| 1. |
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| 2. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 3. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 4. |
- Thompson, B.A., et al.
(författare)
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
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Tidskriftsartikel (refereegranskat)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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| 5. |
- Lagrange, A. -M., et al.
(författare)
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Post-conjunction detection of beta Pictoris b with VLT/SPHERE
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 621
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Tidskriftsartikel (refereegranskat)abstract
- Context. With an orbital distance comparable to that of Saturn in the solar system, beta Pictoris b is the closest (semi-major axis similar or equal to 9 au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to beta Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters.Aims. We aimed at further constraining beta Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit.Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta beta Pictoris b since first light of the instrument in 2014.Results. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6 au) and prevented further detection. We redetected beta Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30 degrees in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 +/- 0.5 au (1 sigma), it definitely excludes previously reported possible long orbital periods, and excludes beta Pictoris b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.
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| 6. |
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| 7. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 8. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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| 9. |
- Anderson, J. P., et al.
(författare)
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A nearby super-luminous supernova with a long pre-maximum plateau and strong C (II) features
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
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Tidskriftsartikel (refereegranskat)abstract
- Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable.Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed.Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H( II )region spectra to constrain the host environment.Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C- II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C (II) lines. ASASSN-18km/SN 2018bsz displays along, slowly rising, red plateau of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of -19.8 mag (r), a mass of M-* = 1.5(-0.33)(+0.08) x 10(9) M-circle dot, and a star formation rate of =0.50(-0.19)(+2.22) M-circle dot yr(-1). A nearby H (II) region has an oxygen abundance (O3N2) of 8.31 +/- 0.01 dex.
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| 10. |
- Beral, V, et al.
(författare)
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Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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| 11. |
- Astuto, L. M., et al.
(författare)
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CDH23 mutation and phenotype heterogeneity : a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness
- 2002
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:2, s. 262-275
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.
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| 12. |
- Choularton, T. W., et al.
(författare)
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The Great Dun Fell Cloud Experiment 1993 : An overview
- 1997
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Ingår i: Atmospheric Environment. - 1352-2310. ; 31:16, s. 2393-2405
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Tidskriftsartikel (refereegranskat)abstract
- The 1993 Ground-based Cloud Experiment on Great Dun Fell used a wide range of measurements of trace gases, aerosol particles and cloud droplets at five sites to study their sources and sinks especially those in cloud. These measurements have been interpreted using a variety of models. The conclusions add to our knowledge of air pollution, acidification of the atmosphere and the ground, eutrophication and climate change. The experiment is designed to use the hill cap cloud as a flow-through reactor, and was conducted in varying levels of pollution typical of much of the rural temperate continental northern hemisphere in spring-time.
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| 13. |
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| 14. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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| 15. |
- Kern, R., et al.
(författare)
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Restoring the valence-shell stabilization in Nd 140
- 2020
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Ingår i: Physical Review C. - 2469-9985. ; 102:4
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Tidskriftsartikel (refereegranskat)abstract
- A projectile Coulomb-excitation experiment was performed at the radioactive-ion beam facility HIE-ISOLDE at CERN to obtain E2 and M1 transition matrix elements of Nd140 using the multistep Coulomb-excitation code gosia. The absolute M1 strengths, B(M1;22+→21+)=0.033(8)μN2,B(M1;23+→21+)=0.26-0.10+0.11μN2, and B(M1;24+→21+)<0.04μN2, identify the 23+ state as the main fragment of the one-quadrupole-phonon proton-neutron mixed-symmetry state of Nd140. The degree of F-spin mixing in Nd140 was quantified with the determination of the mixing matrix element VF-mix<7-7+13keV.
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| 16. |
- Lederman, J. S., et al.
(författare)
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International collaborative follow-up investigation of graduating high school students' understandings of the nature of scientific inquiry : is progress Being made?
