Citizen views on wood as a construction material: results from seven European countries

Multi-story wooden buildings are hailed as a favorable means toward reducing the embodied energy of the construction sector. However, the sector's path- dependent nature hinders acceptance of using wood in multi-story construction. As a result, research predominantly focuses on examining the perceptions of construction professionals to identify means of breaking the path dependency. We propose using citizens' perceptions about the use of wood to inform professional decision makers. Our research thus aims to answer two questions: What are citizens' perceptions about using wood as a construction material, and are there country-based cultural differences between these perceptions? To elicit this spectrum of citizen views, an online survey was deployed in Austria, Denmark, Finland, Germany, Norway, Sweden, and the United Kingdom. Qualitative content analysis was used to analyze 6633 open-ended responses to the survey. Respondents held multi-faceted opinions about the physical properties, environmental, social, and economic aspects of using wood as a construction material. Citizens from Finland, Norway, and Sweden expressed discernably different perspectives about the acceptability of using wood than did citizens from Austria, Denmark, Germany, and the United Kingdom. Overall, respondents from all countries expressed high approval for the use of wood in construction.Peer reviewe

Inhibition of STAT3 prevents bone metastatic progression of prostate cancer in vivo

Background: Prostate cancer (PC) metastasizes to the skeleton forming predominantly sclerotic lesions, and there is currently no cure for bone metastatic disease. The transcription factor signal transducer and activator of transcription 3 (STAT3) is implicated as a metastatic driver, but its potential as therapeutic target in bone metastasis has not been investigated. In this study, we evaluated for the first time a STAT3 inhibitor, Napabucasin, as a therapeutic option for bone metastatic PC.Methods: Effects of STAT3 inhibitors, Stattic and Napabucasin, on metastatic potential in PC cells were studied in vitro by assessment of migration capacity, self-renewal potential, and tumorsphere formation. For evaluation of the role of STAT3 in initial skeletal establishment of PC cells as well as in progressed castration-resistant PC (CRPC) in bone, human VCaP prostate cancer cells were inoculated in the tibia of mice which subsequently were treated with the STAT3 inhibitor Napabucasin. Bone specimens were analyzed using computed tomography (CT), immunohistochemistry, and quantitative polymerase chain reaction.Results: The small molecule STAT3 inhibitors Stattic and Napabucasin both effectively impaired metastatic potential of PC cells in vitro. Furthermore, treatment with Napabucasin prevented metastatic establishment in tibial bones in vivo and thereby also the tumor-induced sclerotic bone response seen in vehicle-treated VCaP xenografts. In addition, treatment with Napabucasin of established bone CRPC significantly decreased both tumor burden and tumor-induced trabecular bone volume compared with effects seen in vehicle-treated animals. Anti-mitotic effects were confirmed by decreased Ki67 staining in Napabucasin-treated xenografts compared with vehicle-treated xenografts. Alterations of gene expression in the femoral bone marrow (BM) niche toward the maintenance of hematopoietic stem cells and the myeloid lineage were demonstrated by quantitative real-time polymerase chain reaction and were further reflected by a substantial increase in the number of erythrocytes in BM of Napabucasin-treated mice. Furthermore, a unique pattern of STAT3 phosphorylation in osteoblasts/stromal cells surrounding the areas of tumor cells was demonstrated immunohistochemically in bone xenograft models using several different PC cell lines.Conclusion: Inhibition of STAT3 activity disrupts the bone metastatic niche and targets both the skeletal establishment of PC and advanced bone metastatic CRPC in mice, suggesting STAT3 as a candidate for molecular targeted therapies of skeletal metastatic disease.</div

Hematologic Safety of Radium-223 Dichloride: Baseline Prognostic Factors Associated With Myelosuppression in the ALSYMPCA Trial.

