high-frequency ultrasound (HFUS) skin image analysis technique, a non-invasive approach that allows for a new level of evaluating the effectiveness of dermatological and cosmetic products. The aim of the present study was to assess the performance of a topical emulsion of liquid crystalline structures containing AA using the 50 MHz HFUS skin image analysis method.Twenty-five healthy female participants between 35 and 60 years were included, all of whom randomly applied a placebo formulation and an AA-containing formulation to each forearm, once a day, for 30 days. HFUS measurements were performed before using the products (T0), 2 h later (T2h), and after 30 days of use (T30d). The analyzed parameters included total skin, dermal, and epidermal echogenicity; variation and mean thickness of total skin, the epidermis and dermis; and surface roughness. Statistical analyses were performed using the Friedman test, followed by Dunn's test for comparisons of multiple means (α = 0.05).A significant increase in total skin and dermal echogenicity was observed after topical AA application.Our findings suggest that collagen synthesis significantly increased after topical therapy with AA, which was responsible for the increment in dermal echogenicity. This study showed, through the HFUS technique, that the topical use of AA promoted dermal redensification after 30 days of application.

The use of thermography in the medical field has been experiencing a renaissance due to advances in the infrared thermographic imaging technology, which improves thermographic equipment and promises cost saving and increased safety. Dermatology is one of the most promising fields of application among the medical areas with potential for the use of thermography.To review the findings on this subject and to describe the use of such technique for dermatology and aesthetic applications.A bibliographic survey was carried out, selecting relevant publications and guidelines, focused on monitoring medical diagnostic applications and benefits of thermography for dermatology, inflammatory skin diseases, and aesthetic applications.Inflammatory skin diseases lead to changes of the IRT image. A quantification of treatment effects and monitoring changes on skin can be possible by repeated measurements over time.Infrared imaging is a noninvasive, powerful tool in the diagnosis and clinical management of skin conditions and monitoring of aesthetic procedures.

The application of questionnaires for the assessment and collection of data on target audiences and new products is a very common practice in the field of cosmetics. However, to obtain reliable results, it is essential to pretest the instrument to detect possible problems and inconsistencies. The aim of this study was to demonstrate the entire pre-testing process of two questionnaires used in the cosmetic claims substantiation area; a skin self-assessment questionnaire and a sensory analysis questionnaire for cosmetic formulations. According to the pretest protocol analysis, 15 women were interviewed for each questionnaire. All difficulties were recorded, categorized, and analyzed. Subsequently, the inconsistencies found were corrected in the final version of the instrument. During the validation of the questionnaires, the biggest problem faced was related to the application of scales and technical concepts within the questions. This difficulty means that respondents are unable to represent their real perception of the evaluated product. This problem can be solved by adding detailed explanations in the footer or within the wording of each question. In conclusion, learning and applying the pre-test in questionnaires can ensure greater reliability and clarity in research results in the cosmetic area. Keywords: Questionnaires, cosmetics, substantiation of claims, self-efficacy, sensory attributes

Banks’ funding sources have changed significantly during the last two decades. The share of non-core funding (NCF) was high before the 2008 crisis but declined substantially after the crisis. We propose a general equilibrium model where NCF provides insurance against idiosyncratic risks faced by banks. Insurance makes leverage and investment more attractive, but it also increases the vulnerability of the banking sector to crises. We show that learning about the likelihood of a crisis could have been important for generating the observed dynamics of NCF and leverage, which in turn affected the dynamics of the macro-economy.

The large-scale implementation of municipal solid waste incineration (MSWI) has put great pressure on waste management and environmental protection. Road construction engineering has also been confronted with the challenges of the heavy consumption of non-renewable mineral resources. Therefore, we evaluated the feasibility of recycling and reusing MSWI residue as an alternative to limestone filler (LF) in transport infrastructure. We investigated the rheological characteristics and fatigue performance of asphalt mastics and mixtures containing MSWI residue. Firstly, a particle size analyzer and environmental scanning electron microscope were adopted to characterize the particle distribution and surface micromorphology of the investigated fillers, respectively. Then, tests for determining the steady shear viscosity and multiple-stress creep recovery were conducted to evaluate the high-temperature rheology of five asphalt mastics. Meanwhile, we used Burgers models with fitting parameters to describe the classic creep recovery measurements and viscoelastic responses. The wheel-tracking test revealed the rutting resistance, and the linear amplitude sweep (LAS) and time sweep tests were combined to investigate the fatigue performances of the five asphalt mastics. A dynamic creep test identified the fatigue life of the asphalt mixtures according to the flow number index. Finally, statistical analysis was conducted to identify the correlations between the rheological and fatigue properties of the mastics and mixtures (R2 over 0.87 and 0.78, respectively). Since the fatigue life predictions for the asphalt mastic decreased by over 42.9% according to the MSWI residue/LF volume ratio, the results of the correlations could improve pavement designs. The substitution of the mineral filler in asphalt mixtures with MSWI residue could be a sustainable strategy for the road construction sector.

The need for safe pedestrian movement implies subtracting and modifying space dedicated to vehicles, especially in urban areas. Traffic control measures aim to reduce or modify the width of the carriageway and force the correct use of the space by pedestrians through two approaches: the former is hard and includes physical barriers and the latter is soft and induces psychological fashion effects on the drivers. This paper presents vertical and horizontal devices integrated by landscaping, planting, or other similar works to slow motor vehicle speed, narrow traffic lanes, and/or create smaller distances for pedestrian crossings. Mobility and boundary issues are considered to discuss their warrants and potential impacts. Indeed, the effects of speed or volume treatments should be investigated through a comprehensive multicriteria analysis without overlooking pedestrian level of service, access and connectivity to residents and emergency vehicles, drainage and snow issues, loss of on-street parking lots, and environmental goals in terms of noise and emissions to air reduction.

Background Platform trial designs are used increasingly in cancer clinical research and are considered an efficient model for evaluating multiple compounds within a single disease or disease subtype. However, these trial designs can be challenging to operationalise. The use of platform trials in oncology clinical research has increased considerably in recent years as advances in molecular biology enable molecularly defined stratification of patient populations and targeted therapy evaluation. Whereas multiple separate trials may be deemed infeasible, platform designs allow efficient, parallel evaluation of multiple targeted therapies in relatively small biologically defined patient sub-populations with the promise of increased molecular screening efficiency and reduced time for drug evaluation. Whilst the theoretical efficiencies are widely reported, the operational challenges associated with these designs (complexity, cost, regulatory, resource) are not always well understood. Main In this commentary, we describe our practical experience of the implementation and delivery of the UK plasmaMATCH trial, a platform trial in advanced breast cancer, comprising an integrated screening component and multiple parallel downstream mutation-directed therapeutic cohorts. plasmaMATCH reported its primary results within 3 years of opening to recruitment. We reflect on the operational challenges encountered and share lessons learnt to inform the successful conduct of future trials. Key to the success of the plasmaMATCH trial was well co-ordinated stakeholder engagement by an experienced clinical trials unit with expert methodology and trial management expertise, a federated model of clinical leadership, a well-written protocol integrating screening and treatment components and including justification for the chosen structure and intentions for future adaptions, and an integrated funding model with streamlined contractual arrangements across multiple partners. Findings based on our practical experience include the importance of early engagement with the regulators and consideration of a flexible resource infrastructure to allow adequate resource allocation to support concurrent trial activities as adaptions are implemented in parallel to the continued management of patient safety and data quality of the ongoing trial cohorts. Conclusion Platform trial designs allow the efficient reporting of multiple treatment cohorts. Operational challenges can be overcome through multidisciplinary engagement, streamlined contracting processes, rationalised protocol and database design and appropriate resourcing.

