149 results on '"Malmström H"'
Search Results
2. Anakinra in Patients With Systemic Juvenile Idiopathic Arthritis: Long-term Safety From the Pharmachild Registry
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Giancane, G. Papa, R. Vastert, S. Bagnasco, F. Swart, J.F. Quartier, P. Antón, J. Kamphuis, S. Sanner, H. Glerup, M. De Benedetti, F. Tsitsami, E. Remesal, A. Moreno, E. De Inocencio, J. Myrup, C. Pallotti, C. Koné-Paut, I. Franck-Larsson, K. Malmström, H. Cederholm, S. Pistorio, A. Wulffraat, N. Ruperto, N. the Paediatric Rheumatology International Trials Organisation (PRINTO)
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musculoskeletal diseases - Abstract
Objective. To evaluate the long-term safety profile of anakinra in patients with systemic juvenile idiopathic arthritis (sJIA). Methods. Data from patients with sJIA enrolled in the Pharmachild registry (ClinicalTrials.gov: NCT03932344) prior to September 30, 2018, and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (SAEs) of at least moderate severity and SAEs, including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall by 6-month time windows, and in different treatment sets represented by those patients treated continuously with anakinra for at least 12, 18, and 24 months (set-12, -18, and -24, respectively). Results. Three hundred six patients were enrolled. Of these patients, 46%, 34%, and 28% had been treated for at least 12, 18, and 24 months, respectively. Two hundred and one AEs, mostly represented by infections, were reported for 509.3 patient-years (PY) with an overall incidence rate (IR) of 39.5 per 100 PY. Among 56 SAEs (IR 11.0/100 PY), 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra treatment, followed by decreasing IRs in the long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most frequently in the first 6 months, because of inefficacy (43%), remission (31%), or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment. Conclusion. The results of the present study confirm the long-term safety profile of anakinra in patients with sJIA and demonstrate an overall decreasing incidence of AEs over time. © 2022 The Journal of Rheumatology.
- Published
- 2022
3. Anakinra in Patients With Systemic Juvenile Idiopathic Arthritis: Long-term Safety From the Pharmachild Registry
- Author
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Giancane G, Papa R, Vastert S, Bagnasco F, Swart JF, Quartier P, Anton-Lopez J, Kamphuis S, Sanner H, Glerup M, De Benedetti F, Tsitsami E, Remesal A, Moreno E, De Inocencio J, Myrup C, Pallotti C, Koné-Paut I, Franck-Larsson K, Malmström H, Cederholm S, Pistorio A, Wulffraat N, Ruperto N, and Paediatric Rheumatology International Trials Organisation (PRINTO)
- Subjects
systemic juvenile idiopathic arthritis ,long-term adverse effects ,anakinra - Abstract
OBJECTIVE: To evaluate the long-term safety profile of anakinra in patients with systemic juvenile idiopathic arthritis (sJIA). METHODS: Data from patients with sJIA enrolled in the Pharmachild registry (ClinicalTrials.gov: NCT03932344) prior to September 30, 2018, and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (SAEs) of at least moderate severity and SAEs, including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall by 6-month time windows, and in different treatment sets represented by those patients treated continuously with anakinra for at least 12, 18, and 24 months (set-12, -18, and -24, respectively). RESULTS: Three hundred six patients were enrolled. Of these patients, 46%, 34%, and 28% had been treated for at least 12, 18, and 24 months, respectively. Two hundred and one AEs, mostly represented by infections, were reported for 509.3 patient-years (PY) with an overall incidence rate (IR) of 39.5 per 100 PY. Among 56 SAEs (IR 11.0/100 PY), 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra treatment, followed by decreasing IRs in the long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most frequently in the first 6 months, because of inefficacy (43%), remission (31%), or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment. CONCLUSION: The results of the present study confirm the long-term safety profile of anakinra in patients with sJIA and demonstrate an overall decreasing incidence of AEs over time. [ClinicalTrials.gov: NCT01399281 and NCT03932344].
- Published
- 2022
4. Tracing genetic change over time using nuclear SNPs in ancient and modern cattle
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Svensson, E. M., Anderung, C., Baubliene, J., Persson, P., Malmström, H., Smith, C., Vretemark, M., Daugnora, L., and Götherström, A.
- Published
- 2007
5. Four millennia of Iberian biomolecular prehistory illustrate the impact of prehistoric migrations at the far end of Eurasia
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Valdiosera, C., Günther, T., Vera-Rodríguez, J.C., Ureña, I., Iriarte, E., Rodríguez-Varela, R., Simões, L.G., Martínez-Sánchez, R.M., Svensson, E.M., Malmström, H., Rodríguez, L., De Castro, J.-M.B., Carbonell, E., Alday, A., Hernández Vera, J.A., Götherström, A., Carretero, J.-M., Arsuaga, J.L., Smith, C.I., and Jakobsson, M.
- Abstract
Population genomic studies of ancient human remains have shown how modern-day European population structure has been shaped by a number of prehistoric migrations. The Neolithization of Europe has been associated with large-scale migrations from Anatolia, which was followed by migrations of herders from the Pontic steppe at the onset of the Bronze Age. Southwestern Europe was one of the last parts of the continent reached by these migrations, and modern-day populations from this region show intriguing similarities to the initial Neolithic migrants. Partly due to climatic conditions that are unfavorable for DNA preservation, regional studies on the Mediterranean remain challenging. Here, we present genome-wide sequence data from 13 individuals combined with stable isotope analysis from the north and south of Iberia covering a four-millennial temporal transect (7, 500–3, 500 BP). Early Iberian farmers and Early Central European farmers exhibit significant genetic differences, suggesting two independent fronts of the Neolithic expansion. The first Neolithic migrants that arrived in Iberia had low levels of genetic diversity, potentially reflecting a small number of individuals; this diversity gradually increased over time from mixing with local hunter-gatherers and potential population expansion. The impact of post-Neolithic migrations on Iberia was much smaller than for the rest of the continent, showing little external influence from the Neolithic to the Bronze Age. Paleodietary reconstruction shows that these populations have a remarkable degree of dietary homogeneity across space and time, suggesting a strong reliance on terrestrial food resources despite changing culture and genetic make-up.
- Published
- 2018
6. Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study
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Arthur, R., primary, Williams, R., additional, Garmo, H., additional, Holmberg, L., additional, Stattin, P., additional, Malmström, H., additional, Lambe, M., additional, Hammar, N., additional, Walldius, G., additional, Robinsson, D., additional, Jungner, I., additional, and Van Hemelrijck, M., additional
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- 2018
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7. Low fructosamine and mortality – A long term follow-up of 215,011 non-diabetic subjects in the Swedish AMORIS study
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Malmström, H., primary, Wändell, P.E., additional, Holzmann, M.J., additional, Ärnlöv, J., additional, Jungner, I., additional, Hammar, N., additional, Walldius, G., additional, and Carlsson, A.C., additional
- Published
- 2016
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8. Fructosamine is a risk factor for myocardial infarction and all-cause mortality – Longitudinal experience from the AMORIS cohort
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Malmström, H., primary, Walldius, G., additional, Grill, V., additional, Jungner, I., additional, and Hammar, N., additional
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- 2015
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9. 1022 High serum glucose and triglycerides are associated with increased risk of severe prostate cancer among Swedish men
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Arthur, R., primary, Møller, H., additional, Garmo, H., additional, Hammar, N., additional, Walldius, G., additional, Jungner, I., additional, Malmström, H., additional, Lambe, M., additional, Holmberg, L., additional, and Van Hemelrijck, M., additional
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- 2015
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10. Association between serum calcium concentration and risk of incident and fatal myocardial infarction and stroke in the AMORIS cohort
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Rohrmann, S., primary, Garmo, H., additional, Malmström, H., additional, Hammar, N., additional, Jungner, I., additional, Walldius, G., additional, and Van Hemelrijck, M., additional
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- 2015
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11. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874)
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Reed, Ns, Mangioni, C, Malmström, H, Scarfone, G, Poveda, A, Pecorelli, S, Tateo, S, Franchi, M, Jobsen, Jj, Coens, C, Teodorovic, I, Vergote, I, Vermorken, Jb, Malmstrom, H, Favalli, G, Jobsen, J, van Bunningen, B, Splinter, T, van der Burg ME, Drouin, P, Zola, Paolo, Frankendaal, B, Schepansky, A, Swenerton, K, Stuart, G, Scarabelli, C, Mangili, G, van Rijswijk, R, Van, Putten, Chevalier, B, Stoot, Je, Beex, L, Souhami, L, Heintz, Ap, Bonnefoi, H, Koelbl, H, Kobierska, A, Guthrie, D, Maggino, T, di Palumbo VS, Bessette, P, van Wijk, A, and Verheijen, R.
