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- Clarke, Robert, et al.
(author)
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Lowering blood homocysteine with folic acid based supplements : Meta-analysis of randomised trials
- 1998
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In: British Medical Journal. - : BMJ. - 0959-8146. ; 316:7135, s. 894-898
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Research review (peer-reviewed)abstract
- Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6. Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentration. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. Subjects: Individual data on 1114 people included in 12 trials. Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P < 0.001) and at lower pretreatment blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 μmol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P < 0.001), with similar effects in the range of 0.5-5 mg folic acid daily. Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction in blood homocysteine. Vitamin B-6 (mean 16.5 mg daily) did not have a significant additional effect. Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 μmol/l to 8-9 μmol/l). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.
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- Holgersson, Per-Henrik, 1964-
(author)
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Musikalisk kunskapsutveckling i högre musikutbildning : en kulturpsykologisk studie av musikerstudenters förhållningssätt i enskild instrumentalundervisning
- 2011
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis is to obtain a deeper understanding of students’ approaches to musical knowledge as it is distributed through one-to-one tuition in higher music education (HME). With a cultural-psychological perspective according to Bruner, the project was designed as a longitudinal, qualitative study of eight students in the performance program that concludes with a Bachelor of Arts degree in music. Two main musical genres were represented: Western classical music, and jazz and contemporary music. The students had one-to-one tuition on violin, classical guitar, saxophone and electric guitar, and were observed at three consecutive lessons per semester during one academic year. Many-sided data were collected: video recordings of instrumental lessons, semi-structured interviews with students and teachers, and the participants’ diary notes in connection with the observed lessons. In the analysis, the students’ approaches to knowledge of music cultural tools were focused. The results show that the students use three main approaches in relation to one-to-one tuition: adaptation, reflected navigation and indifference. These approaches vary and overlap, and are connected to the local cultural situations that are being studied, as well as to differences by instrument and genre. The different strategies used by the students are discussed in relation to apprenticeship in higher music education, and in relation to the consequences for students’ musical learning and knowledge development. The results are also connected to the Bologna process and the development of research-based teaching in HME. Methodological considerations and suggestions for further research are put forward.
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- Machiela, Mitchell J., et al.
(author)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Journal article (peer-reviewed)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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- Bjorkholm, M., et al.
(author)
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Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms
- 2011
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In: Journal of Clinical Oncology. - : American Society of Clinical Oncology: JCO. - 0732-183X .- 1527-7755. ; 29:17, s. 2410-2415
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Journal article (peer-reviewed)abstract
- Purpose: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU). Methods: On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk. Results: Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P32), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P32 greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation. Conclusion: The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P32 and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors. © 2011 by American Society of Clinical Oncology.
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- Brundin, Peik M.A., et al.
(author)
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Blood hormones and torque teno virus in peripheral blood mononuclear cells
- 2020
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In: Heliyon. - : Elsevier. - 2405-8440. ; 6:11
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Journal article (peer-reviewed)abstract
- Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.
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- Ingvarsson, R. F., et al.
(author)
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Good survival rates in systemic lupus erythematosus in southern Sweden, while the mortality rate remains increased compared with the population.
- 2019
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In: Lupus. - : SAGE Publications. - 1477-0962 .- 0961-2033. ; 28:12, s. 1488-1494
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Journal article (peer-reviewed)abstract
- To ascertain the mortality rate and causes of death in patients with systemic lupus erythematosus (SLE) within a defined region in southern Sweden during the time period 1981-2014 and determine whether these have changed over time.In 1981, a prospective observation study of patients with SLE was initiated in southern Sweden. All incident SLE patients within a defined geographic area were identified using previously validated methods including diagnosis and immunology registers. Patients with a confirmed SLE diagnosis were then followed prospectively at the Department of Rheumatology in Lund. Clinical data was collected at regular visits. Patients were recruited from 1981 to 2006 and followed until 2014. The patient cohort was split into two groups based on the year of diagnosis to determine secular trends. Causes of death were retrieved from medical records and from the cause of death registry at The National Board of Health and Welfare in Sweden.In all, 175 patients were diagnosed with SLE during the study period. A total of 60 deaths occurred during a total of 3053 years of follow-up. In the first half of the study inclusion period 46 patients died, compared with 14 in the latter. The majority of patients (51.7%) died of cardiovascular disease. Infections caused 15% of the deaths and malignancy was the cause of death in 13.3% of patients. SLE was the main cause of death for 6.7% of the patients and a contributing factor for half of the patients. Standardized mortality ratio was increased in patients by a factor of 2.5 compared with the general population. Deaths occurred at an even rate throughout the whole observation period. No significant difference in standardized mortality ratio was observed between genders but was increased in older female patients. Furthermore, secular mortality trends were not identified.In this long-term epidemiologic follow-up study of incident SLE, we report a substantially raised mortality rate amongst SLE patients compared with the general population. The mortality rates have not changed significantly during the observation period that spanned three decades. The main cause of death was cardiovascular disease and this finding was consistent over time.
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- Jacobs, Kevin B, et al.
(author)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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In: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Journal article (peer-reviewed)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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- Keiper, D., et al.
