| 1. |
- Peterlongo, Paolo, et al.
(författare)
-
FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5345-5355
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.
|
|
| 2. |
- Kattge, Jens, et al.
(författare)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 4. |
- Arndt, D. S., et al.
(författare)
-
STATE OF THE CLIMATE IN 2017
- 2018
-
Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
-
Forskningsöversikt (refereegranskat)
|
|
| 5. |
- Freitag, Daniel F., et al.
(författare)
-
Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis
- 2015
-
Ingår i: The Lancet Diabetes & Endocrinology. - 2213-8595. ; 3:4, s. 243-253
-
Tidskriftsartikel (refereegranskat)abstract
- Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND.
|
|
| 6. |
- Hollestelle, Antoinette, et al.
(författare)
-
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
|
|
| 7. |
- Lozano, Rafael, et al.
(författare)
-
Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
|
|
| 8. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
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.
|
|
| 9. |
- Arndt, D. S., et al.
(författare)
-
State of the Climate in 2016
- 2017
-
Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
-
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.
|
|
| 10. |
- Bolatto, Alberto D., et al.
(författare)
-
ALMA Imaging of a Galactic Molecular Outflow in NGC 4945
- 2021
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 923:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present the ALMA detection of molecular outflowing gas in the central regions of NGC 4945, one of the nearest starbursts and also one of the nearest hosts of an active galactic nucleus (AGN). We detect four outflow plumes in CO J= 3 - 2 at similar to 0.3 resolution that appear to correspond to molecular gas located near the edges of the known ionized outflow cone and its (unobserved) counterpart behind the disk. The fastest and brightest of these plumes has emission reaching observed line-of-sight projected velocities of over 450 km s(-1) beyond systemic, equivalent to an estimated physical outflow velocity v greater than or similar to 600 km s(-1) for the fastest emission. Most of these plumes have corresponding emission in HCN or HCO + J= 4 - 3. We discuss a kinematic model for the outflow emission where the molecular gas has the geometry of the ionized gas cone and shares the rotation velocity of the galaxy when ejected. We use this model to explain the velocities we observe, constrain the physical speed of the ejected material, and account for the fraction of outflowing gas that is not detected due to confusion with the galaxy disk. We estimate a total molecular mass outflow rate (M) over dot(mol) similar to 20 M-circle dot yr(-1) flowing through a surface within 100 pc of the disk midplane, likely driven by a combination of the central starburst and AGN.
|
|
| 11. |
- Conley, Robert B., et al.
(författare)
-
Secondary Fracture Prevention : Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
-
Ingår i: Journal of Orthopaedic Trauma. - 0890-5339. ; 34:4, s. 125-141
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).
|
|
| 12. |
- Conley, Robert B., et al.
(författare)
-
Secondary Fracture Prevention : Consensus Clinical Recommendations from a Multistakeholder Coalition
- 2020
-
Ingår i: Orthopaedic Nursing. - 0744-6020. ; 39:3, s. 145-161
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk offuture fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the riskfor second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring foradverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). (c) 2019 American Society for Bone and Mineral Research.
|
|
| 13. |
- Conti, David, V, et al.
(författare)
-
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
|
|
| 14. |
- Esserman, Laura J., et al.
