| 1. |
- Kalman, L. V., et al.
(författare)
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Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting
- 2016
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 99:2, s. 172-185
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Tidskriftsartikel (refereegranskat)abstract
- This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
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| 2. |
- Rothe, Sebastian, et al.
(författare)
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Laser photodetachment of radioactive I-128(-)
- 2017
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Ingår i: Journal of Physics G-Nuclear and Particle Physics. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- The first experimental investigation of the electron affinity (EA) of a radioactive isotope has been conducted at the CERN-ISOLDE radioactive ion beam facility. The EA of the radioactive iodine isotope I-128 (t(1/2) = 25 min) was determined to be 3.059 052(38) eV. The experiment was conducted using the newly developed Gothenburg ANion Detector for Affinity measurements by Laser PHotodetachment (GANDALPH) apparatus, connected to a CERNI-SOLDE experimental beamline. I-128 was produced in fission induced by 1.4 GeV protons striking a thorium/tantalum foil target and then extracted as singly charged negative ions at a beam energy of 20 keV. Laser photodetachment of the fast ion beam was performed in a collinear geometry inside the GANDALPH chamber. Neutral atoms produced in the photodetachment process were detected by allowing them to impinge on a glass surface, creating secondary electrons which were then detected using a channel electron multiplier. The photon energy of the laser was tuned across the threshold of the photodetachment process and the detachment threshold data were fitted to a Wigner law function in order to extract the EA. This first successful demonstration of photodetachment at an isotope separator on line facility opens up the opportunity for future studies of the fundamental properties of negatively charged radioactive isotopes such as the EA of astatine and polonium.
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| 3. |
- Gezelius, E., et al.
(författare)
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Low-molecular-weight heparin adherence and effects on survival within a randomised phase III lung cancer trial (RASTEN)
- 2019
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Ingår i: European Journal of Cancer. - : ELSEVIER SCI LTD. - 0959-8049 .- 1879-0852. ; 118, s. 82-90
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Tidskriftsartikel (refereegranskat)abstract
- Background: Coagulation activation is a hallmark of cancer, and anticoagulants have shown tumour-inhibiting properties. However, recent trials have failed to demonstrate improved survival with low-molecular-weight heparin (LMWH) in cancer populations. This has raised the question of suboptimal adherence as a possible explanation for the lack of benefit. Still, there is no standardised method to directly monitor LMWH in patient plasma. Here, we directly determine LMWH levels in patients using the Heparin Red assay to objectively assess adherence and how this associates with the patient outcome in the RASTEN trial. Methods: RASTEN is a multicentre, randomised phase III trial investigating if the addition of LMWH to standard therapy can improve survival in small-cell lung cancer. LMWH was measured in plasma (N = 258) by the Heparin Red assay and compared with the anti-factor Xa (anti-FXa) activity assay. Results: Both methods could differentiate patients in the LMWH arm from the control arm and patients receiving therapeutic LMWH owing to thrombosis. Receiver Operating Characteristic (ROC) analysis yielded adherence rates of 85% for anti-FXa and 68% for Heparin Red. No survival benefits were found in the adherent subgroup compared with the control arm (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 0.95-1.67; P = 0.105 and HR: 1.19; 95% CI: 0.89-1.60; P = 0.248 for anti-FXa and Heparin Red, respectively). Heparin Red could define patients with high probability of adherence to LMWH treatment, which warrants prospective studies for further validation. Our finding that the LMWH-adherent subpopulation did not show improved survival excludes that the negative outcome of RASTEN was due to poor adherence. (C) 2019 The Authors. Published by Elsevier Ltd.
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| 4. |
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| 5. |
- Perry, G. W., et al.
