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| 4. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 5. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 6. |
- de Jong, S, et al.
(författare)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Tidskriftsartikel (refereegranskat)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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| 8. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 9. |
- Black, Melissa H., et al.
(författare)
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Perspectives of key stakeholders on employment of autistic adults across the United States, Australia and Sweden
- 2019
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Ingår i: Autism Research. - : John Wiley & Sons. - 1939-3792 .- 1939-3806. ; 12:11, s. 1648-1662
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Tidskriftsartikel (refereegranskat)abstract
- Despite efforts to improve employment outcomes for autistic individuals, internationally their employment rates remain low. There is a need to better understand the factors influencing successful employment for autistic adults in the labor market from the perspectives of multiple keystakeholders. This study represents the second in a series of papers conducted as part of an International Society for Autism Research policy brief aimed at improving employment outcomes for autistic individuals. A community consultation methodology using focus groups, forums, and interviews was applied with autistic individuals (n = 19), family members (n = 18), service providers (n = 21), employers (n = 11), researchers (n = 5), and advocacy group representatives (n = 5) in Australia, Sweden, and the United States, aiming to identify the factors perceived to determine gaining and maintaining employment for autistic individuals. Directed content analysis, guided by the International Classification of Functioning, Disability and Health (ICF), was conducted to investigate the key factors influencing employment outcomes for autistic individuals. Meaningful verbal concepts, or units of text with common themes, were also derived from the qualitative data and then linked and compared to the ICF Autism Spectrum Disorder (ASD) Core-sets. Across countries, activity and participation and environmental factor categories of the ICF were the most associated with employment outcomes. Results suggest that removal of environmental barriers and enhancing environmental facilitators may assist to remediate ASD-related difficulties in the workplace.LAY SUMMARY: This study sought to understand the perspectives of autistic individuals and key stakeholders on factors influencing if autistic adults get and keep jobs. Across Australia, Sweden, and the UnitedStates, focus groups and interviews were conducted to understand international perspectives on what helps and hinders getting and keeping a job for autistic individuals. The environment, including supports, relationships, attitudes, and services, were perceived to be the most important for workplace success. Intervention targeting barriers and facilitators in the workplace environment may support autistic adults to be successful in the labor market.
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| 11. |
- Bowden, John A., et al.
(författare)
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Harmonizing lipidomics : NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma
- 2017
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 58:12, s. 2275-2288
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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.
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| 12. |
- Chio, Iok In Christine, et al.
(författare)
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NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 166:4, s. 936-976
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is a deadly malignancy that lacks effective therapeutics. We previously reported that oncogenic Kras induced the redox master regulator Nfe2l2/Nrf2 to stimulate pancreatic and lung cancer initiation. Here, we show that NRF2 is necessary to maintain pancreatic cancer proliferation by regulating mRNA translation. Specifically, loss of NRF2 led to defects in autocrine epidermal growth factor receptor (EGFR) signaling and oxidation of specific translational regulatory proteins, resulting in impaired cap-dependent and cap-independent mRNA translation in pancreatic cancer cells. Combined targeting of the EGFR effector AKT and the glutathione antioxidant pathway mimicked Nrf2 ablation to potently inhibit pancreatic cancer ex vivo and in vivo, representing a promising synthetic lethal strategy for treating the disease.
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| 13. |
- Chow, Clara K., et al.
(författare)
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TEXT messages to improve MEDication adherence and Secondary prevention (TEXTMEDS) after acute coronary syndrome: a randomised clinical trial protocol
- 2018
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Ingår i: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important. Objective The TEXTMEDS (TEXT messages to improve MEDiGation adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS). Study design A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and proGess evaluations to assess acceptability, utility and Gost-effectiveness. Summary The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors. Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health District Human Research EthiGs Committee (HREC2012/12/4.1 (3648) AU RED HREC/13ANMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences.
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| 14. |
- Cuomo, Belinda M., et al.