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Adult ,Leiomyosarcoma ,Oncology ,Cancer Research ,medicine.medical_specialty ,Randomization ,Sarcoma, Endometrial Stromal ,medicine.medical_treatment ,Disease-Free Survival ,Carcinosarcoma ,Internal medicine ,medicine ,Humans ,Stage (cooking) ,Aged ,Aged, 80 and over ,uterine sarcoma radiotherapy ,Radiotherapy ,Uterine sarcoma ,business.industry ,Cancer ,Middle Aged ,Pelvic cavity ,medicine.disease ,Surgery ,Radiation therapy ,Clinical trial ,Treatment Outcome ,medicine.anatomical_structure ,Uterine Neoplasms ,Disease Progression ,Female ,Radiotherapy, Adjuvant ,Neoplasm Recurrence, Local ,business ,Adjuvant - Abstract
The management of uterine sarcomas continues to present many difficulties. Primary surgery is the optimal treatment but the role of post-operative radiation remains uncertain. In the mid-1980s, the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study proposed a trial to evaluate adjuvant radiotherapy, as previous non-randomised studies had suggested a survival advantage and improved local control when post-operative radiation was administered. The study opened in 1987 taking 13 years to accrue 224 patients. All uterine sarcoma subtypes were permitted. Patients were required to have undergone as a minimum, TAH and BSO and wahsings (166 patients) but nodal sampling was optional. There were 103 leiomyosarcomas (LMS), 91 carcinosarcomas (CS) and 28 endometrial stromal sarcomas (ESS). Patients were randomised to either observation or pelvic radiation, 51Gy in 28 fractions over 5 weeks. Hundred and twelve were recruited to each arm. The initial analysis has shown a reduction in local relapse (14 versus 24, p =0.004) but no effect on either OS or PFS. No unexpected toxicity was seen in the radiation arm. No difference in either overall or disease-free survival was demonstrated but there is an increased local control for the CS patients receiving radiation but without any benefit for LMS. Prognostic factor analysis shows that stage, age and histological subtype were important predictors of behaviour which may explain differences between CS and LMS. CS appears to show more kinship to poorly differentiated endometrial carcinomas in behaviour. LMS did not show the same benefit from radiation. These results will help shape future management and clinical trials in uterine sarcomas.
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- 2008
12. Extramammary Paget's disease of the vulva
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Eb, Tågsjö, Schmidt H, Malmström H, and Simonsen E
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Paget Disease, Extramammary ,Vulvar Neoplasms ,Humans ,Female ,DNA, Neoplasm ,Flow Cytometry ,Prognosis - Published
- 1997
13. Corrigendum to “Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: An European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874)” [European Journal of Cancer, 44 (2008) 808–818]
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Reed, N.S., primary, Mangioni, C., additional, Malmström, H., additional, Scarfone, G., additional, Poveda, A., additional, Pecorelli, S., additional, Tateo, S., additional, Franchi, M., additional, Jobsen, J.J., additional, Coens, C., additional, Teodorovic, I., additional, Vergote, I., additional, and Vermorken, J.B., additional
- Published
- 2008
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14. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: An European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874)
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Reed, N.S., primary, Mangioni, C., additional, Malmström, H., additional, Scarfone, G., additional, Poveda, A., additional, Pecorelli, S., additional, Tateo, S., additional, Franchi, M., additional, Jobsen, J.J., additional, Coens, C., additional, Teodorovic, I., additional, Vergote, I., additional, and Vermorken, J.B., additional
- Published
- 2008
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15. Prognostic factors in invasive squamous cell carcinoma of the vulva treated with surgery and irradiation
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Malmström H, Sténson S, Ernst Simonsen, Janson H, and Ulf Stendahl
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Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Postoperative irradiation ,Vulva ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Basal cell ,Survival rate ,Aged ,Surgical approach ,Vulvar Neoplasms ,business.industry ,Vulvectomy ,Mortality rate ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,Combined Modality Therapy ,Surgery ,Radiation therapy ,Survival Rate ,medicine.anatomical_structure ,Oncology ,Carcinoma, Squamous Cell ,Female ,Neoplasm Recurrence, Local ,business - Abstract
From 1958 through 1980, 113 women with invasive squamous cell carcinoma of the vulva were treated with vulvectomy. Post-operative irradiation was given with cobalt-60 beam or 10 MV photons from a linear accelerator from anterior fields including the vulva and groins, with the intention of delivering 40-52 Gy with 2-4 Gy/day at a depth of 0.5 cm or 2 cm. The overall corrected five-year survival rate was 68%. The prognosis was shown to worsen significantly with advancing stages (I/96%, II/75%, III/62% and IV/19%), increasing grades (GI/78%, G2/70% and G3/22%) and increasing size of the tumor (T1/90%, T2/71% and T3/37%), as it also did when there were signs of vascular invasion, multifocal tumors or positive nodes in the inguinal regions. Recurrences were diagnoses in 32% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to that reported after more aggressive surgery.
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- 1990
16. Cancer in twins: genetic and nongenetic familial risk factors.
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Ahlbom A, Lichtenstein P, Malmström H, Feychting M, Hemminki K, Pedersen NL, Ahlbom, A, Lichtenstein, P, Malmström, H, Feychting, M, Hemminki, K, and Pedersen, N L
- Abstract
Background: Familial clustering has been observed for cancers that occur at specific sites. Most findings, which leave little doubt about the involvement of a heritable (i.e., genetic) component in the development of some cancers, are based on data from "cancer-prone" families or interviews with subjects who have cancer. The study of twins should be of value in cancer epidemiology because twins either are genetically identical or share half of their segregating genes.Purpose: We linked the Swedish Twin Registry to the Swedish Cancer Registry, thereby identifying cases of cancer diagnosed from 1959 through 1992 in twins born in the period from 1886 through 1958, to assess the importance of both genetic and nongenetic (i.e., environmental) familial factors in determining cancer risk.Methods: Same-sex twin pairs with both individuals alive and living in Sweden in 1959-1961 or 1970-1972 were identified in the old cohort (born from 1886 through 1925) or the young cohort (born from 1926 through 1958), respectively, of the Swedish Twin Registry; pairs for whom zygosity (i.e., the number of eggs that gave rise to the twins) could be determined were considered further. The association of cancer with combined genetic and nongenetic familial factors was tested by comparing all twin pairs (regardless of zygosity) in which at least one member of the pair had been diagnosed with cancer at one of several specific sites with pairs in which neither twin had that cancer. Heritable effects alone were tested by comparing monozygotic (one egg) and dizygotic (two eggs) twin pairs. Statistical methods used in quantitative genetics and standard methods for epidemiologic research were used in parallel to analyze the data.Results and Conclusions: In the 10503 twin pairs from the old cohort, 361.7 cases of malignant cancer were identified; 918 malignant cancers were identified in the 12883 twin pairs from the young cohort. When cancer sites with a total number of at least 200 cases and at least one twin pair concordant (i.e., both twins affected) for the site were evaluated, namely, cancers of the stomach, colon and rectum, lung, female breast, and prostate, as well as total cancer, profound genetic and/or nongenetic familial effects were identified in twins from the old cohort. Similar findings were obtained for twins in the young cohort for cancers of the prostate and female breast, as well as for total cancer. Genetic and nongenetic familial effects were also identified in twins from both cohorts for in situ cancer of the cervix. The increase in risk of colon and rectum, breast, cervical, and especially prostate cancer, but not stomach or lung cancer, tended to be greater if a monozygotic rather than a dizygotic twin were affected.Implications: The identification of familial effects for total cancer in this study is consistent with the idea that individuals may possess a genetic susceptibility to cancer in general. [ABSTRACT FROM AUTHOR]- Published
- 1997
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17. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel.
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Bookman, M A, primary, Malmström, H, additional, Bolis, G, additional, Gordon, A, additional, Lissoni, A, additional, Krebs, J B, additional, and Fields, S Z, additional
- Published
- 1998
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18. Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.
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ten Bokkel Huinink, W, primary, Gore, M, additional, Carmichael, J, additional, Gordon, A, additional, Malfetano, J, additional, Hudson, I, additional, Broom, C, additional, Scarabelli, C, additional, Davidson, N, additional, Spanczynski, M, additional, Bolis, G, additional, Malmström, H, additional, Coleman, R, additional, Fields, S C, additional, and Heron, J F, additional
- Published
- 1997
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19. Protein crystal growth of Ribonuclease A and Pancreatic Trypsin Inhibitor aboard the MASER 3 rocket
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Sjölin, Lennart, primary, Wlodawer, Alexander, additional, Bergqvist, G., additional, Holm, P., additional, Loth, K., additional, Malmström, H., additional, Zaar, J., additional, Svensson, L.Anders, additional, and Gilliland, Gary L., additional
- Published
- 1991
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20. Effect of Thickness of Flowable Resins on Marginal Leakage in Class II Composite Restorations.
