The Genetic Basis of Primary Myelofibrosis and Its Clinical Relevance

Among classical BCR-ABL-negative myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF) is the most aggressive subtype from a clinical standpoint, posing a great challenge to clinicians. Whilst the biological consequences of the three MPN driver gene mutations (JAK2, CALR, and MPL) have been well described, recent data has shed light on the complex and dynamic structure of PMF, that involves competing disease subclones, sequentially acquired genomic events, mostly in genes that are recurrently mutated in several myeloid neoplasms and in clonal hematopoiesis, and biological interactions between clonal hematopoietic stem cells and abnormal bone marrow niches. These observations may contribute to explain the wide heterogeneity in patients’ clinical presentation and prognosis, and support the recent effort to include molecular information in prognostic scoring systems used for therapeutic decision-making, leading to promising clinical translation. In this review, we aim to address the topic of PMF molecular genetics, focusing on four questions: (1) what is the role of mutations on disease pathogenesis? (2) what is their impact on patients’ clinical phenotype? (3) how do we integrate gene mutations in the risk stratification process? (4) how do we take advantage of molecular genetics when it comes to treatment decisions?     

Italian multicentre study on microbial environmental contamination in dental clinics: a pilot study

The dental practice is associated with a high risk of infections, both for patients and healthcare operators, and the environment may play an important role in the transmission of infectious diseases. A microbiological environmental investigation was carried out in six dental clinics as a pilot study for a larger multicentre study that will be performed by the Italian SItI (Society of Hygiene, Preventive Medicine and Public Health) working group "Hygiene in Dentistry". Microbial contamination of water, air and surfaces was assessed in each clinic during the five working days of the week, before and during treatments. Air and surfaces were also examined at the end of the daily activity. A wide variation was found in microbial environmental contamination, both within the participating clinics and relative to the different sampling times. Microbial water contamination in Dental Unit Water Systems (DUWS) reached values of up to 26 × 10⁴ cfu/mL (colony forming units per millilitre). P. aeruginosa was found in 33% of the sampled DUWS and Legionella spp. in 50%. A significant decrease in the Total Viable Count (TVC) was recorded during the activity. Microbial air contamination showed the highest levels during dental treatments and tended to decrease at the end of the working activity (p < 0.05). Microbial buildup on surfaces increased significantly during the working hours. As these findings point out, research on microbial environmental contamination and the related risk factors in dental clinics should be expanded and should also be based on larger collections of data, in order to provide the essential knowledge aimed at targeted preventive interventions.     

Longitudinal analysis of the formation and realisation of preferences to move into homeownership in the Netherlands

This study investigates how life course characteristics and housing market circumstances affect the formation and realisation of preferences to move into homeownership. Using a data set from the Netherlands in which data from three cross-sectional housing surveys are enriched with longitudinal register data for the period 1998–2008, we follow aspiring homeowners regarding their actual residential behaviour. We find that only 31 % of the aspiring homeowners became homeowners within 2 years, approximately 13 % moved to rental homes, and the vast majority did not move at all. Insufficient socioeconomic resources and a high house price-to-rent ratio hamper the realisation of preferences to move into homeownership. However, these hampering factors are at least as important as the extent to which individuals prefer to move into homeownership. This last finding suggests that housing tenure preferences cannot be viewed as ‘pure’ preferences.     

From natural environment to artificial system: Chang'an and its water system in the Western Han Dynasty

People around the world have shaped societies and urban spaces around water for millennia. They have transformed natural water structures and patterns to serve their diverse needs. The ways in which historical decisions affect contemporary water systems and influence future planning of urban systems still need to be fully recognized. This paper explores the multiple roles of water systems in Chang'an during the Western Han Dynasty. Chang’an, one of the ancient names for the city of Xi’an, was a typical capital city of China and East Asia in early ancient times. This study explores everyday practices pertaining to water as well as its role in defense, gardening, politics and culture.Drawing upon three historical theories, this study presents findings that water was embedded in the design of traditional Chinese capitals. The siting and construction of capital cities was first based on the Theory of Choosing the Center (3rd century BCE) and the Theory of Conforming to Nature (5th–3rd century BCE). However, the final maturation of this urban morphology, including the water system, was closely related to the Theory of Symbolizing and Modeling Heaven and Earth (4th–3rd century BCE), in a way that manifested the imperial power's organization and control of space and time.Through close analysis of historical documents, archaeological reports and modern investigations, the paper aims to clarify, analyze and summarize the historical context and evolution, functional and structural characteristics, as well as the economic, political, cultural and military connotations of water systems in Chang'an. It argues that the coordination of urban construction and the water environment was a key foundation for capital city development. It proposes that people shaped urban water supply in many ways, including daily life, waterway transportation, agricultural irrigation, aquaculture promotion, military defense and fire prevention.The water system in Chang'an also provided an important place for royalty and nobility to go fishing, to hunt and to engage in leisure and naval training. The landscape with this water system as the core, including Taiye Lake and Kunming Lake, had also inspired Chinese gardening history, and had a profound impact on future generations. More importantly, the capital's urban morphology design was a miniature of the world recognized by the monarch, as well as the symbolic image of the supreme rulers' political and cultural desire to control and possess Tianxia, which essentially means the whole world. In conclusion, the paper calls for a closer study of water-based design as a foundation for urban planning.     

Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.     

Wear Performance of Dental Materials: A Comparison of Substructure Ceramics,Veneering Ceramics,and Non‐Precious Alloys

The aim of this in vitro study was to compare the two‐body wear resistance of different dental ceramics and non‐precious alloys. Two‐body wear tests were performed in a chewing simulator with steatite antagonists. A pin‐on‐block design with a vertical load of 50 N for 1.2 × 10⁵ cycles (f = 1.6 Hz; lateral movement: 1 mm, mouth opening: 2 mm) was used for the wear test. Surface roughness R_a (SP6, Perthen‐Feinprüf, G) and wear depth were determined using a 3D‐Profilometer (Laserscan 3D, Willytec, G). Scanning electron microscopy (Quanta FEG 400, FEI, NL) was applied for evaluating wear performance of both, materials and antagonists. Statistics: one‐way ANOVA (α = 0.05). The in vitro wear test showed that the wear performance of dental materials is strongly influenced by the type of material (ceramic, zirconia, or alloy). Zirconia and alloy provided low wear in contrast to glass‐ceramic systems. In contradiction to common expectations, hard zirconia and alloy systems showed even lower antagonistic wear than glass‐ceramics.     

Academic trajectories of newcomer immigrant youth.

Immigration to the United States presents both challenges and opportunities that affect students' academic achievement. Using a 5-year longitudinal, mixed-methods approach, we identified varying academic trajectories of newcomer immigrant students from Central America, China, the Dominican Republic, Haiti, and Mexico. Latent class growth curve analysis revealed that although some newcomer students performed at high or improving levels over time, others showed diminishing performance. Multinomial logistic regressions identified significant group differences in academic trajectories, particularly between the high-achieving youth and the other groups. In keeping with ecological–developmental and stage–environment fit theories, School Characteristics (school segregation rate, school poverty rate, and student perceptions of school violence), Family Characteristics (maternal education, parental employment, and household structure), and Individual Characteristics (academic English proficiency, academic engagement, psychological symptoms, gender, and 2 age-related risk factors, number of school transitions and being overaged for grade placement) were associated with different trajectories of academic performance. A series of case studies triangulate many of the quantitative findings as well as illuminate patterns that were not detected in the quantitative data. Thus, the mixed-methods approach sheds light on the cumulative developmental challenges that immigrant students face as they adjust to their new educational settings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)