(författare)
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Effectiveness of Sleep-Based Interventions for Children with Autism Spectrum Disorder : A Meta-Synthesis
- 2017
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Ingår i: Pharmacotherapy. - : John Wiley & Sons. - 0277-0008 .- 1875-9114. ; 37:5, s. 555-578
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Forskningsöversikt (refereegranskat)abstract
- Sleep problems are common in children with autism spectrum disorder (ASD). This meta-synthesis collated eight previously published systematic reviews examining the efficacy of sleep interventions in children with ASD in an attempt to present a clear analysis of trialed interventions. The collated reviews consider five major groups of sleep interventions for children with ASD: melatonin therapy, pharmacologic treatments other than melatonin, behavioral interventions, parent education/education programs, and alternative therapies (massage therapy, aromatherapy, and multivitamin and iron supplementation). These eight reviews were based on 38 original studies and address the efficacy of interventions across 17 sleep problem domains. The results of this meta-synthesis suggest that no single intervention is effective across all sleep problems in children with ASD. However, melatonin, behavioral interventions, and parent education/education program interventions appear the most effective at ameliorating multiple domains of sleep problems compared with other interventions. Due to the heterogeneous causative factors and presentations of disordered sleep, further research into the effectiveness of sleep interventions may target specific phenotypic subgroups rather than a broad analysis across the general ASD population. Similarly, future research needs to consider the efficacy of different polytherapeutic approaches in order to provide clinicians with evidence to inform best practice. In the meantime, this review supports clinicians' decision making for a majority of the identified sleep problems in the ASD population.
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| 15. |
- Gibbs, Kevin, et al.
(författare)
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Exploring the emergence of an 'Aquatic' Neolithic in the Russian Far East : organic residue analysis of early hunter-gatherer pottery from Sakhalin Island
- 2017
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Ingår i: Antiquity. - : Antiquity Publications. - 0003-598X .- 1745-1744. ; 91:360, s. 1484-1500
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Tidskriftsartikel (refereegranskat)abstract
- The Neolithic in north-east Asia is defined by the presence of ceramic containers, rather than agriculture, among hunter-gatherer communities. The role of pottery in such groups has, however, hitherto been unclear. This article presents the results of organic residue analysis of Neolithic pottery from Sakhalin Island in the Russian Far East. Results indicate that early pottery on Sakhalin was used for the processing of aquatic species, and that its adoption formed part of a wider Neolithic transition involving the reorientation of local lifeways towards the exploitation of marine resources.
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| 16. |
- Iderberg, Hanna, et al.
(författare)
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Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist.
- 2015
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Ingår i: Neuropharmacology. - : Elsevier BV. - 1873-7064 .- 0028-3908. ; 95, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- Metabotropic glutamate receptor 4 (mGlu4) negatively modulates GABA and glutamate release in the 'indirect pathway' of the basal ganglia, and has thus been proposed as a potential target to treat motor symptoms in Parkinson's disease. Here, we present an extensive comparison of the behavioural effects produced by the mGlu4 positive allosteric modulator (PAM), VU0364770, and the mGlu4 orthosteric agonist, LSP1-2111, in rats with unilateral 6-OHDA lesions. The compounds' activity was initially assessed in a test of haloperidol-induced catalepsy in intact rats, and effective doses were then evaluated in the hemiparkinsonian animal model. Neither of the two compounds modified the development of dyskinetic behaviours elicited by chronic treatment with full doses of l-DOPA. When given together with l-DOPA to rats with already established dyskinesias, neither VU0364770 nor LSP1-2111 modified the abnormal involuntary movement scores. VU0364770 potentiated, however, the motor stimulant effect of a subthreshold l-DOPA dose in certain behavioural tests, whereas LSP1-2111 lacked this ability. Taken together, these results indicate that a pharmacological stimulation of mGlu4 lacks intrinsic antidyskinetic activity, but may have DOPA-sparing activity in Parkinson's disease. For the latter indication, mGlu4 PAMs appear to provide a better option than orthosteric agonists.
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| 17. |
- Jefferson, Amanda, et al.
(författare)
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Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesWe developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians.MethodsAn initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions.ResultsAgreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended.ConclusionA clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity.
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| 18. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 19. |
- Liu, Xueping, et al.
(författare)
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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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| 20. |
- Lunetta, Kathryn L., et al.
(författare)
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Rare coding variants and X-linked loci associated with age at menarche
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
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| 21. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 24. |
- Rådholm, Karin, et al.