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Malmström, H., Schlueter, M., Roach, T., and Moss, M. E.
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GUMS & resins ,GINGIVA ,DENTAL fillings ,ANALYSIS of variance ,DENTAL occlusion - Abstract
Despite limited scientific evaluation, there is an increased use of low elastic modulus flowable resin composite (FRC) as a stress-relieving gingival increment in Class II restorations. This study compared marginal leakage in preparation with gingival margins in enamel or dentin/cementum (sub-CEJ and supra-CEJ) after FRC was used as a gingival increment to hybrid resin composite used alone. In addition, the extent of leakage around restorations with or without the use of FRC gingival increments when light curing the resin composites from occlusal direction only or buccal, lingual and occlusal directions was compared. Sixty extracted human molars were prepared with two identical Clas II (MO and OD) preparations (30 were 1 mm sub-CEJ and 30 were 1 mm supra-CEJ) and randomly assigned to six groups. After etching, dentin-bonding agent was applied to all prepared tooth surfaces according to the manufacturer's specifications. One of the Three different thicknesses of FRC (0.5 mm, 1 mm or 2 mm) was placed on the gingival floor, cured and a hybrid resin composite was placed occlusally to complete the restoration. The control preparation on each tooth was restored in the same manner, except that a hybrid resin composite was used for both the gingival and occlusal increments. The restored teeth were thermocycled (300 cycles), then immersed in 50 % silver nitrate prior to the hemi-section and measured for leakage under a light microscope. The data were evaluated using paired measures analysis of variance (ANOVA). Most of the occlusal margins showed no leakage, while almost every gingival margin demonstrated some silver nitrate penetration regardless of whether it was located sub or supra-CEJ, although significantly less leakage was found in restorations with supra-CEJ margins (p=0.0001). Among supra-CEJ restorations, there was a pronounced reduction in leakage as FRC thickness increased (p=0.0005). In the teeth restored with the gingival-margin located supra-CEJ, the 2 mm thickness FRC gingival increment showed significantly less leakage (p<0.01) compared with the 0.5 mm thickness of FRC gingival increment. The direction of the curing light did not affect the extent of leakage (p>0.05). The use of FRC material as a gingival increments sub-CEJ in posterior hybrid resin restorations produced no significant difference in leakage (p>0.05). The results of this study indicated that restorations located supra CEJ (with gingival margins in enamel) with 2 mm thick FRC gingival increment demonstrated significantly less leakage than did those with 0.5 mm FRC. When the margin of the restoration was located sub-CEJ (in dentin/cementum), neither the thickness nor the presence of FRC as a gingival increment significantly influenced the marginal leakage. [ABSTRACT FROM AUTHOR]
- Published
- 2002
21. Primary invasive cancer of the vagina.
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MALMSTRÖM, H. and ENGQUIST, M.
- Abstract
The study comprised 63 patients with primary carcinoma of the vagina (PCV) treated between 1964 and 1994 and retrospectively analyses the survival rates and time in relation to various prognostic factors. The overall median age at diagnosis was 64 (range 27-94) years. Forty-one (65%) of the cases were squamous cell carcinomas. The number of patients in various stages were: I/6(9%), II/34 (54%), III/13 (21%) and IV/10 (16%), and according to histologic dedifferentiation: high grade 23 (37%), medium grade 17 (27%), and low grade 12 (19%); not recorded, 11 (18%).In 12 patients the primary treatment was surgical and five of these patients were operated on a second time at a later occasion (two vaginectomies and 10 vaginal resections); surgical treatment after previous radiotherapy or chemotherapy was given to another 12 patients (four vaginectomies and eight vaginal resections). In summary, 24 (38%) patients were given surgical treatment alone or in combination with other treatment modalities. Fifty-five(87%) patients were treated alone or in combination with other treatment modalities. Fifty-five (87%) patients were treated with external irradiation with a median dose of 40 (range, 21-76) Gray. Fifty (79%) patients were administered brachytherapy with a median dose of 2880 (range, 400-4900) mgRaH. In only eight (13%) patients no radiotherapy was given. Chemotherapy was given to 10 (16%) patients, three of these also received second-line chemotherapy. Chemotherapy after surgical or irradiation therapy was given to six (9%) patients.The 5-year corrected survival rate (5YSR) and median survival time (MST) were 52%/93 months for stage I patients, 50%/30 months for stage II, 24%/10 months for stage III, and 20%/11 months for stage IV. The 5YSR/MST in high grade tumors was 32%/8, in medium grade 36%/13, and in low grade tumors 43%/15 months. The median recurrence-free interval was 18 months (range, 6-94). A trend for better survival was found in patients without a history of serious illness and in a subgroup of patients who were not administered chemotherapy. The most important prognostic factors in this study were tumor stage (P=0.02), patient age (P=0.002) and our Prognostic Index (P=0.01). No differences in survival were found analyzing other patient or tumor characteristics. Of all the patients studied, 14 (22%) are living without evidence of cancer, 10 (16%) have died due to intercurrent disease and 39 (62%) have died of PCV. [ABSTRACT FROM AUTHOR]
- Published
- 1997
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22. Human placental lactogen serum levels in venous and capillary blood from women in late pregnancy.
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Axelsson, Ove, Malmström, Henric, Axelsson, O, and Malmström, H
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- 1983
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23. English for academic purposes at Swedish universities: Teachers' objectives and practices | Inglés con fines académicos en las universidades suecas: Objetivos y prácticas de los profesores
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Diane Pecorari, Shaw, P., Irvine, A., and Malmström, H.
24. Uterine Rupture as a Complication of Second-Trimester Abortion when Using Prostaglandin F2αTogether with other Oxytocic Agents
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Malmström, H., primary and Hemmingsson, E., additional
- Published
- 1984
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25. High frequency of lactose intolerance in a prehistoric hunter-gatherer population in northern Europe
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Holmlund Gunilla, Molnar Petra, Storå Jan, Lidén Kerstin, Linderholm Anna, Malmström Helena, Jakobsson Mattias, and Götherström Anders
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Evolution ,QH359-425 - Abstract
Abstract Background Genes and culture are believed to interact, but it has been difficult to find direct evidence for the process. One candidate example that has been put forward is lactase persistence in adulthood, i.e. the ability to continue digesting the milk sugar lactose after childhood, facilitating the consumption of raw milk. This genetic trait is believed to have evolved within a short time period and to be related with the emergence of sedentary agriculture. Results Here we investigate the frequency of an allele (-13910*T) associated with lactase persistence in a Neolithic Scandinavian population. From the 14 individuals originally examined, 10 yielded reliable results. We find that the T allele frequency was very low (5%) in this Middle Neolithic hunter-gatherer population, and that the frequency is dramatically different from the extant Swedish population (74%). Conclusions We conclude that this difference in frequency could not have arisen by genetic drift and is either due to selection or, more likely, replacement of hunter-gatherer populations by sedentary agriculturalists.
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- 2010
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26. Barking up the wrong tree: Modern northern European dogs fail to explain their origin
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Holmlund Gunilla, Willerslev Eske, Storå Jan, Gilbert M, Vilà Carles, Malmström Helena, and Götherström Anders
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Evolution ,QH359-425 - Abstract
Abstract Background Geographic distribution of the genetic diversity in domestic animals, particularly mitochondrial DNA, has often been used to infer centers of domestication. The underlying presumption is that phylogeographic patterns among domesticates were established during, or shortly after the domestication. Human activities are assumed not to have altered the haplogroup frequencies to any great extent. We studied this hypothesis by analyzing 24 mtDNA sequences in ancient Scandinavian dogs. Breeds originating in northern Europe are characterized by having a high frequency of mtDNA sequences belonging to a haplogroup rare in other populations (HgD). This has been suggested to indicate a possible origin of the haplogroup (perhaps even a separate domestication) in central or northern Europe. Results The sequences observed in the ancient samples do not include the haplogroup indicative for northern European breeds (HgD). Instead, several of them correspond to haplogroups that are uncommon in the region today and that are supposed to have Asian origin. Conclusion We find no evidence for local domestication. We conclude that interpretation of the processes responsible for current domestic haplogroup frequencies should be carried out with caution if based only on contemporary data. They do not only tell their own story, but also that of humans.