BACKGROUND: Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity. PATIENTS AND METHODS: Hematologic parameters and adverse events were analyzed. Multivariate analyses assessing baseline risk factors for hematologic toxicities were performed separately for radium-223 and placebo patients. RESULTS: Nine hundred one patients received radium-223 (n = 600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus placebo patients (6% vs. 2%). Logistic regression analyses identified significant baseline predictors for grade 2-4 hematologic toxicities related to radium-223 treatment: extent of disease (6-20 vs. < 6 bone metastases; odds ratio [OR] = 2.76; P = .022) and elevated prostate-specific antigen (OR = 1.65; P = .006) for anemia; prior docetaxel (OR = 2.16; P = .035), decreased hemoglobin (OR = 1.35; P = .008), and decreased platelets (OR = 1.44; P = .030) for thrombocytopenia. Neutropenia events were too few in placebo patients for a comparative analysis. There were no significant associations between hematologic toxicities and number of radium-223 injections received (4-6 vs. 1-3). CONCLUSION: Radium-223 has a favorable safety profile with a low myelosuppression incidence. Understanding baseline factors associated with myelosuppression may assist clinicians in avoiding severe myelosuppression events with radium-223

Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial

Background Metastatic castration-resistant prostate cancers are enriched for DNA repair gene defects (DRDs) that can be susceptible to synthetic lethality through inhibition of PARP proteins. We evaluated the anti-tumour activity and safety of the PARP inhibitor niraparib in patients with metastatic castration-resistant prostate cancers and DRDs who progressed on previous treatment with an androgen signalling inhibitor and a taxane. Methods In this multicentre, open-label, single-arm, phase 2 study, patients aged at least 18 years with histologically confirmed metastatic castration-resistant prostate cancer (mixed histology accepted, with the exception of the small cell pure phenotype) and DRDs (assessed in blood, tumour tissue, or saliva), with progression on a previous next-generation androgen signalling inhibitor and a taxane per Response Evaluation Criteria in Solid Tumors 1.1 or Prostate Cancer Working Group 3 criteria and an Eastern Cooperative Oncology Group performance status of 0–2, were eligible. Enrolled patients received niraparib 300 mg orally once daily until treatment discontinuation, death, or study termination. For the final study analysis, all patients who received at least one dose of study drug were included in the safety analysis population; patients with germline pathogenic or somatic biallelic pathogenic alterations in BRCA1 or BRCA2 (BRCA cohort) or biallelic alterations in other prespecified DRDs (non-BRCA cohort) were included in the efficacy analysis population. The primary endpoint was objective response rate in patients with BRCA alterations and measurable disease (measurable BRCA cohort). This study is registered with ClinicalTrials.gov, NCT02854436. Findings Between Sept 28, 2016, and June 26, 2020, 289 patients were enrolled, of whom 182 (63%) had received three or more systemic therapies for prostate cancer. 223 (77%) of 289 patients were included in the overall efficacy analysis population, which included BRCA (n=142) and non-BRCA (n=81) cohorts. At final analysis, with a median follow-up of 10·0 months (IQR 6·6–13·3), the objective response rate in the measurable BRCA cohort (n=76) was 34·2% (95% CI 23·7–46·0). In the safety analysis population, the most common treatment-emergent adverse events of any grade were nausea (169 [58%] of 289), anaemia (156 [54%]), and vomiting (111 [38%]); the most common grade 3 or worse events were haematological (anaemia in 95 [33%] of 289; thrombocytopenia in 47 [16%]; and neutropenia in 28 [10%]). Of 134 (46%) of 289 patients with at least one serious treatment-emergent adverse event, the most common were also haematological (thrombocytopenia in 17 [6%] and anaemia in 13 [4%]). Two adverse events with fatal outcome (one patient with urosepsis in the BRCA cohort and one patient with sepsis in the non-BRCA cohort) were deemed possibly related to niraparib treatment. Interpretation Niraparib is tolerable and shows anti-tumour activity in heavily pretreated patients with metastatic castration-resistant prostate cancer and DRDs, particularly in those with BRCA alterations

Voices at the Borders, Prose on the Margins : Exploring the Contemporary Pashto Short Story in a Context of War and Crisis

