Diversity in the internal functional feeding elements of sympatric morphs of Arctic charr (Salvelinus alpinus).

The diversity of functional feeding anatomy is particularly impressive in fishes and correlates with various interspecific ecological specializations. Intraspecific polymorphism can manifest in divergent feeding morphology and ecology, often along a benthic-pelagic axis. Arctic charr (Salvelinus alpinus) is a freshwater salmonid known for morphological variation and sympatric polymorphism and in Lake Þingvallavatn, Iceland, four morphs of charr coexist that differ in preferred prey, behaviour, habitat use, and external feeding morphology. We studied variation in six upper and lower jaw bones in adults of these four morphs using geometric morphometrics and univariate statistics. We tested for allometric differences in bone size and shape among morphs, morph effects on bone size and shape, and divergence along the benthic-pelagic axis. We also examined the degree of integration between bone pairs. We found differences in bone size between pelagic and benthic morphs for two bones (dentary and premaxilla). There was clear bone shape divergence along a benthic-pelagic axis in four bones (dentary, articular-angular, premaxilla and maxilla), as well as allometric shape differences between morphs in the dentary. Notably for the dentary, morph explained more shape variation than bone size. Comparatively, benthic morphs possess a compact and taller dentary, with shorter dentary palate, consistent with visible (but less prominent) differences in external morphology. As these morphs emerged in the last 10,000 years, these results indicate rapid functional evolution of specific feeding structures in arctic charr. This sets the stage for studies of the genetics and development of rapid and parallel craniofacial evolution.

Public Preferences for Digital Health Data Sharing: Discrete Choice Experiment Study in 12 European Countries.

BACKGROUND: With new technologies, health data can be collected in a variety of different clinical, research, and public health contexts, and then can be used for a range of new purposes. Establishing the public's views about digital health data sharing is essential for policy makers to develop effective harmonization initiatives for digital health data governance at the European level. OBJECTIVE: This study investigated public preferences for digital health data sharing. METHODS: A discrete choice experiment survey was administered to a sample of European residents in 12 European countries (Austria, Denmark, France, Germany, Iceland, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) from August 2020 to August 2021. Respondents answered whether hypothetical situations of data sharing were acceptable for them. Each hypothetical scenario was defined by 5 attributes ("data collector," "data user," "reason for data use," "information on data sharing and consent," and "availability of review process"), which had 3 to 4 attribute levels each. A latent class model was run across the whole data set and separately for different European regions (Northern, Central, and Southern Europe). Attribute relative importance was calculated for each latent class's pooled and regional data sets. RESULTS: A total of 5015 completed surveys were analyzed. In general, the most important attribute for respondents was the availability of information and consent during health data sharing. In the latent class model, 4 classes of preference patterns were identified. While respondents in 2 classes strongly expressed their preferences for data sharing with opposing positions, respondents in the other 2 classes preferred not to share their data, but attribute levels of the situation could have had an impact on their preferences. Respondents generally found the following to be the most acceptable: a national authority or academic research project as the data user; being informed and asked to consent; and a review process for data transfer and use, or transfer only. On the other hand, collection of their data by a technological company and data use for commercial communication were the least acceptable. There was preference heterogeneity across Europe and within European regions. CONCLUSIONS: This study showed the importance of transparency in data use and oversight of health-related data sharing for European respondents. Regional and intraregional preference heterogeneity for "data collector," "data user," "reason," "type of consent," and "review" calls for governance solutions that would grant data subjects the ability to control their digital health data being shared within different contexts. These results suggest that the use of data without consent will demand weighty and exceptional reasons. An interactive and dynamic informed consent model combined with oversight mechanisms may be a solution for policy initiatives aiming to harmonize health data use across Europe.

Activity of osimertinib in a patient with stage IV non-small cell lung cancer harboring HER2 exon 19, p.L755P mutation: case report.