(författare)
-
Use of Molecular Tools to Identify Patients With Indolent Breast Cancers With Ultralow Risk Over 2 Decades
- 2017
-
Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:11, s. 1503-1510
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The frequency of cancers with indolent behavior has increased with screening. Better tools to identify indolent tumors are needed to avoid overtreatment. OBJECTIVE To determine if a multigene classifier is associated with indolent behavior of invasive breast cancers in women followed for 2 decades. DESIGN, SETTING, AND PARTICIPANTS This is a secondary analysis of a randomized clinical trial of tamoxifen vs no systemic therapy, with more than 20-year follow-up. An indolent threshold (ultralow risk) of the US Food and Drug Administration-cleared MammaPrint 70-gene expression score was established above which no breast cancer deaths occurred after 15 years in the absence of systemic therapy. Immunohistochemical markers (n = 727 women) and Agilent microarrays, for MammaPrint risk scoring (n = 652 women), were performed from formalin-fixed paraffin-embedded primary tumor blocks. Participants were postmenopausal women with clinically detected node-negative breast cancers treated with mastectomy or lumpectomy and radiation enrolled in the Stockholm tamoxifen (STO-3) trial, 1976 to 1990. EXPOSURES After 2 years of tamoxifen vs no systemic therapy, regardless of hormone receptor status, patients without relapse who reconsented were further randomized to 3 additional years or none. MAIN OUTCOMES AND MEASURES Breast cancer-specific survival assessed by Kaplan-Meier analyses and multivariate Cox proportional hazard modeling, adjusted for treatment, patient age, year of diagnosis, tumor size, grade, hormone receptors, and ERBB2/HER2 and Ki67 status. RESULTS In this secondary analysis of node-negative postmenopausal women, conducted in the era before mammography screening, among the 652 women with MammaPrint scoring available (median age, 62.8 years of age), 377 (58%) and 275 (42%) were MammaPrint low and high risk, respectively, while 98 (15%) were ultralow risk. At 20 years, women with 70-gene high and low tumors but not ultralow tumors had a significantly higher risk of disease-specific death compared with ultralow-risk patients by Cox analysis (hazard ratios, 4.73 [95% CI, 1.38-16.22] and 4.54 [95% CI, 1.40-14.80], respectively). There were no deaths in the ultralow-risk tamoxifen-treated arm at 15 years, and these patients had a 20-year disease-specific survival rate of 97%, whereas for untreated patients the survival rate was 94%. Recursive partitioning identified ultralow risk as the most significant predictor of good outcome. In tumors "not ultralow risk," tumor size greater than 2 cm was the most predictive of outcome. CONCLUSIONS AND RELEVANCE The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low.
|
|
| 15. |
- Groenewold, Nynke A., et al.
(författare)
-
Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
- 2023
-
Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
-
Tidskriftsartikel (refereegranskat)abstract
- There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
|
|
| 16. |
|
|
| 17. |
- Jones, Gregory T., et al.
(författare)
-
Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
-
Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
|
|
| 18. |
- Lindstrom, Linda S., et al.
(författare)
-
Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer
- 2018
-
Ingår i: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 110:7, s. 726-733
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Raos quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P amp;lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio (HR] = 1.98, 95% confidence interval (CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI -1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.
|
|
| 19. |
- Lunetta, Kathryn L., et al.
(författare)
-
Rare coding variants and X-linked loci associated with age at menarche
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
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.
|
|
| 20. |
- Thompson, Paul M., et al.
(författare)
-
The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
-
Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
-
Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
|
|
| 21. |
- Wang, Anqi, et al.
(författare)
-
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
-
Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
|
|
| 22. |
|
|
| 23. |
- Abazajian, Kevork, et al.
(författare)
-
CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
-
Tidskriftsartikel (refereegranskat)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
|
|
| 24. |
- Anney, Richard, et al.
(författare)
-
A genome-wide scan for common alleles affecting risk for autism.
- 2010
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
-
Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
|
|
| 25. |
- Arzoumanian, Doris, et al.
(författare)
-
Dust polarized emission observations of NGC 6334: BISTRO reveals the details of the complex but organized magnetic field structure of the high-mass star-forming hub-filament network
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 647