BACKGROUND: Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in advanced breast cancer and the ability of ctDNA testing to select patients for mutation-directed therapy.METHODS: We did an open-label, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed advanced breast cancer and an Eastern Cooperative Oncology Group performance status 0–2. Patients had completed at least one previous line of treatment for advanced breast cancer or relapsed within 12 months of neoadjuvant or adjuvant chemotherapy. Patients were recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: cohort A comprised patients with ESR1 mutations (treated with intramuscular extended-dose fulvestrant 500 mg); cohort B comprised patients with HER2 mutations (treated with oral neratinib 240 mg, and if oestrogen receptor-positive with intramuscular standard-dose fulvestrant); cohort C comprised patients with AKT1 mutations and oestrogen receptor-positive cancer (treated with oral capivasertib 400 mg plus intramuscular standard-dose fulvestrant); and cohort D comprised patients with AKT1 mutations and oestrogen receptor-negative cancer or PTEN mutation (treated with oral capivasertib 480 mg). Each cohort had a primary endpoint of confirmed objective response rate. For cohort A, 13 or more responses among 78 evaluable patients were required to infer activity and three or more among 16 were required for cohorts B, C, and D. Recruitment to all cohorts is complete and long-term follow-up is ongoing. This trial is registered with ClinicalTrials.gov, NCT03182634; the European Clinical Trials database, EudraCT2015-003735-36; and the ISRCTN registry, ISRCTN16945804.FINDINGS: Between Dec 21, 2016, and April 26, 2019, 1051 patients registered for the study, with ctDNA results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 96–99% (n=800, kappa 0·89–0·93). Sensitivity of digital PCR ctDNA testing for mutations identified in tissue sequencing was 93% (95% CI 83–98) overall and 98% (87–100) with contemporaneous biopsies. In all cohorts, combined median follow-up was 14·4 months (IQR 7·0–23·7). Cohorts B and C met or exceeded the target number of responses, with five (25% [95% CI 9–49]) of 20 patients in cohort B and four (22% [6–48]) of 18 patients in cohort C having a response. Cohorts A and D did not reach the target number of responses, with six (8% [95% CI 3–17]) of 74 in cohort A and two (11% [1–33]) of 19 patients in cohort D having a response. The most common grade 3–4 adverse events were raised gamma-glutamyltransferase (13 [16%] of 80 patients; cohort A); diarrhoea (four [25%] of 20; cohort B); fatigue (four [22%] of 18; cohort C); and rash (five [26%] of 19; cohort D). 17 serious adverse reactions occurred in 11 patients, and there was one treatment-related death caused by grade 4 dyspnoea (in cohort C).INTERPRETATION: ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations, confirming these mutations could be targetable for breast cancer treatment.FUNDING: Cancer Research UK, AstraZeneca, and Puma Biotechnology.

Despite Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -induced Oxidative Stress (OxS) being well documented in different organs, the molecular pathways underlying placental OxS in late-pregnancy women with SARS-CoV-2 infection are poorly understood. Herein, we performed an observational study to determine whether placentae of women testing positive for SARS-CoV-2 during the third trimester of pregnancy showed redox-related alterations involving Catalase (CAT) and Superoxide Dismutase (SOD) antioxidant enzymes as well as placenta morphological anomalies relative to a cohort of healthy pregnant women. Next, we evaluated if placental redox-related alterations and mitochondria pathological changes were correlated with the presence of maternal symptoms. We observed ultrastructural alterations of placental mitochondria accompanied by increased levels of oxidative stress markers Thiobarbituric Acid Reactive Substances (TBARS) and Hypoxia Inducible Factor-1 α (HIF-1α) in SARS-CoV-2 women during the third trimester of pregnancy. Importantly, we found an increase in placental CAT and SOD antioxidant enzymes accompanied by physiological neonatal outcomes. Our findings strongly suggest a placenta-mediated OxS inhibition in response to SARS-CoV-2 infection, thus contrasting the cytotoxic profile caused by Coronavirus Disease 2019 (COVID-19).