Background: Recurrent in-frame insertions within exon 20 causing duplication of amino acids Tyrosine-Valine-Methionine-Alanine (YVMA) represent 80% of all HER2 alterations in non-small cell lung cancer (NSCLC). HER2 tyrosine kinase inhibitors (TKI), anti-HER2 monoclonal antibodies and HER2 directed antibody-drug conjugates have been evaluated in patients with HER2 mutated NSCLC. Limited data are available regarding the activity of these agents in exon 19 alterations. Osimertinib, a 3rd generation EGFR-TKI, has been found in pre-clinical studies to decrease growth of NSCLC with HER2 exon 19 aberrations. Case Description: A 68-year-old female with a past medical history of type 2 diabetes and minimal smoking was diagnosed with stage IV NSCLC. Next generation sequencing on tumor tissue demonstrated an ERBB2 exon 19 c.2262_2264delinsTCC, p.(L755P) mutation. After five lines of treatment that included chemotherapy, chemoimmunotherapy and investigational agents the patient's disease was progressing. At this time her functional status remained good, therefore clinical trials were explored however, none were available. Based on findings from pre-clinical studies, the patient was commenced on osimertinib 80 mg OD and achieved a partial response (PR) according to RESIST criteria both intra- and extracranially. Conclusions: This is the first report to our knowledge to demonstrate activity of osimertinib in a patient with NSCLC harboring HER2 exon 19, p.L755P mutation resulting in intra- and extracranial response. In the future, osimertinib could become a targeted treatment for patients harboring exon19 ERBB2 point mutations.

The half-painted picture: Reviewing the mental health impacts of cancer screening.

Cancer screening is recommended for select cancers worldwide. Cancer screening has become increasingly effective and accessible and often increases overall survival. However, the mental health effects of cancer screening, such as its impact on depression, anxiety, and post-traumatic stress disorder, are largely unknown. Conflicting available literature indicates the negative, neutral, and positive mental health effects of cancer screening across cancer types. There are a limited number of randomized controlled trials measuring the mental health effects of cancer screening. Overall, the more negative and life-threatening the screening results, the greater the mental health effects. Screening for cancer without a known precursor, for example, due to family history, can have positive impacts such as decreased worry and increased quality of life. However, receiving a cancer diagnosis often has negative mental effects that increase with the life-threatening potential of malignancy. In this study, we review the existing literature and provide recommendations for future research to determine if and when cancer screening is the best practice.

Are We Only Detecting the Tip of the Iceberg? A Nationwide Study on Primary Aldosteronism with up to 8-Year Follow-up.

BACKGROUND: Long-term follow-up studies on primary aldosteronism (PA) are lacking. OBJECTIVE: We aim to review results of diagnostic procedures and histopathology for patients diagnosed during 2012-2016 in Iceland, compare unilateral (UD) and bilateral disease (BD) and assess treatment response. METHODS: Thirty-two patients aged 28-88 were diagnosed and treated according to guidelines. RESULTS: The majority had BD. Everyone needed potassium supplementation at case detection. We saw a reduction in systolic blood pressure (p < .001, both groups), antihypertensive agents (p = .002 UD and p = .04 BD) and potassium supplementation (p < .001, both groups). CONCLUSION: Similar treatment response was seen in both subgroups. Ratio of hypokalemia and number of cases indicates severe PA underdiagnosis in Iceland.

Cumulative exposure to melphalan chemotherapy and subsequent risk of developing acute myeloid leukemia and myelodysplastic syndromes in patients with multiple myeloma.

OBJECTIVES: The aim of this study was to determine risk factors for development of acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) in patients with multiple myeloma (MM). METHODS: We identified all patients diagnosed with MM in Sweden from January 1st, 1958 to December 31, 2011. A total of 26 627 patients were diagnosed with MM with during the study period. Of these, 124 patients (0.5%) developed subsequent AML/MDS. For each patient with MM and a subsequent AML/MDS diagnosis, we randomly selected a matched (age, sex, and date of MM diagnosis) MM patient without a subsequent second malignancy diagnosis. RESULTS: The cumulative melphalan exposure was significantly higher (OR = 2.8, 95% CI 1.7-5.2; P < .001) among cases (median 988 mg; IQR 644-1640) compared with controls (median 578 mg; IQR 360-967). Median time to AML/MDS development was 3.8 years (IQR 2.8-5.8). Risk of AML/MDS was not statistically altered by M protein isotype, anemia, renal failure, hypercalcemia, lytic bone lesions, or radiation therapy. CONCLUSION: In this nationwide population-based study, we show that increased cumulative doses of alkylating therapy with melphalan increases the subsequent risk of developing AML/MDS in patients with MM. Given improved survival in MM patients over the last decade future studies will be important to better define long-term risks.