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Molecular filaments and hubs have received special attention recently thanks to new studies showing their key role in star formation. While the (column) density and velocity structures of both filaments and hubs have been carefully studied, their magnetic field (B-field) properties have yet to be characterized. Consequently, the role of B-fields in the formation and evolution of hub-filament systems is not well constrained. Aims. We aim to understand the role of the B-field and its interplay with turbulence and gravity in the dynamical evolution of the NGC 6334 filament network that harbours cluster-forming hubs and high-mass star formation. Methods. We present new observations of the dust polarized emission at 850 μm toward the 2 pc × 10 pc map of NGC 6334 at a spatial resolution of 0.09 pc obtained with the James Clerk Maxwell Telescope (JCMT) as part of the B-field In STar-forming Region Observations (BISTRO) survey. We study the distribution and dispersion of the polarized intensity (PI), the polarization fraction (PF), and the plane-of-The-sky B-field angle (χB_POS) toward the whole region, along the 10 pc-long ridge and along the sub-filaments connected to the ridge and the hubs. We derived the power spectra of the intensity and χBPOS along the ridge crest and compared them with the results obtained from simulated filaments. Results. The observations span 3 orders of magnitude in Stokes I and PI and 2 orders of magnitude in PF (from 0.2 to 20%). A large scatter in PI and PF is observed for a given value of I. Our analyses show a complex B-field structure when observed over the whole region ( 10 pc); however, at smaller scales (1 pc), χBPOS varies coherently along the crests of the filament network. The observed power spectrum of χBPOS can be well represented with a power law function with a slope of-1.33 ± 0.23, which is 20% shallower than that of I. We find that this result is compatible with the properties of simulated filaments and may indicate the physical processes at play in the formation and evolution of star-forming filaments. Along the sub-filaments, χBPOS rotates frombeing mostly perpendicular or randomly oriented with respect to the crests to mostly parallel as the sub-filaments merge with the ridge and hubs. This variation of the B-field structure along the sub-filaments may be tracing local velocity flows of infalling matter in the ridge and hubs. Our analysis also suggests a variation in the energy balance along the crests of these sub-filaments, from magnetically critical or supercritical at their far ends to magnetically subcritical near the ridge and hubs. We also detect an increase in PF toward the high-column density (NH2 â 1023 cm-2) star cluster-forming hubs. These latter large PF values may be explained by the increase in grain alignment efficiency due to stellar radiation from the newborn stars, combined with an ordered B-field structure. Conclusions. These observational results reveal for the first time the characteristics of the small-scale (down to 0.1 pc) B-field structure of a 10 pc-long hub-filament system. Our analyses show variations in the polarization properties along the sub-filaments that may be tracing the evolution of their physical properties during their interaction with the ridge and hubs. We also detect an impact of feedback from young high-mass stars on the local B-field structure and the polarization properties, which could put constraints on possible models for dust grain alignment and provide important hints as to the interplay between the star formation activity and interstellar B-fields.
|
|
| 26. |
- Barth, Claudia, et al.
(författare)
-
In vivo white matter microstructure in adolescents with early-onset psychosis : a multi-site mega-analysis
- 2023
-
Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28, s. 1159-1169
-
Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset <18 years). However, as neuroimaging methods vary and sample sizes are modest, results remain inconclusive. Using harmonized data processing protocols and a mega-analytic approach, we compared white matter microstructure in EOP and healthy controls using diffusion tensor imaging (DTI). Our sample included 321 adolescents with EOP (median age=16.6 years, interquartile range (IQR)=2.14, 46.4% females) and 265 adolescent healthy controls (median age=16.2 years, IQR=2.43, 57.7% females) pooled from nine sites. All sites extracted mean fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for 25 white matter regions of interest per participant. ComBat harmonization was performed for all DTI measures to adjust for scanner differences. Multiple linear regression models were fitted to investigate case-control differences and associations with clinical variables in regional DTI measures. We found widespread lower FA in EOP compared to healthy controls, with the largest effect sizes in the superior longitudinal fasciculus (Cohen's d=0.37), posterior corona radiata (d=0.32), and superior fronto-occipital fasciculus (d=0.31). We also found widespread higher RD and more localized higher MD and AD. We detected significant effects of diagnostic subgroup, sex, and duration of illness, but not medication status. Using the largest EOP DTI sample to date, our findings suggest a profile of widespread white matter microstructure alterations in adolescents with EOP, most prominently in male individuals with early-onset schizophrenia and individuals with a shorter duration of illness.
|
|
| 27. |
- Botvinik-Nezer, Rotem, et al.
(författare)
-
Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
-
Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
|
|
| 28. |
|
|
| 29. |
- Bustamante, Mercedes, et al.
(författare)
-
Ten new insights in climate science 2023
- 2023
-
Ingår i: Global Sustainability. - : CAMBRIDGE UNIV PRESS. - 2059-4798. ; 7
-
Forskningsöversikt (refereegranskat)abstract
- Non-technical summary We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5 degrees C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.Technical summary The Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5 degrees C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.Social media summary We highlight recent and policy-relevant advances in climate change research - with input from more than 200 experts.
|
|
| 30. |
- Cable, Jennifer, et al.
(författare)
-
Progress in vaccine development for infectious diseases : a Keystone Symposia report
- 2023
-
Ingår i: Annals of the New York Academy of Sciences. - : John Wiley & Sons. - 0077-8923 .- 1749-6632. ; 1524:1, s. 65-86
-
Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
|
|
| 31. |
- Carroll, Harriet A., et al.
