| 1. |
- Niemi, MEK, et al.
(author)
-
- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
-
- 2023
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swepub:Mat__t
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| 3. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Arndt, D. S., et al.
(author)
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State of the Climate in 2016
- 2017
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
-
Journal article (peer-reviewed)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 5. |
- Arndt, D. S., et al.
(author)
-
STATE OF THE CLIMATE IN 2017
- 2018
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In: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
-
Research review (peer-reviewed)
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| 6. |
- Berndt, Sonja, I, et al.
(author)
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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
- 2022
-
In: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
-
Journal article (peer-reviewed)abstract
- Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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| 7. |
- Cerhan, James R., et al.
(author)
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Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:11, s. 1233-1238
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Journal article (peer-reviewed)abstract
- Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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| 8. |
- Durosini, Ilaria, et al.
(author)
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Patient Preferences for Lung Cancer Treatment: A Qualitative Study Protocol Among Advanced Lung Cancer Patients
- 2021
-
In: Frontiers In Public Health. - : Frontiers Media SA. - 2296-2565. ; 9
-
Journal article (peer-reviewed)abstract
- Introduction: Lung cancer is the deadliest and most prevalent cancer worldwide. Lung cancer treatments have different characteristics and are associated with a range of benefits and side effects for patients. Such differences may raise uncertainty among drug developers, regulators, payers, and clinicians regarding the value of these treatment effects to patients. The value of conducting patient preference studies (using qualitative and/or quantitative methods) for benefits and side effects of different treatment options has been recognized by healthcare stakeholders, such as drug developers, regulators, health technology assessment bodies, and clinicians. However, evidence-based guidelines on how and when to conduct and use these studies in drug decision-making are lacking. As part of the Innovative Medicines Initiative PREFER project, we developed a protocol for a qualitative study that aims to understand which treatment characteristics are most important to lung cancer patients and to develop attributes and levels for inclusion in a subsequent quantitative preference survey.Methods: The study protocol specifies a four-phased approach: (i) a scoping literature review of published literature, (ii) four focus group discussions with stage III and IV Non-Small Cell Lung Cancer patients, (iii) two nominal group discussions with stage III and IV Non-Small Cell Lung Cancer patients, and (iv) multi-stakeholder discussions involving clinicians and preference experts.Discussion: This protocol outlines methodological and practical steps as to how qualitative research can be applied to identify and develop attributes and levels for inclusion in patient preference studies aiming to inform decisions across the drug life cycle. The results of this study are intended to inform a subsequent quantitative preference survey that assesses patient trade-offs regarding lung cancer treatment options. This protocol may assist researchers, drug developers, and decision-makers in designing qualitative studies to understand which treatment aspects are most valued by patients in drug development, regulation, and reimbursement.
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| 9. |
- Falster, Daniel, et al.
(author)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
-
In: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
-
Journal article (peer-reviewed)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 10. |
- Machiela, Mitchell J., et al.
(author)
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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
- 2016
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:8, s. 1663-1676
-
Journal article (peer-reviewed)abstract
- Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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| 11. |
- Monzani, Dario, et al.
(author)
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Patient Preferences for Lung Cancer Treatments: A Study Protocol for a Preference Survey Using Discrete Choice Experiment and Swing Weighting
- 2021
-
In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 8
-
Journal article (peer-reviewed)abstract
- Background: Advanced treatment options for non-small cell lung cancer (NSCLC) consist of immunotherapy, chemotherapy, or a combination of both. Decisions surrounding NSCLC can be considered as preference-sensitive because multiple treatments exist that vary in terms of mode of administration, treatment schedules, and benefit–risk profiles. As part of the IMI PREFER project, we developed a protocol for an online preference survey for NSCLC patients exploring differences in preferences according to patient characteristics (preference heterogeneity). Moreover, this study will evaluate and compare the use of two different preference elicitation methods, the discrete choice experiment (DCE) and the swing weighting (SW) task. Finally, the study explores how demographic (i.e., age, gender, and educational level) and clinical (i.e., cancer stage and line of treatment) information, health literacy, health locus of control, and quality of life may influence or explain patient preferences and the usefulness of a digital interactive tool in providing information on preference elicitation tasks according to patients.Methods: An online survey will be implemented with the aim to recruit 510 NSCLC patients in Belgium and Italy. Participants will be randomized 50:50 to first receive either the DCE or the SW. The survey will also collect information on participants' disease-related status, health locus of control, health literacy, quality of life, and perception of the educational tool.Discussion: This protocol outlines methodological and practical steps to quantitatively elicit and study patient preferences for NSCLC treatment alternatives. Results from this study will increase the understanding of which treatment aspects are most valued by NSCLC patients to inform decision-making in drug development, regulatory approval, and reimbursement. Methodologically, the comparison between the DCE and the SW task will be valuable to gain information on how these preference methods perform against each other in eliciting patient preferences. Overall, this protocol may assist researchers, drug developers, and decision-makers in designing quantitative patient preferences into decision-making along the medical product life cycle.