Preferences of the Public for Sharing Health Data: Discrete Choice Experiment.

BACKGROUND: Digital technological development in the last 20 years has led to significant growth in digital collection, use, and sharing of health data. To maintain public trust in the digital society and to enable acceptable policy-making in the future, it is important to investigate people's preferences for sharing digital health data. OBJECTIVE: The aim of this study is to elicit the preferences of the public in different Northern European countries (the United Kingdom, Norway, Iceland, and Sweden) for sharing health information in different contexts. METHODS: Respondents in this discrete choice experiment completed several choice tasks, in which they were asked if data sharing in the described hypothetical situation was acceptable to them. Latent class logistic regression models were used to determine attribute-level estimates and heterogeneity in preferences. We calculated the relative importance of the attributes and the predicted acceptability for different contexts in which the data were shared from the estimates. RESULTS: In the final analysis, we used 37.83% (1967/5199) questionnaires. All attributes influenced the respondents' willingness to share health information (P<.001). The most important attribute was whether the respondents were informed about their data being shared. The possibility of opting out from sharing data was preferred over the opportunity to consent (opt-in). Four classes were identified in the latent class model, and the average probabilities of belonging were 27% for class 1, 32% for class 2, 23% for class 3, and 18% for class 4. The uptake probability varied between 14% and 85%, depending on the least to most preferred combination of levels. CONCLUSIONS: Respondents from different countries have different preferences for sharing their health data regarding the value of a review process and the reason for their new use. Offering respondents information about the use of their data and the possibility to opt out is the most preferred governance mechanism.

Bullying and Harassment in Downsized Workplaces: What Can We Learn from the 2008 Icelandic Economic Collapse?

Research shows that bullying is a significant workplace issue. A previous study showed increased sickness-related absences among municipality employees during the Icelandic economic crisis in 2008. This led to the following research questions: has bullying and/or harassment increased between the time points of the study up to seven years after the crisis? Did bullying and/or harassment change depending on downsizing? Are quantitative job demands, role conflicts and social support connected to bullying and/or harassment at work and if so, how? The study is based on a four-wave longitudinal balanced panel dataset consisting of those who work within the education and care services operated by Icelandic municipalities. It was seen that bullying and harassment had increased between the time points of the study. Furthermore, employees in downsized workplaces, workplaces with higher quantitative job demands, more role conflicts and less support were more likely to experience bullying and/or harassment than employees in other workplaces. Since the effects may prevail for several years, the study demonstrates that the consequences of downsizing need to be carefully considered and that managers must be supported in that role. As economic crises tend to occur periodically, presently due to COVID-19, the knowledge is both of theoretical and practical importance.

Changes in occupational mental and physical health and health symptoms during the economic recession.

BACKGROUND: In 2008, many Western countries faced a great economic recession, the result of which was increased unemployment and reduced public expenditure. OBJECTIVE: This article focuses on changes in the self-reported mental and physical health and health symptoms of the remaining employees of Icelandic municipalities who worked within the educational system and the care service during the economic recession. We examine gender differences in health and differences between downsized workplaces and workplaces where no downsizing occurred and differences between workplaces with heavy workload and light workload. METHODS: The study is based on a balanced panel online survey and focus groups. RESULTS: The main finding is that both the mental and physical health of employees deteriorated year by year between 2010, 2011 and 2013 in all workplaces although the downsized workplaces and workplaces with heavy workloads fared worse. At the same time, public expenditure on the health care system was reduced. CONCLUSIONS: We hope that our results encourage further studies in the field and that they will be taken into account when dealing with prevention and rehabilitation initiatives.