(författare)
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Older age is a strong predictor for poor outcome in intracerebral haemorrhage : the INTERACT2 study
- 2015
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 44:3, s. 422-427
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE:: Global ageing contributes greatly to the burden of stroke. We investigated the influence of age on the baseline profile and on outcomes in acute intracerebral haemorrhage (ICH) among participants of the INTERACT2 study.METHODS:: INTERACT2 was an international, randomised controlled trial in 2839 patients with spontaneous ICH within 6 h of onset and elevated systolic blood pressure (SBP; 150-220 mmHg) who were allocated to receive intensive (target SBP <140 mmHg within 1 h) or guideline-recommended (target SBP <180 mmHg) blood pressure lowering treatment. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Poor outcome was defined as death or major disability ('dependency', modified Rankin Scale scores 3-6) at 90 days. Health-related quality of life (HRQoL) was assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. Associations between age and outcomes were analysed in multivariable logistic regression models.RESULTS:: Stroke severity increased in categories of older age (P-trend 0.002). Stroke patients over 75 years old were four times more likely to die or be disabled at 90 days than those <52 years when other confounders were accounted for (odds ratio 4.36, 95% confidence interval 3.12-6.08). Older age was also associated with decreasing HRQoL, across mobility, self-care, usual activities and depression (all P-trend <0.001), and pain or discomfort (P-trend 0.022).CONCLUSION:: In the INTERACT2 cohort, older people had more severe ICH and worse outcomes (death, major disability and HRQoL). These data will help guide clinicians manage older people with haemorrhagic stroke. Clinical Trial Registration: http://www.clinicaltrials.gov (NCT00716079).
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| 25. |
- Sathyendranath, Shubha, et al.
(författare)
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An Ocean-Colour Time Series for Use in Climate Studies : The Experience of the Ocean-Colour Climate Change Initiative (OC-CCI)
- 2019
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Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 19:19
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Tidskriftsartikel (refereegranskat)abstract
- Ocean colour is recognised as an Essential Climate Variable (ECV) by the Global Climate Observing System (GCOS); and spectrally-resolved water-leaving radiances (or remote-sensing reflectances) in the visible domain, and chlorophyll-a concentration are identified as required ECV products. Time series of the products at the global scale and at high spatial resolution, derived from ocean-colour data, are key to studying the dynamics of phytoplankton at seasonal and inter-annual scales; their role in marine biogeochemistry; the global carbon cycle; the modulation of how phytoplankton distribute solar-induced heat in the upper layers of the ocean; and the response of the marine ecosystem to climate variability and change. However, generating a long time series of these products from ocean-colour data is not a trivial task: algorithms that are best suited for climate studies have to be selected from a number that are available for atmospheric correction of the satellite signal and for retrieval of chlorophyll-a concentration; since satellites have a finite life span, data from multiple sensors have to be merged to create a single time series, and any uncorrected inter-sensor biases could introduce artefacts in the series, e.g., different sensors monitor radiances at different wavebands such that producing a consistent time series of reflectances is not straightforward. Another requirement is that the products have to be validated against in situ observations. Furthermore, the uncertainties in the products have to be quantified, ideally on a pixel-by-pixel basis, to facilitate applications and interpretations that are consistent with the quality of the data. This paper outlines an approach that was adopted for generating an ocean-colour time series for climate studies, using data from the MERIS (MEdium spectral Resolution Imaging Spectrometer) sensor of the European Space Agency; the SeaWiFS (Sea-viewing Wide-Field-of-view Sensor) and MODIS-Aqua (Moderate-resolution Imaging Spectroradiometer-Aqua) sensors from the National Aeronautics and Space Administration (USA); and VIIRS (Visible and Infrared Imaging Radiometer Suite) from the National Oceanic and Atmospheric Administration (USA). The time series now covers the period from late 1997 to end of 2018. To ensure that the products meet, as well as possible, the requirements of the user community, marine-ecosystem modellers, and remote-sensing scientists were consulted at the outset on their immediate and longer-term requirements as well as on their expectations of ocean-colour data for use in climate research. Taking the user requirements into account, a series of objective criteria were established, against which available algorithms for processing ocean-colour data were evaluated and ranked. The algorithms that performed best with respect to the climate user requirements were selected to process data from the satellite sensors. Remote-sensing reflectance data from MODIS-Aqua, MERIS, and VIIRS were band-shifted to match the wavebands of SeaWiFS. Overlapping data were used to correct for mean biases between sensors at every pixel. The remote-sensing reflectance data derived from the sensors were merged, and the selected in-water algorithm was applied to the merged data to generate maps of chlorophyll concentration, inherent optical properties at SeaWiFS wavelengths, and the diffuse attenuation coefficient at 490 nm. The merged products were validated against in situ observations. The uncertainties established on the basis of comparisons with in situ data were combined with an optical classification of the remote-sensing reflectance data using a fuzzy-logic approach, and were used to generate uncertainties (root mean square difference and bias) for each product at each pixel.