- 2021
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Ingår i: International Journal of Science Education. - : Informa UK Limited. - 0950-0693 .- 1464-5289. ; 43:7, s. 991-1016
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Tidskriftsartikel (refereegranskat)abstract
- Understandings of the nature of scientific inquiry (NOSI), as opposed to engaging students in inquiry learning experiences, are included in science education reform documents around the world. However, little is known about what students have learned about NOSI during their pre-college school years. The purpose of this large-scale follow-up international project (i.e. 32 countries and regions, spanning six continents and including 3917 students for the high school sample) was to collect data on what exiting high school students have learned about NOSI. Additionally, the study investigated changes in 12th grade students' NOSI understandings compared to seventh grade (i.e. 20 countries and regions) students' understandings from a prior investigation [Lederman et al. (2019). An international collaborative investigation of beginning seventh grade students' understandings of scientific inquiry: Establishing a baseline. Journal of Research in Science Teaching, 56(4), 486-515. ]. This study documents and discusses graduating high school students' understandings and compares their understandings to seventh grade students' understandings of the same aspects of scientific inquiry for each country. It is important to note that collecting data from each of the 130+ countries globally was not feasible. Similarly, it was not possible to collect data from every region of each country. A concerted effort was made, however, to provide a relatively representative picture of each country and the world.
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| 17. |
- Guerova, G., et al.
(författare)
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National Status Reports
- 2020
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Ingår i: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 403-481
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In this section a summary of the national progress reports is given. GNSS4SWEC Management Committee (MC) members provided outline of the work conducted in their countries combining input from different partners involved. In the COST Action paticipated member from 32 COST countries, 1 Near Neighbour Country and 8 Intrantional Partners from Australia, Canada, Hong Kong and USA. The text reflects the state as of 1 January 2018.
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| 18. |
- Hasan, A, et al.
(författare)
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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia : Part 1: Update 2012 on the acute treatment of schizophrenia and the management of treatment resistance.
- 2012
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Ingår i: The World Journal of Biological Psychiatry. - : Informa UK Limited. - 1562-2975 .- 1814-1412. ; 13:5, s. 318-378
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Tidskriftsartikel (refereegranskat)abstract
- These updated guidelines are based on a first edition of the World Federation of Societies of Biological Psychiatry Guidelines for Biological Treatment of Schizophrenia published in 2005. For this 2012 revision, all available publications pertaining to the biological treatment of schizophrenia were reviewed systematically to allow for an evidence-based update. These guidelines provide evidence-based practice recommendations that are clinically and scientifically meaningful and these guidelines are intended to be used by all physicians diagnosing and treating people suffering from schizophrenia. Based on the first version of these guidelines, a systematic review of the MEDLINE/PUBMED database and the Cochrane Library, in addition to data extraction from national treatment guidelines, has been performed for this update. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into six levels of evidence (A–F; Bandelow et al. 2008b, World J Biol Psychiatry 9:242). This first part of the updated guidelines covers the general descriptions of antipsychotics and their side effects, the biological treatment of acute schizophrenia and the management of treatment-resistant schizophrenia.
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| 19. |
- Kimberling, W. J., et al.
(författare)
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Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11
- 1992
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Ingår i: Genomics. - 0888-7543 .- 1089-8646. ; 14:4, s. 988-994
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome is the most commonly recognized cause of combined visual and hearing loss in technologically developed countries. There are several different types and all are inherited in an autosomal recessive manner. There may be as many as five different genes responsible for at least two closely related phenotypes. The nature of the gene defects is unknown, and positional cloning strategies are being employed to identify the genes. This is a report of the localization of one gene for Usher syndrome type I to chromosome 11q, probably distal to marker D11S527. Another USH1 gene had been previously localized to chromosome 14q, and this second localization establishes the existence of a new and independent locus for Usher syndrome.
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| 20. |
- Moschner, K., et al.
(författare)
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Relativistic Coulomb excitation of 88Kr
- 2016
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Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 94:5
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the systematics of mixed-symmetry states in N=52 isotones, a relativistic Coulomb excitation experiment was performed during the PreSPEC campaign at the GSI Helmholtzzentrum für Schwerionenforschung to determine E2 transition strengths to 2+ states of the radioactive nucleus 88Kr. Absolute transition rates could be measured towards the first and third 2+ states. For the latter a mixed-symmetry character is suggested on the basis of the indication for a strong M1 transition to the fully symmetric 2+1 state, extending the knowledge of the N=52 isotones below Z=40. A comparison with the proton-neutron interacting boson model and shell-model predictions is made and supports the assignment.
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| 21. |
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| 22. |
- Hartoog, O. E., et al.