Background: Circulating tumour DNA (ctDNA) testing may provide a more current assessment of the genetic profile of advanced breast cancer (BC) compared with analysis of the primary tumour, with repeat advanced disease biopsy conducted infrequently in routine clinical practice. The plasmaMATCH trial was designed to assess the clinical utility of using ctDNA testing to select patients for targeted therapies. Methods: The plasmaMATCH trial was an open-label, multi-centre, multi-cohort platform trial, consisting of ctDNA testing in ~1000 patients with advanced BC, with patients recruited into four parallel treatment cohorts with therapies matched to mutations identified in ctDNA (A: ESR1 mutation - extended-dose fulvestrant 500mg every 2 weeks, B: HER2 mutation - neratinib +/- fulvestrant (standard dosing), C: AKT1 in ER positive BC -capivasertib + fulvestrant (standard dosing), D: AKT1 in ER negative BC or PTEN inactivating mutation - capivasertib). A fifth cohort (E) recruited patients with triple negative BC with no actionable mutation to receive olaparib + AZD6738, and will be reported separately. Each cohort had a specific phase II single arm design. ctDNA testing was conducted with two technologies: digital droplet PCR (ddPCR) at a central laboratory prospectively in all patients, and error corrected sequencing with Guardant360 prospectively from part-way through recruitment and retrospectively for the remaining patients. Tumour sequencing from an advanced disease biopsy was conducted retrospectively, not influencing cohort entry. The primary endpoint for Cohorts A-D is confirmed objective response rate by RECIST v1.1. Secondary endpoints include clinical benefit rate, progression-free survival, safety and frequency of mutations identified in ctDNA screening. Results: Entry into ctDNA testing for Cohorts A-D was closed on 26/Apr/2019 with 1044 patients registered. ctDNA screening results were received for 1033 patients (99%), with 142 patients entered into Cohorts A-D (A 84, B 21, C 18, D 19). Agreement between ctDNA digital PCR and sequencing results was high (individual gene level agreement 95.5%-99.4%, kappa 0.89-0.93). Predefined efficacy criteria were met in Cohorts B (neratinib for HER2 mutations) and C (capivasertib for AKT mutations), with exploratory analysis of Cohort D identifying activity of capivasertib in AKT1 mutations (Table 1). Efficacy criteria were not met in Cohort A (extended-dose fulvestrant for ESR1 mutations). Adverse events were consistent with prior reports, with extended-dose fulvestrant well tolerated. Table 1: Efficacy results from plasmaMATCHMutationCohortConfirmed response rate, % (95%CI; n/N)Median PFS (IQR), monthsAll patientsFirst 16 evaluable patients*ESR1A8.1% (3.0-16.8; 6/74)-2.2 (1.7-5.3)HER2B25.0% (8.7-49.1; 5/20)25.0% (7.3-52.4; 4/16)5.4 (3.4-9.1)AKT1C22.2% (6.4-47.6; 4/18)18.8% (4.0-45.6; 3/16)10.2 (3.2-18.2)AKT basketD10.5% (1.3-33.1; 2/19)12.5% (1.6-38.3; 2/16)3.4 (1.8-5.5)AKT133.3% (4.3-77.7; 2/6)--PTEN0 % (0/13)--*Predefined cohort efficacy thresholds for response were set: 13/78 (A); 3/16 (B, C, D) Conclusion: Circulating tumour DNA testing offers accurate tumour genotyping, sufficient for routine clinical practice. This approach can be used to identify patients with rare HER2 and AKT1 mutations, who have clinically relevant response rates with matched targeted therapies. Citation Format: Nicholas Turner, Belinda Kingston, Lucy Kilburn, Sarah Kernaghan, Andrew M Wardley, Iain Macpherson, Richard D Baird, Rebecca Roylance, Peter Stephens, Olga Oikonomidou, Jeremy P Braybrooke, Mark Tuthill, Jacinta Abraham, Matthew C Winter, Hannah Bye, Michael Hubank, Claire Snowdon, Daniel Rea, David Cameron, Abeer Shaaban, Katrina Randle, Katie Wilkinson, Laura Moretti, Judith M Bliss, Alistair Ring, on behalf of the plasmaMATCH Trial Management Group. Results from the plasmaMATCH trial: A multiple parallel cohort, multi-centre clinical trial of circulating tumour DNA testing to direct targeted therapies in patients with advanced breast cancer (CRUK/15/010) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS3-06.

This paper compared two approaches used to analyze a modular pedestrian pavement made of hexagonal basalt pavers. In presence of occasional heavy traffic roads, the pavement should be verified using methods currently used for road pavements. Different loading conditions were examined varying the geometry of the blocks, and the magnitude of the vertical load. In all cases, the results obtained from the analytical theory of Westergaard were higher than those obtained from a finite element model (FEM). Therefore, a parametric study was performed in order to use the analytical method as an alternative to the costly FEM approach. The results of comparison gave a correction factor, valid for hexagonal pavers: it permits to analytically estimate with good approximation the stresses induced by heavy loads applied to natural stone blocks.

We tested the pro-angiogenic and anti-inflammatory effects of human placenta-derived mesenchymal stromal cells (hPDMSCs)-derived conditioned media (CM) on a mouse model of preeclampsia (PE), a severe human pregnancy-related syndrome characterized by maternal hypertension, proteinuria, endothelial damage, inflammation, often associated with fetal growth restriction (FGR). At d11 of pregnancy, PE was induced in pregnant C57BL/6N mice by bacterial lipopolysaccharide (LPS) intravenous injection. At d12, 300 μL of unconditioned media (control group) or 300 μL PDMSCs-CM (CM group) were injected. Maternal systolic blood pressure was measured from 9 to 18 days of pregnancy. Urine protein content were analyzed at days 12, 13, and 17 of pregnancy. At d19, mice were sacrificed. Number of fetuses, FGR, fetal reabsorption, and placental weight were evaluated. Placentae were analyzed for sFlt-1, IL-6, and TNF-α gene and protein expressions. No FGR and/or reabsorbed fetuses were delivered by PDMSCs-CM-treated PE mice, while five FGR fetuses were found in the control group accompanied by a lower placental weight. PDMSCs-CM injection significantly decreased maternal systolic blood pressure, proteinuria, sFlt-1, IL-6, and TNF-α levels in PE mice. Our data indicate that hPDMSCs-CM can reverse PE-like features during pregnancy, suggesting a therapeutic role for hPDMSCs for the treatment of preeclampsia.

The ongoing climate change is manifesting itself through the increasing expansion of Urban Heat Island (UHI) effects. This paper evaluates the microclimate benefits due to cool road pavements, greenery, and photovoltaic canopies in a parking lot in Fondi (Italy), identifying the best strategy to counteract the negative effects of UHIs. The ENVI-met software allowed a microclimatic analysis of the examined area in July 2022 through the comparison of the thermal performances between the current asphalt pavement and ten alternative scenarios. The proposed layouts were investigated in terms of air temperature (AT), surface temperature (ST), mean radiant temperature (MRT), and predicted mean vote (PMV). The results showed that the existing asphalt pavement is the worst one, while the cool pavement integrated with vegetation provides appreciable benefits. Compared to the current layout, a new scenario characterized by light porous concrete for carriageable pavements and sidewalks, concrete grass grid pavers for parking stalls, a 2-m-high border hedge, and 15-m-high trees implies reductions of AT above 3 °C, ST above 30 °C, MRT above 20 °C, and a maximum PMV value equal to 2.2.

The genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2− disease that associate with poor overall survival (p = 0.0092), and multiple PIK3CA mutations in HR + disease that associate with short progression free survival on fulvestrant (p = 0.0036). The fraction of cancer with a mutation, the clonal dominance of a mutation, varied between genes, and within hotspot mutations of ESR1 and PIK3CA. In ER-positive breast cancer subclonal mutations were enriched in an APOBEC mutational signature, with second hit PIK3CA mutations acquired subclonally and at sites characteristic of APOBEC mutagenesis. This study utilises circulating tumour DNA analysis in a large clinical trial to demonstrate the subclonal diversification of pre-treated advanced breast cancer, identifying distinct mutational processes in advanced ER-positive breast cancer, and novel therapeutic opportunities., Circulating tumour DNA can provide useful information on disease burden. Here, the authors analysed circulating tumour DNA from 800 patients from a breast cancer clinical trial and investigate the subclonal nature of the disease, and identify DNA mutations associated with resistance and poor survival.

