| 1. |
|
|
| 2. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Figlioli, G, et al.
(författare)
-
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
-
Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Olalde, I., et al.
(författare)
-
The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
-
Tidskriftsartikel (refereegranskat)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
|
|
| 8. |
|
|
| 9. |
- Nicolas, Aude, et al.
(författare)
-
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
-
Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
-
Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Wilder, F. D., et al.
(författare)
-
Observations of large-amplitude, parallel, electrostatic waves associated with the Kelvin-Helmholtz instability by the magnetospheric multiscale mission
- 2016
-
Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:17, s. 8859-8866
-
Tidskriftsartikel (refereegranskat)abstract
- On 8 September 2015, the four Magnetospheric Multiscale spacecraft encountered a Kelvin-Helmholtz unstable magnetopause near the dusk flank. The spacecraft observed periodic compressed current sheets, between which the plasma was turbulent. We present observations of large-amplitude (up to 100 mV/m) oscillations in the electric field. Because these oscillations are purely parallel to the background magnetic field, electrostatic, and below the ion plasma frequency, they are likely to be ion acoustic-like waves. These waves are observed in a turbulent plasma where multiple particle populations are intermittently mixed, including cold electrons with energies less than 10 eV. Stability analysis suggests a cold electron component is necessary for wave growth.
|
|
| 13. |
- Bowden, John A., et al.
(författare)
-
Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
- 2017
-
Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
-
Tidskriftsartikel (refereegranskat)abstract
- As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra-and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium.jlr While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
|
|
| 14. |
- Tremblay, Mark S, et al.
(författare)
-
Sedentary Behavior Research Network (SBRN) - Terminology Consensus Project process and outcome.
- 2017
-
Ingår i: The international journal of behavioral nutrition and physical activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The prominence of sedentary behavior research in health science has grown rapidly. With this growth there is increasing urgency for clear, common and accepted terminology and definitions. Such standardization is difficult to achieve, especially across multi-disciplinary researchers, practitioners, and industries. The Sedentary Behavior Research Network (SBRN) undertook a Terminology Consensus Project to address this need.First, a literature review was completed to identify key terms in sedentary behavior research. These key terms were then reviewed and modified by a Steering Committee formed by SBRN. Next, SBRN members were invited to contribute to this project and interested participants reviewed and provided feedback on the proposed list of terms and draft definitions through an online survey. Finally, a conceptual model and consensus definitions (including caveats and examples for all age groups and functional abilities) were finalized based on the feedback received from the 87 SBRN member participants who responded to the original invitation and survey.Consensus definitions for the terms physical inactivity, stationary behavior, sedentary behavior, standing, screen time, non-screen-based sedentary time, sitting, reclining, lying, sedentary behavior pattern, as well as how the terms bouts, breaks, and interruptions should be used in this context are provided.It is hoped that the definitions resulting from this comprehensive, transparent, and broad-based participatory process will result in standardized terminology that is widely supported and adopted, thereby advancing future research, interventions, policies, and practices related to sedentary behaviors.
|
|
| 15. |
- Desnick, Robert J., et al.
(författare)
-
Roscoe Owen Brady, MD : Remembrances of co-investigators and colleagues
- 2017
-
Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 120:1-2, s. 1-7
-
Tidskriftsartikel (refereegranskat)abstract
- To celebrate the research visions and accomplishments of the late Roscoe O. Brady (1923-2016), remembrance commentaries were requested from several of his postdoctoral research fellows and colleagues. These commentaries not only reflect on the accomplishments of Dr. Brady, but they also share some of the backstories and experiences working in the Brady laboratory. They provide insights and perspectives on Brady's research activities, and especially on his efforts to develop an effective treatment for patients with Type 1 Gaucher disease. These remembrances illuminate Brady's efforts to implement the latest scientific advances with an outstanding team of young co-investigators to develop and demonstrate the safety and effectiveness of the first enzyme replacement therapy for a lysosomal storage disease. Brady's pursuit and persistence in accomplishing his research objectives provide insights into this remarkably successful physician scientist who paved the way for the development of treatments for patients with other lysosomal storage diseases.
|
|
| 16. |
|
|
| 17. |
- Paterson, R. W., et al.