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- 2008
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27. POPULATION GENETICS. Genomic evidence for the Pleistocene and recent population history of Native Americans
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Maanasa, Raghavan, Matthias, Steinrücken, Kelley, Harris, Stephan, Schiffels, Simon, Rasmussen, Michael, DeGiorgio, Anders, Albrechtsen, Cristina, Valdiosera, María C, Ávila-Arcos, Anna-Sapfo, Malaspinas, Anders, Eriksson, Ida, Moltke, Mait, Metspalu, Julian R, Homburger, Jeff, Wall, Omar E, Cornejo, J Víctor, Moreno-Mayar, Thorfinn S, Korneliussen, Tracey, Pierre, Morten, Rasmussen, Paula F, Campos, Peter, de Barros Damgaard, Morten E, Allentoft, John, Lindo, Ene, Metspalu, Ricardo, Rodríguez-Varela, Josefina, Mansilla, Celeste, Henrickson, Andaine, Seguin-Orlando, Helena, Malmström, Thomas, Stafford, Suyash S, Shringarpure, Andrés, Moreno-Estrada, Monika, Karmin, Kristiina, Tambets, Anders, Bergström, Yali, Xue, Vera, Warmuth, Andrew D, Friend, Joy, Singarayer, Paul, Valdes, Francois, Balloux, Ilán, Leboreiro, Jose Luis, Vera, Hector, Rangel-Villalobos, Davide, Pettener, Donata, Luiselli, Loren G, Davis, Evelyne, Heyer, Christoph P E, Zollikofer, Marcia S, Ponce de León, Colin I, Smith, Vaughan, Grimes, Kelly-Anne, Pike, Michael, Deal, Benjamin T, Fuller, Bernardo, Arriaza, Vivien, Standen, Maria F, Luz, Francois, Ricaut, Niede, Guidon, Ludmila, Osipova, Mikhail I, Voevoda, Olga L, Posukh, Oleg, Balanovsky, Maria, Lavryashina, Yuri, Bogunov, Elza, Khusnutdinova, Marina, Gubina, Elena, Balanovska, Sardana, Fedorova, Sergey, Litvinov, Boris, Malyarchuk, Miroslava, Derenko, M J, Mosher, David, Archer, Jerome, Cybulski, Barbara, Petzelt, Joycelynn, Mitchell, Rosita, Worl, Paul J, Norman, Peter, Parham, Brian M, Kemp, Toomas, Kivisild, Chris, Tyler-Smith, Manjinder S, Sandhu, Michael, Crawford, Richard, Villems, David Glenn, Smith, Michael R, Waters, Ted, Goebel, John R, Johnson, Ripan S, Malhi, Mattias, Jakobsson, David J, Meltzer, Andrea, Manica, Richard, Durbin, Carlos D, Bustamante, Yun S, Song, Rasmus, Nielsen, Eske, Willerslev, Raghavan M, Steinrücken M, Harris K, Schiffels S, Rasmussen S, DeGiorgio M, Albrechtsen A, Valdiosera C, Ávila-Arcos MC, Malaspinas AS, Eriksson A, Moltke I, Metspalu M, Homburger JR, Wall J, Cornejo OE, Moreno-Mayar JV, Korneliussen TS, Pierre T, Rasmussen M, Campos PF, Damgaard Pde B, Allentoft ME, Lindo J, Metspalu E, Rodríguez-Varela R, Mansilla J, Henrickson C, Seguin-Orlando A, Malmström H, Stafford T Jr, Shringarpure SS, Moreno-Estrada A, Karmin M, Tambets K, Bergström A, Xue Y, Warmuth V, Friend AD, Singarayer J, Valdes P, Balloux F, Leboreiro I, Vera JL, Rangel-Villalobos H, Pettener D, Luiselli D, Davis LG, Heyer E, Zollikofer CP, Ponce de León MS, Smith CI, Grimes V, Pike KA, Deal M, Fuller BT, Arriaza B, Standen V, Luz MF, Ricaut F, Guidon N, Osipova L, Voevoda MI, Posukh OL, Balanovsky O, Lavryashina M, Bogunov Y, Khusnutdinova E, Gubina M, Balanovska E, Fedorova S, Litvinov S, Malyarchuk B, Derenko M, Mosher MJ, Archer D, Cybulski J, Petzelt B, Mitchell J, Worl R, Norman PJ, Parham P, Kemp BM, Kivisild T, Tyler-Smith C, Sandhu MS, Crawford M, Villems R, Smith DG, Waters MR, Goebel T, Johnson JR, Malhi RS, Jakobsson M, Meltzer DJ, Manica A, Durbin R, Bustamante CD, Song YS, Nielsen R, and Willerslev E
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Gene Flow ,Siberia ,Models, Genetic ,Athabascans and Amerindians ,Human Migration ,Genetic history of Native American ,Indians, North American ,Humans ,Genomics ,Americas ,Population genetic ,History, Ancient ,Article - Abstract
How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we find that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Following their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 KYA, one that is now dispersed across North and South America and the other is restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative ‘Paleoamerican’ relict populations, including the historical Mexican Pericúes and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
- Published
- 2015
28. Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel
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Alan Gordon, Giorgio Bolis, Jacqueline B. Krebs, Andrea Lissoni, Scott Z. Fields, Henric Malmström, Michael A. Bookman, Bookman, M, Malmström, H, Bolis, G, Gordon, A, Lissoni, A, Krebs, J, and Fields, S
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Adult ,Cancer Research ,medicine.medical_specialty ,Neutropenia ,Paclitaxel ,medicine.medical_treatment ,Phases of clinical research ,Antineoplastic Agents ,Gastroenterology ,Drug Administration Schedule ,Carboplatin ,Antineoplastic Agent ,chemistry.chemical_compound ,Internal medicine ,medicine ,Carcinoma ,Humans ,Aged ,Cisplatin ,Ovarian Neoplasms ,Chemotherapy ,business.industry ,Ovarian Neoplasm ,Leukopenia ,Middle Aged ,medicine.disease ,Thrombocytopenia ,Surgery ,Regimen ,Treatment Outcome ,Oncology ,chemistry ,Topotecan ,Female ,Neoplasm Recurrence, Local ,business ,medicine.drug ,Human - Abstract
PURPOSE Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.
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- 1998
29. READv2: advanced and user-friendly detection of biological relatedness in archaeogenomics.
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Alaçamlı E, Naidoo T, Güler MN, Sağlıcan E, Aktürk Ş, Mapelli I, Vural KB, Somel M, Malmström H, and Günther T
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- Humans, Genomics methods, Pedigree, DNA, Ancient analysis, Software, Archaeology methods
- Abstract
The advent of genome-wide ancient DNA analysis has revolutionized our understanding of prehistoric societies. However, studying biological relatedness in these groups requires tailored approaches due to the challenges of analyzing ancient DNA. READv2, an optimized Python3 implementation of the most widely used tool for this purpose, addresses these challenges while surpassing its predecessor in speed and accuracy. For sufficient amounts of data, it can classify up to third-degree relatedness and differentiate between the two types of first-degree relatedness, full siblings and parent-offspring. READv2 enables user-friendly, efficient, and nuanced analysis of biological relatedness, facilitating a deeper understanding of past social structures., (© 2024. The Author(s).)
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- 2024
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30. Repeated plague infections across six generations of Neolithic Farmers.
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Seersholm FV, Sjögren KG, Koelman J, Blank M, Svensson EM, Staring J, Fraser M, Pinotti T, McColl H, Gaunitz C, Ruiz-Bedoya T, Granehäll L, Villegas-Ramirez B, Fischer A, Price TD, Allentoft ME, Iversen AKN, Axelsson T, Ahlström T, Götherström A, Storå J, Kristiansen K, Willerslev E, Jakobsson M, Malmström H, and Sikora M
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- Female, Humans, Male, Cemeteries history, Genome, Bacterial genetics, History, Ancient, Phylogeny, Scandinavian and Nordic Countries epidemiology, Time Factors, Virulence Factors genetics, Farmers history, Genomics, Pedigree, Plague epidemiology, Plague history, Plague microbiology, Plague mortality, Population Dynamics, Yersinia pestis genetics, Yersinia pestis isolation & purification
- Abstract
In the period between 5,300 and 4,900 calibrated years before present (cal. BP), populations across large parts of Europe underwent a period of demographic decline
1,2 . However, the cause of this so-called Neolithic decline is still debated. Some argue for an agricultural crisis resulting in the decline3 , others for the spread of an early form of plague4 . Here we use population-scale ancient genomics to infer ancestry, social structure and pathogen infection in 108 Scandinavian Neolithic individuals from eight megalithic graves and a stone cist. We find that the Neolithic plague was widespread, detected in at least 17% of the sampled population and across large geographical distances. We demonstrate that the disease spread within the Neolithic community in three distinct infection events within a period of around 120 years. Variant graph-based pan-genomics shows that the Neolithic plague genomes retained ancestral genomic variation present in Yersinia pseudotuberculosis, including virulence factors associated with disease outcomes. In addition, we reconstruct four multigeneration pedigrees, the largest of which consists of 38 individuals spanning six generations, showing a patrilineal social organization. Lastly, we document direct genomic evidence for Neolithic female exogamy in a woman buried in a different megalithic tomb than her brothers. Taken together, our findings provide a detailed reconstruction of plague spread within a large patrilineal kinship group and identify multiple plague infections in a population dated to the beginning of the Neolithic decline., (© 2024. The Author(s).)- Published
- 2024
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31. Identification of microbial pathogens in Neolithic Scandinavian humans.