(författare)
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Spatiotemporally resolved electrodynamic properties of a Sun-aligned arc over Resolute Bay
- 2015
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 120:11, s. 9977-9987
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Tidskriftsartikel (refereegranskat)abstract
- Common volume measurements by the Resolute Bay Incoherent Scatter Radar-North (RISR-N) and Optical Mesosphere and Thermosphere Imagers (OMTI) have been used to clarify the electrodynamic structure of a Sun-aligned arc in the polar cap. The plasma parameters of the dusk-to-dawn drifting arc and surrounding ionosphere are extracted using the volumetric imaging capabilities of RISR-N. Multipoint line-of-sight RISR-N measurements of the plasma drift are inverted to construct a time sequence of the electric field and field-aligned current system of the arc. Evidence of dramatic electrodynamic and plasma structuring of the polar cap ionosphere due to the arc is described. One notable feature of the arc is a meridionally extended plasma density depletion on its leading edge, located partially within a downward field-aligned current region. The depletion is determined to be a by-product of enhanced chemical recombination operating on a time scale of 15 min. A similarly shaped electric field structure of over 100 mV/m and line-of-sight ion temperatures nearing 3000 K were collocated with the depletion.
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| 6. |
- Andersson, Håkan S., 1967-, et al.
(författare)
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The toxicity of ribbon worms: alpha-nemertides or tetrodotoxin, or both?
- 2016
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Ingår i: Planta Medica. - : Georg Thieme Verlag KG. - 0032-0943 .- 1439-0221. ; 82:Supplement 1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The marine ribbon worms (nemerteans) are predators which capture their prey by everting a proboscis carrying a mixture of toxins which brings on rapid paralysis [1]. Moreover, ribbon worms have a thick layer of epidermal mucus of similar constitution. Tetrodotoxin (TTX) has been identified as one of these toxins [2]. The extreme toxicity of TTX (lethal by ingestion of 0.5-2 mg) is due to its ability to block voltage-gated sodium channels. Although several bacterial species (among these Vibrio sp.) have been linked to its synthesis, the biogenic origin and biosynthesis is unclear. One hypothesis is that TTX production occurs in a symbiotic relationship with its host, in this case the ribbon worm [3]. We have made significant effort to identify TTX in a setup for production through the cultivation of Vibrio alginolyticus in nutrient broth infused with mucus from the ribbon worm Lineus longissimus. Toxicity was demonstrated by fraction injections into shore crabs, but no TTX was found, and it could be shown conclusively that toxicity was unrelated to TTX and the Vibrio culture itself, and rather a constituent of the ribbon worm mucus [4]. The following studies led us to the discovery of a new class of peptides, the alpha-nemertides, in the mucus of the ribbon worms, which could be directly linked to the toxic effects. A literature review of the available evidence for TTX in ribbon worms show that the evidence in most cases are indirect, although notable exceptions exist. This points to the necessity to further investigate the presence and roles of TTX and alpha-nemertides in ribbon worms.
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| 7. |
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| 8. |
- Bygdell, Joakim, et al.
(författare)
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Protein expression in tension wood formation monitored at high tissue resolution in Populus
- 2017
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Ingår i: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 68:13, s. 3405-3417
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Tidskriftsartikel (refereegranskat)abstract
- Tension wood (TW) is a specialized tissue with contractile properties that is formed by the vascular cambium in response to gravitational stimuli. We quantitatively analysed the proteomes of Populus tremula cambium and its xylem cell derivatives in stems forming normal wood (NW) and TW to reveal the mechanisms underlying TW formation. Phloem-, cambium-, and wood-forming tissues were sampled by tangential cryosectioning and pooled into nine independent samples. The proteomes of TW and NW samples were similar in the phloem and cambium samples, but diverged early during xylogenesis, demonstrating that reprogramming is an integral part of TW formation. For example, 14-3-3, reactive oxygen species, ribosomal and ATPase complex proteins were found to be up-regulated at early stages of xylem differentiation during TW formation. At later stages of xylem differentiation, proteins involved in the biosynthesis of cellulose and enzymes involved in the biosynthesis of rhamnogalacturonan-I, rhamnogalacturonan-II, arabinogalactan-II and fasciclin-like arabinogalactan proteins were up-regulated in TW. Surprisingly, two isoforms of exostosin family proteins with putative xylan xylosyl transferase function and several lignin biosynthesis proteins were also up-regulated, even though xylan and lignin are known to be less abundant in TW than in NW. These data provided new insight into the processes behind TW formation.
