| 1. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 2. |
- Lazarevic, Vladimir, et al.
(författare)
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Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience
- 2014
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Ingår i: Blood Cancer Journal. - London, United Kingdom : Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group. - 2044-5385. ; 4:e188
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8; 21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with greater than= 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients less than80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both Pless than0.001), followed by sex (P = 0.0135) and a karyotype including - 7/del(7q) (P = 0.048).
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| 3. |
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| 4. |
- Uggla, L, et al.
(författare)
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Music therapy can lower the heart rates of severely sick children.
- 2016
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 105:10, s. 1225-30
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Paediatric recipients of haematopoietic stem cell transplants (HSCT) are at increased risk of developing post-traumatic stress disorder (PTSD), and there is a need to identify interventions that can alleviate stress in this group. The aim of this study was to examine the previously unexplored effect of music therapy on children undergoing HSCT, by analysing physiological parameters and comparing them with a control group.METHODS: We performed a randomised clinical pilot study of 24 patients up to the age of 16 undergoing HSCT at Karolinska University Hospital, Huddinge, Sweden. Music therapy, including expressive and receptive elements, was performed twice a week in the treatment group and compared to standard care in the control group. Physiological parameters were evaluated according to the hospital's protocols.RESULTS: The music therapy group had significantly reduced evening heart rates compared to the control group (p < 0.001), and the effect was sustainable for four to eight hours after the intervention. There were no significant differences in saturation or blood pressure observed between the groups.CONCLUSION: Music therapy significantly lowered the heart rate of children undergoing HSCT for at least four to eight hours, indicating reduced stress levels and potentially lowering the risk of developing PTSD.
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| 5. |
- Miller-Podraza, Halina, 1948, et al.
(författare)
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Helicobacter pylori and neutrophils: sialic acid-dependent binding to various isolated glycoconjugates.
- 1999
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Ingår i: Infection and immunity. - 0019-9567. ; 67:12, s. 6309-13
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori has been shown to agglutinate erythrocytes in a sialic acid-dependent manner. However, very few studies have examined relevant target cells in the human stomach. Neutrophils are required for the onset of gastritis, and the inflammatory reaction may be induced on contact between bacteria and neutrophils. In the present work, glycolipids and glycoproteins were isolated from neutrophils and were studied for binding by overlay with radiolabeled bacteria on thin-layer chromatograms and on membrane blots. There was a complex pattern of binding bands. The only practical binding activity found was sialic acid dependent, since treatment of glycoconjugates with neuraminidase or mild periodate eliminated binding. As shown before for binding to erythrocytes and other glycoconjugates, bacterial cells grown on agar bound to many glycoconjugates, while growth in broth resulted in bacteria that would bind only to polyglycosylceramides, which are highly heterogeneous and branched poly-N-acetyllactosamine-containing glycolipids. Approximately seven positive bands were found for glycoproteins, and the traditional ganglioside fraction showed a complex, slow-moving interval with very strong sialic-acid-dependent binding, probably explained by Fuc substitutions on GlcNAc.
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| 6. |
- Schacht, Ryan, et al.
(författare)
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Adult sex ratios : causes of variation and implications for animal and human societies
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Forskningsöversikt (refereegranskat)abstract
- Converging lines of inquiry from across the social and biological sciences target the adult sex ratio (ASR; the proportion of males in the adult population) as a fundamental population-level determinant of behavior. The ASR, which indicates the relative number of potential mates to competitors in a population, frames the selective arena for competition, mate choice, and social interactions. Here we review a growing literature, focusing on methodological developments that sharpen knowledge of the demographic variables underlying ASR variation, experiments that enhance understanding of the consequences of ASR imbalance across societies, and phylogenetic analyses that provide novel insights into social evolution. We additionally highlight areas where research advances are expected to make accelerating contributions across the social sciences, evolutionary biology, and biodiversity conservation. A detailed Review across animal and human societies provides insight on the causes and consequences of adult sex ratio skew.
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| 7. |
- Uggla, L, et al.
(författare)
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An Explorative Study of Qualities in Interactive Processes with Children and Their Parents in Music Therapy during and after Pediatric Hematopoietic Stem Cell Transplantation
- 2019
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Ingår i: Medicines (Basel, Switzerland). - : MDPI AG. - 2305-6320. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hematopoietic stem cell transplantation (HSCT) is an established treatment for severe disorders of the pediatric hematopoietic system. However, there is a need for supportive interventions due to physiological and psychological strain. Music therapy is used in health care to help patients through difficult experiences and enable well-being. Our previous randomized studies showed significantly reduced heart rates four to eight hours after intervention as well as increased health-related quality of life. Methods: The aim of this qualitative study was to explore the participants’ and parents’ own experiences of the interactive processes during the music therapy intervention. Six families were included. The data collection used collaborative research interviews. An independent psychologist facilitated the interviews with the children, the parents, and the music therapist and also performed the analysis. Results: Three main themes emerged: experiences of competency and recognition of self, interactive affect regulation as change potential, and importance of the therapeutic relationship. Conclusions: For the participants, music therapy developed into a significant and helpful experience, an important ingredient in coping with and managing the treatment period at the hospital.
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