1024 Background: The plasmaMATCH trial was an open label platform trial, consisting of circulating tumour DNA (ctDNA) testing in ̃1000 patients with advanced breast cancer (ABC) linked to parallel treatment cohorts with therapies matched to mutations identified in ctDNA. Cohorts A-D have already reported (Turner N et al, Lancet Oncol 2020). Cohort E recruited patients with triple negative breast cancer (TNBC) without a targetable mutation identified at ctDNA screening, treating with olaparib (PARP inhibitor) plus ceralasertib (ATR inhibitor). Methods: Patients with TNBC who had received 1 or 2 lines of chemotherapy for advanced disease or relapsed within 12 months of (neo)adjuvant chemotherapy were eligible. Treatment was olaparib 300mg b.i.d continuously and ceralasertib 160mg qd on days 1–7 on a 28 day cycle, until disease progression. The primary endpoint was confirmed objective response rate by RECIST v1.1. Secondary endpoints included clinical benefit rate, progression-free survival (PFS) and safety. Biomarker analysis included response according to BRCA and somatic DNA repair gene status and ATM loss. Using a two-stage design with a target response rate of 25%, unacceptable response rate of 10%, alpha=2% and power=90%, ≥13 responses out of 69 evaluable stage 2 patients were required to infer efficacy (5/37 stage 1). Results: Between 17/09/18 and 5/10/20 75 patients enrolled in Cohort E of whom 70 were evaluable for response. The median age was 55.6 years. 42 (56%) patients had 1 and 13 (17.3%) had 2 prior line(s) of chemotherapy for metastatic disease. Efficacy is shown in Table. The most common grade ≥3 adverse events were: hypertension 12 (17%) and anaemia 9 (13%). Dose reductions and interruptions occurred in 19 (26.4%) and 34 (47.2%) patients respectively. Conclusions: The response rate to olaparib and ceralasertib did not meet pre-specified criteria for efficacy in the overall evaluable population. Responses were observed in patients without germline or somatic BRCA1/2 mutations. Translational analyses are underway to identify potential biomarkers of response in this population and will be presented at the meeting. Clinical trial information: ISRCTN16945804. [Table: see text]

1009 Background: The selective estrogen receptor modulator (SERD) fulvestrant is commonly used to treat patients with hormone receptor positive advanced breast cancer, although potential mechanisms of acquired resistance are poorly understood. plasmaMATCH cohort A (NCT03182634) investigated the activity of fulvestrant in patients with activating ESR1 mutations in circulating tumor DNA (ctDNA). Here we present analysis of baseline and end-of-treatment (EOT) ctDNA to identify potential resistance mutations to fulvestrant. Methods: Paired baseline and EOT plasma samples from patients enrolled into plasmaMATCH underwent ctDNA sequencing (Guardant360, Guardant Health) to identify acquired mutations. For F404 analysis, MCF-7 cells were transiently transfected with estrogen receptor expression constructs containing either wildtype ESR1 (WT), single ESR1 mutations (D538G, E380Q, F404L), or compound mutations (D538G_F404L, E380Q_F404L), alongside an estrogen response element (ERE)-luciferase reporter construct. Transfected cells were treated with or without fulvestrant and ERE-luciferase activity compared. Results: Of 84 patients enrolled in cohort A, 69 had paired baseline and EOT sequencing. Patients with baseline ESR1 Y537S had shorter progression free survival (PFS), and Y537C longer PFS, than those wild-type for each respective mutation (p = 0.03 and p = 0.04). Patients frequently acquired mutations at EOT (n = 35, 51%), including potentially targetable mutations in 25% (including 3 PTEN, 3 BRCA1/2, 2 PIK3CA, 2 HER2, 1 BRAF). Three (4%) patients acquired ESR1 p.F404 mutations (F404L, F404I, F404V), with 7 mutations in total. Of 26 patients with PFS of ≥16 weeks, 3 patients (12%) acquired ESR1 F404. In 800 patients screened for entry to plasmaMATCH, one harbored a F404 mutation (0.13%), with a prior history of fulvestrant. F404 mutations resided in cis with E380Q in 6/7 assessable mutations. In vitro structural modelling revealed that ESR1 p.F404 resides within the ESR1 ligand binding domain, and contributes to estrogen and fulvestrant binding through a pi-stacking bond between the aromatic ring of phenylalanine and estrogen/fulvestrant, with all F404 mutations disrupting this bond. Transient transfection demonstrated that single mutations D538G, E380Q, F404L and wild-type ESR1 were sensitive to fulvestrant (p < 0.0001, p = 0.0006, p = 0.04 and p = 0.0001), whereas compound mutations D538G_F404L and E380Q_F404L were resistant. Further investigation of relative sensitivity of the F404 mutant ESR1 to other anti-estrogens will be presented. Conclusions: We have identified a novel resistance mechanism to fulvestrant, with F404 mutations acquired in patients with pre-existing activating ESR1 mutations. F404 confers fulvestrant resistance through the loss of a pi-stacking bond and likely reduced fulvestrant binding affinity, identifying a new potential target to overcome endocrine therapy resistance.

Background: Early changes in circulating tumour DNA (ctDNA) levels may identify which patients respond to therapy earlier than imaging, with ctDNA levels falling rapidly in patients who respond to therapy. The plasmaMATCH trial assessed the utility of ctDNA testing with an error-corrected 73-gene targeted panel (Guardant360, Guardant Health) to allocate patients to four mutation matched therapy cohorts. ESR1-extended fulvestrant (A), HER2-neratinib +/- fulvestrant (B), AKT1-capivasertib + fulvestrant (C), AKT basket-capivasertib (D). Here, we report paired baseline and early on treatment ctDNA analysis from plasmaMATCH, to establish the optimal criteria for predicting progression free survival (PFS). Methods: In plasmaMATCH treatment cohorts, plasma samples were collected for ctDNA analysis pre-treatment at cycle 1-day 1 (C1D1) and cycle 2-day 1 (C2D1) timepoints, and sequenced with the Guardant 360 assay. Patients were included if they had a minimum of 14 days of treatment in the first cycle. Multiple different methods were investigated to integrate variant allele fractions (VAF) of mutations identified at each timepoint to estimate the level of ctDNA, including maximum VAF, mean VAF and weighted mean VAF, and weighted mean VAF of clonal mutations at C1D1. Variants with a VAF Table 1ctDNA dynamics categoryMedian PFS months (95%CI)6-month PFSORRUndetectable (N=11) CDR=018.2 (10.2-NA)91%9/11 (82%)Suppressed (N=14) CDR 05.4 (4.6-NA)48%6/14 (43%)High (N=52) CDR >=0.1322.4 (2.0-3.7)8%4/52 (8%) Citation Format: Javier Pascual, Rosalind J Cutts, Belinda Kingston, Sarah Hrebien, Lucy S Kilburn, Sarah Kernaghan, Laura Moretti, Katie Wilkinson, Andrew M Wardley, Iain R Macpherson, Richard D Baird, Rebecca Roylance, Michael Hubank, Giselle Walsh, Iris Faull, Kimberly C Banks, Richard B Lanman, Isaac Garcia-Murillas, Judith M Bliss, Alistair Ring, Nicholas C Turner. Assessment of early ctDNA dynamics to predict efficacy of targeted therapies in metastatic breast cancer: Results from plasmaMATCH trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-02.