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| 9. |
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| 10. |
- Crafoord, M.-T., et al.
(författare)
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Patients’ usage and perception of an interactive app for symptom management and self-care during cancer treatment
- 2019
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Ingår i: Annals of Oncology. - : Elsevier. - 0923-7534 .- 1569-8041. ; 30:s5, s. v816-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEmploying apps in assessment of symptoms during cancer treatment facilitates detection of adverse events and may improve patient outcomes. Our interactive app Interaktor supports patients’ symptom management by regular symptom reporting, alerts for rapid access to staff in case of severe symptoms and continual access to relevant self-care advice. The aim of this study was to describe usage and explore perceptions of using Interaktor during cancer treatment.MethodsThe study includes the participants from the intervention arms of two separate randomized controlled trials (RCT) on patients with breast cancer (n = 74) during neoadjuvant chemotherapy and locally advanced prostate cancer (n = 75) during radiotherapy. It comprises usage metrics analysed by descriptive statistics and interviews analyzed by conventional content analysis.ResultsAdherence to daily reporting during treatment was in median above 80 %. Most patients viewed the information pages with self-care advice numerous times. The app was perceived user-friendly, faciliating interaction with health care professionals and supporting self care. Symptom reporting was a quick and comfortable way to access help. Using the app generated feelings of being monitored, involved and cared for. Further it supported attentiveness to and reflection of own well- being but could also serve as a reminder of illness. Some patients described that vigor, comorbidity, and cognitive side effects from the treatment influenced the motivation for and ability to symptom report. The information pages with self care advice were useful and appreciated and gave an idea of what was to be expected during treatment. Patients requested added and more comprehensive information on psychological symptoms and dietary advice.ConclusionsThe Interaktor app is a userfriendly and convenient alternative for patients contact and involvement with health care that aided symptom management, self-care and further enhanced patients participation in their care.Clinical trial identificationNCT02479607 and NCT02477137.
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| 11. |
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| 12. |
- Ewart, L, et al.
(författare)
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Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery
- 2018
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Ingår i: Annual review of pharmacology and toxicology. - : Annual Reviews. - 1545-4304 .- 0362-1642. ; 58, s. 65-82
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Tidskriftsartikel (refereegranskat)abstract
- Enhancing the early detection of new therapies that are likely to carry a safety liability in the context of the intended patient population would provide a major advance in drug discovery. Microphysiological systems (MPS) technology offers an opportunity to support enhanced preclinical to clinical translation through the generation of higher-quality preclinical physiological data. In this review, we highlight this technological opportunity by focusing on key target organs associated with drug safety and metabolism. By focusing on MPS models that have been developed for these organs, alongside other relevant in vitro models, we review the current state of the art and the challenges that still need to be overcome to ensure application of this technology in enhancing drug discovery.
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| 13. |
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| 14. |
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| 15. |
- Gedin, F, et al.