The impact of prior malignancies on second malignancies and survival in MM patients: a population-based study.

In the present study, we aimed to evaluate 2 hypotheses. First, we hypothesize that prior malignancy is a proxy for genetic susceptibility that could be a risk factor for subsequent malignancy development in multiple myeloma (MM) patients. Second, we hypothesize that survival after MM is influenced by a prior malignancy. All patients diagnosed with MM from 1 January 1973 to 31 December 2010 were identified from the Swedish Cancer Register. Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) where prior malignancy was compared in MM patients who developed a subsequent malignancy and MM patients who did not. In another Cox regression model, survival was compared in MM patients with and without a prior malignancy diagnosis. A total of 19 791 patients were diagnosed with MM. Patients with a prior malignancy diagnosis had a significantly increased risk of developing a subsequent malignancy compared with MM patients without (HR 1.42, 95% CI 1.23-1.65, P < .001). MM patients with a prior malignancy diagnosis had a significant 1.21-fold increased risk of death (95% CI 1.115-1.26, P < .001) compared with MM patients without. MM patients with 2 or more prior malignancy diagnoses had a 1.34-fold increased risk of death (95% CI 1.19-1.52, P < .001). In this large population-based study, we report that prior malignancy increases the risk of subsequent malignancy development in MM patients. Furthermore, we found that prior malignancy negatively impacts survival and that >1 prior malignancy reduces survival even further.

Primary aldosteronism: from case detection to histopathology with up to 6 years of follow-up.

The authors aimed to investigate the clinical characteristics, accuracy of diagnostic tests, and long-term outcomes after interventions in patients diagnosed with primary aldosteronism (PA) in Iceland throughout 5 years. A retrospective chart review was performed for all patients diagnosed with PA during the years 2007-2011 at Landspitali Hospital in Iceland, a referral center for the whole country. Workup after detection included salt loading test, positional test, computed tomography, and adrenal vein sampling. Patients with unilateral disease were offered treatment with adrenalectomy. A total of 33 patients were diagnosed with PA during the study period: 17 patients with bilateral disease and 16 with unilateral disease. Results from salt loading test were positive in 90% of patients. In patients with adenoma, 36% were responsive on their positional test and computed tomography scan showed a nodule in 73%. All patients with unilateral disease had a lateralization index ≥3. After surgery, patients had lower systolic blood pressure (P<.001) and number of hypertensive medications (P<.01).

Public opinion on childhood immunisations in Iceland.

INTRODUCTION: In recent years, vaccine preventable diseases such as measles and pertussis have been re-emerging in Western countries, maybe because of decreasing participation in childhood vaccination programs in some countries. There is clear evidence for vaccine efficacy and the risk of adverse effects is low. This needs to be communicated to the general public. The aim of the study was to evaluate the public opinion on childhood vaccinations in Iceland. MATERIALS AND METHODS: An internet based study was used to evaluate the opinion on childhood immunisations in Iceland. The cohort was divided in three groups: (a) general public (b) employees of the University Hospital Iceland and (c) employees (teachers and staff) of the University of Iceland. The cohorts could be stratified according to age, gender, education, household income, parenthood and residency. RESULTS: Responses were received from 5584 individuals (53% response rate). When asked about childhood vaccinations in the first and second year of life, approximately 95% of participants were "positive" or "very positive", approximately 1% were "negative" or "very negative". When participants were asked whether they would have their child immunized according to the Icelandic childhood vaccination schedule, 96% were "positive" or "very positive", 1.2% were "negative" or "very negative". Similarly, 92% trust Icelandic Health authorities to decide on childhood vaccination schedule, 2.3% did not. In total, 9.3% "rather" or "strongly" agreed to the statement "I fear that vaccinations can cause severe adverse effects", 17.5% were undecided and 66.9% "disagreed" or "strongly disagreed". Individuals with higher education were more likely to disagree with this statement (OR=1.45, CI95=1.29-1.64, p<0.001) as did males (OR=1.22, CI95=1.087-1.379, p=0.001). CONCLUSION: This study shows a very positive attitude towards vaccinations raising expectations for an ongoing success in preventing preventable communicable diseases in childhood in Iceland.