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Bergfeldt N, Kırdök E, Oskolkov N, Mirabello C, Unneberg P, Malmström H, Fraser M, Sanchez-Quinto F, Jorgensen R, Skar B, Lidén K, Jakobsson M, Storå J, and Götherström A
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- Humans, Agriculture, Europe, History, Ancient, DNA, Mitochondrial genetics, Yersinia classification, Yersinia isolation & purification, Microbiota
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With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts., (© 2024. The Author(s).)
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- 2024
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32. The genetic legacy of the expansion of Bantu-speaking peoples in Africa.
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Fortes-Lima CA, Burgarella C, Hammarén R, Eriksson A, Vicente M, Jolly C, Semo A, Gunnink H, Pacchiarotti S, Mundeke L, Matonda I, Muluwa JK, Coutros P, Nyambe TS, Cikomola JC, Coetzee V, de Castro M, Ebbesen P, Delanghe J, Stoneking M, Barham L, Lombard M, Meyer A, Steyn M, Malmström H, Rocha J, Soodyall H, Pakendorf B, Bostoen K, and Schlebusch CM
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- Humans, Africa, Western, Datasets as Topic, Democratic Republic of the Congo, Founder Effect, Gene Flow genetics, Genetic Variation genetics, History, Ancient, Linguistics history, Zambia, Geographic Mapping, DNA, Ancient analysis, Emigration and Immigration history, Genetics, Population, Language history
- Abstract
The expansion of people speaking Bantu languages is the most dramatic demographic event in Late Holocene Africa and fundamentally reshaped the linguistic, cultural and biological landscape of the continent
1-7 . With a comprehensive genomic dataset, including newly generated data of modern-day and ancient DNA from previously unsampled regions in Africa, we contribute insights into this expansion that started 6,000-4,000 years ago in western Africa. We genotyped 1,763 participants, including 1,526 Bantu speakers from 147 populations across 14 African countries, and generated whole-genome sequences from 12 Late Iron Age individuals8 . We show that genetic diversity amongst Bantu-speaking populations declines with distance from western Africa, with current-day Zambia and the Democratic Republic of Congo as possible crossroads of interaction. Using spatially explicit methods9 and correlating genetic, linguistic and geographical data, we provide cross-disciplinary support for a serial-founder migration model. We further show that Bantu speakers received significant gene flow from local groups in regions they expanded into. Our genetic dataset provides an exhaustive modern-day African comparative dataset for ancient DNA studies10 and will be important to a wide range of disciplines from science and humanities, as well as to the medical sector studying human genetic variation and health in African and African-descendant populations., (© 2023. The Author(s).)- Published
- 2024
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33. Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe.
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Mattila TM, Svensson EM, Juras A, Günther T, Kashuba N, Ala-Hulkko T, Chyleński M, McKenna J, Pospieszny Ł, Constantinescu M, Rotea M, Palincaș N, Wilk S, Czerniak L, Kruk J, Łapo J, Makarowicz P, Potekhina I, Soficaru A, Szmyt M, Szostek K, Götherström A, Storå J, Netea MG, Nikitin AG, Persson P, Malmström H, and Jakobsson M
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- Humans, Europe, Europe, Eastern, Population Dynamics, Gene Flow, Genome
- Abstract
The genomic landscape of Stone Age Europe was shaped by multiple migratory waves and population replacements, but different regions do not all show similar patterns. To refine our understanding of the population dynamics before and after the dawn of the Neolithic, we generated and analyzed genomic sequence data from human remains of 56 individuals from the Mesolithic, Neolithic, and Eneolithic across Central and Eastern Europe. We found that Mesolithic European populations formed a geographically widespread isolation-by-distance zone ranging from Central Europe to Siberia, which was already established 10,000 years ago. We found contrasting patterns of population continuity during the Neolithic transition: people around the lower Dnipro Valley region, Ukraine, showed continuity over 4000 years, from the Mesolithic to the end of the Neolithic, in contrast to almost all other parts of Europe where population turnover drove this cultural change, including vast areas of Central Europe and around the Danube River., (© 2023. The Author(s).)
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- 2023
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34. Patrilocality and hunter-gatherer-related ancestry of populations in East-Central Europe during the Middle Bronze Age.
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Chyleński M, Makarowicz P, Juras A, Krzewińska M, Pospieszny Ł, Ehler E, Breszka A, Górski J, Taras H, Szczepanek A, Polańska M, Włodarczak P, Lasota-Kuś A, Wójcik I, Romaniszyn J, Szmyt M, Kośko A, Ignaczak M, Sadowski S, Matoga A, Grossman A, Ilchyshyn V, Yahodinska MO, Romańska A, Tunia K, Przybyła M, Grygiel R, Szostek K, Dabert M, Götherström A, Jakobsson M, and Malmström H
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- Humans, History, Ancient, Europe, Poland, Social Change, Human Migration, Genome, Human genetics
- Abstract
The demographic history of East-Central Europe after the Neolithic period remains poorly explored, despite this region being on the confluence of various ecological zones and cultural entities. Here, the descendants of societies associated with steppe pastoralists form Early Bronze Age were followed by Middle Bronze Age populations displaying unique characteristics. Particularly, the predominance of collective burials, the scale of which, was previously seen only in the Neolithic. The extent to which this re-emergence of older traditions is a result of genetic shift or social changes in the MBA is a subject of debate. Here by analysing 91 newly generated genomes from Bronze Age individuals from present Poland and Ukraine, we discovered that Middle Bronze Age populations were formed by an additional admixture event involving a population with relatively high proportions of genetic component associated with European hunter-gatherers and that their social structure was based on, primarily patrilocal, multigenerational kin-groups., (© 2023. The Author(s).)
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- 2023
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35. Alterations in Biomarkers Related to Glycemia, Lipid Metabolism, and Inflammation up to 20 Years Before Diagnosis of Type 1 Diabetes in Adults: Findings From the AMORIS Cohort.
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Herzog K, Andersson T, Grill V, Hammar N, Malmström H, Talbäck M, Walldius G, and Carlsson S
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- Adult, Biomarkers, Humans, Inflammation, Lipid Metabolism, Middle Aged, Risk Factors, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 epidemiology
- Abstract
Objective: Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycemic, lipid, and other metabolic biomarkers were associated with future type 1 diabetes risk in adults., Research Design and Methods: We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design., Results: We identified 1,122 type 1 diabetes cases during follow-up (average age of patient at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the ratio of apolipoprotein (apo)B to apoA-I, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. Higher apoA-I was associated with lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared with control subjects., Conclusions: Alterations in biomarker levels related to glycemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis., (© 2022 by the American Diabetes Association.)
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- 2022
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36. Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study.
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Walldius G, de Faire U, Alfredsson L, Leander K, Westerholm P, Malmström H, Ivert T, and Hammar N
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- Adult, Aged, Aged, 80 and over, Area Under Curve, Cohort Studies, Confidence Intervals, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myocardial Infarction, ROC Curve, Risk Factors, Sweden, Time Factors, Treatment Outcome, Apolipoprotein A-I blood, Apolipoproteins B blood, Cardiovascular Diseases blood
- Abstract
Background: Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop., Methods and Findings: In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study., Conclusions: An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines., Competing Interests: No authors have competing interests.
- Published
- 2021
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37. Philippine Ayta possess the highest level of Denisovan ancestry in the world.