(författare)
-
Effect of acute hypohydration on glycemic regulation in healthy adults : A randomized crossover trial
- 2019
-
Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 126:2, s. 422-430
-
Tidskriftsartikel (refereegranskat)abstract
- he aim of this study was to investigate the acute effect of hydration status on glycemic regulation in healthy adults and explore underlying mechanisms. In this randomized crossover trial, 16 healthy adults (8 men, 8 women) underwent an oral glucose tolerance test (OGTT) when hypohydrated and rehydrated after 4 days of pretrial standardization. One day before OGTT, participants were dehydrated for 1 h in a heat tent with subsequent fluid restriction (HYPO) or replacement (RE). The following day, an OGTT was performed with metabolic rate measurements and pre- and post-OGTT muscle biopsies. Peripheral quantitative computer tomography thigh scans were taken before and after intervention to infer changes in cell volume. HYPO (but not RE) induced 1.9% (SD 1.2) body mass loss, 2.9% (SD 2.7) cell volume reduction, and increased urinary hydration markers, serum osmolality, and plasma copeptin concentration (all P 0.007). Fasted serum glucose [HYPO 5.10 mmol/l (SD 0.42), RE 5.02 mmol/l (SD 0.40); P 0.327] and insulin [HYPO 27.1 pmol/l (SD 9.7), RE 27.6 pmol/l (SD 9.2); P 0.809] concentrations were similar between HYPO and RE. Hydration status did not alter the serum glucose (P 0.627) or insulin (P 0.200) responses during the OGTT. Muscle water content was lower before OGTT after HYPO compared with RE [761 g/kg wet wt (SD 13) vs. 772 g/kg wet wt (SD 18) RE] but similar after OGTT [HYPO 779 g/kg wet wt (SD 15) vs. RE 780 g/kg wet wt (SD 20); time P 0.011; trial time P 0.055]. Resting energy expenditure was similar between hydration states (stable between 1.21 and 5.94 kJ·kg 1 ·day 1 ; trial P 0.904). Overall, despite acute mild hypohydration increasing plasma copeptin concentrations and decreasing fasted cell volume and muscle water, we found no effect on glycemic regulation.
|
|
| 32. |
- Carroll, Harriet A., et al.
(författare)
-
Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults : A randomised crossover trial
- 2019
-
Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384. ; 212
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have investigated the effect of hydration status on appetite for food in healthy adults. Prior work suggests hydration status does not alter appetite or energy intake, with mixed findings regarding appetite hormone secretion. However, an extensive investigation into both the psychological and physiological appetitive responses to hydration status has never been conducted. Objective: To investigate the effect of hydration status on multiple facets of appetite. Design: After 3 days pre-trial standardization, a range of appetite tasks were conducted when hypohydrated (HYPO) and euhydrated (EUHY) in 16 healthy participants (8 men). Hydration status was manipulated via dehydration in a heat tent for 60 min and subsequent fluid restriction (HYPO) or replacement (EUHY). The next day, a food reward computer task was completed followed by an ad libitum pasta meal. Pre- and post-prandial visual analogue scales assessing hunger, fullness, and flavour desires (sweet, salty, savoury and fatty) were additionally completed. Blood samples were taken the previous day before the hydration interventions in a euhydrated state, and in the fasted and post-prandial state during HYPO and EUHY. Results: HYPO induced -1.9 ± 1.2% body mass change, compared to -0.2 ± 0.6%, with accompanying changes in markers of hypohydration which were not seen during EUHY. A higher desire for foods was associated with a higher water content but the association was weaker in EUHY compared to HYPO, (β= -0.33 mm/g of food water content, p < 0.001) in the food reward task. Visual analogue scales showed similar hunger and fullness between interventions, but during HYPO there was consistently higher thirst (average range in difference 27–32 mm across all time points) and lower fasted desire for salt (−23, 95% CI −10, −35 mm). Ad libitum energy intake (HYPO 1953 ± 742 kJ, EUHY 2027 ± 926 kJ; p = 0.542) and post-prandial ghrelin concentrations (HYPO 180 ± 65 pg mL−1, EUHY 188 ± 71 pg mL−1; p = 0.736) were similar by hydration status. Conclusions: An acute manipulation to hydration status altered desire for salt and foods of differing water contents, but did not influence energy intake at an ad libitum pasta meal. Further research should investigate whether these appetites would alter food choice.
|
|
| 33. |
- Carter, Aarynn L., et al.
(författare)
-
A benchmark JWST near-infrared spectrum for the exoplanet WASP-39 b
- 2024
-
Ingår i: Nature Astronomy. - 2397-3366. ; In Press
-
Tidskriftsartikel (refereegranskat)abstract
- A combined analysis of datasets across four JWST instrument modes provides a benchmark transmission spectrum for the Saturn-mass WASP-39 b. The broad wavelength range and high resolution constrain orbital and stellar parameters to below 1%.
|
|
| 34. |
- Ching, Tao-Chung, et al.