(författare)
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Patient-reported improvements of pain, disability, and health-related quality of life following chiropractic care for back pain - A national observational study in Sweden
- 2019
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Ingår i: Journal of Bodywork & Movement Therapies. - : Elsevier. - 1360-8592 .- 1532-9283. ; 23:2, s. 241-246
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chiropractic care is a common but not often investigated treatment option for back pain in Sweden. The aim of this study was to explore patient-reported outcomes (PRO) for patients with back pain seeking chiropractic care in Sweden.METHODS: Prospective observational study. Patients 18 years and older, with non-specific back pain of any duration, seeking care at 23 chiropractic clinics throughout Sweden were invited to answer PRO questionnaires at baseline with the main follow-up after four weeks targeting the following outcomes: Numerical Rating Scale for back pain intensity (NRS), Oswestry Disability Index for back pain disability (ODI), health-related quality of life (EQ-5D index) and a visual analogue scale for self-rated health (EQ VAS).RESULTS: 246 back pain patients answered baseline questionnaires and 138 (56%) completed follow-up after four weeks. Statistically significant improvements over the four weeks were reported for all PRO by acute back pain patients (n = 81), mean change scores: NRS -2.98 (p < 0.001), ODI -13.58 (p < 0.001), EQ VAS 9.63 (p < 0.001), EQ-5D index 0.22 (p < 0.001); and for three out of four PRO for patients with chronic back pain (n = 57), mean change scores: NRS -0.90 (p = 0.002), ODI -2.88 (p = 0.010), EQ VAS 3.77 (p = 0.164), EQ-5D index 0.04 (p = 0.022).CONCLUSIONS: Patients with acute and chronic back pain reported statistically significant improvements in PRO four weeks after initiated chiropractic care. Albeit the observational study design limits causal inference, the relatively rapid improvements of PRO scores warrant further clinical investigations.
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| 16. |
- Gitau, James K., et al.
(författare)
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Implications on Livelihoods and the Environment of Uptake of Gasifier Cook Stoves among Kenya's Rural Households
- 2019
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Ingår i: APPLIED SCIENCES-BASEL. - : MDPI. - 2076-3417. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- A majority of people in developing countries use biomass energy for cooking and heating due to its affordability, accessibility and convenience. However, unsustainable biomass use leads to forest degradation and climate change. Therefore, this study was carried out in Kwale County, Kenya, on the use of a biochar-producing gasifier cook stove and implications of its uptake on livelihoods and the environment. Fifty households were trained and issued with a gasifier for free. After 2-3 months of gasifier use, a survey was conducted to investigate the implications of its uptake. The direct impacts included reduced fuel consumption by 38%, reduced time spent in firewood collection, reduced expenditure on cooking fuel, diversification of cooking fuels, improved kitchen conditions and reduced time spent on cooking. The potential benefits included income generation, increased food production, reduced impacts on environment and climate change and reduced health problems. Improved biomass cook stoves can alleviate problems with current cooking methods, which include inefficient fuel use, health issues caused by smoke, and environmental problems. These benefits could contribute to development through alleviating poverty and hunger, promoting gender equality, enhancing good health and sustainable ecosystems and mitigating climate change. The study recommends the promotion of cleaner cooking stoves, particularly gasifiers, among households in rural areas while paying attention to user needs and preferences.
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| 17. |
- Gitau, James K., et al.
(författare)
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Use of Biochar-Producing Gasifier Cookstove Improves Energy Use Efficiency and Indoor Air Quality in Rural Households
- 2019
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Ingår i: Energies. - : MDPI. - 1996-1073. ; 12:22
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Tidskriftsartikel (refereegranskat)abstract
- Biomass fuels dominate the household energy mix in sub-Saharan Africa. Much of it is used inefficiently in poorly ventilated kitchens resulting in indoor air pollution and consumption of large amounts of wood fuel. Micro-gasification cookstoves can improve fuel use efficiency and reduce indoor air pollution while producing char as a by-product. This study monitored real-time concentrations of carbon monoxide (CO), carbon dioxide (CO2) and fine particulate matter (PM2.5), and amount of firewood used when households were cooking dinner. Twenty-five households used the gasifier cookstove to cook and five repeated the same test with three-stone open fire on a different date. With the gasifier, the average corresponding dinner time CO, CO2, and PM2.5 concentrations were reduced by 57%, 41%, and 79% respectively compared to three-stone open fire. The gasifier had average biomass-to-char conversion efficiency of 16.6%. If the produced char is used as fuel, households could save 32% of fuel compared to use of three-stone open fire and 18% when char is used as biochar, for instance. Adoption of the gasifier can help to reduce the need for firewood collection, hence reducing impacts on the environment while saving on the amount of time and money spent on cooking fuel.