Aqueous extracts from Menyanthes trifoliate and Achillea millefolium affect maturation of human dendritic cells and their activation of allogeneic CD4+ T cells in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Menyanthes trifoliate and Achillea millefolium have been used in traditional medicine to ameliorate chronic inflammatory conditions. The aim of this study was to identify the effects of ethanol and aqueous extracts of Menyanthes trifoliate and Achillea millefolium on maturation of dendritic cells (DCs) and their ability to activate allogeneic CD4(+) T cells. MATERIALS AND METHODS: Human monocyte-derived DCs were matured in the absence or presence of lyophilised aqoueous or ethanol extracts from Menyanthes trifoliate or Achillea millefolium and their expression of surface molecules analysed with flow cytometry and cytokine secretion measured by ELISA. DCs matured in the presence of aqueous extracts from Menyanthes trifoliate and Achillea millefolium were co-cultured with allogeneic CD4(+) T cells and the expression of surface molecules by T cells and their cytokine secretion and cell proliferation determined. RESULTS: Maturation of DCs in the presence of aqueous extracts from Menyanthes trifoliate or Achillea millefolium did not affect expression of the surface molecules examined but reduced the ratio of secreted IL-12p40/IL-10, compared with that by DCs matured in the absence of extracts. Allogeneic CD4(+) T cells co-cultured with DCs matured in the presence of aqueous extract from Menyanthes trifoliate secreted less IFN-γ, IL-10 and IL-17 than CD4(+) T cells co-cultured with DCs matured without an extract. Maturation of DCs in the presence of aqueous extract from Achillea millefolium decreased IL-17 secretion but did not affect IFN-γ and IL-10 secretion by allogeneic CD4(+) T cells. CONCLUSIONS: Aqueous extract from Menyanthes trifoliate induces a suppressive phenotype of DCs that has reduced capacity to induce Th1 and Th17 stimulation of allogeneic CD4(+) T cells, whereas aqueous extract from Achillea millefolium reduces the capacity of DCs to induce a Th17 response.

Mechanism of thrombin mediated eNOS phosphorylation in endothelial cells is dependent on ATP levels after stimulation.

Conflicting results have been reported concerning the role of AMP-activated protein kinase (AMPK) in mediating thrombin stimulation of endothelial NO-synthase (eNOS). We examined the involvement of two upstream kinases in AMPK activation in cultured human umbilical endothelial cells, LKB1 stimulated by a rise in intracellular AMP/ATP ratio, and Ca(+2)/CaM kinase kinase (CaMKK) responding to elevation of intracellular Ca(+2). We also studied the effects of AMPK activation on the downstream target eNOS. In culture medium 1640 the level of intracellular ATP was unchanged after thrombin stimulation and the CaMKK inhibitor STO-609 totally inhibited phosphorylation of AMPK and acetyl coenzyme A carboxylase (ACC) but not eNOS. In Morgan's medium 199 thrombin caused a significant lowering of intracellular ATP and STO-609 only partially inhibited the phosphorylation of AMPK, ACC and eNOS. Inhibition of AMPK by Compound C or AMPK downregulation using siRNA partially inhibited the phosphorylation of eNOS in medium 199 but not in 1640, underscoring a clear difference in the pathways mediating thrombin-stimulated eNOS phosphorylation in different culture media. Thus, conditions subjecting endothelial cells to a fall in ATP after thrombin stimulation facilitate activation of pathways partly dependent on AMPK causing downstream phosphorylation of eNOS. In contrast, under culture conditions that do not facilitate a fall in ATP after stimulation, AMPK activation is exclusively mediated by CaMKK and does not contribute to the phosphorylation of eNOS.