(författare)
-
SILK studies — capturing the turnover of proteins linked to neurodegenerative diseases
- 2019
-
Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 15:7, s. 419-427
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer disease (AD) is one of several neurodegenerative diseases characterized by dysregulation, misfolding and accumulation of specific proteins in the CNS. The stable isotope labelling kinetics (SILK) technique is based on generating amino acids labelled with naturally occurring stable (that is, nonradioactive) isotopes of carbon and/or nitrogen. These labelled amino acids can then be incorporated into proteins, enabling rates of protein production and clearance to be determined in vivo and in vitro without the use of radioactive or chemical labels. Over the past decade, SILK studies have been used to determine the turnover of key pathogenic proteins amyloid-β (Aβ), tau and superoxide dismutase 1 (SOD1) in the cerebrospinal fluid of healthy individuals, patients with AD and those with other neurodegenerative diseases. These studies led to the identification of several factors that alter the production and/or clearance of these proteins, including age, sleep and disease-causing genetic mutations. SILK studies have also been used to measure Aβ turnover in blood and within brain tissue. SILK studies offer the potential to elucidate the mechanisms underlying various neurodegenerative disease mechanisms, including neuroinflammation and synaptic dysfunction, and to demonstrate target engagement of novel disease-modifying therapies. © 2019, Springer Nature Limited.
|
|
| 18. |
- Szlachetko, Jakub, et al.
(författare)
-
Establishing nonlinearity thresholds with ultraintense X-ray pulses
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray techniques have evolved over decades to become highly refined tools for a broad range of investigations. Importantly, these approaches rely on X-ray measurements that depend linearly on the number of incident X-ray photons. The advent of X-ray free electron lasers (XFELs) is opening the ability to reach extremely high photon numbers within ultrashort X-ray pulse durations and is leading to a paradigm shift in our ability to explore nonlinear X-ray signals. However, the enormous increase in X-ray peak power is a double-edged sword with new and exciting methods being developed but at the same time well-established techniques proving unreliable. Consequently, accurate knowledge about the threshold for nonlinear X-ray signals is essential. Herein we report an X-ray spectroscopic study that reveals important details on the thresholds for nonlinear X-ray interactions. By varying both the incident X-ray intensity and photon energy, we establish the regimes at which the simplest nonlinear process, two-photon X-ray absorption (TPA), can be observed. From these measurements we can extract the probability of this process as a function of photon energy and confirm both the nature and sub-femtosecond lifetime of the virtual intermediate electronic state.
|
|
| 19. |
- Wallace, SJ, et al.
(författare)
-
A core outcome set for aphasia treatment research: The ROMA consensus statement
- 2019
-
Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:2, s. 180-185
-
Tidskriftsartikel (refereegranskat)abstract
- A core outcome set (COS; an agreed, minimum set of outcomes) was needed to address the heterogeneous measurement of outcomes in aphasia treatment research and to facilitate the production of transparent, meaningful, and efficient outcome data. Objective The Research Outcome Measurement in Aphasia (ROMA) consensus statement provides evidence-based recommendations for the measurement of outcomes for adults with post-stroke aphasia within phases I–IV aphasia treatment studies. Methods This statement was informed by a four-year program of research, which comprised investigation of stakeholder-important outcomes using consensus processes, a scoping review of aphasia outcome measurement instruments, and an international consensus meeting. This paper provides an overview of this process and presents the results and recommendations arising from the international consensus meeting. Results Five essential outcome constructs were identified: Language, communication, patient-reported satisfaction with treatment and impact of treatment, emotional wellbeing, and quality of life. Consensus was reached for the following measurement instruments: Language: The Western Aphasia Battery Revised (WAB-R) (74% consensus); emotional wellbeing: General Health Questionnaire (GHQ)-12 (83% consensus); quality of life: Stroke and Aphasia Quality of Life Scale (SAQOL-39) (96% consensus). Consensus was unable to be reached for measures of communication (where multiple measures exist) or patient-reported satisfaction with treatment or impact of treatment (where no measures exist). Discussion Harmonization of the ROMA COS with other core outcome initiatives in stroke rehabilitation is discussed. Ongoing research and consensus processes are outlined. Conclusion The WAB-R, GHQ-12, and SAQOL-39 are recommended to be routinely included within phases I–IV aphasia treatment studies. This consensus statement has been endorsed by the Collaboration of Aphasia Trialists, the British Aphasiology Society, the German Society for Aphasia Research and Therapy, and the Royal College of Speech Language Therapists.
|
|
| 20. |
- Bellm, Eric C., et al.