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| 18. |
- Gitau, K. J., et al.
(författare)
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Factors influencing the adoption of biochar-producing gasifier cookstoves by households in rural Kenya
- 2019
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Ingår i: Energy for Sustainable Development. - : ELSEVIER. - 0973-0826 .- 2352-4669. ; 52, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- Fuel wood is the main source of cooking and heating energy in developing countries. However, it is combusted in inefficient cookstoves, leading to more fuel use and human health problems resulting from exposure to smoke. Thus new, efficient cooking systems that can address some of these problems are required. This study examined gasifier cookstove use in Kwale County, Kenya, and factors influencing adoption. Gasifier stoves were issued for free to 50 households, which were surveyed after 2-3 months of use. The results showed that the stove was used by 96% of the households at varying frequencies, 40% of them used it almost every day with 4% switching to only using the new stove. All the users appreciated it because it saved fuel, produced less smoke, and produced charcoal to use for either cooking or soil amendment. Compared with the traditional three-stone open fire, the gasifier stove was reported to be easier to clean (98% of respondents), easier to adjust the heat (88%), easier to handle (58%), caused less exposure to heat (96%) and was cleaner for pots and the kitchen (98%). Another reported benefit of the gasifier stove was that it needed no tending (i.e., adjusting wood and blowing to keep the flames burning). The gasifier stove was mainly used to cook foods that required a short cooking time and many preferred to use it to cook dinner. However, the households encountered some challenges with using the gasifier stoves. For example, fuel preparation, reloading, and lighting were reported as challenges by 42%, 77% and 19%, respectively, of the 83% of households who reported challenges. These challenges could be overcome by improving stove design and by devising innovative ways of cutting fuel into small pieces. 2019 The Authors. Published by Elsevier Inc. on behalf of International Energy Initiative.
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Henryson, K., et al.
(författare)
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Accounting for long-term soil fertility effects when assessing the climate impact of crop cultivation
- 2018
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Ingår i: Agricultural Systems. - : Elsevier. - 0308-521X .- 1873-2267. ; 164, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- Soil organic carbon (SOC) dynamics influence the climate impact of crop cultivation, both through affecting net carbon exchange between the soil and the atmosphere and through affecting soil fertility. Higher soil fertility can enhance yield, and consequently make more plant residues available for carbon sequestration in the soil. This feedback mechanism between SOC and yield is commonly not included when assessing the environmental impact of crop production using system analysis tools like life cycle assessment (LCA). Therefore, this study developed a modelling framework where the SOC-yield feedback mechanism is included in climate impact assessment of crop cultivation, and which could be applied in LCAs. The framework was constructed by combining a model for SOC dynamics, yield response to SOC changes in a Swedish long-term field experiment and climate impact assessment. The framework employs a dynamic approach, with a time-distributed emissions inventory and a time-dependent climate impact assessment model, complemented by the most common climate metric, global warming potential (GWP). A case study applying the framework to barley cultivation was performed to explore the quantitative effect of including the feedback mechanism on the calculated climate impact. The case study involved simulating a fertiliser-induced 10% yield increase during one year and assessing the climate impact over 100 years. The effect of solely including SOC dynamics without the yield response to SOC decreased climate impact per kg barley by about three-fold more than only accounting for the 10% temporary yield increase. When the feedback mechanism was included, the estimated climate impact decreased five-fold more than when SOC changes were not included. These results show that SOC changes affect the climate impact of cultivation, not only through affecting net CO2 exchanges between soil and atmosphere, as previously acknowledged by other studies, but also through changing the system performance. The quantitative results obtained in this study show that this could be an important aspect to include in order to avoid introducing systematic error when assessing the long-term climate impact of crop management changes that affect yield or SOC dynamics.
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| 23. |
- K Gitau, James, et al.