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Larena M, McKenna J, Sanchez-Quinto F, Bernhardsson C, Ebeo C, Reyes R, Casel O, Huang JY, Hagada KP, Guilay D, Reyes J, Allian FP, Mori V, Azarcon LS, Manera A, Terando C, Jamero L Jr, Sireg G, Manginsay-Tremedal R, Labos MS, Vilar RD, Latiph A, Saway RL, Marte E, Magbanua P, Morales A, Java I, Reveche R, Barrios B, Burton E, Salon JC, Kels MJT, Albano A, Cruz-Angeles RB, Molanida E, Granehäll L, Vicente M, Edlund H, Loo JH, Trejaut J, Ho SYW, Reid L, Lambeck K, Malmström H, Schlebusch C, Endicott P, and Jakobsson M
- Subjects
- Animals, Asia, Asia, Southeastern, Australia, Humans, Philippines, Racial Groups, Hominidae genetics, Neanderthals genetics
- Abstract
Multiple lines of evidence show that modern humans interbred with archaic Denisovans. Here, we report an account of shared demographic history between Australasians and Denisovans distinctively in Island Southeast Asia. Our analyses are based on ∼2.3 million genotypes from 118 ethnic groups of the Philippines, including 25 diverse self-identified Negrito populations, along with high-coverage genomes of Australopapuans and Ayta Magbukon Negritos. We show that Ayta Magbukon possess the highest level of Denisovan ancestry in the world-∼30%-40% greater than that of Australians and Papuans-consistent with an independent admixture event into Negritos from Denisovans. Together with the recently described Homo luzonensis, we suggest that there were multiple archaic species that inhabited the Philippines prior to the arrival of modern humans and that these archaic groups may have been genetically related. Altogether, our findings unveil a complex intertwined history of modern and archaic humans in the Asia-Pacific region, where distinct Islander Denisovan populations differentially admixed with incoming Australasians across multiple locations and at various points in time., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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38. Maternal genetic origin of the late and final Neolithic human populations from present-day Poland.
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Juras A, Ehler E, Chyleński M, Pospieszny Ł, Spinek AE, Malmström H, Krzewińska M, Szostek K, Pasterkiewicz W, Florek M, Wilk S, Mnich B, Kruk J, Szmyt M, Kozieł S, Götherström A, Jakobsson M, and Dabert M
- Subjects
- Anthropology, Physical, Haplotypes genetics, History, Ancient, Humans, Poland, DNA, Ancient, DNA, Mitochondrial genetics, White People genetics
- Abstract
Objective: We aim to identify maternal genetic affinities between the Middle to Final Neolithic (3850-2300 BC) populations from present-day Poland and possible genetic influences from the Pontic steppe., Materials and Methods: We conducted ancient DNA studies from populations associated with Złota, Globular Amphora, Funnel Beaker, and Corded Ware cultures (CWC). We sequenced genomic libraries on Illumina platform to generate 86 complete ancient mitochondrial genomes. Some of the samples were enriched for mitochondrial DNA using hybridization capture., Results: The maternal genetic composition found in Złota-associated individuals resembled that found in people associated with the Globular Amphora culture which indicates that both groups likely originated from the same maternal genetic background. Further, these two groups were closely related to the Funnel Beaker culture-associated population. None of these groups shared a close affinity to CWC-associated people. Haplogroup U4 was present only in the CWC group and absent in Złota group, Globular Amphora, and Funnel Beaker cultures., Discussion: The prevalence of mitochondrial haplogroups of Neolithic farmer origin identified in Early, Middle and Late Neolithic populations suggests a genetic continuity of these maternal lineages in the studied area. Although overlapping in time - and to some extent - in cultural expressions, none of the studied groups (Złota, Globular Amphora, Funnel Beaker), shared a close genetic affinity to CWC-associated people, indicating a larger extent of cultural influence from the Pontic steppe than genetic exchange. The higher frequency of haplogroup U5b found in populations associated with Funnel Beaker, Globular Amphora, and Złota cultures suggest a gradual maternal genetic influx from Mesolithic hunter-gatherers. Moreover, presence of haplogroup U4 in Corded Ware groups is most likely associated with the migrations from the Pontic steppe at the end of the Neolithic and supports the observed genetic distances., (© 2021 Wiley Periodicals LLC.)
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- 2021
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39. The rate by which mortality increase with age is the same for those who experienced chronic disease as for the general population.
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Ebeling M, Rau R, Malmström H, Ahlbom A, and Modig K
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- Adult, Chronic Disease, Humans, Sweden epidemiology, Aging, Myocardial Infarction
- Abstract
Background: Mortality doubles approximately every 6-7 years during adulthood. This exponential increase in death risk with chronological age is the population-level manifestation of ageing, and often referred to as the rate-of-ageing., Objective: We explore whether the onset of severe chronic disease alters the rate-of-ageing., Methods: Using Swedish register data covering the entire population of the birth cohorts 1927-30, we analyse whether being diagnosed with myocardial infarction, diabetes or cancer results in a deviation of the rate-of-ageing from those of the total population. We also quantify the long-term mortality effects of these diseases, using ages with equivalent mortality levels for those with disease and the total population., Results: None of the diseases revealed a sustained effect on the rate-of-ageing. After an initial switch upwards in the level of mortality, the rate-of-ageing returned to the same pace as for the total population. The time it takes for the rate to return depends on the disease. The long-term effects of diabetes and myocardial infarction amount to mortality levels that are equivalent to those aged 5-7 years older in the total population. For cancer, the level of mortality returns to that of the total population., Conclusion: Our results suggest an underlying process of ageing that causes mortality to increase at a set pace, with every year older we become. This process is not affected by disease history. The persistence of the rate-of-ageing motivates a critical discussion of what role disease prevention can play in altering the progression of ageing., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society.)
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- 2021
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40. Elevated Apolipoprotein B/A-1 Ratio is Associated With an Increased Risk of Aortic Stenosis: Experience From the AMORIS Cohort.
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Ivert T, Hammar N, Talbäck M, Malmström H, Leander K, and Walldius G
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- Apolipoprotein A-I, Apolipoproteins, Child, Preschool, Cohort Studies, Female, Humans, Risk Factors, Aortic Valve Stenosis diagnosis, Aortic Valve Stenosis epidemiology, Apolipoproteins B
- Abstract
Background: Lipoproteins are associated with acquired aortic valve stenosis (AS). This study investigated whether an elevated apolipoprotein (apo)B/apoA-1 ratio was associated with an increased risk of AS and if this association was influenced by a history of a major adverse cardiovascular event (MACE) defined as stroke, myocardial infarction or revascularisation., Methods: A study was undertaken of 131,816 individuals, aged ≥30 years, from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort, with measurements of apolipoproteins B and A-1 at health examinations during 1985-1996., Results: There were fewer women and the average age was 4 years older in the highest apoB/apoA-1 quintile compared with the lowest. Being overweight, having reduced renal function and diabetes mellitus were more frequent. Low-density lipoprotein cholesterol, triglyceride and apolipoprotein B levels were higher in the top apoB/apoA-1 quintile. During follow-up through 2011, non-rheumatic aortic valve disease was diagnosed in 2,999 individuals (2.3%). Using ICD-10 codes from 1997, AS was identified in 1,887 patients. An elevated apoB/apoA-1 ratio was associated with an increased incidence of aortic valve disease after multivariable adjustment [hazard ratio (HR) (95% CI) for the fifth vs first quintile of 1.28 (1.09-1.50)]. Restricting the analyses to incident AS during 1997-2011 yielded an HR of 1.41 (1.15-1.72). This increased incidence was primarily seen in women and individuals aged ≥65 years. History of MACE did not influence these associations., Conclusions: An elevated apoB/apoA-1 ratio was associated with an increased incidence of AS, particularly in women and individuals aged ≥65 years, regardless of previous MACE., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)
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- 2021
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41. Later Stone Age human hair from Vaalkrans Shelter, Cape Floristic Region of South Africa, reveals genetic affinity to Khoe groups.
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Coutinho A, Malmström H, Edlund H, Henshilwood CS, van Niekerk KL, Lombard M, Schlebusch CM, and Jakobsson M
- Subjects
- Anthropology, Physical, Black People history, Ethnicity history, Genome, Human genetics, History, 19th Century, History, Ancient, Human Migration history, Humans, Polymorphism, Single Nucleotide genetics, South Africa, Black People genetics, Ethnicity genetics, Genetics, Population methods, Hair chemistry
- Abstract
Previous studies show that the indigenous people of the southern Cape of South Africa were dramatically impacted by the arrival of European colonists starting ~400 years ago and their descendants are today mixed with Europeans and Asians. To gain insight on the occupants of the Vaalkrans Shelter located at the southernmost tip of Africa, we investigated the genetic make-up of an individual who lived there about 200 years ago. We further contextualize the genetic ancestry of this individual among prehistoric and current groups. From a hair sample excavated at the shelter, which was indirectly dated to about 200 years old, we sequenced the genome (1.01 times coverage) of a Later Stone Age individual. We analyzed the Vaalkrans genome together with genetic data from 10 ancient (pre-colonial) individuals from southern Africa spanning the last 2000 years. We show that the individual from Vaalkrans was a man who traced ~80% of his ancestry to local southern San hunter-gatherers and ~20% to a mixed East African-Eurasian source. This genetic make-up is similar to modern-day Khoekhoe individuals from the Northern Cape Province (South Africa) and Namibia, but in the southern Cape, the Vaalkrans man's descendants have likely been assimilated into mixed-ancestry "Coloured" groups. The Vaalkrans man's genome reveals that Khoekhoe pastoralist groups/individuals lived in the southern Cape as late as 200 years ago, without mixing with non-African colonists or Bantu-speaking farmers. Our findings are also consistent with the model of a Holocene pastoralist migration, originating in Eastern Africa, shaping the genomic landscape of historic and current southern African populations., (© 2021 The Authors. American Journal of Physical Anthropology published by Wiley Periodicals LLC.)