(författare)
-
The JCMT BISTRO-2 Survey: Magnetic Fields of the Massive DR21 Filament
- 2022
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:2
-
Tidskriftsartikel (refereegranskat)abstract
- We present 850 mu m dust polarization observations of the massive DR21 filament from the B-fields In STar-forming Region Observations (BISTRO) survey, using the POL-2 polarimeter and the SCUBA-2 camera on the James Clerk Maxwell Telescope. We detect ordered magnetic fields perpendicular to the parsec-scale ridge of the DR21 main filament. In the subfilaments, the magnetic fields are mainly parallel to the filamentary structures and smoothly connect to the magnetic fields of the main filament. We compare the POL-2 and Planck dust polarization observations to study the magnetic field structures of the DR21 filament on 0.1-10 pc scales. The magnetic fields revealed in the Planck data are well-aligned with those of the POL-2 data, indicating a smooth variation of magnetic fields from large to small scales. The plane-of-sky magnetic field strengths derived from angular dispersion functions of dust polarization are 0.6-1.0 mG in the DR21 filament and similar to 0.1 mG in the surrounding ambient gas. The mass-to-flux ratios are found to be magnetically supercritical in the filament and slightly subcritical to nearly critical in the ambient gas. The alignment between column density structures and magnetic fields changes from random alignment in the low-density ambient gas probed by Planck to mostly perpendicular in the high-density main filament probed by James Clerk Maxwell Telescope. The magnetic field structures of the DR21 filament are in agreement with MHD simulations of a strongly magnetized medium, suggesting that magnetic fields play an important role in shaping the DR21 main filament and subfilaments.
|
|
| 35. |
- Coscieme, Luca, et al.
(författare)
-
Multiple conceptualizations of nature are key to inclusivity and legitimacy in global environmental governance
- 2020
-
Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011 .- 1873-6416. ; 104, s. 36-42
-
Tidskriftsartikel (refereegranskat)abstract
- Despite increasing scientific understanding of the global environmental crisis, we struggle to adopt the policies science suggests would be effective. One of the reasons for that is the lack of inclusive engagement and dialogue among a wide range of different actors. Furthermore, there is a lack of consideration of differences between languages, worldviews and cultures. In this paper, we propose that engagement across the science-policy interface can be strengthened by being mindful of the breadth and depth of the diverse human-nature relations found around the globe. By examining diverse conceptualizations of nature in more than 60 languages, we identify three clusters: inclusive conceptualizations where humans are viewed as an integral component of nature; non-inclusive conceptualizations where humans are separate from nature; and deifying conceptualizations where nature is understood and experienced within a spiritual dimension. Considering and respecting this rich repertoire of ways of describing, thinking about and relating to nature can help us communicate in ways that resonate across cultures and worldviews. This repertoire also provides a resource we can draw on when defining policies and sustainability scenarios for the future, offering opportunities for finding solutions to global environmental challenges.
|
|
| 36. |
- Dee, Laura E., et al.
(författare)
-
Operationalizing Network Theory for Ecosystem Service Assessments
- 2017
-
Ingår i: Trends in Ecology & Evolution. - : ELSEVIER SCIENCE LONDON. - 0169-5347 .- 1872-8383. ; 32:2, s. 118-130
-
Forskningsöversikt (refereegranskat)abstract
- Managing ecosystems to provide ecosystem services in the face of global change is a pressing challenge for policy and science. Predicting how alternative management actions and changing future conditions will alter services is complicated by interactions among components in ecological and socioeconomic systems. Failure to understand those interactions can lead to detrimental outcomes from management decisions. Network theory that integrates ecological and socioeconomic systems may provide a path to meeting this challenge. While network theory offers promising approaches to examine ecosystem services, few studies have identified how to operationalize networks for managing and assessing diverse ecosystem services. We propose a framework for how to use networks to assess how drivers and management actions will directly and indirectly alter ecosystem services.
|
|
| 37. |
- Dima, Danai, et al.
(författare)
-
Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
-
Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
|
|
| 38. |
- Edvardsson, David, et al.