(författare)
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Cleaner cooking while producing biochar: factors affecting adoption of gasifier cookstoves in rural areas
- 2019
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Konferensbidrag (refereegranskat)abstract
- A majority of households in developing countries use biomass energy for cooking and heating due to its affordability and accessibility. However, unsustainable biomass use leads to deforestation, environmental degradation and climate change. The pollution from open burning of biomass is a major health concern especially for women and children as they spend a lot of time in the kitchen. Biochar-producing gasifier cookstoves offer an opportunity to address many of these problems, while also producing biochar, which can be used as a soil amendment. A study was carried out in order to investigate factors influencing the adoption of these cookstoves in three sites in Kenya (Kwale, Embu and Siaya). After an introductory training, 150 households received cookstoves and were asked to use them to produce biochar for upcoming field experiments. User experiences were collected throughsurveys after 2-3 months and about 2 years, and at workshops. The main benefits of the cookstove identified by the users were fuel saving with significant impacts on household economies, reduced smoke and production of biochar for either cooking or soil amendment. Challenges were related to lighting, a need to refill the fuel canister, fuel preparation and different suitability for different typesof meals and meal sizes. The gasifier use frequency and biochar production rates differed between the sites, which had different climate, socio-economic conditions and fuel accessibility. The results will be of relevance for inclusion of user participation in cookstove designing and performance assessment as well as for stakeholders involved in marketing. They can also give guidance on therelevance of gasifier cookstoves for production of biochar for use on farms.
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| 24. |
- Lee, Mi-Young, et al.
(författare)
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Role of cytochrome P450 2C8*3 (CYP2C8*3) in paclitaxel metabolism and paclitaxel-induced neurotoxicity
- 2015
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Ingår i: Pharmacogenomics (London). - : Future Medicine. - 1462-2416 .- 1744-8042. ; 16:9, s. 929-937
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The CYP2C8*3 allele has been suggested as a risk factor for paclitaxel-induced neuropathy but the data hitherto published are conflicting. Materials and methods: In total 435 patients were investigated with respect to maximum neuropathy grade and accumulated paclitaxel dose. The enzymatic properties of CYP2C8.3 variant were analyzed using heterologous mammalian HEK293 cell expression system. Results: No significant association between CYP2C8*3 allele and neuropathy was found, although a trend was observed. The paclitaxel and amodiaquine metabolism by CYP2C8.3 were found similar to CYP2C8.1, whereas CYP2C8.3 was more efficient in the metabolism of rosiglitazone. Conclusion: These results indicate a difference in substrate specificity between CYP2C8.1 and CYP2C8.3; however, the CYP2C8*3 allele has no major impact on paclitaxel metabolism in vitro or of paclitaxel-induced neuropathy in vivo. Original submitted on 6 February 2015; revision submitted on 9 April 2015
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| 25. |
- Mahmoud, Yahia, et al.
(författare)
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Biochar production and application in small-scale farming in Kenya : Yield increases and local perceptions
- 2019
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Konferensbidrag (refereegranskat)abstract
- Degradation of agricultural soils and forest resources are two pervasive challenges in rural landscapes of sub-Saharan Africa. Biochar-producing biomass gasification technologies attract evermore interest because these can empower small-scale farmers to produce energy and food more sustainably byimproving energy use efficiencies, lowering emissions and strengthening climate resilience. In order to assess the potential impacts and the feasibility of soil biochar amendments we are carrying out on-farm trials with 150 households in three agroecosystems in Kenya. A participatory approach was followed for testing uptake of gasifier cook stoves and effects of biochar use on crop production. The outcomes that will be presented include: (a) the degree of feasibility, (b) the effects on crop yields, (c) the general attitudes towards the idea of using the cookstoves to produce biochar, and (d) patterns of biomass fuel use. Effects of domestically produced biochar, at rates of 1-10 t DW ha-1, on the production of maize (Zea mays) and kale (Brassica oleracea) were compared with normal farming practices. At the site located in Kwale the yield increases of maize showed a strong positive correlation with biochar dose. In the first season, yields increased from 0.9 Mg ha-1 in the control plot to 4.4Mg ha-1 in average in the biochar-amended plots. At another site (Siaya), an average biochar dose of 2.8 Mg ha-1 lead to an increase in maize yields from 2.9 to 3.8 Mg ha-1 in average in the first season and from 1.7 to 2.5 Mg ha-1 in the second season after biochar addition. Findings from this action research indicate that producing and using biochar on small-scale farms offers suitable opportunities to close yield gaps across Kenya and in similar agro-ecological environments.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Ravnskov, U., et al.