(författare)
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VLT/X-Shooter spectroscopy of the afterglow of the Swift GRB 130606A Chemical abundances and reionisation at z similar to 6
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- Context: The reionisation of the Universe is a process that is thought to have ended around z similar to 6, as inferred from spectroscopy of distant bright background sources, such as quasars (QSO) and gamma-ray burst (GRB) afterglows. Furthermore, spectroscopy of a GRB afterglow provides insight in its host galaxy, which is often too dim and distant to study otherwise.Aims: For the Swift GRB 130606A at z = 5.913 we have obtained a high S/N spectrum covering the full optical and near-IR wavelength region at intermediate spectral resolution with VLT/X-Shooter. We aim to measure the degree of ionisation of the intergalactic medium (IGM) between z = 5.02-5.84 and to study the chemical abundance pattern and dust content of its host galaxy.Methods: We estimated the UV continuum of the GRB afterglow using a power-law extrapolation, then measured the flux decrement due to absorption at Ly alpha,beta, and gamma wavelength regions. Furthermore, we fitted the shape of the red damping wing of Lya. The hydrogen and metal absorption lines formed in the host galaxy were fitted with Voigt profiles to obtain column densities. We investigated whether ionisation corrections needed to be applied.Results: Our measurements of the Ly alpha-forest optical depth are consistent with previous measurements of QSOs, but have a much smaller uncertainty. The analysis of the red damping wing yields a neutral fraction x(HI) < 0.05 (3 sigma). We obtain column density measurements of H, Al, Si, and Fe; for C, O, S and Ni we obtain limits. The ionisation due to the GRB is estimated to be negligible (corrections < 0.03 dex), but larger corrections may apply due to the pre-existing radiation field (up to 0.4 dex based on sub-DLA studies). Assuming that [Si/Fe] = +0.79 +/- 0.13 is due to dust depletion, the dust-to-metal ratio is similar to the Galactic value.Conclusions: Our measurements confirm that the Universe is already predominantly ionised over the redshift range probed in this work, but was slightly more neutral at z > 5.6. GRBs are useful probes of the ionisation state of the IGM in the early Universe, but because of internal scatter we need a larger statistical sample to draw robust conclusions. The high [Si/Fe] in the host can be due to dust depletion, a-element enhancement, or a combination of both. The very high value of [Al/Fe] = 2.40 +/- 0.78 might be due to a proton capture process and is probably connected to the stellar population history. We estimate the host metallicity to be -1.7 < [M/H] < -0.9 (2%-13% of solar).
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| 23. |
- Lindström, Ulf, et al.
(författare)
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Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration
- 2021
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1410-1418
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
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| 24. |
- Weston, M. D., et al.
(författare)
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Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIa (USH2A)
- 2000
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 66:4, s. 199-210
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type IIa (USHIIa) is an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa. This disorder maps to human chromosome 1q41. Recently, mutations in USHIIa patients were identified in a novel gene isolated from this chromosomal region. The USH2A gene encodes a protein with a predicted molecular weight of 171.5 kD and possesses laminin epidermal growth factor as well as fibronectin type III domains. These domains are observed in other protein components of the basal lamina and extracellular matrixes; they may also be observed in cell-adhesion molecules. The intron/exon organization of the gene whose protein we name "Usherin" was determined by direct sequencing of PCR products and cloned genomic DNA with cDNA-specific primers. The gene is encoded by 21 exons and spans a minimum of 105 kb. A mutation search of 57 independent USHIIa probands was performed with a combination of direct sequencing and heteroduplex analysis of PCR-amplified exons. Fifteen new mutations were found. Of 114 independent USH2A alleles, 58 harbored probable pathologic mutations. Ten cases of USHIIa were true homozygotes and 10 were compound heterozygotes; 18 heterozygotes with only one identifiable mutation were observed. Sixty-five percent (38/58) of cases had at least one mutation, and 51% (58/114) of the total number of possible mutations were identified. The allele 2299delG (previously reported as 2314delG) was the most frequent mutant allele observed (16%; 31/192). Three new missense mutations (C319Y, N346H, and C419F) were discovered; all were restricted to the previously unreported laminin domain VI region of Usherin. The possible significance of this domain, known to be necessary for laminin network assembly, is discussed in the context of domain VI mutations from other proteins.
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| 25. |
- Willerslev, E, et al.