Background New technologies, such as sonic devices, have been developed to optimize the skin cleansing process and improve its efficiency. To evaluate the effectiveness of these cosmetic procedures, skin bioengineering is an objective method to assess the biophysical parameters of the skin. Aims This study aimed to assess the effect of facial cleansing on the physiological properties of the skin by comparing a cleansing process with cosmetic product applied manually to cleansing with cosmetic product associated with the use of an electric sonic device. Patients/methods A gentle skin cleanser was applied to the entire face of 12 subjects; the sonic device was used on one half of the face and the manual process was performed on the other half. Instrumental skin analyses included sebummetry, corneometry, transepidermal water loss (TEWL), infrared thermography, and high-frequency ultrasound and were measured before and up to 90 min after cleansing. Results were compared using two-way ANOVA and Friedman tests. Results Data obtained from the statistical analysis of sebummetry, TEWL, thermography, and ultrasound parameters did not show any significant difference. When assessing the corneometry parameters, a significant reduction in hydration values (17.19%) was observed in the manual cleansing area, while the values remained similar to baseline values in the area where the sonic device was used. Conclusion The cleansing process with a sonic device did not cause a significant hydration reduction, suggesting better preservation of skin homeostasis when compared to manual cleansing.

BACKGROUND: To determine if following specific diets was associated with responding positively to eating disorder/disordered eating (ED/DE) screening tools compared to non-diet-adherent athletes. We hypothesized that athletes adhering to specific diets were more likely to respond positively on ED/DE screening tools than those not following a diet. METHODS: 1000 female athletes (15-30 y) completed a comprehensive survey about athletic health and wellness. Athletes were asked to specify their diet and completed 3 ED/DE screening tools: the Brief Eating Disorder in Athletes Questionnaire, the Eating Disorder Screen for Primary Care, and self-reported current or past history of ED/DE. Descriptive statistics were calculated for all study measures and chi-squared tests assessed relationships between athletes’ dietary practices and their responses to ED/DE screening tools. Statistical significance was defined as p RESULTS: 234 of 1000 female athletes reported adherence to specific diets. 69 of the 234 diet-adhering athletes (29.5%) were excluded due to medically-indicated dietary practices or vague dietary descriptions. Of the 165 diet-adherent athletes, 122 (67.9%) responded positively to ≥1 of the 3 ED/DE screening tools. Athletes practicing vegetarian, vegan, low-carbohydrate, low-dairy, or ≥2 diets were more likely to respond positively to ≥1 ED/DE screening tool vs. athletes without dietary restrictions (70.0%, 77.8%, 79.5%, 60.0%, and 65.6%, respectively vs. 41.8%; p≤0.048). CONCLUSION: Specific diet adherence in female athletes is associated with positive responses to ED/DE screening tools. Health practitioners should consider further ED/DE questioning of athletes reporting specific diet adherence in order to enhance nutritional knowledge and help treat and prevent ED/DE.

Don Quixote, Robinson Crusoe, The Lord of the Rings, Harry Potter, Star Wars: likes or dislikes aside, few would dispute that these are cult narratives, which have generated adaptations across time, space, and media. Equally, few would object that fictional characters like Don Quixote and Robinson Crusoe have become some sort of “unkillable protagonists.” Many, though, would raise an eyebrow if the name Chikusai were to be added to the list. Students of early modern Japanese popular prose might have encountered him cursorily in their readings, but hardly anyone else is likely to have heard of the wandering quack doctor Chikusai and his fictional story, which was printed for the first time in Kyoto in the 1620s under the title of Chikusai.

