Malignant melanoma and other malignancies of the nasal cavity and the paranasal sinuses in Sweden

Background: Malignancies emerging in the nasal cavity and the paranasal sinuses are rare and accounts for 5% of all head and neck malignancies and 0.1% of all malignancies in Sweden. The incidence of sinonasal malignancy (SNM), except sinonasal malignant melanoma (SNMM), has been reported to decrease since 1960 in Sweden. Despite similar improvement in the prognosis of other malignancies, treatment of SNM still yields a poor survival outcome. About 1–2% of all malignant melanomas originate from mucosal membranes in the genitourinary, digestive and the respiratory regions, whereas mucosal melanomas are most frequently located in the nasal cavity, followed by sites in paranasal sinuses in the head and neck region. The incidence of cutaneous malignant melanoma (CMM) continues to increase in many parts of the world, possibly due mainly to the effects of sun-related behaviour; however, the incidence of mucosal melanomas such as vulvar and ano-rectal melanoma display a more complicated pattern with a stable or decreasing incidence rate. We now know that the incidence of SNMM is increasing in Sweden, as we have documented one of the largest consecutively studied SNMM groups in the world. Nevertheless, the underlying mechanism remains unclear. The treatment options for these patients have remained the same over the years; mainly radical surgery followed by radiotherapy. Alternatively, recent molecular-targeted therapy has become available for sub-groups of patients with malignant melanomas. Such therapeutic advances stress the importance of investigating the aetiology and molecular characteristics of SNMM, which are not yet well. Aims: Given the rarity of SNM and SNMM, relevant knowledge is limited. Therefore, the overall aim of this thesis was to examine the clinical characteristics and features of SNMM and SNM and to determine the occurrence of molecular alterations. They include KIT, NRAS and BRAF mutation frequencies and mutation frequency of the TERT (Telomerase Reverse Transcriptase) promotor gene in SNMM. Results: In the first project, we identified 3221 patients from the Swedish National Cancer Registry diagnosed with primary malignancies arising from the nasal cavity, paranasal sinuses, or both, during the period 1960 through 2011. The anatomical site, gender and age, incidence and survival were scrutinized. We found that the incidence of sinonasal malignancies decreased except for SNMM and adenoid cystic cancer during the study period. More than 50% of these malignancies involved the nasal cavity. The five-year relative survival was highest for patients with adenoid cystic cancer followed by adenocarcinoma. Those with SNMM and undifferentiated carcinoma had the poorest prognosis. In the second project we identified 186 SNMM patients during the period 1960 through 2000 in Sweden from the National Swedish Cancer Registry (SCR). We investigated the incidence, gender, age, primary anatomical sites, geographic distribution, treatment and survival. In this population the incidence of SNMM increased during the study period. The incidence for females was higher than for males, and the incidence increased with age for both genders. We found that about 70% of the tumours were clinically described as amelanotic. Surgery was the most common primary treatment. The five-year disease- specific survival rates were poor for both genders, but females had a better survival than males. The survival rate improved for both genders during the study period, regardless of therapeutic strategy. We conclude that the incidence of SNMM in Sweden increased significantly from 1960 through 2000 but not as rapidly as that of CMM. In the third project, we analysed 56 primary SNMMs, the largest number, as far as we know, for mutations in KIT (exons 11, 13 and 17), NRAS (exons 1 and 2) and BRAF (exon 15) identified by using direct sequencing. Twelve of the 56 (21%) tumours contained mutations in these oncogenes, 2 tumours harboured KIT mutations, another 2 harboured BRAF mutation and 8 had NRAS mutations. We found a higher frequency of mutations in tumours originating from the paranasal sinuses compared to tumours from the nasal cavity (p=0.027). In the fourth project we analysed 49 SNMM tumours for TERT promotor gene mutations, since former investigators found only a few driver mutations for these patients, who were never previously examined for this mutation. Recent studies of CMM have shown a high frequency (>70%) of driver mutations in this gene. TERT promoter mutations occur at a moderate frequency in SNMM. We suggest that SNMM tumours should be included in molecular characterization, since these alterations probably will be therapeutic targets in the near future

A Readability Survey of the Science Textbooks used in University Place Elementary School, District No. 83

The purpose of this study was to determine: 1) the readability of an intermediate series of science textbooks, Concepts in Science, published by Harcourt, Brace and World; 2) if the text was readable for the students at University Place Elementary School near Tacoma, Washington; 3) whether the gradation or slope of difficulty rises progressively from the beginning of the book to the ending of the book

Understanding TERT promoter mutations: a common path to immortality

Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients.Support was provided from a generous gift from the Dabbiere family(RJB,AM,JFC), the Hana Jabsheh Research Initiative (RJB,AM,JFC), and NIH grants NCI P50CA097257 (RJB,AM,JFC), P01CA118816-06 (RJB,AM,JFC), R01HG003008 (HTR), and R01CA163336 (JSS). Additional support was provided from the Sontag Foundation Distinguished Scientist Award (JSS), Fundação para a Ciência e Tecnologia SFRH/BD/88220/2012 (AXM), IF/00601/2012 (BMC), Programa Operacional Regional do Norte (ON.2—O Novo Norte) (BMC), Quadro de Referência Estratégico Nacional (BMC), and Fundo Europeu de Desenvolvimento Regional (BMC).info:eu-repo/semantics/publishedVersio

Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multi-national data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar was found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-negligible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic

Author Correction: National identity predicts public health support during a global pandemic

Correction to: Nature Communications https://doi.org/10.1038/s41467-021-27668-9, published online 26 January 2022

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics

Social and moral psychology of COVID-19 across 69 countries

The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables

Predicting attitudinal and behavioral responses to COVID-19 pandemic using machine learning

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multinational data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar results were found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, and collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-neglible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic.Peer reviewe