Actinic keratoses show variable histological basal growth patterns - a proposed classification adjustment

Background: Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied. Objective: To investigate the extent of atypical keratinocytes throughout the epidermis and variation in basal growth patterns of AK. Methods: AK lesions occurring on the head/face from patients seen in routine practice were assessed histologically. We determined histological grade (AK I-III), basal growth patterns of atypical keratinocytes (crowding, budding, papillary sprouting) and accompanying parameters. Results: Of the 246 lesions included, 28.0% were histologically classified as AK I, 46.7% as AK II, and 25.2% as AK III. 26.4% of the basal growth patterns were classified as crowding (pro I), 49.6% as budding (pro II), 17.9% as papillary sprouting (pro III) and 6.1% without basal directed growth. No significant correlation of the histological AK I-III grading and underlying growth patterns was observed (P= 0.4666). However, adnexal structure involvement (OR= 2.37; 95%CI 1.21-4.65), infiltration (OR= 2.53; 95%CI 1.31-4.90) and increased number of vessels (OR= 2.56; 95%CI 1.42-4.65) were independent positive predictive markers for pro II and pro III basal growth patterns. Conclusions: Basal growth patterns (pro I-III) in AK do not correlate with the established AK I-III histological grading system. Besides the degree of upward extension, varying degrees of downward extension exist. Histological classification should consider both, upwards and downward growth patterns when assessing AK

Germanisms in the Upper Silesian ethnolect in Poland: Commodification and Revitalization Germanismen im oberschlesischen Ethnolekt in Polen: Kommodifizierung und Revitalisierung

In this thesis, I examine how commodification of the Upper Silesian ethnolect may contribute to the revitalization of the ethnolect. This project focuses specifically on the Germanisms, which are German loanwords in the Slavic Upper Silesian ethnolect. The Germanisms have contributed to the stigmatization of the ethnolect in the past, and they continue to be a contentious issue in the codification of the ethnolect and in the recognition of the ethnolect as a regional language by the Polish state (Hentschel, 2018). Since the change of the Polish political system in 1989, there has been an ‘ethnic awakening’ in Upper Silesia, a region in southwestern Poland. The results of the Polish National Census in 2002 and a subsequent one in 2011 show the Upper Silesians as the largest minority of the Republic of Poland with over 500,000 speakers of the Upper Silesian ethnolect. Polish legislation does not recognize Upper Silesians as an ethnic or linguistic minority (Michna, 2019). Grassroots movements in efforts to revitalize the ethnolect include a new generation of Upper Silesian speakers who use the Internet for blogging in the ethnolect or for entrepreneurial endeavors that feature the ethnolect in numerous ways. The corpus of merchandise (mainly T-shirts) analyzed in this research project was taken from an online store, the Gryfnie.com company in Upper Silesia, Poland. In support of my thesis argument that commodification of the Upper Silesian ethnolect, as exemplified on the Gryfnie.com printed T-shirts, may contribute to the revitalization of the ethnolect, I evaluated the extent to which Germanisms are promoted on the T-shirts, which revealed that the company features Germanisms on the majority of the Gryfnie.com T-shirts. Many of these Germanisms are in the category of underutilized lexemes by current ethnolect speakers. I also examined the role of the T-shirts in the linguistic landscape and propose that in this context the T-shirts increase the visibility of the ethnolect by shifting the ethnolect from the colloquial setting of individual speakers into the public domain, which allows for an integration of the minority language across the community. Multimodal critical discourse methodology guided my examination of Upper Silesian identity construction on the T-shirts and product labels and showed that the Germanisms are used as distinct markers of Upper Silesianness, and as boundary-markers that define speakers of the ethnolect as members of an ethnic group. The same methodology revealed how the images and texts on the Gryfnie.com T-shirts for young children can aid transmission of the ethnolect by functioning similarly to picture books. Gryfnie.com T-shirts and other merchandise designed for students signal a stance toward inclusion of the ethnolect in the education environment. Enhancing the prestige of the ethnolect and conveying modernity is another strategy employed by the Gryfnie company that can aid transmission of the ethnolect to adolescents and young adults. By drawing on principles of translanguaging as a language practice, I describe how the Gryfnie.com T-shirts may support a shift in the perception of the Germanisms from stigmatized elements of the ethnolect to dynamic forms of linguistic creativity