(författare)
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Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review
- 2016
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue. Setting, participants and outcome measures We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals 60years from the general population. Results We identified 19 cohort studies including 30 cohorts with a total of 68094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found. Conclusions High LDL-C is inversely associated with mortality in most people over 60years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.
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| 31. |
- Ravnskov, U., et al.
(författare)
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LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature
- 2018
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Ingår i: Expert Review of Clinical Pharmacology. - : Informa UK Limited. - 1751-2433 .- 1751-2441. ; 11:10, s. 959-970
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit. Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This article delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis. Expert commentary: Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.
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| 32. |
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| 33. |
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| 34. |
- Scherer, K. R., et al.
(författare)
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The expression of emotion in the singing voice : Acoustic patterns in vocal performance
- 2017
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Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 142:4, s. 1805-1815
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Tidskriftsartikel (refereegranskat)abstract
- There has been little research on the acoustic correlates of emotional expression in the singing voice. In this study, two pertinent questions are addressed: How does a singer's emotional interpretation of a musical piece affect acoustic parameters in the sung vocalizations? Are these patterns specific enough to allow statistical discrimination of the intended expressive targets? Eight professional opera singers were asked to sing the musical scale upwards and downwards (using meaningless content) to express different emotions, as if on stage. The studio recordings were acoustically analyzed with a standard set of parameters. The results show robust vocal signatures for the emotions studied. Overall, there is a major contrast between sadness and tenderness on the one hand, and anger, joy, and pride on the other. This is based on low vs high levels on the components of loudness, vocal dynamics, high perturbation variation, and a tendency for high low-frequency energy. This pattern can be explained by the high power and arousal characteristics of the emotions with high levels on these components. A multiple discriminant analysis yields classification accuracy greatly exceeding chance level, confirming the reliability of the acoustic patterns.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Tan, Biyue, et al.
(författare)
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Evaluating the accuracy of genomic prediction of growth and wood traits in two Eucalyptus species and their F-1 hybrids
- 2017
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Ingår i: BMC Plant Biology. - : BioMed Central. - 1471-2229. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic prediction is a genomics assisted breeding methodology that can increase genetic gains by accelerating the breeding cycle and potentially improving the accuracy of breeding values. In this study, we use 41,304 informative SNPs genotyped in a Eucalyptus breeding population involving 90 E. grandis and 78 E. urophylla parents and their 949 F-1 hybrids to develop genomic prediction models for eight phenotypic traits-basic density and pulp yield, circumference at breast height and height and tree volume scored at age three and six years. We assessed the impact of different genomic prediction methods, the composition and size of the training and validation set and the number and genomic location of SNPs on the predictive ability (PA). Results: Heritabilities estimated using the realized genomic relationship matrix (GRM) were considerably higher than estimates based on the expected pedigree, mainly due to inconsistencies in the expected pedigree that were readily corrected by the GRM. Moreover, the GRM more precisely capture Mendelian sampling among related individuals, such that the genetic covariance was based on the true proportion of the genome shared between individuals. PA improved considerably when increasing the size of the training set and by enhancing relatedness to the validation set. Prediction models trained on pure species parents could not predict well in F-1 hybrids, indicating that model training has to be carried out in hybrid populations if one is to predict in hybrid selection candidates. The different genomic prediction methods provided similar results for all traits, therefore either GBLUP or rrBLUP represents better compromises between computational time and prediction efficiency. Only slight improvement was observed in PA when more than 5000 SNPs were used for all traits. Using SNPs in intergenic regions provided slightly better PA than using SNPs sampled exclusively in genic regions. Conclusions: The size and composition of the training set and number of SNPs used are the two most important factors for model prediction, compared to the statistical methods and the genomic location of SNPs. Furthermore, training the prediction model based on pure parental species only provide limited ability to predict traits in interspecific hybrids. Our results provide additional promising perspectives for the implementation of genomic prediction in Eucalyptus breeding programs by the selection of interspecific hybrids.