(författare)
-
The Zwicky Transient Facility : System Overview, Performance, and First Results
- 2019
-
Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
-
Tidskriftsartikel (refereegranskat)abstract
- The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
|
|
| 21. |
- Coughlin, Michael W., et al.
(författare)
-
2900 Square Degree Search for the Optical Counterpart of Short Gamma-Ray Burst GRB 180523B with the Zwicky Transient Facility
- 2019
-
Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:998
-
Tidskriftsartikel (refereegranskat)abstract
- There is significant interest in the models for production of short gamma-ray bursts (GRBs). Until now, the number of known short GRBs with multi-wavelength afterglows has been small. While the Fermi GRB Monitor detects many GRBs relative to the Neil Gehrels Swift Observatory, the large localization regions makes the search for counterparts difficult. With the Zwicky Transient Facility (ZTF) recently achieving first light, it is now fruitful to use its combination of depth (m(AB) similar to 20.6), field of view (approximate to 47 square degrees), and survey cadence (every similar to 3 days) to perform Target of Opportunity observations. We demonstrate this capability on GRB 180523B, which was recently announced by the Fermi GRB Monitor as a short GRB. ZTF imaged approximate to 2900 square degrees of the localization region, resulting in the coverage of 61.6% of the enclosed probability over two nights to a depth of m(AB) similar to 20.5. We characterized 14 previously unidentified transients, and none were found to be consistent with a short GRB counterpart. This search with the ZTF shows it is an efficient camera for searching for coarsely localized short GRB and gravitational-wave counterparts, allowing for a sensitive search with minimal interruption to its nominal cadence.
|
|
| 22. |
- Frederick, Sara, et al.
(författare)
-
A New Class of Changing-look LINERs
- 2019
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 883:1
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of six active galactic nuclei (AGNs) caught turning on during the first nine months of the Zwicky Transient Facility (ZTF) survey. The host galaxies were classified as low-ionization nuclear emissionline region galaxies (LINERs) by weak narrow forbidden line emission in their archival SDSS spectra, and detected by ZTF as nuclear transients. In five of the cases, we found via follow-up spectroscopy that they had transformed into broad-line AGNs, reminiscent of the changing-look LINER iPTF16bco. In one case, ZTF18aajupnt/ AT2018dyk, follow-up Hubble Space Telescope ultraviolet and ground-based optical spectra revealed the transformation into a narrow-line Seyfert 1 with strong [Fe VII, X, XIV] and He II lambda 4686 coronal lines. Swift monitoring observations of this source reveal bright UV emission that tracks the optical flare, accompanied by a luminous soft X-ray flare that peaks similar to 60 days later. Spitzer follow-up observations also detect a luminous midinfrared flare, implying a large covering fraction of dust. Archival light curves of the entire sample from CRTS, ATLAS, and ASAS-SN constrain the onset of the optical nuclear flaring from a prolonged quiescent state. Here we present the systematic selection and follow-up of this new class of changing-look LINERs, compare their properties to previously reported changing-look Seyfert galaxies, and conclude that they are a unique class of transients well-suited to test the uncertain physical processes associated with the LINER accretion state.
|
|
| 23. |
- Ho, Anna Y. Q., et al.
(författare)
-
Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova : Pre-explosion Emission and a Rapidly Rising Luminous Transient
- 2019
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 887:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 +/- 0.1 mag hr(-1)) and luminous (M-g,M- peak = -20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (L-bol greater than or similar to 3 x 10(44) erg s(-1)), the short rise time (t(rise) = 3 days in g band), and the blue colors at peak (g-r similar to -0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T-eff greater than or similar to 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M-g similar to M-r approximate to -14 mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E-gamma,E- iso < 4.9 x 10(48) erg, a limit on X-ray emission L-X < 10(40) erg s(-1), and a limit on radio emission nu L-v less than or similar to 10(37) erg s(-1). Taken together, we find that the early (< 10 days) data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M-circle dot) at large radii (3 x 10(14) cm) that was ejected in eruptive pre-explosion mass-loss episodes. The late-time (> 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56.
|
|
| 24. |
- Löwemark, Ludvig, et al.