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| 26. |
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| 27. |
- Testor, Pierre, et al.
(författare)
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OceanGliders: A component of the integrated GOOS
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
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Forskningsöversikt (refereegranskat)abstract
- The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
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| 28. |
- Thompson, Craig, et al.
(författare)
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To be understood : Transitioning to adult life for people with Autism Spectrum Disorder
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The purpose of this study was to explore the viewpoints of parents of young people with Autism Spectrum Disorder (ASD) in relation to their child's transition to adulthood.Methods: Data were collected during four structured focus groups with 19 parents of young people with ASD with average to high intellectual capacities. Condensed meaning units were identified and checked during focus groups, and were subsequently linked to the International Classification of Functioning, Disability and Health (ICF).Results: Three major themes emerged: to be understood, to understand the world and to succeed. The ICF domains of activity and participation and environmental factors emerged as having the greatest potential to influence transition outcomes.Conclusions: Policies and services should focus on strengths to maximise participation in higher education, employment and independent living amongst young people with ASD. Interventions targeting environmental factors could be effective in improving participation in adult life. Person-centred and individualised approaches could further complement this approach supporting the transition to adulthood for people with ASD, ultimately improving outcomes in adulthood.
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| 29. |
- Thompson, Craig, et al.
(författare)
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Viewpoints on how students with autism can best navigate university.
- 2019
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Ingår i: Scandinavian Journal of Occupational Therapy. - : Taylor & Francis. - 1103-8128 .- 1651-2014. ; 26:4, s. 294-305
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Despite recognition of the challenges faced by students with autism spectrum disorders (ASD) there is limited understanding of the barriers and facilitators to participation in major life areas, such as being a university student.AIM/OBJECTIVE:This research aimed to examine viewpoints on what affects the success of Australian university students with ASD.MATERIAL AND METHOD:Q-methodology was used to describe the viewpoints of university students with ASD, their parents and their mentors, on success at university for students with ASD. A total of 57 participants completed the Q-sort.RESULTS/FINDINGS:Three viewpoints emerged; Individualised Support, Contextual Support and Social Support.CONCLUSIONS:This study highlighted that supports need to be individualized to the barriers and facilitators faced by Australian students with ASD. Supports also need to be contextualized to the built and social environments of universities.SIGNIFICANCE:This study supports the premise that environmental interventions can be effective in facilitating participation in major life areas, such as university education. Peer mentoring for students with ASD may have utility for this group, but should be extended to include social, emotional and psychological support.
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| 30. |
- Thompson, Luke R., et al.
(författare)
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A communal catalogue reveals Earth's multiscale microbial diversity
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7681, s. 457-463
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.
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| 31. |
- Thompson, Michael D, et al.
(författare)
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Low Leakage-Current InAsSb Nanowire Photodetectors on Silicon.
- 2016
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 16:1, s. 182-187
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Tidskriftsartikel (refereegranskat)abstract
- Axially doped p-i-n InAs0.93Sb0.07 nanowire arrays have been grown on Si substrates and fabricated into photodetectors for shortwave infrared detection. The devices exhibit a leakage current density around 2 mA/cm(2) and a 20% cutoff of 2.3 μm at 300 K. This record low leakage current density for InAsSb based devices demonstrates the suitability of nanowires for the integration of III-V semiconductors with silicon technology.
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| 32. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 33. |
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