(författare)
-
Advancing Long-Term Care Science Through Using Common Data Elements : Candidate Measures for Care Outcomes of Personhood, Well-Being, and Quality of Life
- 2019
-
Ingår i: Gerontology and geriatric medicine. - : Sage Publications. - 2333-7214. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- To support the development of internationally comparable common data elements (CDEs) that can be used to measure essential aspects of long-term care (LTC) across low-, middle-, and high-income countries, a group of researchers in medicine, nursing, behavioral, and social sciences from 21 different countries have joined forces and launched the Worldwide Elements to Harmonize Research in LTC Living Environments (WE-THRIVE) initiative. This initiative aims to develop a common data infrastructure for international use across the domains of organizational context, workforce and staffing, person-centered care, and care outcomes, as these are critical to LTC quality, experiences, and outcomes. This article reports measurement recommendations for the care outcomes domain, focusing on previously prioritized care outcomes concepts of well-being, quality of life (QoL), and personhood for residents in LTC. Through literature review and expert ranking, we recommend nine measures of well-being, QoL, and personhood, as a basis for developing CDEs for long-term care outcomes across countries. Data in LTC have often included deficit-oriented measures; while important, reductions do not necessarily mean that residents are concurrently experiencing well-being. Enhancing measurement efforts with the inclusion of these positive LTC outcomes across countries would facilitate international LTC research and align with global shifts toward healthy aging and person-centered LTC models.
|
|
| 39. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
-
Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
-
Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
|
|
| 40. |
- Eswaraiah, Chakali, et al.
(författare)
-
The JCMT BISTRO Survey: Revealing the Diverse Magnetic Field Morphologies in Taurus Dense Cores with Sensitive Submillimeter Polarimetry
- 2021
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 912:2
-
Tidskriftsartikel (refereegranskat)abstract
- We have obtained sensitive dust continuum polarization observations at 850 μm in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope as part of the B-fields in STar-forming Region Observations (BISTRO) survey. These observations allow us to probe magnetic field (B-field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis-Chandrasekhar-Fermi method, we estimate the B-field strengths in K04166, K04169, and Miz-8b to be 38 ± 14, 44 ± 16, and 12 ± 5 μG, respectively. These cores show distinct mean B-field orientations. The B-field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B-field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. The B-field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B-field and not well correlated with other axes. In contrast, Miz-8b exhibits a disordered B-field that shows no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B-field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B-field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux.
|
|
| 41. |
- Felipe-Lucia, María R., et al.
(författare)
-
Conceptualizing ecosystem services using social–ecological networks
- 2022
-
Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 37:3, s. 211-222
-
Tidskriftsartikel (refereegranskat)abstract
- Social–ecological networks (SENs) represent the complex relationships between ecological and social systems and are a useful tool for analyzing and managing ecosystem services. However, mainstreaming the application of SENs in ecosystem service research has been hindered by a lack of clarity about how to match research questions to ecosystem service conceptualizations in SEN (i.e., as nodes, links, attributes, or emergent properties). Building from different disciplines, we propose a typology to represent ecosystem service in SENs and identify opportunities and challenges of using SENs in ecosystem service research. Our typology provides guidance for this growing field to improve research design and increase the breadth of questions that can be addressed with SEN to understand human–nature interdependencies in a changing world.
|
|
| 42. |
- Frangou, Sophia, et al.
(författare)
-
Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
-
Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
-
Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
|
|
| 43. |
- Gould, Rebecca, et al.
(författare)
-
Acceptance and Commitment Therapy for people living with motor neuron disease : an uncontrolled feasibility study
- 2023
-
Ingår i: Pilot and Feasibility Studies. - : Springer Nature. - 2055-5784. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND.Methods: PlwMND aged >= 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (>= 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (>= 70% completing >= 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months.Results: Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended >= 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status.Conclusions: There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway.
|
|
| 44. |
- Gould, Rebecca L., et al.
(författare)
-
A randomised controlled trial of acceptance and commitment therapy plus usual care compared to usual care alone for improving psychological health in people with motor neuron disease (COMMEND) : study protocol
- 2022
-
Ingår i: BMC Neurology. - : Springer Nature. - 1471-2377. ; 22
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2-3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health.Aims: To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND.Methods: The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged >= 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling.Discussion: This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND.
|
|
| 45. |
- Gould, Rebecca L., et al.
