We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke.

Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10−7), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.

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Tumor-associated macrophages (TAM) have been ascribed both pro- and anti-tumor properties, but the majority of clinical cancer studies have shown that the presence of a high number of TAM is related to poor prognosis, suggesting that TAM predominantly exert pro-tumoral activity. The prognostic role of TAM in patients with diffuse large B-cell lymphoma (DLBCL), however, is so far unknown. Therefore, TAM were immunohistochemically stained with a CD68 antibody in a retrospective, population-based study including 176 DLBCL patients treated with curative intent. With the exception that patients >60 years of age had a larger number of CD68+ cells (1143 vs 1018 cells/mm2; P = 0.05), no significant differences were found between the number of CD68+ cells and other clinical factors. Similarly, germinal center B-cell (GCB)/non-GCB immunophenotype or low/high Ki-67 percentage were not associated with CD68 expression. Finally, no significant correlation was found between the number of CD68+ cells and progression-free survival (P = 0.34) or overall survival (P = 0.94). These data indicate that the pro-tumor effect of TAM has limited clinical relevance in DLBCL patients, which could imply that therapeutic strategies aimed at enhancing their anti-tumor activity are of continuous clinical interest.

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Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

The flipped classroom offers a new approach to student-centred teaching and learning by moving the lecture out of the classroom. Research on the topic reveals that the flexibility of viewing the recorded lectures at a time and speed that is convenient to the student is what students appreciate mostly in the flipped classroom. This article examines the viewing pattern of students regarding recorded lectures in a course that has been flipped. The findings reveal a decline in the number of students who view the recordings over the duration of the course semester. Furthermore, the findings support earlier research results revealing that women and older students rely more on recorded lectures than other students. In addition, the study shows that there is a positive correlation between viewing the recorded material and the final grade of students in the course. It is thus surmised that even if in-class activity is very important for the flipped classroom to work, the recordings do have additional value, which is reflected by higher final course grades for students who view them. The flexibility of viewing recordings more than once and at the most relevant and convenient time seems to increase students' understanding, and is regarded an important asset of flipped classroom teaching.

The prognostic role of overexpression of Ki-67 protein in diffuse large B-cell lymphoma (DLBCL) is still unclear. Furthermore, immunohistochemical studies have suggested a correlation between markers of proliferation, B-cell differentiation and apoptosis, but the prognostic relevance of these findings has not been clarified. To investigate the prognostic impact of Ki-67, in the context of this correlation, a retrospective immunohistochemical study was performed on 199 DLBCL patients treated with curative intent. Patients with low Ki-67 expression (<49%) had significantly worse progression-free (PFS) and overall (OS) survival, independent of clinical risk factors. In addition, low Ki-67 correlated to bcl-2 expression but not to non-germinal centre B-cell-like (non-GCB) phenotype. Each of these factors had negative impact on PFS and OS, but low Ki-67 expression also remained as an adverse prognostic factor independent of non-GCB phenotype and bcl-2 expression. Together, these results suggest that low rather than high Ki-67 protein expression is of prognostic importance in DLBCL.