(författare)
-
Practical guidelines and recent advances in the Itrax XRF core-scanning procedure
- 2019
-
Ingår i: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 514, s. 16-29
-
Tidskriftsartikel (refereegranskat)abstract
- XRF core scanning has evolved to become a standard analytical technique for the rapid assessment of elemental, density and textural variations in a wide range of sediments and other materials, with applications ranging from palaeoceanography, paleoclimatology, geology, and environmental forensics to environmental protection. In general, scanning provides rapid, non-destructive acquisition of elemental and textural variations at sub-millimetre resolution for a wide range of materials. Numerous procedural adaptations have been developed for the growing number of applications, such as analyses of unconsolidated, water-rich sediments, powdered soil samples, or resin bags. Here, practical expertise and guidance from the Itrax community, gained over 15 years, is presented that should provide insights for new and experienced users.
|
|
| 25. |
- Patterson, Christopher C., et al.
(författare)
-
Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25year period 1989-2013 : a multicentre prospective registration study
- 2019
-
Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 62:3, s. 408-417
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6years.Methods: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends.Results: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012.Conclusions/interpretation: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4year periodicity, no plausible explanation for this can be given.
|
|
| 26. |
- Patterson, Cc, et al.
(författare)
-
Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008 : little short-term influence of sunshine hours or average temperature
- 2015
-
Ingår i: Pediatric Diabetes. - : Wiley-Blackwell. - 1399-543X .- 1399-5448. ; 16:8, s. 573-580
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation.OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008.METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends.RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ±11 to ±38% (median ±17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours.CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.
|
|
| 27. |
|
|
| 28. |
- Bowen, Kathryn J., et al.
(författare)
-
Implementing the Sustainable Development Goals : towards addressing three key governance challenges-collective action, trade-offs, and accountability
- 2017
-
Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 26-27, s. 90-96
-
Forskningsöversikt (refereegranskat)abstract
- Realising the aspirations of the Sustainable Development Goals (SDGs) to reduce inequality, limit ecological damage, and secure resilient livelihoods is a grand challenge for sustainability science, civil society and government. We identify three key governance challenges that are central for implementing the SDGs: (i) cultivating collective action by creating inclusive decision spaces for stakeholder interaction across multiple sectors and scales; (ii) making difficult trade-offs, focusing on equity, justice and fairness; and (iii) ensuring mechanisms exist to hold societal actors to account regarding decision-making, investment, action, and outcomes. The paper explains each of these three governance challenges, identifying possible avenues for addressing them, and highlights the importance of interlinkages between the three challenges.
|
|
| 29. |
|
|
| 30. |
- Chaboyer, B., et al.
(författare)
-
Testing Metal-poor Stellar Models and Isochrones with HST Parallaxes of Metal-poor Stars
- 2017
-
Ingår i: Astrophysical Journal. - : IOP PUBLISHING LTD. - 0004-637X .- 1538-4357. ; 835:2
-
Tidskriftsartikel (refereegranskat)abstract
- Hubble Space Telescope (HST) fine guidance sensor observations were used to obtain parallaxes of eight metal-poor ([Fe/H] < -1.4) stars. The parallaxes of these stars determined by the new Hipparcos reduction average 17% accuracy, in contrast to our new HST parallaxes, which average 1% accuracy and have errors on the individual parallaxes ranging from 85 to 144 mu as. These parallax data were combined with HST Advanced Camera for Surveys photometry in the F606W and F814W filters to obtain the absolute magnitudes of the stars with an accuracy of 0.02-0.03 mag. Six of these stars are on the main sequence (MS) (with -2.7 < [Fe/H] < -1.8) and are suitable for testing metal-poor stellar evolution models and determining the distances to metal-poor globular clusters (GCs). Using the abundances obtained by O'Malley et al., we find that standard stellar models using the VandenBerg & Clem color transformation do a reasonable job of matching five of the MS stars, with HD 54639 ([Fe/H] = -2.5) being anomalous in its location in the color-magnitude diagram. Stellar models and isochrones were generated using a Monte Carlo analysis to take into account uncertainties in the models. Isochrones that fit the parallax stars were used to determine the distances and ages of nine GCs (with -2.4 <= [Fe/H] <= -1.9). Averaging together the age of all nine clusters led to an absolute age of the oldest, most metal-poor GCs of 12.7 +/- 1.0 Gyr, where the quoted uncertainty takes into account the known uncertainties in the stellar models and isochrones, along with the uncertainty in the distance and reddening of the clusters.
|
|
| 31. |
- Jones, Robert P., et al.
(författare)
-
Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
-
Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
|
|
| 32. |
- Macri, Erin M., et al.