(författare)
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Fifty thousand years of arctic vegetation change and megafauna diet
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 506:7486, s. 47-47
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Tidskriftsartikel (refereegranskat)abstract
- Although it is generally agreed that the Arctic flora is among the youngest and least diverse on Earth, the processes that shaped it are poorly understood. Here we present 50 thousand years (kyr) of Arctic vegetation history, derived from the first large-scale ancient DNA metabarcoding study of circumpolar plant diversity. For this interval we also explore nematode diversity as a proxy for modelling vegetation cover and soil quality, and diets of herbivorous megafaunal mammals, many of which became extinct around 10 kyr bp (before present). For much of the period investigated, Arctic vegetation consisted of dry steppe-tundra dominated by forbs (non-graminoid herbaceous vascular plants). During the Last Glacial Maximum (25–15 kyr bp), diversity declined markedly, although forbs remained dominant. Much changed after 10 kyr bp, with the appearance of moist tundra dominated by woody plants and graminoids. Our analyses indicate that both graminoids and forbs would have featured in megafaunal diets. As such, our findings question the predominance of a Late Quaternary graminoid-dominated Arctic mammoth steppe.
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| 26. |
- Bashkanov, M., et al.
(författare)
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Two-pion production in proton-proton collisions
- 2004
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Ingår i: Hadron Spectroscopy, Tenth International Conference on Hadron Spectrscopy, Aschaffenburg, Germany 31 August - 6 September 2003. - 0735401977 ; , s. 241-244
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 27. |
- Fynbo, J. P. U., et al.
(författare)
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The galaxy counterpart and environment of the dusty damped Lyman-α absorber at z = 2.226 towards Q 1218+0832
- 2023
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 679
-
Tidskriftsartikel (refereegranskat)abstract
- We report on further observations of the field of the quasar Q 1218+0832. Geier et al. (2019, A&A, 625, L9) presented the discovery of the quasar resulting from a search for quasars reddened and dimmed by dust in foreground damped Lyman-α absorbers (DLAs). The DLA is remarkable by having a very large H I column density close to 1022 cm−2. Its dust extinction curve shows the 2175 Å bump known from the Local Group. It also shows absorption from cold gas exemplified by C I and CO molecules. For this paper, we present narrow-band observations of the field of Q 1218+0832 and also use an archival Hubble Space Telescope (HST) image to search for the galaxy counterpart of the DLA. No emission from the DLA galaxy is found in either the narrow-band imaging or in the HST image. In the HST image, we could probe down to an impact parameter of 0.3 arcsec and a 3-σ detection limit of 26.8 mag per arcsec2. In the narrow-band image, we probed down to a 0 arcsec impact parameter and detected nothing down to a 3-σ detection limit of about 3 × 10−17 erg s−1 cm−2. We did detect a bright Lyman-α emitter 59 arcsec south of Q 1218+0832 with a flux of 3 × 10−16 erg s−1 cm−2. We conclude that the DLA galaxy must be located at a very small impact parameter (< 0.3 arcsec, 2.5 kpc) or it is optically dark. Also, the DLA galaxy most likely is part of a galaxy group.
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| 28. |
- Grahn, T., et al.
(författare)
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Collectivity and configuration mixing in Pb186,188 and Po194
- 2006
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:6
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Tidskriftsartikel (refereegranskat)abstract
- Lifetimes of prolate intruder states in Pb186 and oblate intruder states in Po194 have been determined by employing, for the first time, the recoil-decay tagging technique in recoil distance Doppler-shift lifetime measurements. In addition, lifetime measurements of prolate states in Pb188 up to the 8+ state were carried out using the recoil-gating method. The B(E2) values have been deduced from which deformation parameters |β2|=0.29(5) and |β2|=0.17(3) for the prolate and the oblate bands, respectively, have been extracted. The results also shed new light on the mixing between different shapes.
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| 29. |
- Jhingan, A., et al.
(författare)
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Hg 178 and asymmetric fission of neutron-deficient pre-actinides
- 2022
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Ingår i: Physical Review C. - 2469-9985. ; 106:4
-
Tidskriftsartikel (refereegranskat)abstract
- Fission at low excitation energy is an ideal playground to probe the impact of nuclear structure on nuclear dynamics. While the importance of structural effects in the nascent fragments is well established in the (trans-)actinide region, the observation of asymmetric fission in several neutron-deficient pre-actinides can be explained by various mechanisms. To deepen our insight into that puzzle, an innovative approach based on inverse kinematics and an enhanced version of the VAMOS++ heavy-ion spectrometer was implemented at the GANIL facility, Caen. Fission of Hg178 was induced by fusion of Xe124 and Fe54. The two fragments were detected in coincidence using VAMOS++ supplemented with a new SEcond Detection arm. For the first time in the pre-actinide region, access to the pre-neutron mass and total kinetic energy distributions, and the simultaneous isotopic identification of one the fission fragment, was achieved. The present work describes the experimental approach, and discusses the pre-neutron observables in the context of an extended asymmetric-fission island located southwest of Pb208. A comparison with different models is performed, demonstrating the importance of this new asymmetric-fission island for elaborating on driving effects in fission.