Ultra-thin graphene–polymer heterostructure membranes

The fabrication of arrays of ultra-thin conductive membranes remains a major challenge in realising large-scale micro/nano-electromechanical systems (MEMS/NEMS), since processing-stress and stiction issues limit the precision and yield in assembling suspended structures. We present the fabrication and mechanical characterisation of a suspended graphene–polymer heterostructure membrane that aims to tackle the prevailing challenge of constructing high yield membranes with minimal compromise to the mechanical properties of graphene. The fabrication method enables suspended membrane structures that can be multiplexed over wafer-scales with 100% yield. We apply a micro-blister inflation technique to measure the in-plane elastic modulus of pure graphene and of heterostructure membranes with a thickness of 18 nm to 235 nm, which ranges from the 2-dimensional (2d) modulus of bare graphene at 173 ± 55 N m$^{-1}$ to the bulk elastic modulus of the polymer (Parylene-C) as 3.6 ± 0.5 GPa as a function of film thickness. Different ratios of graphene to polymer thickness yield different deflection mechanisms and adhesion and delamination effects which are consistent with the transition from a membrane to a plate model. This system reveals the ability to precisely tune the mechanical properties of ultra-thin conductive membranes according to their applications

Constellation Commodities Studies Summary

Constellation program was NASA's long-term program for space exploration. The goal of the commodities studies was to solicit industry expertise in production, storage, and transportation required for future use and to improve efficiency and life cycle cost over legacy methods. Objectives were to consolidate KSC, CCAFS and other requirements; extract available industry expertise; identify commercial opportunities; and establish synergy with State of Florida partnerships. Study results are reviewed

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma

Background: Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy-to-use tool to assess the severity of AK on the head. Objective: To determine the association between chronically UV-induced tumours such as basal cell carcinomas (BCC) or squamous cell carcinomas (SCC) and AKASI. Methods: We performed a retrospective analysis of patients who had undergone oncological surgery due to UV-induced tumours and who were assessed for AKASI and Physician's Global Assessment (PGA) prior to surgery. Statistical analysis was performed to evaluate correlation between AKASI, PGA and invasive carcinomas. Results: Of the 210 patients included, 26 patients had histologically diagnosed SCCs and presented with a median (range) AKASI of 6.9 (0 – 13.0) and PGA of 2 (0 - 4). In contrast, the 82 patients with BCCs showed a median (range) AKASI of 3.3 (0 -15.2) and PGA of 1 (0 - 4). The Mann-Whitney U test showed significant differences (p= 0.0018) between AKASI of patients with SCC and BCC. In addition, we found a significantly higher AKASI in patients with SCC compared to patients with non-invasive lesions like AK and Bowen disease (BD) (p= 0.0275). Spearman's coefficient of rank correlation between AKASI and PGA indicates that these measures of AK severity were strongly correlated (p< 0.0001; r = 0.90; 95%CI 0,865 to 0,920). Conclusions: Patients with SCC show significantly higher AKASI than patients with BCC or patients without invasive tumours. Hence, AKASI may be used to stratify risk for developing invasive SCC

The Use of Polyurethane Composites with Sensing Polymers as New Coating Materials for Surface Acoustic Wave-Based Chemical Sensors—Part I: Analysis of the Coating Results, Sensing Responses and Adhesion of the Coating Layers of Polyurethane–Polybutylmethacrylate Composites

