| 1. |
- Patterson, Nick, et al.
(author)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
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Journal article (peer-reviewed)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 2. |
- Guldbrand, Hans, et al.
(author)
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In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss
- 2012
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In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 55:8, s. 2118-2127
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: The study aimed to compare the effects of a 2 year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD), based on four group meetings to achieve compliance. METHODS: This was a prospective randomised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and randomised by drawing ballots. Patients that did not speak Swedish could not be recruited. The primary outcomes in this non-blinded study were weight and HbA(1c). Patients on the LFD aimed for 55-60 energy per cent (E%) and those on LCD for 20 E% from carbohydrate. RESULTS: The mean BMI and HbA(1c) of the participants were 32.7 ± 5.4 kg/m(2) and 57.0 ± 9.2 mmol/mol, respectively. No patients were lost to follow-up. Weight loss did not differ between groups and was maximal at 6 months: LFD -3.99 ± 4.1 kg (n = 31); LCD -4.31 ± 3.6 kg (n = 30); p < 0.001 within groups. At 24 months, patients on the LFD had lost -2.97 ± 4.9 kg and those on LCD -2.34 ± 5.1 kg compared with baseline (p = 0.002 and p = 0.020 within groups, respectively). HbA(1c) fell in the LCD group only (LCD at 6 months -4.8 ± 8.3 mmol/mol, p = 0.004, at 12 months -2.2 ± 7.7 mmol/mol, p = 0.12; LFD at 6 months -0.9 ± 8.8 mmol/mol, p = 0.56). At 6 months, HDL-cholesterol had increased with the LCD (from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l, p = 0.018) while LDL-cholesterol did not differ between groups. Insulin doses were reduced in the LCD group (0 months, LCD 42 ± 65 E, LFD 39 ± 51 E; 6 months, LCD 30 ± 47 E, LFD 38 ± 48 E; p = 0.046 for between-group change). CONCLUSIONS/INTERPRETATION: Weight changes did not differ between the diet groups, while insulin doses were reduced significantly more with the LCD at 6 months, when compliance was good. Thus, aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative. TRIAL REGISTRATION: ClinicalTrials.gov NCT01005498 FUNDING: University Hospital of Linköping Research Funds, Linköping University, the County Council of Östergötland, and the Diabetes Research Centre of Linköping University.
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| 3. |
- Guldbrand, Hans, et al.
(author)
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Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus
- 2014
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In: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 106:2, s. 221-227
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Journal article (peer-reviewed)abstract
- AimsTo compare the effects on health-related quality of life (HRQoL) of a 2-year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD) based on four group-meetings to achieve compliance. To describe different aspects of taking part in the intervention following the LFD or LCD.MethodsProspective, randomized trial of 61 adults with Type 2 diabetes mellitus. The SF-36 questionnaire was used at baseline, 6, 12 and 24 months. Patients on LFD aimed for 55–60 energy percent (E%) and those on LCD for 20 E% from carbohydrates. The patients were interviewed about their experiences of the intervention.ResultsMean body-mass-index was 32.7 ± 5.4 kg/m2 at baseline. Weight-loss did not differ between groups and was maximal at 6 months, LFD: −3.99 ± 4.1 kg, LCD: −4.31 ± 3.6 kg (p < 0.001 within groups). There was an increase in the physical component score of SF-36 from 44.1 (10.0) to 46.7 (10.5) at 12 months in the LCD group (p < 0.009) while no change occurred in the LFD group (p < 0.03 between groups). At 12 months the physical function, bodily pain and general health scores improved within the LCD group (p values 0.042–0.009) while there was no change within the LFD group.ConclusionsWeight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD. No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight.
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| 4. |
- Hagell, Peter, et al.
(author)
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Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease
- 2020
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In: Journal of Neurology. - 0340-5354 .- 1432-1459. ; 267:11, s. 3411-3417
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Journal article (peer-reviewed)abstract
- Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.
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| 5. |
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| 6. |
- Pihlstrom, L., et al.
(author)
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Fine mapping and resequencing of the PARK16 locus in Parkinson's disease
- 2015
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In: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 60:7, s. 357-362
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Journal article (peer-reviewed)abstract
- The PARK16 locus, spanning five genes on chromosome 1, was among the first genetic regions to show genome-wide association in Parkinson's disease (PD). Subsequent investigations have found variability in PARK16 top-hits and association patterns across populations, and the implicated genes and mechanisms are currently unclear. In the present study, we aimed to explore the contribution of PARK16 variability to PD risk in a Scandinavian population. We genotyped 17 single-nucleotide polymorphisms in a case-control sample set of 2570 individuals from Norway and Sweden to fine map the locus. Targeted resequencing of the full coding regions of SLC45A3, NUCKS1, RAB7L1, SLC41A1 and PM20D1 was performed in DNA pools from a subset of 387 patient samples. We find evidence for an association with PD for rs1775143 as well as a haplotype located around the 5' region of RAB7L1, implicating variants which are not in high linkage disequilibrium with the strongest signal from a recent large meta-analysis in Caucasians. We also provide suggestive support for epistasis between RAB7L1 and LRRK2 as previously hypothesized by others. Comparing our results with previous work, allelic heterogeneity at PARK16 appears likely, and further studies are warranted to disentangle the complex patterns of association and pinpoint the functionally relevant variants.
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| 7. |
- Pihlstrom, L., et al.
(author)
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Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease
- 2013
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:6
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Journal article (peer-reviewed)abstract
- enome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.
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| 8. |
- Pålhagen, S. E., et al.
(author)
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Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease
- 2012
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In: Acta Neurologica Scandinavica. - : John Wiley & Sons. - 0001-6314 .- 1600-0404. ; 126:6, s. e29-e33
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Journal article (peer-reviewed)abstract
- Background - This interim 12-month analysis is a part of an open-label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health-related quality of life (HRQoL) effects in routine care. Methods - Unified PD rating scale (UPDRS) was the primary efficacy measurement. PD QoL questionnaire 39 (PDQ-39) assessed HRQoL. Subjects were assessed at baseline, andgt;= 3 months after surgery, and then every 3 months. Results - Twenty-seven treatment-naive subjects when started with LCIG showed a decrease in UPDRS score that was statistically significant throughout the year: UPDRS total score (mean +/- SD), baseline = 52.1 +/- 16.1, N = 27, month 0 (first visit; at least 3 months after permanent LCIG) = 43.1 +/- 16.7, N = 27, P = 0.003; month 12 = 42.5 +/- 22.6, n = 25, P = 0.017. PDQ-39 results also showed a tendency for improvement: PDQ-39 (mean +/- SD), baseline = 33.6 +/- 10.8, N = 27, month 0 = 27.1 +/- 11.8, N = 27, P = 0.001; 12 months = 28.8 +/- 12.8, n = 23, P = 0.126. Conclusions - LCIG provides functional improvement beginning at first visit that is sustained for 12 months.
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