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| 30. |
- Kuschmierz, Paul, et al.
(författare)
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European first-year university students accept evolution but lack substantial knowledge about it : A standardized European cross-country assessment
- 2021
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Ingår i: Evolution. - : BioMed Central (BMC). - 1936-6426 .- 1936-6434. ; 14:1, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Investigations of evolution knowledge and acceptance and their relation are central to evolution education research. Ambiguous results in this field of study demonstrate a variety of measuring issues, for instance differently theorized constructs, or a lack of standardized methods, especially for cross-country comparisons. In particular, meaningful comparisons across European countries, with their varying cultural backgrounds and education systems, are rare, often include only few countries, and lack standardization. To address these deficits, we conducted a standardized European survey, on 9200 first-year university students in 26 European countries utilizing a validated, comprehensive questionnaire, the “Evolution Education Questionnaire”, to assess evolution acceptance and knowledge, as well as influencing factors on evolution acceptance. Results: We found that, despite European countries’ different cultural backgrounds and education systems, European first-year university students generally accept evolution. At the same time, they lack substantial knowledge about it, even if they are enrolled in a biology-related study program. Additionally, we developed a multilevel-model that determines religious faith as the main influencing factor in accepting evolution. According to our model, knowledge about evolution and interest in biological topics also increase acceptance of evolution, but to a much lesser extent than religious faith. The effect of age and sex, as well as the country’s affiliation, students’ denomination, and whether or not a student is enrolled in a biology-related university program, is negligible. Conclusions: Our findings indicate that, despite all their differences, most of the European education systems for upper secondary education lead to acceptance of evolution at least in university students. It appears that, at least in this sample, the differences in knowledge between countries reflect neither the extent to which school curricula cover evolutionary biology nor the percentage of biology-related students in the country samples. Future studies should investigate the role of different European school curricula, identify particularly problematic or underrepresented evolutionary concepts in biology education, and analyze the role of religious faith when teaching evolution.
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| 31. |
- Li, Constance H., et al.
(författare)
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Sex differences in oncogenic mutational processes
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Smith, R. J., et al.
(författare)
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Clinical diagnosis of the Usher syndromes : Usher Syndrome Consortium
- 1994
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Ingår i: American Journal of Medical Genetics. - : Wiley. - 0148-7299 .- 1096-8628. ; 50:1, s. 32-38
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Tidskriftsartikel (refereegranskat)abstract
- The Usher syndromes are genetically distinct disorders which share specific phenotypic characteristics. This paper describes a set of clinical criteria recommended for the diagnosis of Usher syndrome type I and Usher syndrome type II. These criteria have been adopted by the Usher Syndrome Consortium and are used in studies reported by members of this Consortium.
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| 36. |
- Yang, Y, et al.
(författare)
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Ring opening of benzo[a]pyrene in the germ-free rat is a novel pathway for formation of potentially genotoxic metabolites
- 2000
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 39:50, s. 15585-15591
-
Tidskriftsartikel (refereegranskat)abstract
- The metabolism of benzo[a]pyrene (BP) is known to lead to a large number of oxygenated compounds, some of which can bind covalently to DNA. We have studied the integrated metabolism of BP in vivo in germ-free rats given C-14-labeled BP. Urinary metabolites were separated into groups according to acidity using lipophilic ion exchangers. The groups were analyzed by mass spectrometry and were further fractionated by high-performance liquid chromatography. The fraction of urinary metabolites previously shown to contain N-acetylcysteine and glucuronic acid conjugates was found to contain derivatives of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid as major components. These compounds, which were identified by mass spectrometry and NMR, accounted for about 30% of the total metabolites in urine, demonstrating that, surprisingly, ring opening is a major pathway for metabolism of BP in the germ-free rat. The dicarboxylic acid may be excreted in urine as an ester glucuronide. By using the single cell gel electrophoresis or COMET assay, we were able to demonstrate that the anhydride of 7-oxo-benz[d]anthracene-3,4-dicarboxylic acid was an efficient inducer of DNA damage. Taken together, these results indicate that the novel ring opening metabolic pathway may provide alternative mechanisms for the toxicity of BP.