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- 2021
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42. Multiple migrations to the Philippines during the last 50,000 years.
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Larena M, Sanchez-Quinto F, Sjödin P, McKenna J, Ebeo C, Reyes R, Casel O, Huang JY, Hagada KP, Guilay D, Reyes J, Allian FP, Mori V, Azarcon LS, Manera A, Terando C, Jamero L Jr, Sireg G, Manginsay-Tremedal R, Labos MS, Vilar RD, Latiph A, Saway RL, Marte E, Magbanua P, Morales A, Java I, Reveche R, Barrios B, Burton E, Salon JC, Kels MJT, Albano A, Cruz-Angeles RB, Molanida E, Granehäll L, Vicente M, Edlund H, Loo JH, Trejaut J, Ho SYW, Reid L, Malmström H, Schlebusch C, Lambeck K, Endicott P, and Jakobsson M
- Subjects
- Agriculture, Asia, Southeastern ethnology, Australia ethnology, Female, Genetic Drift, Genomics, History, Ancient, Humans, Male, Oryza, Philippines, Population Groups genetics, Taiwan ethnology, Human Migration history, Population Groups history
- Abstract
Island Southeast Asia has recently produced several surprises regarding human history, but the region's complex demography remains poorly understood. Here, we report ∼2.3 million genotypes from 1,028 individuals representing 115 indigenous Philippine populations and genome-sequence data from two ∼8,000-y-old individuals from Liangdao in the Taiwan Strait. We show that the Philippine islands were populated by at least five waves of human migration: initially by Northern and Southern Negritos (distantly related to Australian and Papuan groups), followed by Manobo, Sama, Papuan, and Cordilleran-related populations. The ancestors of Cordillerans diverged from indigenous peoples of Taiwan at least ∼8,000 y ago, prior to the arrival of paddy field rice agriculture in the Philippines ∼2,500 y ago, where some of their descendants remain to be the least admixed East Asian groups carrying an ancestry shared by all Austronesian-speaking populations. These observations contradict an exclusive "out-of-Taiwan" model of farming-language-people dispersal within the last four millennia for the Philippines and Island Southeast Asia. Sama-related ethnic groups of southwestern Philippines additionally experienced some minimal South Asian gene flow starting ∼1,000 y ago. Lastly, only a few lowlanders, accounting for <1% of all individuals, presented a low level of West Eurasian admixture, indicating a limited genetic legacy of Spanish colonization in the Philippines. Altogether, our findings reveal a multilayered history of the Philippines, which served as a crucial gateway for the movement of people that ultimately changed the genetic landscape of the Asia-Pacific region., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)
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- 2021
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43. Preliminary study of the impact of elevated circulating plasma levels of catecholamines on opioid requirements for acute surgical pain.
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Uribe-Rivera A, Rasubala L, Machado-Perez AC, Ren YF, Malmström H, and Carinci A
- Abstract
Introduction: The objective of this study is to determine whether elevated circulating plasma catecholamine levels significantly impact opioid requirements during the first 24 hours postoperative period in individuals with acute surgical pain., Methods: We retrospectively reviewed 15 electronic medical records (EMRs) from adults 18 years and older, with confirmed elevated plasma catecholamine levels (experimental) and 15 electronic health records (EHRs) from matched-controls for age, gender, race and type of surgery, with a follow up of 24 hours postoperatively., Results: The total morphine milligram equivalents (MMEs) requirements from the experimental group were not statistically different when compared with controls [44.1 (13 to 163) mg versus 47.5 (13 to 151) mg respectively; p 0.4965]. However, the intraoperative MMEs showed a significant difference, among the two groups; [(experimental) 32.5 (13. to 130) mg, (control) 15 (6.5 to 130) mg; p 0.0734]. The intraoperative dosage of midazolam showed a highly significant positive correlation to the total MMEs (p 0.0005). The subjects with both elevated plasma catecholamines and hypertension used significantly higher intraoperative MMEs compared to controls [34.1 (13 to 130) mg versus 15 (6.5 to 130) mg, respectively; p 0.0292)]. Those 51 years and younger, with elevated circulating levels of catecholamines, required significantly higher levels of both the postoperative MMEs [29.1 (0 to 45) mg versus 12 (0 to 71.5) mg; (p 0.0553)] and total MMEs [544.05 (13 to 81) mg versus 29.42 (13 to 92.5) mg; (p 0.00018), when compared to controls with history of nicotine and alcohol use., Conclusion: This preliminary study evaluated a biologic factor, which have promising clinical usefulness for predicting analgesic requirements that can drive clinical decisions on acute surgical pain., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2021.)
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- 2021
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44. Khoe-San Genomes Reveal Unique Variation and Confirm the Deepest Population Divergence in Homo sapiens.
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Schlebusch CM, Sjödin P, Breton G, Günther T, Naidoo T, Hollfelder N, Sjöstrand AE, Xu J, Gattepaille LM, Vicente M, Scofield DG, Malmström H, de Jongh M, Lombard M, Soodyall H, and Jakobsson M
- Subjects
- Africa South of the Sahara, Humans, Phylogeography, Biological Evolution, Genome, Human, Human Migration, Indigenous Peoples genetics, Population Density
- Abstract
The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene regions with extreme values in genome-wide scans for selection, potentially caused by natural selection in the lineage leading to Homo sapiens and more recent in time. These gene regions included immunity-, sperm-, brain-, diet-, and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of-Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
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- 2020
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45. The Neolithic Pitted Ware culture foragers were culturally but not genetically influenced by the Battle Axe culture herders.
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Coutinho A, Günther T, Munters AR, Svensson EM, Götherström A, Storå J, Malmström H, and Jakobsson M
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- Burial history, Chromosomes, Human, Y genetics, DNA, Ancient analysis, DNA, Mitochondrial genetics, Female, Genetics, Population, Genome, Human genetics, History, Ancient, Humans, Male, Scandinavian and Nordic Countries ethnology, Tooth chemistry, Human Migration history, White People ethnology, White People genetics
- Abstract
Objectives: In order to understand contacts between cultural spheres in the third millennium BC, we investigated the impact of a new herder culture, the Battle Axe culture, arriving to Scandinavia on the people of the sub-Neolithic hunter-gatherer Pitted Ware culture. By investigating the genetic make-up of Pitted Ware culture people from two types of burials (typical Pitted Ware culture burials and Battle Axe culture-influenced burials), we could determine the impact of migration and the impact of cultural influences., Methods: We sequenced and analyzed the genomes of 25 individuals from typical Pitted Ware culture burials and from Pitted Ware culture burials with Battle Axe culture influences in order to determine if the different burial types were associated with different gene-pools., Results: The genomic data show that all individuals belonged to one genetic population-a population associated with the Pitted Ware culture-irrespective of the burial style., Conclusion: We conclude that the Pitted Ware culture communities were not impacted by gene-flow, that is, via migration or exchange of mates. These different cultural expressions in the Pitted Ware culture burials are instead a consequence of cultural exchange., (© 2020 The Authors. American Journal of Physical Anthropology published by Wiley Periodicals, Inc.)
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- 2020
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46. Y-Chromosome Variation in Southern African Khoe-San Populations Based on Whole-Genome Sequences.