(författare)
-
Does patellar alignment or trochlear morphology predict worsening of patellofemoral disease within the first 5 years after anterior cruciate ligament reconstruction?
- 2019
-
Ingår i: European Journal of Radiology. - : ELSEVIER IRELAND LTD. - 0720-048X .- 1872-7727. ; 113, s. 32-38
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: We described patellofemoral alignment and trochlear morphology at one and five years after anterior cruciate ligament reconstruction (ACLR), and evaluated the associations between alignment and trochlear morphology (at one year) and worsening patellofemoral osteoarthritis (OA) features by five years. We also evaluated the associations between alignment and morphology to self-reported pain and function (Knee injury and Osteoarthritis Outcome Score, KOOS) at five years. Materials and methods: In this longitudinal observational study, we followed 73 participants (mean age 29[9] years, 40% women) from one-to five-years after ACLR. Using MRI, we measured alignment and morphology, and scored cartilage and bone marrow lesions at both time points. We used mixed effects and linear regression models to achieve our stated aims. Results: Greater lateral patella displacement increased risk of cartilage worsening (Odds Ratio [95% CI]: 1.09 [1.01, 1.16]); while less lateral tilt (0.91 [0.83, 0.99]) and greater trochlear angle (0.88 [0.77, 1.00]) were protective. Greater medial trochlear inclination increased risk of bone marrow lesion worsening (1.12 [1.04, 1.19]); while greater trochlear angle was protective (0.80 [0.67, 0.96]). Greater lateral displacement was associated with worse self-reported KOOS sport and recreation scores (beta [95% CI]: -11.0 [-20.9, -1.2]) and quality of life scores (-10.5 [-20.4, -0.7]). Conclusions: Lateral displacement, lateral tilt, and morphology at 1 year post-ACLR altered the risk of worsening patellofemoral OA features four years later. Lateral displacement was the only measure associated with worse self-reported symptoms at five years. These findings may lead to novel treatment strategies for secondary prevention after ACLR.
|
|
| 33. |
- Marques, Tatiana M., 1980-, et al.
(författare)
-
Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model
- 2016
-
Ingår i: Beneficial Microbes. - Wageningen, Netherlands : Wageningen Academic Publishers. - 1876-2883 .- 1876-2891. ; 7:3, s. 409-420
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~10(9)microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~10(9) L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.
|
|
| 34. |
- Nardi, Bonnie, et al.
(författare)
-
Computing within Limits
- 2018
-
Ingår i: Communications of the ACM. - : Association for Computing Machinery (ACM). - 0001-0782 .- 1557-7317. ; 61:10, s. 86-93
-
Forskningsöversikt (refereegranskat)abstract
- COMPUTING RESEARCHERS AND practitioners are often seen as inventing the future. As such, we are implicitly also in the business of predicting the future. We plot trajectories for the future in the problems we select, the assumptions we make about technology and societal trends, and the ways we evaluate research. However, a great deal of computing research focuses on one particular type of future, one very much like the present, only more so. This vision of the future assumes that current trajectories of ever-increasing production and consumption will continue. This focus is perhaps not surprising, since computing machinery as we know it has existed for only 80 years, in a period of remarkable industrial and technological expansion. But humanity is rapidly approaching, or has already exceeded, a variety of planet-scale limits related to the global climate system, fossil fuels, raw materials, and biocapacity. (28,32,38) It is understandable that in computing we would not focus on limits. While planetary limits are obvious in areas such as extractive capacity in mining or fishing,
|
|
| 35. |
|
|
| 36. |
- Patterson, James J., et al.
(författare)
-
Political feasibility of 1.5 degrees C societal transformations : the role of social justice
- 2018
-
Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 31, s. 1-9
-
Forskningsöversikt (refereegranskat)abstract
- Constraining global climate change to 1.5 degrees C is commonly understood to require urgent and deep societal transformations. Yet such transformations are not always viewed as politically feasible; finding ways to enhance the political feasibility of ambitious decarbonization trajectories is needed. This paper reviews the role of social justice as an organizing principle for politically feasible 1.5 degrees C transformations. A social justice lens usefully focuses attention on first, protecting vulnerable people from climate change impacts, second, protecting people from disruptions of transformation, and finally, enhancing the process of envisioning and implementing an equitable post-carbon society. However, justice-focused arguments could also have unintended consequences, such as being deployed against climate action. Hence proactively engaging with social justice is critical in navigating 1.5 degrees C societal transformations.
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
