Therese Nilsson

A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences.

Summary. The cytogenetic features (ploidy, complexity, breakpoints, imbalances) were ascertained in 783 abnormal multiple myeloma (MM) cases to identify frequently involved chromosomal regions as well as a possible impact of age/sex. The series included MM patients from the Mitelman Database of Chromosome Aberrations in Cancer and from our own laboratory. Hyperdiploidy was most common, followed by hypodiploidy, pseudodiploidy and tri‐/tetraploidy. Most cases were complex, with a median of eight changes per patient. The distribution of modal numbers differed between younger and older patients, but was not related to sex. No sex‐ or age‐related differences regarding the number of anomalies were found. The most frequent genomic breakpoints were 14q32, 11q13, 1q10, 8q24, 1p11, 1q21, 22q11, 1p13, 1q11, 19q13, 1p22, 6q21 and 17p11. Breaks in 1p13, 6q21 and 11q13 were more common in the younger age group. The most frequent imbalances were + 9, – 13, + 15, + 19, + 11 and – Y. Trisomy 11 and monosomy 16 were more common among men, while –X was more frequent among women. Loss of Y as the sole change and + 5 were more common in elderly patients, and – 14 was more frequent in the younger age group. The present findings strongly suggest that some karyotypic features of MM are influenced by endogenous and/or exogenous factors.

Income Inequality and Health: Importance of a Cross-Country Perspective

This paper uses a unique dataset-containing information collected in 2006 on individuals aged 40-79 in 21 countries throughout the world to examine whether individual income, relative income in a reference group, and income inequality are related to health status across middle/low and high-income countries. The dependent variable is self-assessed health (SAH), and as a robustness check, activities of daily living (ADL) are considered. The focus is particularly on assumptions regarding an individuals reference group and on how the estimated relationships depend on the level of economic development. Correcting for national differences in health reporting behavior, individual absolute income is found to be positively related to individual health. Furthermore, in the high-income sample, there is strong evidence that average income within a peer-age group is negatively related to health, thus supporting the relative income hypothesis. In middle/low-income countries, it is instead average regional income that is negatively associated with health. Finally, there is evidence of a negative relationship between income inequality and individual health in high-income countries. Overall, the results suggest that there might be important differences in these relationships between high-income and middle/low-income countries.

Does Economic Freedom Foster Tolerance

Tolerance has the potential to affect both economic growth and wellbeing. It is therefore important to discern its determinants. We add to the literature by investigating whether the degree to which economic institutions and policies are market-oriented is related to different measures of tolerance. Regression analysis of up to 65 countries reveals that economic freedom is positively related to tolerance towards homosexuals, especially in the longer run, while tolerance towards people of a different race and a willingness to teach kids tolerance are not strongly affected by how free markets are. Stable monetary policy and outcomes is the area of economic freedom most consistently associated with greater tolerance, but the quality of the legal system seems to matter as well. We furthermore find indications of a causal relationship and of social trust playing a role as a mechanism in the relationship between economic freedom and tolerance and as an important catalyst: the more trust in society, the more positive the effect of economic freedom on tolerance.

MDS/AML-associated cytogenetic abnormalities in multiple myeloma and monoclonal gammopathy of undetermined significance: Evidence for frequent de novo occurrence and multipotent stem cell involvement of del(20q)

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are characterized cytogenetically by 14q32 rearrangements, −13/13q−, and various trisomies. Occasionally, karyotypic patterns characteristic of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) occur in MM, often signifying therapy‐related (t)‐MDS/t‐AML. Comparison of cytogenetic features in all published MMs (n = 993) and t‐MDS/t‐AML post‐MM (n = 117) revealed significant differences in complexity and ploidy levels and in most genomic changes. Thus, these features often can be used to distinguish between MM and t‐MDS/t‐AML. Rarely, myeloid‐associated aberrations are detected in MM without any signs of MDS/AML. To characterize such abnormalities in MM/MGUS, we ascertained all 122 MM and 26 MGUS/smoldering MM (SMM) cases analyzed in our department. Sixty‐six (54%) MMs and 8 (31%) MGUS/SMMs were karyotypically abnormal, of which 6 (9%) MMs and 3 (38%) MGUS/SMMs displayed myeloid abnormalities, that is, +8 (1 case) and 20q− (8 cases) as the sole anomalies, without any evidence of MDS/AML. One patient developed AML, whereas no MDS/AML occurred in the remaining 8 patients. In one MGUS with del(20q), fluorescence in situ hybridization analyses revealed its presence in CD34+CD38− (hematopoietic stem cells), CD34+CD38+ (progenitors), CD19+ (B cells), and CD15+ (myeloid cells). The present data indicate that 20q− occurs in 10% of karyotypically abnormal MM/MGUS cases and that it might arise at a multipotent progenitor/stem cell level.

Effects of Compulsory Schooling on Mortality: Evidence from Sweden

Theoretically, there are several reasons to expect education to have a positive effect on health. Empirical research suggests that education can be an important health determinant. However, it has not yet been established whether education and health are indeed causally related, and the effects found in previous studies may be partially attributable to methodological weaknesses. Moreover, existing evidence on the education-health relationship generally uses information of fairly recent schooling reforms, implying that health outcomes are observed only over a limited time period. This paper examines the effect of education on mortality using information on a national roll-out of a reform leading to one extra year of compulsory schooling in Sweden. In 1936, the national government made a seventh school year compulsory; however, the implementation was decided at the school district level, and the reform was implemented over 12 years. Taking advantage of the variation in the timing of the implementation across school districts, by using county-level proportions of reformed districts, census data and administrative mortality data, we find that the extra compulsory school year reduced mortality. In fact, the mortality reduction is discernible already before the age of 30 and then grows in magnitude until the age of 55–60.