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| 37. |
- Andersson, Mike, et al.
(författare)
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Field Effect Based Gas Sensors, from Basic Mechanisms to the Latest Commercial Device Designs
- 2016
-
Ingår i: SENSORS AND ELECTRONIC INSTRUMENTATION ADVANCES (SEIA). - : INT FREQUENCY SENSOR ASSOC-IFSA. - 9788460899631 ; , s. 19-21
-
Konferensbidrag (refereegranskat)abstract
- This contribution treats the latest developments in the understanding of basic principles regarding device design, transduction mechanisms, gas-materials-interactions, and materials processing for the tailored design and fabrication of SiC FET gas sensor devices, mainly intended as products for the automotive sector.
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| 38. |
- Arnold, L.J., et al.
(författare)
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Paper II - Dirt, dates and DNA: OSL and radiocarbon chronologies of perennially-frozen sediments in Siberia, and their implications for sedimentary ancient DNA studies
- 2011
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Ingår i: Boreas. - : Wiley. - 1502-3885 .- 0300-9483. ; 40:3, s. 417-445
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedThe sedimentary ancient DNA (sedaDNA) technique offers a potentially invaluable means of investigating species evolution and extinction dynamics in high-latitude environments. An implicit assumption of the sedaDNA approach is that the extracted DNA is autochthonous with the host deposit and that it has not been physically transported from older source deposits or reworked within the sedimentary profile by postdepositional mixing. In this paper we investigate whether these fundamental conditions are upheld at seven perennially frozen wetland sites across the Taimyr Peninsula and coastal lowlands of north-central Siberia. Optically stimulated luminescence (OSL) and radiocarbon (C-14) dating are used to constrain the ages of both the inorganic and organic fractions of perennially frozen deposits from which sedaDNA of extinct and extant species have been recovered. OSL and C-14 age/depth profiles, as well as single-grain equivalent dose (De) distribution characteristics, are used to assess the stratigraphic integrity of these sedaDNA sequences by (i) identifying the presence of primary or reworked organic and inorganic material, and (ii) examining the types of depositional and postdepositional processes that have affected specific sedimentary facies. The results of this study demonstrate that even though DNA preservation and stratigraphic integrity are commonly superior in perennially frozen settings, this does not, in itself, guarantee the suitability of the sedaDNA approach. The combined OSL and C-14 chronologies reveal that certain perennially frozen sites may be poorly suited for sedaDNA analysis, and that careful site selection is paramount to ensuring the accuracy of any sedaDNA study - particularly for 'latest appearance date' estimates of extinct taxa.
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| 39. |
- Astuto, Lisa M., et al.
(författare)
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Genetic heterogeneity of Usher syndrome : analysis of 151 families with Usher type 1
- 2000
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 67:6, s. 1569-1574
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.
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| 40. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
- 2018
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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| 41. |
- Claassen, Yvette H. M., et al.
(författare)
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Treatment and survival of rectal cancer patients over the age of 80 years : a EURECCA international comparison
- 2018
-
Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 119:4, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+.METHODS: Patients of >= 80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients.RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO.CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.
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| 42. |
- Gülen, T, et al.
(författare)
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Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis.
- 2017
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 47:7, s. 909-917
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype.OBJECTIVE: To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM.METHODS: were measured, as well as ex vivo basophil histamine release.RESULTS: Mast cell mediators in the blood and urine were significantly higher in patients with SM than in HC and A controls. Responsiveness to local activation of skin MCs (by morphine) and airway MCs (by mannitol) was similar in SM and HC groups. Likewise, end-organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in SM patients.CONCLUSIONS AND CLINICAL RELEVANCE: Mast cells in the skin and airways of subjects with SM do not exhibit hyper-reactivity towards the MC-activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of MC mediators in SM are most likely due to increased MC numbers, rather than altered MC responsiveness. The underlying mechanisms could involve leakage of MC mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis.
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| 43. |
- Hartel, Bas P., et al.