Background: Circulating tumor DNA (ctDNA) testing may provide a contemporary assessment of the genomic profile of advanced cancer, without need to repeat tumor biopsy. The plasmaMATCH trial was designed to assess the clinical utility of using ctDNA testing to select advanced breast cancer patients for targeted treatment. Methods: plasmaMATCH is an open label, multi-center, multi-cohort platform trial of ctDNA testing in ~1000 patients with advanced breast cancer, with patients recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: A:ESR1 mutation, B:HER2 mutation, C:AKT1 mutation (ER-positive cancer), D:AKT activation basket (AKT1 mutation ER-negative cancer or PTEN mutation). ctDNA testing was conducted with digital PCR and error-corrected targeted sequencing. Tumour sequencing from an advanced disease biopsy was conducted retrospectively, not influencing cohort entry. Each cohort had a phase II single-arm design with primary endpoint of confirmed objective response rate using RECISTv1.1 in evaluable patients. Findings: 1051 patients registered, with ctDNA testing results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 95.5%-99.4% (n=800, kappa 0.89-0.93). ctDNA testing had 93-98% sensitivity for mutations identified in tissue sequencing. In patients with HER2 mutations, response rate with neratinib, plus fulvestrant in ER-positive cancer, was 25.0% (5/20, 95%CI 8.7-49.1%). In patients with AKT1 mutations and ER-positive cancer, response rate with capivasertib plus fulvestrant was 22.2% (4/18, 95%CI 6.4-47.6%). In patients with AKT1 mutations and ER-negative cancer, 33.3% (2/6, 95%CI,4.3-77.7) responded to capivasertib, although 0/13 patients with PTEN mutation responded. Response rate of ESR1 mutations with extended-dose fulvestrant was 8.1% (6/74, 95%CI 3.0-16.8%). Adverse events were consistent with prior reports. Interpretation: ctDNA testing offers accurate, rapid genotyping that enables the selection of patients for mutation-directed therapies. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations. Trial Registration: ISRCTN16945804 ClinicalTrials.gov Identifier: NCT03182634 Funding: Cancer Research UK (CRUK/15/010,C30746/A19505), AstraZeneca, and Puma Biotechnology. Declaration of Interests: NCT, AR, JMB, LSK, CS, LM, SK, KW, SM, HB, MH, BK and RC report grants from Cancer Research UK, grants and non-financial support in the form of study drug provision from AstraZeneca and Puma Biotechnology and non-financial support in the form of ctDNA sequencing from Guardant Health and provision of reagents from BioRad during the conduct of the study. NCT also reports grants and personal fees from AstraZeneca, Pfizer, and Roche/Genentech, personal fees from Bristol-Myers Squibb, Lilly, MSD, Novartis, Bicycle Theraputics, Taiiho, Zeno Pharmaceuticals and Repare Therapeutics and grants from BioRad, Clovis, Merck Sharpe and Dohme, and Guardant Health outside the submitted work. BK also reports personal fees from Guardant Health outside the submitted work. AMW reports personal fees from Roche, personal fees and other support from Novartis, Pfizer, Lilly, Daiichi-Sankyo, MSD, AstraZeneca, Athenex and other support from Seattle Genetics, Andrew Wardley Ltd, Manchester Cancer Academy and Outreach Research and Innovation Group Limited outside the submitted work. IRM reports personal fees and non-financial support from Roche Products UK Ltd, Eli Lilly and Eisai and personal fees from Novartis, Pfizer, Daichi Sankyo, Genomic Health, Pierre Fabre and MSD outside the submitted work. RDB reports grants from AstraZeneca and Roche/Genentech outside the submitted work. RR reports personal fees from Novartis, Eli-Lilly and Pfizer, personal fees and non-financial support from Daiichi Sankyo and G1Therapeutics and non-financial support from Roche and AstraZeneca outside the submitted work. PS reports personal fees from Novartis, Eisai and Daiichi Sankyo outside the submitted work.OO reports grants and personal fees from Pfizer and Eisai, personal fees from Roche/GNE and Tesaro, non-financial support from AstraZeneca, personal fees and non-financial support from Eli Lilly, grants from Novartis outside the submitted work. MT reports personal fees from Pfizer, Novartis, Roche, Vaccitech, Oxford Vacmedix, Lilly, Astellas, Genomic Health and Esai, personal fees and non-financial support from Janssen, BMS, Ipsen and non-financial support from EUSA Pharma outside the submitted work. JA reports grant and personal fees from Eisai and personal fees from Merck outside the submitted work. MCW reports personal fees and non-financial support from Easai, Lilly and Roche and personal fees from Pfizer, Genomic Health and Novartis outside the submitted work. HB also reports personal fees from AstraZeneca outside of the submitted work. MH also reports personal fees from Bristol Myers Squibb, Boehringer Ingelheim, Roche Diagnostics and Eli Lilly during the conduct of the study. AS reports grants from Ventana Roche and Genomic Heath, personal fees from Daiichi Sankyo, Hologic, Genomic Health and Ventana Roche outside the submitted work. JMB also reports grants and non-financial support from AstraZeneca, Novartis, Janssen-Cilag, Merck Sharpe & Dohme, Pfizer, Roche, and Clovis Oncology and grants from Medivation outside the submitted work. AR also reports personal fees from Roche Products Limited, Pfizer, Novartis, Lilly and MSD outside the submitted work. JPB, HG, DR, DC and KR have nothing to disclose. Ethics Approval Statement: The study was co-sponsored by The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust and approved by a Research Ethics Committee (16/SC/0271). All participants gave written informed consent prior to registration for ctDNA testing, and again prior to treatment cohort entry. Safety and efficacy data were reviewed regularly by an Independent Data Monitoring Committee (IDMC). Trial oversight was provided by an independent Trial Steering Committee.

This paper analysed and verified an existing block stone pavement in an urban shared area. Fatigue and rutting verification was performed respectively for bound and unbound pavement materials using analytical curves available in the literature. The commercial finite element (FE) software Abaqus® was used to calculate the response of the pavement when subjected to different loading, construction and geometrical configurations (i.e. type of analysis, shape and size of meshes, boundary conditions, and bonding contacts between the pavements layers). At the end of this study, a static model of a structure with hexahedral blocks having sides of 0.02 m, with full bonded layers and restrained horizontal displacements on the model sides, was implemented to evaluate the maximum tensile stress induced in a block when the load is applied at its centre. This analysis highlighted the need for rigorous criteria for a correct design, in order to avoid inappropriate and expensive use of road materials. Keywords: Block pavement, Commercial vehicle loads, Finite element model, Hexagonal Stone block, Pedestrian pavement, Shared area

The attention to airport safety-related issues has grown fast in recent decades. The experience gained in these themes reveals the importance of assessing and mitigating the accident risk in the airport context. This work presents a quantitative risk assessment method useful to calculate the current level of risk for different runway codes and types of movement. The model consists of cumulative probability distributions, which describe the final position of an aircraft after a veer-off, and a damage model, which considers statistical mechanical damages and injuries observed in the examined database. The current levels of veer off risk range between the orders of magnitude 10−8 and 10−10, varying for runway code and type of movement. Geotechnical and geometrical characteristics of the Cleared and Graded Area (CGA) width play a fundamental role in reducing veer-off risk. An enlargement of CGA could be an effective strategy, as demonstrated by the carried-out sensitivity analysis: the obtained results demonstrate important reduction (up to 63%) of the risk of the main landing gear departing beyond the CGA (RCGA_GEAR). For instrument runways, the average reduction of RCGA_GEAR is sensitive, even when the CGA enlargement is only 5 m-wide (i.e. 10% for landing and 7% for take-off). The strategy proposed by the authors does not require modification of airplane technologies and safety devices for passengers, moreover it complies with the ICAO investigation for mitigating consequence of this type of accidents. Therefore, the results of the study could have a significant impact on the risk management in airport.

Postprint

Introduction Circulating tumour DNA (ctDNA) is found in the plasma of over 90% of patients with advanced breast cancer (BC). Screening for the presence of mutations in ctDNA provides a current assessment of the genetic profile of the patient's recurrent BC. The plasmaMATCH trial is designed to assess the potential of ctDNA screening to direct targeted therapies in patients with advanced breast cancer. Methods plasmaMATCH is a multi-centre phase IIa umbrella trial platform of ctDNA screening and a therapeutic trial. The study will screen 1000 women with advanced breast cancer, who have received prior systemic treatment in the advanced setting, with digital PCR ctDNA assays for hotspot mutations in ESR1, HER2, AKT1, and PIK3CA, with HER2 copy number assessment, in a central laboratory. The study will recruit from up to 50 sites in the UK. Patients with mutations identified will enter the matching treatment cohort, ESR1 – extended dose fulvestrant 500mg every two weeks, HER2 – neratinib +/- fulvestrant, AKT1 – AZD5363 +/- fulvestrant. Mutation prevalence is presented with corresponding exact 95% confidence intervals (CIs) both overall and excluding 14 patients who were known to have mutations from a prior screening program. Patients with more than one mutation are included once in each relevant row. Results We report the results of prospective ctDNA mutation testing in the first 92 patients. plasmaMATCH opened to recruitment on 15/12/2016. As of 08/06/2017, 120 patients have been registered for ctDNA screening from 7 UK centres, of which 92 have ctDNA screening results available: plasmaMATCH ctDNA screening resultsMutationPrevalence (95% CI)Prevalence excluding 14 patients with known mutations (95% CI)ESR134/92: 37% (27%-48%)26/78: 33% (23%-45%)HER25/90: 6% (2%-12%)2/76: 3% (0%-9%)AKT17/92: 8% (3%-15%)4/78: 5% (1%-13%)PIK3CA*22/92: 24% (16%-34%)21/78: 27% (18%-38%)*No corresponding plasmaMATCH treatment cohort 14 patients had more than one mutation detected (10 ESR1+PIK3CA, 3 ESR1+AKT1, 1 ESR1+ +HER2+AKT1). ctDNA results were reported in a median of 8 working days. Of the 40 patients with one or more actionable mutation, 15 have entered a cohort, 16 are being screened for entry into a cohort, 5 are currently receiving further systemic treatment prior to cohort entry and 4 will not enter a cohort. One additional patient has entered a treatment cohort on the basis of a mutation detected in an alternative tumour sequencing initiative. Conclusions plasmaMATCH ctDNA demonstrates the feasibility and accuracy of ctDNA testing as a screening tool for patients with advanced BC, with a high rate of subsequent recruitment into matching therapeutic trials. Citation Format: Turner N, Bye H, Kernaghan S, Proszek P, Fribbens C, Moretti L, Morden J, Snowdon C, Macpherson I, Wardley A, Roylance R, Baird R, Bliss J, Ring A. The plasmaMATCH trial: A multiple parallel cohort, open-label, multi-centre phase II clinical trial of ctDNA screening to direct targeted therapies in patients with advanced breast cancer (CRUK/15/010) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-06-03.