Cytogenetic features of multiple myeloma: impact of gender, age, disease phase, culture time, and cytokine stimulation

Abstract: Relatively little is known about the cytogenetic features of multiple myeloma (MM) when compared to other hematologic malignancies. The reasons for this are most likely manifold, and include a low mitotic index of the malignant cells and the presence of cytogenetically cryptic abnormalities as well as of complex karyotypes with poor chromosome morphology. In the present study, we have investigated whether various culture conditions may influence the yield of abnormal metaphases in MM and, in the related plasma cell dyscrasias, monoclonal gammopathy of undetermined significance (MGUS) and plasmacytomas (PC). In addition, the possible impact of age, gender, and disease phase on the cytogenetic features has been analyzed. A total of 95 samples from 74 cases (68 MM, three PC, and three MGUS patients) were obtained for cytogenetic analysis. The samples were cultured either in conventional medium or in medium containing IL‐6 and GM‐CSF, and the culture times varied from 24 to 120 h. In total, 186 cultures were analyzed. Metaphase fluorescence in situ hybridization analysis using probes specific for 14q32, i.e. IGH rearrangements, could be performed in 57 of the 74 cases, and revealed 14q32 aberrations in 10 cases not seen by conventional G‐banding. Abnormal karyotypes were detected in 77 (41%) of the 186 cultures, 46 (48%) of the 95 samples, and in 41 (55%) of the 74 patients, revealing a total of 20 chromosomal aberrations previously not reported in plasma cell dyscrasias. We found no evidence that gender, age, disease phase, culture time, or cytokine stimulation significantly influences the karyotypic features of MM.

The impact of the 1918 Spanish flu epidemic on economic performance in Sweden: an investigation into the consequences of an extraordinary mortality shock.

We study the impact of the 1918 influenza pandemic on short- and medium-term economic performance in Sweden. The pandemic was one of the severest and deadliest pandemics in human history, but it has hitherto received only scant attention in the economic literature--despite representing an unparalleled labour supply shock. In this paper, we exploit seemingly exogenous variation in incidence rates between Swedish regions to estimate the impact of the pandemic. The pandemic led to a significant increase in poorhouse rates. There is also evidence that capital returns were negatively affected by the pandemic. However, contrary to predictions, we find no discernible effect on earnings.

Globalization and Institutional Quality - A Panel Data Analysis

Using data on institutional quality and the KOF Globalization Index, we examine over 100 countries from 1992 to 2010 to analyse the relationship between economic and social globalization and six measures of institutional quality, thereby testing Montesquieus doux commerce thesis, that economic and social interaction lead to improved institutional quality. Results suggest that increasing economic flows and social globalization associate with improving institutions in rich countries, while correlations are negative in poor countries. Our findings also indicate that the negative relationship in poor countries relates to the abundance of natural resources, and should not be interpreted as a causal effect. In summary, results are consistent with the doux commerce thesis but also suggest that the previous findings of positive effects of trade on institutional quality are driven by the relationship in rich countries. We should not expect globalization alone to mitigate the adverse effects of the resource curse in developing countries.

ETV6/ABL fusion is rare in Ph-negative chronic myeloid disorders

1 Saglio G, Guerrasio A, Rosso C, Zaccaria A, Tassinari A, Serra A, Rege-Cambrin G, Mazza U, Gavosto F. New Type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia. Blood 1990; 76: 1819–1824. 2 Wada H, Mizutani S, Nishimura J, Usuki Y, Kohsaki M, Komai M, Kaneka H, Sakamoto S, Delia D, Kanamura A, Kakishita E. Establishment and molecular characterization of a novel leukemic

High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation.

Although many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non‐neoplastic cells are more prone to divide in culture than neoplastic cells. Direct chromosome preparations (DCP) would be one way to circumvent this methodological problem. We have investigated 47 bone marrow samples from 39 patients by DCP. A median of 58 metaphases (range 9–158) was analysed per sample. Interphase FISH analyses using probes to detect IGH rearrangements, ‐13/13q‐, +3, +7, and +11 were also performed. Abnormal karyotypes were detected in 15 (63%) of 24 MM and in 4 (50%) of eight MGUS/smouldering MM (SMM) cases that could be successfully cytogenetically analysed. Age, sex, or degree of bone marrow plasma cell (PC) infiltration did not influence the karyotypic patterns (P > 0·05). However, the frequencies of aberrant karyotypes varied in relation to the Colcemide concentrations used – 7% (30 ng/ml) versus 69% and 67% (100 and 200 ng/ml, respectively) (P = 0·01). Combining the G‐banding and FISH results, abnormalities were detected in 29 of 31 (94%) MM and in six of eight (75%) MGUS/SMM patients. Thus, cytogenetic and FISH analyses after DCP using 100–200 ng Colcemide/ml identified aberrations in most MM/MGUS/SMM, irrespective of PC percentages.