This dissertation is a study of contemporary Pashto prose writing in a context of war and crisis based on a corpus of digitally published and/or printed short stories from the 1990s onwards. Out of this larger corpus, 16 stories have been selected and analysed under four topics: "The Terrorist", Female agency: Representations of and by, "The Madman", and Axtar: Longing for peace or imaging disillusion. A central idea is that the analysis should be text-oriented, but the contextualisation of the analysed texts is a secondary important focus. Chapter one presents the material and gives a general context to the study. In the second chapter, after a general conceptualisation of the short story genre, I discuss the borders between prose and poetry. In chapter three I provide an overview of Pashto literature where the aim is to pinpoint certain characteristics of literature in what I call a poeticised community, such as that of the Pashtuns. The fourth chapter contains an introduction to the four topics mentioned above, a summary of each of the four stories belonging to the specific topic with selected parts in direct translation from the Pashto original, as well as a discussion of form and contents of each topic separately. Chapter five consists of a general conclusion. An appendix with the original Pashto text of translated sections is found before the bibliography. One feature that has emerged from this study is the notion of how the narratives are often found to communicate and respond to their immediate surroundings, in time as well as in space. Another important conclusion is that devices normally regarded as belonging to the realm of poetry are not uncommon in Pashto short story writing

Voices at the Borders, Prose on the Margins : Exploring the Contemporary Pashto Short Story in a Context of War and Crisis

This dissertation is a study of contemporary Pashto prose writing in a context of war and crisis based on a corpus of digitally published and/or printed short stories from the 1990s onwards. Out of this larger corpus, 16 stories have been selected and analysed under four topics: "The Terrorist", Female agency: Representations of and by, "The Madman", and Axtar: Longing for peace or imaging disillusion. A central idea is that the analysis should be text-oriented, but the contextualisation of the analysed texts is a secondary important focus. Chapter one presents the material and gives a general context to the study. In the second chapter, after a general conceptualisation of the short story genre, I discuss the borders between prose and poetry. In chapter three I provide an overview of Pashto literature where the aim is to pinpoint certain characteristics of literature in what I call a poeticised community, such as that of the Pashtuns. The fourth chapter contains an introduction to the four topics mentioned above, a summary of each of the four stories belonging to the specific topic with selected parts in direct translation from the Pashto original, as well as a discussion of form and contents of each topic separately. Chapter five consists of a general conclusion. An appendix with the original Pashto text of translated sections is found before the bibliography. One feature that has emerged from this study is the notion of how the narratives are often found to communicate and respond to their immediate surroundings, in time as well as in space. Another important conclusion is that devices normally regarded as belonging to the realm of poetry are not uncommon in Pashto short story writing

The currency of influence: a study of the external impact of Teamfight Tactics' metagame and its effect on player strategy.

This research paper presents a study of the Teamfight Tactics (Riot Games, 2019) metagame and its evolution over time. For this research purpose, we have defined metagames as the ways in which games exist within broader social and cultural contexts. By using a mixed-methods approach, we explore players' relationship with the TFT metagame, their strategies used to succeed, and the factors that influence the metagame's evolution, as well as how TFT metamedia impacts players' relationship with the metagame. Our research's theoretical framework is based on the idea of metagame analysis presented in 2017 by Boluk and LeMieux. The main results of our study show that most players consume some kind of TFT-related metamedia, which suggests that metamedia has a big influence on how players approach TFT and formulate their gameplay strategies. Players with varying skill-levels may consume different kinds of metamedia, which raises the possibility that they may be persuaded to adopt distinct approaches to playing the game and thereby contribute to the emergence of the metagame. This implies that the impact of metamedia on the metagame is not ubiquitous for all players and that additional study is required to properly comprehend the connection between the consumption of metamedia, skill level, and the metagame evolution. Due to the focus on TFT and the small sample size of our data collection, our research is restricted. However, our findings may be intriguing to TFT players, game developers, and researchers who are interested in game design, player behavior, and competitive gaming. With a particular focus on highlighting insights of the TFT metagame and its relation with metamedia, this study contributes to the larger discussion on game metagames and their development over time