Cool pavements are reflective and/or permeable pavements that improve microclimate of urban areas where heat islands cause discomfort to citizens. Stone pavements lower surface temperatures and reduce the amount of heat absorbed. This study assessed, using ENVI-met 4.3 LITE software, how air temperature and predicted mean vote depend on physical properties of the road pavement. A comparative microclimatic analysis was implemented on a rectangular square in Rome (Italy) in the summer, paved in three different ways: asphalt, traditional sampietrini, and permeable sampietrini. The model considered local weather parameters, surrounding fabric, and vegetation to give reliable results in terms of numerical and graphical output using the application tool Leonardo. The tested pavement types affected air temperature during the day, but did not influence this variable in the early morning. Permeable sampietrini pavement was more effective than traditional sampietrini pavement in reducing air temperature compared to the current asphalt surface. The road pavement did not, however, affect human comfort in terms of predicted mean vote. The obtained results are useful for further investigation of parameters that could modify the microclimatic conditions of urban areas.

Cosmetic films are structures made of a polymer capable of forming a continuous matrix. Collagen and hyaluronic acid (HA) are components of the skin extracellular matrix and act to maintain its elasticity and resistance. Ascorbic acid (AA) acts in the formation of collagen fibers, contributing to the maintenance of their firmness and elasticity. This study aimed to evaluate the moisturizing properties of cosmetic films with AA or HA in their composition. It was also investigated whether the presence of caprylyl glycol would interfere with the TWEL of the formulations. The occlusive properties of the films were assessed based on the reduction of transepidermal water loss (TEWL) in 20 healthy participants using a Tewameter probe. At T30, 30 minutes after application, all formulations showed a reduction in TEWL compared to the control. In general, the formulations that included caprylyl glycol presented the best TEWL results after 30 min of application. However, after 60 minutes, the transepidermal water loss began to return to its basal levels. This study showed a significant difference in the TEWL value, suggesting that the topical application of the films can contribute to the improvement and maintenance of skin hydration. Keywords: cosmetic films; collagen; hyaluronic acid; ascorbic acid; skin barrier

Airport pavements should ensure regular and safe movements during their service life, the management body has to monitor the functional and structural characteristics, and schedule maintenance work, balancing the often conflicting goals of safety, economic and technical issues. This paper presents a remote monitoring system to evaluate the structural performance of a runway composed of concrete thresholds and a flexible central runway. Thermometers, strain gauges, and pressure cells will be embedded at different depths to continuously monitor the pavement’s response to traffic and environmental loads. An innovative system allows data acquisition and processing with specific calculation models, in order to inform the infrastructure manager, in real time, about the actual conditions of the pavement. In this way, the authors aim to develop a system that provides useful information for the correct implementation of an airport pavement management system (APMS) based on real-life data. Indeed, it permits comprehensive monitoring functions to be performed, based on the embedded sensing network.

The interest for environmentally related issues in the construction industry has grown faster in recent years, demonstrating the neccesity to promote both a more responsible use of non-renewable resources and a better use of renewable resources. As a consequence, there is an increasing number of environmental documents and institutional acts on this topic that demonstrate the need for greener approaches in the area of construction engineering. The objective of this study is to evaluate the environmental impact of the Italian gray cement and clinker industry, after distinguishing between the upstream and the core phases of these processes. The study considered clinker and cement generated during 2014 in eleven Italian plants that produced materials complying with the European standard EN 197-1 “Cement - Part 1: Composition, specifications and conformity criteria for common cements”. The environmental assessment was conducted through a Life Cycle Analysis (LCA) of these industrial processes, following the standard EN 15804 “Sustainability of construction works, environmental product declarations, core rules for the product category of construction products” and the Product Category Rules (PCR) 2010:09 version 2.1 “Cement”. The results permitted to construct the first sector Environmental Product Declaration (EPD) related to cement production published until now by the International EPD System. The analysis of the results demonstrated that among the different phases involved in the production process of these materials (i.e. extraction and production of raw materials and fuels, transportation and core production process), the core phase is responsible for most of the greenhouse emissions (i.e. more than 85% of the total process for clinker, and more than 79% of the total process for cement), and the acidification and eutrophization potential (i.e. 43% and 62% of the total process for clincker, and 33% and 55% of the total process for cement). It was also found that the cement production is mainly responsible for the following environmental impact categories: the overall electrical consumption required as part of these industrial processes (116 kWh/Mg), the output flows of components for re-use and materials for recycling (0.21 and 0.17 kg/Mg, respectively), and the biogenic CO 2 emissions (16 kg/Mg). The results highlight the environmental benefits of applying Best Available Techniques (BAT) for this industry, as reported in the European Reference document for the “Production of Cement, Lime and Magnesium Oxide”.