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Naidoo T, Xu J, Vicente M, Malmström H, Soodyall H, Jakobsson M, and Schlebusch CM
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- Africa, Southern, Female, Genetic Variation, Haplotypes, Humans, Male, Phylogeny, Whole Genome Sequencing, Chromosomes, Human, Y, Genome, Human
- Abstract
Although the human Y chromosome has effectively shown utility in uncovering facets of human evolution and population histories, the ascertainment bias present in early Y-chromosome variant data sets limited the accuracy of diversity and TMRCA estimates obtained from them. The advent of next-generation sequencing, however, has removed this bias and allowed for the discovery of thousands of new variants for use in improving the Y-chromosome phylogeny and computing estimates that are more accurate. Here, we describe the high-coverage sequencing of the whole Y chromosome in a data set of 19 male Khoe-San individuals in comparison with existing whole Y-chromosome sequence data. Due to the increased resolution, we potentially resolve the source of haplogroup B-P70 in the Khoe-San, and reconcile recently published haplogroup A-M51 data with the most recent version of the ISOGG Y-chromosome phylogeny. Our results also improve the positioning of tentatively placed new branches of the ISOGG Y-chromosome phylogeny. The distribution of major Y-chromosome haplogroups in the Khoe-San and other African groups coincide with the emerging picture of African demographic history; with E-M2 linked to the agriculturalist Bantu expansion, E-M35 linked to pastoralist eastern African migrations, B-M112 linked to earlier east-south gene flow, A-M14 linked to shared ancestry with central African rainforest hunter-gatherers, and A-M51 potentially unique to the Khoe-San., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
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- 2020
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47. Mitochondrial genomes from Bronze Age Poland reveal genetic continuity from the Late Neolithic and additional genetic affinities with the steppe populations.
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Juras A, Makarowicz P, Chyleński M, Ehler E, Malmström H, Krzewińska M, Pospieszny Ł, Górski J, Taras H, Szczepanek A, Polańska M, Włodarczak P, Szyca A, Lasota-Kuś A, Wójcik I, Jakobsson M, and Dabert M
- Subjects
- Adult, Anthropology, Physical, Cemeteries, Child, Female, Haplotypes genetics, History, Ancient, Human Migration, Humans, Male, Poland, DNA, Ancient analysis, Genetics, Population, Genome, Mitochondrial genetics, White People genetics
- Abstract
Objective: In this work we aim to investigate the origins and genetic affinities of Bronze Age populations (2,400-1,100 BC) from the region of southern Poland and to trace maternal kinship patterns present in the burials of those populations by the use of complete mitochondrial genomes., Materials and Methods: We performed ancient DNA analyses for Bronze Age individuals from present-day Poland associated with the Strzyżow culture, the Mierzanowice culture, and the Trzciniec Cultural circle. To obtain complete mitochondrial genomes, we sequenced genomic libraries using Illumina platform. Additionally, hybridization capture was used to enrich some of the samples for mitochondrial DNA. AMS
14 C-dating was conducted for 51 individuals to verify chronological and cultural attribution of the analyzed samples., Results: Complete ancient mitochondrial genomes were generated for 80 of the Bronze Age individuals from present-day Poland. The results of the population genetic analyses indicate close maternal genetic affinity between Mierzanowice, Trzciniec, and Corded Ware culture-associated populations. This is in contrast to the genetically more distant Strzyżów people that displayed closer maternal genetic relation to steppe populations associated with the preceding Yamnaya culture and Catacomb culture, and with later Scythians. Potential maternal kinship relations were identified in burials of Mierzanowice and Trzciniec populations analyzed in this study., Discussion: Results revealed genetic continuity from the Late Neolithic Corded Ware groups to Bronze Age Mierzanowice and Trzciniec-associated populations, and possible additional genetic contribution from the steppe to the formation of the Strzyżów-associated group at the end of 3rd millennium BC. Mitochondrial patterns indicated several pairs of potentially maternally related individuals mostly in Trzciniec-associated group., (© 2020 Wiley Periodicals, Inc.)- Published
- 2020
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48. The genomic ancestry of the Scandinavian Battle Axe Culture people and their relation to the broader Corded Ware horizon.
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Malmström H, Günther T, Svensson EM, Juras A, Fraser M, Munters AR, Pospieszny Ł, Tõrv M, Lindström J, Götherström A, Storå J, and Jakobsson M
- Subjects
- Baltic States, Base Sequence, DNA, Ancient, Europe, Farmers, Genomics, Humans, Poland, Population Dynamics, Scandinavian and Nordic Countries, Sweden, White People, Culture, History, Ancient, Human Migration
- Abstract
The Neolithic period is characterized by major cultural transformations and human migrations, with lasting effects across Europe. To understand the population dynamics in Neolithic Scandinavia and the Baltic Sea area, we investigate the genomes of individuals associated with the Battle Axe Culture (BAC), a Middle Neolithic complex in Scandinavia resembling the continental Corded Ware Culture (CWC). We sequenced 11 individuals (dated to 3330-1665 calibrated before common era (cal BCE)) from modern-day Sweden, Estonia, and Poland to 0.26-3.24× coverage. Three of the individuals were from CWC contexts and two from the central-Swedish BAC burial 'Bergsgraven'. By analysing these genomes together with the previously published data, we show that the BAC represents a group different from other Neolithic populations in Scandinavia, revealing stratification among cultural groups. Similar to continental CWC, the BAC-associated individuals display ancestry from the Pontic-Caspian steppe herders, as well as smaller components originating from hunter-gatherers and Early Neolithic farmers. Thus, the steppe ancestry seen in these Scandinavian BAC individuals can be explained only by migration into Scandinavia. Furthermore, we highlight the reuse of megalithic tombs of the earlier Funnel Beaker Culture (FBC) by people related to BAC. The BAC groups likely mixed with resident middle Neolithic farmers (e.g. FBC) without substantial contributions from Neolithic foragers.
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- 2019
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49. Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort.
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Essén A, Santaolalla A, Garmo H, Hammar N, Walldius G, Jungner I, Malmström H, Holmberg L, and Van Hemelrijck M
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- Adult, Aged, Aged, 80 and over, Cohort Studies, Diet, Female, Humans, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk, Sweden, Breast Neoplasms blood, Folic Acid blood, Prostatic Neoplasms blood, Vitamin B 12 blood
- Abstract
Purpose: The roles of folate and vitamin B12 in prostate cancer (PCa) or breast cancer (BC) development are unclear. We investigated their roles using the prospective Swedish Apolipoprotein MOrtality RISk (AMORIS) study., Methods: 8,783 men and 19,775 women with vitamin B12 and folate serum measurements were included. Their associations with PCa and BC risk categories were evaluated using Cox proportional hazards regression., Results: During mean follow-up of 13 years, 703 men developed PCa. There was an inverse association between folate > 32 nmol/L and high-risk PCa [hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02-0.90], and a positive association between folate < 5 nmol/L and metastatic PCa (HR 5.25, 95% CI 1.29-21.41), compared with folate 5-32 nmol/L. No associations with vitamin B12 were found. 795 women developed BC during mean follow-up of 14 years. When restricting to the fasting population, there was a positive association between folate > 32 nmol/L and BC (HR 1.47, 95% CI 1.06-2.04)., Conclusion: High folate levels may protect against PCa and low folate levels may increase risk of metastatic PCa. High fasting folate levels may be associated with an increased BC risk. Vitamin B12 was not found to be linked with risk of PCa or BC. Longitudinal studies with serum and dietary information could help define new prevention targets and add information on the role of folate fortification.
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- 2019
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50. Megalithic tombs in western and northern Neolithic Europe were linked to a kindred society.
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Sánchez-Quinto F, Malmström H, Fraser M, Girdland-Flink L, Svensson EM, Simões LG, George R, Hollfelder N, Burenhult G, Noble G, Britton K, Talamo S, Curtis N, Brzobohata H, Sumberova R, Götherström A, Storå J, and Jakobsson M
- Subjects
- Agriculture history, Burial, Female, History, Ancient, Humans, Male, United Kingdom, Archaeology, Chromosomes, Human, Y genetics, Genome, Human, Haplotypes
- Abstract
Paleogenomic and archaeological studies show that Neolithic lifeways spread from the Fertile Crescent into Europe around 9000 BCE, reaching northwestern Europe by 4000 BCE. Starting around 4500 BCE, a new phenomenon of constructing megalithic monuments, particularly for funerary practices, emerged along the Atlantic façade. While it has been suggested that the emergence of megaliths was associated with the territories of farming communities, the origin and social structure of the groups that erected them has remained largely unknown. We generated genome sequence data from human remains, corresponding to 24 individuals from five megalithic burial sites, encompassing the widespread tradition of megalithic construction in northern and western Europe, and analyzed our results in relation to the existing European paleogenomic data. The various individuals buried in megaliths show genetic affinities with local farming groups within their different chronological contexts. Individuals buried in megaliths display (past) admixture with local hunter-gatherers, similar to that seen in other Neolithic individuals in Europe. In relation to the tomb populations, we find significantly more males than females buried in the megaliths of the British Isles. The genetic data show close kin relationships among the individuals buried within the megaliths, and for the Irish megaliths, we found a kin relation between individuals buried in different megaliths. We also see paternal continuity through time, including the same Y-chromosome haplotypes reoccurring. These observations suggest that the investigated funerary monuments were associated with patrilineal kindred groups. Our genomic investigation provides insight into the people associated with this long-standing megalith funerary tradition, including their social dynamics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)
- Published
- 2019
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