(author)
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Metalorganic vapour phase epitaxy growth of InP-based heterojunction bipolar transistors with carbon doped InGaAs base using tertiarybutylarsine and tertiarybutylphosphine in N-2 ambient
- 2000
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In: Japanese Journal of Applied Physics. - 0021-4922 .- 1347-4065. ; 39:11, s. 6162-6165
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Journal article (peer-reviewed)abstract
- A process for growth of heterostructure bipolar transistors (HBT) using tertiarybutylarsine (TBA) and tertiarybutylphosphine (TBP) in N-2 ambient is realised, which is compatible with a high temperature overgrowth, thus suitable for the vertical integration Of a laser structure on top of an HBT. A high growth temperature for the C-InGaAs base is favourable, to ensure no: degradation during subsequent growth. Increasing the growth temperature after the base from 500 degreesC to 680 degreesC within the emitter layer instead of at the base-emitter interface was found to improve the ideality factors, the de gain and the turn-on voltage.
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- Vukusic, J., et al.
(author)
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Fabrication and characterization of diffractive optical elements in InP for monolithic integration with surface-emitting components
- 2000
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In: Applied Optics. - 1559-128X .- 2155-3165. ; 39:3, s. 398-401
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Journal article (peer-reviewed)abstract
- We report on the fabrication and subsequent characterization of binary diffractive optical elements (DOE's) in InP for operation at 1.3 mu m. Fresnel lenses of different focal, lengths and a DOE that splits and focuses an incident beam into a 1 x 4 array of spots (optical fan-out) were fabricated. We realized the surface reliefs by patterning resist, using electron-beam lithography and etching with a chemically assisted ion beam, which produced well-defined patterns with smooth sidewalls and little if no surface roughness. The measured efficiency for the lenses was 36%. For the fan-out element the efficiency and the uniformity error were 26% and 30%, respectively. Spot sizes small as 16 mu m were measured.
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- Wittström, F., et al.
(author)
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Risk Factors for Sexual Offending in Self-Referred Men With Pedophilic Disorder: A Swedish Case-Control Study
- 2020
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In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11
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Journal article (peer-reviewed)abstract
- Background: The risk of child sexual abuse among non-forensic, non-correctional patients with Pedophilic Disorder (PD) is largely unknown. Methods: We recruited a consecutive sample of 55 help-seeking, non-correctional adult men diagnosed with DSM-5 PD at a university-affiliated sexual medicine outpatient unit in Sweden. PD participants were compared with 57 age-matched, non-clinical control men on four literature-based dynamic risk domains and self-rated child sexual abuse risk. Results: PD participants scored higher than controls on all tested domains (0–3 points); expectedly so for pedophilic attraction (2.5 vs. 0.0, Cohen’s d = 2.40, 95% confidence interval (CI): [1.91–2.89]), but also for sexual preoccupation (1.6 vs. 1.0, d = 1.11, 95% CI: [0.71–1.51]), impaired self-regulation (1.4 vs. 1.0, d = 0.44, 95% CI: [0.06 to 0.81]), impaired cognitive empathy and antisocial traits (0.9 vs. 0.1, d = 1.18, 95% CI: [0.78–1.59]), and self-rated child sexual abuse risk (1.0 vs. 0.0, d = 1.56, 95% CI: [1.13–1.98]). When summarizing all five domains into a pre-specified composite score (0–15 points), PD subjects scored substantially higher than matched control men (7.5 vs. 2.1, d = 2.12, 95% CI: [1.65–2.59]). Five (9%) PD participants self-reported any previous conviction for a contact child sexual offense and eight (15%) for possession of child sexual abuse material or non-contact sexual offending (adult or child victim). Eighteen subjects (34%) acknowledged past week, child-related sexual behaviors. Conclusion: Self-referred, help-seeking men with PD scored higher (small to very large effect sizes) than non-clinical control men on psychiatric measures of dynamic risk of child sexual abuse suggested in prior research with correctional samples diagnosed with PD. Our findings, including the composite risk measure, might inform clinical practice, but needs validation against actual sexual offending behavior. © Copyright © 2020 Wittström, Långström, Landgren and Rahm.
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- Yellapantula, V, et al.
(author)
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Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma
- 2019
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In: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 9:12, s. 101-
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Journal article (peer-reviewed)abstract
- Recent genomic research efforts in multiple myeloma have revealed clinically relevant molecular subgroups beyond conventional cytogenetic classifications. Implementing these advances in clinical trial design and in routine patient care requires a new generation of molecular diagnostic tools. Here, we present a custom capture next-generation sequencing (NGS) panel designed to identify rearrangements involving the IGH locus, arm level, and focal copy number aberrations, as well as frequently mutated genes in multiple myeloma in a single assay. We sequenced 154 patients with plasma cell disorders and performed a head-to-head comparison with the results from conventional clinical assays, i.e., fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarray. Our custom capture NGS panel had high sensitivity (>99%) and specificity (>99%) for detection of IGH translocations and relevant chromosomal gains and losses in multiple myeloma. In addition, the assay was able to capture novel genomic markers associated with poor outcome such as bi-allelic events involving TP53. In summary, we show that a multiple myeloma designed custom capture NGS panel can detect IGH translocations and CNAs with very high concordance in relation to FISH and SNP microarrays and importantly captures the most relevant and recurrent somatic mutations in multiple myeloma rendering this approach highly suitable for clinical application in the modern era.
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