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| 39. |
- Tan, Biyue, 1986-
(författare)
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Genomic selection and genome-wide association studies to dissect quantitative traits in forest trees
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The convergence of quantitative genetics of complex traits with genomic technologies is quickly becoming an innovative approach to explore fundamental genetic questions and also have practical consequences for implementations in tree breeding. In this thesis, I used genomic selection and genome-wide association studies (GWAS) to dissect the genetic basis of quantitative traits, i.e. growth, phenology and wood property traits. I also assessed the importance of dominance and epistatic effects in hybrid Eucalyptus. Both dominance and epistasis are important in hybrids, as they are the likely contributing to the genetic basis of heterosis. To successfully implement genomic selection models, several important factors have to be considered. I found that for a good model establishment, both the size and composition of the training population, as well as the number of SNPs to be important considered. Based on the optimal models, additive, dominance and epistasis genetic effects of growth and wood traits have been estimated to evaluate genetic parameters and how these influence the prediction accuracy, which can be used in selecting elite breeding individuals or clones. I also addressed the advantage of genotyping-based analyses by showing that we could accurately correct pedigree information errors. More importantly, genotyping-based analyses capture both Mendelian segregation variation within full-sib families and cryptic genetic links through unknown common ancestors, which are not available from traditional pedigree data. GWAS were used to analyse growth and phenology related traits. Using a single-trait GWAS method, we identified a region strongly associated with the timing of bud set in Populus tremula, a trait with high heritability. For the growth related traits, we found that a multi-traits GWAS approach was more powerful than single-trait analyses as it identified more associated SNPs in hybrid Eucalyptus. Moreover, many more novel associated SNPs were identified from considering over-dominance effects in the GWAS analyses. After annotating the associated SNPs I show that these functional candidate genes were related to growth and responding to abiotic and biotic stress. In summary, the results of genomic selection and GWAS provided a deeper understanding of the genetic backgrounds of quantitative traits in forest trees.
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| 40. |
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| 41. |
- van der Wouden, C. H., et al.
(författare)
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Implementing Pharmacogenomics in Europe : Design and Implementation Strategy of the Ubiquitous Pharmacogenomics Consortium
- 2017
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 101:3, s. 341-358
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Tidskriftsartikel (refereegranskat)abstract
- Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. Opportunely, several implementation studies and programs have been initiated over recent years. This article presents an overview of these studies and identifies current research gaps. Importantly, one such gap is the undetermined collective clinical utility of implementing a panel of PGx-markers into routine care, because the evidence base is currently limited to specific, individual drug-gene pairs. The Ubiquitous Pharmacogenomics (U-PGx) Consortium, which has been funded by the European Commission's Horizon-2020 program, aims to address this unmet need. In a prospective, block-randomized, controlled clinical study (PREemptive Pharmacogenomic testing for prevention of Adverse drug REactions [PREPARE]), pre-emptive genotyping of a panel of clinically relevant PGx-markers, for which guidelines are available, will be implemented across healthcare institutions in seven European countries. The impact on patient outcomes and cost-effectiveness will be investigated. The program is unique in its multicenter, multigene, multidrug, multi-ethnic, and multi-healthcare system approach.
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| 42. |
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