The sensing layers for surface acoustic wave-based (SAW) sensors are the main factor in defining the selectivity and reproducibility of the responses of the sensor systems. Among the materials used as sensing layers for SAW sensors, polymers present a wide range of advantages, from availability to a large choice of chemical-sensing environments. However, depending on the physical–chemical properties of the polymer, issues about the chemical and mechanical stability of the sensing layer have been reported that can compromise the application of sensor systems in the long-term. The sensor properties are defined basically by the properties of the coating material and the quality of the coating process. The strategy used to improve the properties of polymeric coating layers for SAW technology involved the use of polyurethane (PU) in combination with a second polymer that is responsible for the sensing properties of the resulting layer; this is obtained by a reproducible and robust coating procedure. In this first part of our research, we used polymer composites of different compositions of polybutylmetacrylate (PBMA) as the sensing polymer with polyurethane. The analysis of the coating (ultrasonic parameters), the relative sensor responses and the adhesion results for the PU–PBMA composites were determined. The ultrasonic analysis and the relative sensor responses showed very reproducible and precise results, indicating the reproducibility and robustness of the coating process. Accurate correlations between the results of the ultrasonic parameters due to the coating and the relative sensor responses for the organic analytes analyzed were obtained, showing a precise quantitative relationship between the results and the constitution of the composite coating materials. The composites show practically no significant sensor responses to water. The PU–PBMA composites substantially enhanced adhesion to the surface of the piezoelectric sensor element in comparison to the coating with pure PBMA, without loss of its sensing properties. Other PU–polymer composites will be presented in the future, as well as an analysis of the selectivity for the organic analytes for these types of coating materials

Long-term safety and efficacy of trifarotene 50 μg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BackgroundTreatment for both facial and truncal acne has not sufficiently been studied.ObjectivesTo evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne.MethodsIn a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 μg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET.ResultsOf 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit.ConclusionIn this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne

A randomized, multinational, noninferiority, phase III trial to evaluate the safety and efficacy of BF-200 aminolaevulinic acid gel vs. methyl aminolaevulinate cream in the treatment of nonaggressive basal cell carcinoma with photodynamic therapy

Background: Basal cell carcinoma (BCC) represents the most common non-melanoma skin cancer worldwide affecting mainly adult, fair-skinned individuals. The WHO distinguishes aggressive and non-aggressive forms of which prototypical variants of the latter are primary nodular and superficial BCC. Objectives: To demonstrate non-inferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared to MAL (a cream containing methyl-aminolevulinate) in the treatment of non-aggressive BCC with photodynamic therapy (PDT). Non-inferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of Δ = -15%. Patients/Methods: The study was a randomized, phase III trial performed in Germany and the UK with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA, 143 with MAL. Patients received two PDT sessions one week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J/cm2). Results shown include clinical endpoints as well as patients’ reassessment 12 months after the last PDT. Results: Of the BF-200 ALA-treated patients, 93.4% were complete responders compared to 91.8% in the MAL group. The difference of means was 1.6 with a one-sided 97.5% CI of -6.5, establishing non-inferiority (p<0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%. Conclusions: Treatment of non-aggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven non-inferiority to MAL-PDT and demonstrates low recurrence rates after 1-year follow-up

Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses

Background: In addition to the extent of atypical keratinocytes throughout the epidermis, actinic keratoses (AKs) are histologically characterized by downward directed basal layer expansion. It is not known if this growth pattern correlates with the risk of developing invasive squamous cell carcinoma (iSCC). Objective: To characterize the prevalence of downward directed basal layer expansion of AKs adjacent to iSCC. Methods: The epidermis overlying and adjacent to iSCCs was assessed histologically. We determined the histological grade (AKI‐III), basal growth pattern (PROI‐III) and accompanying parameters such as adnexal involvement. Results: Of 307 lesions, 52.4% of AKs were histologically classified as AKI, 38.1% as AKII, and 6.8% as AKIII (chi‐squared; P<0.0001). 2.6% of adjacent epidermis did not show any atypical keratinocytes. The epidermis adjacent to iSCCs was classified as having a PROI basal growth pattern in 25.7%, PROII in 31.9%, and PROIII in 39.4% cases. 2.9% of AKs showed no basal growth (chi‐squared; P<0.0001).118 (48.8%) AKs showed extension into adnexal structures. These AKs were graded as PROI in 18.6%, PROII in 30.5%, and PROIII in 50.8%. The epidermis above iSCCs could only be assessed for upwards directed growth and showed no significant differences in the three AK grades (P=0.4211). Conclusions: Basal proliferative AKs as well as atypical keratinocytes restricted to the lower third of the epidermis are most commonly seen adjacent to iSCC with less evidence for full thickness epidermal dysplasia. Our study supports the important role of dysplastic keratinocytes in the epidermal basal layer and their potential association with iSCC