(författare)
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A combination of two truncating mutations in USH2A causes more severe and progressive hearing impairment in Usher syndrome type IIa
- 2016
-
Ingår i: Hearing Research. - Amsterdam, Netherlands : Elsevier. - 0378-5955 .- 1878-5891. ; 339, s. 60-68
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Usher syndrome is an inherited disorder that is characterized by hearing impairment (HI), retinitis pigmentosa, and in some cases vestibular dysfunction. Usher syndrome type IIa is caused by mutations in USH2A. HI in these patients is highly heterogeneous and the present study evaluates the effects of different types of USH2A mutations on the audiometric phenotype. Data from two large centres of expertise on Usher Syndrome in the Netherlands and Sweden were combined in order to create a large combined sample of patients to identify possible genotype-phenotype correlations.Design: A retrospective study on HI in 110 patients (65 Dutch and 45 Swedish) genetically diagnosed with Usher syndrome type IIa. We used methods especially designed for characterizing and testing differences in audiological phenotype between patient subgroups. These methods included Age Related Typical Audiograms (ARTA) and a method to evaluate the difference in the degree of HI developed throughout life between subgroups.Results: Cross-sectional linear regression analysis of last-visit audiograms for the best hearing ear demonstrated a gradual decline of hearing over decades. The congenital level of HI was in the range of 16-33 dB at 0.25-0.5 kHz, and in the range of 51-60 dB at 1-8 kHz. The annual threshold deterioration was in the range of 0.4-0.5 dB/year at 0.25-2 kHz and in the range of 0.7-0.8 dB/year at 4-8 kHz. Patients with two truncating mutations, including homozygotes for the common c.2299delG mutation, developed significantly more severe HI throughout life than patients with one truncating mutation combined with one nontruncating mutation, and patients with two nontruncating mutations.Conclusions: The results have direct implications for patient counselling in terms of prognosis of hearing and may serve as baseline measures for future (genetic) therapeutic interventions.
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| 44. |
- Hellman, J., et al.
(författare)
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INFLUENCE OF BOLUS INJECTION DOSING FREQUENCY AND SMART PEN ENGAGEMENT ON GLYCAEMIC CONTROL IN PATIENTS WITH TYPE 1 DIABETES
- 2022
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 24:Suppl. 1, s. A64-A65
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Smart pen injection data can provide unique insight into routine diabetes treatment. NovoPen 6 users may consent to share their injection and continuous glucose monitoring (CGM) data anonymously for research purposes. Here, based on real-world data from people with type 1 diabetes (T1D), we explored the association between the number of daily bolus doses, and smart pen engagement, with time-in-range (TIR).Methods: We included adults with T1D in Sweden administering Fiasp with a NovoPen 6 device for days with bolus injections and CGM data (‡70% coverage). CGM parameters were used as glycaemic control measures. Smart pen engagement was characterised by the number of injection data uploads over the previous 14 days. A linear mixed model was used to determine relationship between TIR and covariates, adjusted for known confounders.Results: Overall, data from 224 patients were analysed. The number of daily bolus doses was significantly associated with improved TIR (p <0.0001). Patients with an average£3 daily bolus had <10% chance of reaching the target TIR >70% (Fig-ure). The number of uploads was also significantly associated with improved TIR (p <0.0001). Days where uploads were conducted daily over the previous 14 days had 5% greater TIR than days without any uploads during the previous 14 days.Conclusions: Daily bolus dose number and smart pen engagement are strong predictors of TIR. Most patients take too few bolus doses to reach treatment targets.
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| 45. |
- Hunt, B., et al.