Emulsões são formas farmacêuticas muito empregadas nos cosméticos. O estudo de estabilidade dessas formulações têm sido um desafio para as indústrias farmacêutica e cosmética, sendo essa influenciada principalmente pela escolha do surfactante e pela energia de agitação aplicada durante o preparo. O objetivo dessa pesquisa foi realizar um estudo de estabilidade preliminar de formulações com mesma fase oleosa, empregando-se diferentes tensoativos e submetendo-as, ou não, à homogeneização de alta pressão (200 bar). As formulações selecionadas foram armazenadas em temperatura ambiente (25º +/-2ºC ) e em estufa (37º +/-2ºC) e avaliadas quanto suas características organolépticas, separação de fases, pH e por microscopia ótica nos tempos 24 horas, 30 e 60 dias. As emulsões desenvolvidas com Metosulfato de behenila e com álcool graxo mais Álcool Cetoestearílico Etoxilado, permaneceram estáveis com ou sem homogeneização de alta pressão. Já as formulações preparadas com éster de álcool Cetoestearílico Etoxilado e Ácido de oliva não alcançaram estabilidade quando homogeneizadas no agitador mecânico e armazenadas em temperatura ambiente ou em estufa. A importância do método de agitação para a estabilidade final pôde ser verificada uma vez que todas as formulações homogeneizadas a 200 bar e armazenadas em temperatura ambiente ou em estufa não apresentaram separação de fases durante o período estudado.

A encapsulacao de substâncias ativas e uma tecnologia muito empregada nas industrias cosmetica e farmaceutica que compreende o empacotamento de compostos em camadas polimericas, formando estruturas solidas ou semi-solidas denominadas particulas ou vesiculas. O objetivo desse estudo foi desenvolver vesiculas polimericas de k-carragena revestidas ou nao de quitosana e avaliar a influencia do revestimento na liberacao do azul de metileno. Metodologia: Para a preparacao das vesiculas foi utilizada a tecnica de gelificacao ionica a partir da extrusao de emulsoes multicamadas em solucao ionica de KCl. As vesiculas mais circulares e estaveis foram inseridas em veiculo aquoso e fotografadas pelo microscopio Dino-Lite AM 2111 para verificacao da formacao do halo de liberacao de azul de metileno e afericao de sua area. Resultados e Discussao: O uso de KCl mais concentrado facilitou a formacao das particulas e a extrusao da emulsao multicamada com seringa com agulha permitiu a maior reprodutibilidade do processo. Nao houve diferencas significativas na formacao dos halos entre as formulacoes com ou sem revestimento de quitosana. Conclusoes: As diferentes composicoes das vesiculas de k-Carragena influenciaram no desenvolvimento das particulas, mas nao houve diferencas significativas na liberacao do Azul de Metileno pelas vesiculas revestidas ou nao de quitosana. Esse polissacarideo nao demonstrou ser ideal para revestimento de vesiculas inseridas em veiculo aquoso.

CIPA is contributing with its technical knowledge in saving the heritage of Syria by constructing an open access database based on the data that the CIPA members have collected during various projects in Syria over the years before the civil war in the country broke out in 2011. In this way we wish to support the protection and preservation of the environment, sites, monuments, and artefacts and the memory of the cultural region that has been crucial for the human past and the emergence of civilizations. Apart from the countless human atrocities and loss, damage, destruction and looting of the cultural heritage have taken place in a large scale. The CIPA’s initiative is one of the various international projects that have been set up after the conflict started. The Directorate-General of the Antiquities and Museums (DGAM) of Syria as well as UNESCO with its various sub-organizations have been central in facing the challenges during the war. Digital data capture, storage, use and dissemination are in the heart of CIPA’s strategies in recording and documenting cultural heritage, also in Syria. It goes without saying that for the conservation and restoration work the high quality data providing metric information is of utmost importance.

Comfort is a major requirement in planning pedestrian facilities. Pedestrians walk where they feel comfortable and when they do not feel at ease, they walk elsewhere. A typical example is that filthy, distressed, or too narrow sidewalks induce pedestrians to walk on carriageways. This behaviour jeopardizes road safety and highly dangerous to most users, leave them vulnerable. Unsuitable pavements can be the result of irregular maintenance operations to restore evenness after shock damage, weather phenomena, installation of equipment (e.g., posts, fences, urban furniture) with a reduction of walkable surface, or substandard repair work on pavements and patches due to emergency operations. These problems can be solved with an appropriate maintenance management system, which optimizes financial resources to make smart decisions about how to intervene with an adequate and lasting maintenance operation. This paper defines an evaluation index for sidewalk conditions as a part of an efficient set-up of a Sidewalk Management System, which is similar to the better known Road Management System. The study relies on surveys, as well as the classification and analysis of sidewalk distresses. The authors adapted an index already standardized by ASTM for roads and airports: the Pavement Condition Index (PCI). PCI has been modified to consider the specific types on the sidewalks studied within this paper. To validate the method, a case study of a residential district in Rome, Italy, was carried out. The chosen area lacks regular maintenance and has therefore resulted in a network of unsafe sidewalks. Frequent detour routes were surveyed and related to the level of distresses within a general assessment of safety. This study concentrates on sidewalks with flexible pavements because this type of pavement is the only one adopted in the survey areas and, in general, throughout Italy.

This paper investigates how an office-motivated incumbent can use transparency enhancement on public spending to signal his budgetary management ability and win re-election. We show that, when the incumbent faces a popular challenger, transparency policy can be an effective signaling device. A more popular challenger can reduce the probability to enhance transparency, while voters can be better off due to a more informative signaling. It is also shown that a higher level of public interest in fiscal issues can increase the probability of enhancing transparency, while voters can be worse off by a less informative signaling. (This abstract was borrowed from another version of this item.)

This paper presents a life cycle cost analysis, which compares construction, maintenance, and lighting costs needed to manage a highway tunnel. As regards the decision making process, it often considers only construction costs. Instead even maintenance and lighting, especially related to road tunnels, cause important cash flows. Therefore, both construction and managing costs have to be planned, in order to assess the cheapest solution. The lighting system of a road tunnel must guarantee the visual guidance for users moving at design speed and without hazardous actions. In this case study, the authors designed the pavement according to Italian standards and the lighting system according to Italian and European technical rules (UNI and UNI EN standards). They used LED technologies to maximize energy saving and road safety. The examined case study shows the importance of the surface pavement material, since it may contribute to the inter-reflected light and reduce electric energy consumption.

In the road construction sector, soil treatment is a method for increasing the strength and durability of fine soils that would otherwise be waste: the treatment with lime allows building embankments with clayey soils. However, in-situ and laboratory tests should be carried out to verify the correct addiction of lime during earthworks. This study deals with SEM-EDS analyses in order to identify the most reliable method to prepare specimens and obtain relationship between added quicklime and Calcium content after treatment. A natural clayey soil has been tested: more than one thousand values of Calcium content have been analyzed with statistical approach. The results from one-way and two-way ANalysis Of VAriance (ANOVA) and Tukey’s test confirmed the usefulness of SEM-EDS analyses to verify quickly the quantity of added quicklime in treated soils. The most reliable method for specimen preparation consists of a sequence of procedures similar to those that occur in worksite. The high variability of Ca content in the natural soil did not allow definition of a linear reliable relationship between the added quicklime and the after-treatment Ca content. Therefore, further experimentation is on-going to define a method based on SEM-EDS analyses and valid for clays with non-uniform chemical composition.