(författare)
-
Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND) : a multicentre, parallel, randomised controlled trial in the UK
- 2024
-
Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 403:10442, s. 2381-2394
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease.Methods: We conducted a parallel, multicentre, two -arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory -supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web -based system, stratified by site. Participants were followed up at 6 months and 9 months post -randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire -Revised (MQOL-R) at 6 months post -randomisation. Primary analyses were multi -level modelling and modified intention to treat among participants with available data. This trial was pre -registered with the ISRCTN Registry (ISRCTN12655391).Findings: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63⋅1 years (SD 11⋅0). 155 (81%) participants had primary outcome data at 6 months post -randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0⋅66 [95% CI 0⋅22-1⋅10]; d=0⋅46 [0⋅16-0⋅77]; p=0⋅0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention.Interpretation: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services.
|
|
| 46. |
- Guzman, Laura Melissa, et al.
(författare)
-
Accounting for temporal change in multiple biodiversity patterns improves the inference of metacommunity processes
- 2022
-
Ingår i: Ecology. - : John Wiley & Sons. - 0012-9658 .- 1939-9170. ; 103:6
-
Tidskriftsartikel (refereegranskat)abstract
- In metacommunity ecology, a major focus has been on combining observational and analytical approaches to identify the role of critical assembly processes, such as dispersal limitation and environmental filtering, but this work has largely ignored temporal community dynamics. Here, we develop a "virtual ecologist" approach to evaluate assembly processes by simulating metacommunities varying in three main processes: density-independent responses to abiotic conditions, density-dependent biotic interactions, and dispersal. We then calculate a number of commonly used summary statistics of community structure in space and time and use random forests to evaluate their utility for inferring the strength of these three processes. We find that (i) both spatial and temporal data are necessary to disentangle metacommunity processes based on the summary statistics we test, and including statistics that are measured through time increases the explanatory power of random forests by up to 59% compared to cases where only spatial variation is considered; (ii) the three studied processes can be distinguished with different descriptors; and (iii) each summary statistic is differently sensitive to temporal and spatial sampling effort. Including repeated observations of metacommunities over time was essential for inferring the metacommunity processes, particularly dispersal. Some of the most useful statistics include the coefficient of variation of species abundances through time and metrics that incorporate variation in the relative abundances (evenness) of species. We conclude that a combination of methods and summary statistics is probably necessary to understand the processes that underlie metacommunity assembly through space and time, but we recognize that these results will be modified when other processes or summary statistics are used.
|
|
| 47. |
- Hibar, Derrek P., et al.
(författare)
-
Novel genetic loci associated with hippocampal volume
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
|
|
| 48. |
- Hilbert, Kevin, et al.
(författare)
-
Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
-
Ingår i: The American Journal of Psychiatry. - 1535-7228. ; 181:8, s. 728-740
-
Tidskriftsartikel (refereegranskat)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
|
|
| 49. |
|
|
| 50. |
- Hwang, Jihye, et al.
(författare)
-
The JCMT BISTRO Survey: A Spiral Magnetic Field in a Hub-filament Structure, Monoceros R2
- 2022
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present and analyze observations of polarized dust emission at 850 μm toward the central 1 × 1 pc hub-filament structure of Monoceros R2 (Mon R2). The data are obtained with SCUBA-2/POL-2 on the James Clerk Maxwell Telescope (JCMT) as part of the B-fields in Star-forming Region Observations survey. The orientations of the magnetic field follow the spiral structure of Mon R2, which are well described by an axisymmetric magnetic field model. We estimate the turbulent component of the magnetic field using the angle difference between our observations and the best-fit model of the underlying large-scale mean magnetic field. This estimate is used to calculate the magnetic field strength using the Davis–Chandrasekhar–Fermi method, for which we also obtain the distribution of volume density and velocity dispersion using a column density map derived from Herschel data and the C18O (J = 3 - 2) data taken with HARP on the JCMT, respectively. We make maps of magnetic field strengths and mass-to-flux ratios, finding that magnetic field strengths vary from 0.02 to 3.64 mG with a mean value of 1.0 ± 0.06 mG, and the mean critical mass-to-flux ratio is 0.47 ± 0.02. Additionally, the mean Alfvén Mach number is 0.35 ± 0.01. This suggests that, in Mon R2, the magnetic fields provide resistance against large-scale gravitational collapse, and the magnetic pressure exceeds the turbulent pressure. We also investigate the properties of each filament in Mon R2. Most of the filaments are aligned along the magnetic field direction and are magnetically subcritical.
|
|