(författare)
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Evaluating the long-term cost-effectiveness of introducing a smart insulin pen in standard-of-care treatment of type 1 diabetes in Sweden
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:Suppl. 1, s. S381-S381
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: The development and application of digital technologies to healthcare is a key component in meeting the increasing demand from patients for chronic disease management. Healthcare payers need evidence to support value-based decisions on new technologies. Smart insulin pens record the timing and dose of insulin, and data can integrate with continuous glucose monitoring (CGM) to improve diabetes self-management. The present analysis assessed the cost-effectiveness of introducing a smart insulin pen from a Swedish public healthcare payer perspective.Materials andmethods: The IQVIA CORE DiabetesModel was used to project clinical outcomes and healthcare costs (2018 Swedish krona [SEK]) over patients’ lifetimes in a Swedish type 1 diabetes (T1D) population. The model projected the development of complications, mortality, HbA1c, hypoglycaemia and insulin dosing to estimate cost effectiveness. Clinical model inputs were informed by an observational study of the introduction of an NFC-enabled smart insulin pen (NovoPen® 6) in 94 adults with T1D receiving basal-bolus insulin and using CGM. Smar tinsulin pen use (median follow up 7 months) was associated with an additional 1.89 h/day time in range (TIR 3.9-10.0 mmol/L [70-180 mg/dL]) compared with baseline. Change in TIR was converted to change in HbA1c using a published regression equation to allow long-term outcomes to be modelled based on published risk equations. Additional TIR with the smart insulin pen translated to a 0.62% (6.8 mmol/mol) HbA1c reduction and there were 33 fewer CGM-documented non-severe hypoglycaemic events/patient/year (≥15 min <3.0 mmol/L [54 mg/dL]) relative to baseline. Baseline characteristics were taken from the study cohort or, if unavailable, adults with T1D from the Swedish National Diabetes Register. Future costs and clinical benefits were discounted at 3% annually. Costs were converted to Euros (EUR) using a 0.091 SEK exchange rate.Results: Over patients’ lifetimes, smart insulin pen use was associated with improved mean discounted quality-adjusted life expectancy (1.13 quality-adjusted life years) and cost savings (EUR11,091) vs standard care. Improvements in quality-adjusted life expectancy were driven by a lower frequency and delayed onset of complications predicted with the smart insulin pen relative to standard care. Higher treatment costs (due to the higher bolus insulin dose) with the smart insulin pen were offset by the lower cost of complications compared with standard care (Fig).Conclusion: In this long-term modelling analysis, lifelong use of a smart insulin pen improved clinical outcomes at a lower cost relative to standard care in a T1D population, suggesting that the smart insulin pen represents an efficient use of Swedish public healthcare resources in this patient population.
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| 46. |
- Kimberling, William J., et al.
(författare)
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Gene mapping of Usher syndrome type IIa : localization of the gene to a 2.1-cM segment on chromosome 1q41
- 1995
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 56:1, s. 216-223
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor β2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.
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| 47. |
- Kimberling, W. J., et al.
(författare)
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Genetic studies of Usher syndrome
- 1991
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 630:1, s. 167-175
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Tidskriftsartikel (refereegranskat)
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| 48. |
- Kirsebom, O. S., et al.
(författare)
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Discovery of an Exceptionally Strong β -Decay Transition of F 20 and Implications for the Fate of Intermediate-Mass Stars
- 2019
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Ingår i: Physical Review Letters. - 0031-9007. ; 123:26
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Tidskriftsartikel (refereegranskat)abstract
- A significant fraction of stars between 7 and 11 solar masses are thought to become supernovae, but the explosion mechanism is unclear. The answer depends critically on the rate of electron capture on Ne20 in the degenerate oxygen-neon stellar core. However, because of the unknown strength of the transition between the ground states of Ne20 and F20, it has not previously been possible to fully constrain the rate. By measuring the transition, we establish that its strength is exceptionally large and that it enhances the capture rate by several orders of magnitude. This has a decisive impact on the evolution of the core, increasing the likelihood that the star is (partially) disrupted by a thermonuclear explosion rather than collapsing to form a neutron star. Importantly, our measurement resolves the last remaining nuclear physics uncertainty in the final evolution of degenerate oxygen-neon stellar cores, allowing future studies to address the critical role of convection, which at present is poorly understood
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| 49. |
- Kwan, Wanda, et al.
(författare)
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Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease.
- 2012
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Ingår i: The Journal of Neuroscience : the official journal of the Society for Neuroscience. - 1529-2401. ; 32:1, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is caused by an expanded polyglutamine tract in the protein huntingtin (htt). Although HD has historically been viewed as a brain-specific disease, htt is expressed ubiquitously, and recent studies indicate that mutant htt might cause changes to the immune system that could contribute to pathogenesis. Monocytes from HD patients and mouse models are hyperactive in response to stimulation, and increased levels of inflammatory cytokines and chemokines are found in pre-manifest patients that correlate with pathogenesis. In this study, wild-type (WT) bone marrow cells were transplanted into two lethally irradiated transgenic mouse models of HD that ubiquitously express full-length htt (YAC128 and BACHD mice). Bone marrow transplantation partially attenuated hypokinetic and motor deficits in HD mice. Increased levels of synapses in the cortex were found in HD mice that received bone marrow transplants. Importantly, serum levels of interleukin-6, interleukin-10, CXC chemokine ligand 1, and interferon-γ were significantly higher in HD than WT mice but were normalized in mice that received a bone marrow transplant. These results suggest that immune cell dysfunction might be an important modifier of pathogenesis in HD.
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