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| 12. |
- Oliveri, Serena, et al.
(author)
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Opportunities and Challenges of Web-Based and Remotely Administered Surveys for Patient Preference Studies in a Vulnerable Population
- 2021
-
In: Patient Preference and Adherence. - : Informa UK Limited. - 1177-889X. ; 15, s. 2509-2517
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Journal article (peer-reviewed)abstract
- The application of web-based and remotely administered surveys is becoming increasingly popular due to the fact that it offers numerous advantages over traditional paper-based or computer-based surveys completed in the presence of the researcher. However, it is unclear whether complex preference elicitation tasks administered online in highly vulnerable patient populations are also feasible. This commentary discusses opportunities and challenges of conducting quantitative patient preference studies in lung cancer patients using web-based modes of data collection. We refer to our recent experience in the context of the Patient Preference in Benefit-Risk Assessments during the Drug Life Cycle (PREFER) project. Among the main advantages were the possibility of reaching a wider and geographically distant population in a shorter timeframe while reducing the financial costs of testing, the greater flexibility offered and the reduced burden on the patients. Some limitations were also identified and should be the object of further research, including the potential lack of inclusiveness of the research, the lack of control over who is completing the survey, a poor comprehension of the study material, and ultimately a lower level of engagement with the study. Despite these limitations, experience from the PREFER project suggests that online quantitative methods for data collection may provide a valuable method to explore preferences in vulnerable patient populations beyond the COVID-19 pandemic.
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| 13. |
- Palmer, Nicholette D, et al.
(author)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
-
In: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
-
Journal article (peer-reviewed)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 14. |
- Pattaro, Cristian, et al.
(author)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 15. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
-
Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 16. |
- Skibola, Christine F, et al.
(author)
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Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region.
- 2014
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 95:4, s. 462-471
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
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| 17. |
- Sodergren, Erica, et al.
(author)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Journal article (peer-reviewed)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 18. |
- Vijai, Joseph, et al.
(author)
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A genome-wide association study of marginal zone lymphoma shows association to the HLA region
- 2015
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Journal article (peer-reviewed)abstract
- Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P - 3.95 x 10(-15)) and HLA-B (rs2922994, P - 2.43 x 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
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| 19. |
- Adare, A., et al.
(author)
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Nuclear modification factors of phi mesons in d plus Au, Cu plus Cu, and Au plus Au collisions at root s(NN)=200 GeV
- 2011
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 83:2
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Journal article (peer-reviewed)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has performed systematic measurements of phi meson production in the K+K- decay channel at midrapidity in p + p, d + Au, Cu + Cu, and Au + Au collisions at root s(NN) = 200 GeV. Results are presented on the phi invariant yield and the nuclear modification factor R-AA for Au + Au and Cu + Cu, and R-dA for d + Au collisions, studied as a function of transverse momentum (1 < p(T) < 7 GeV/c) and centrality. In central and midcentral Au + Au collisions, the R-AA of phi exhibits a suppression relative to expectations from binary scaled p + p results. The amount of suppression is smaller than that of the pi(0) and the. in the intermediate p(T) range (2-5 GeV/c), whereas, at higher p(T), the phi, pi(0), and. show similar suppression. The baryon (proton and antiproton) excess observed in central Au + Au collisions at intermediate p(T) is not observed for the phi meson despite the similar masses of the proton and the phi. This suggests that the excess is linked to the number of valence quarks in the hadron rather than its mass. The difference gradually disappears with decreasing centrality, and, for peripheral collisions, the R-AA values for both particle species are consistent with binary scaling. Cu + Cu collisions show the same yield and suppression as Au + Au collisions for the same number of N-part. The R-dA of phi shows no evidence for cold nuclear effects within uncertainties.
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| 20. |
- Adare, A., et al.
(author)
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Photon-hadron jet correlations in p plus p and Au plus Au collisions at s(NN)=200 GeV
- 2009
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:2
-
Journal article (peer-reviewed)abstract
- We report the observation at the Relativistic Heavy Ion Collider of suppression of back-to-back correlations in the direct photon+jet channel in Au+Au relative to p+p collisions. Two-particle correlations of direct photon triggers with associated hadrons are obtained by statistical subtraction of the decay photon-hadron (gamma-h) background. The initial momentum of the away-side parton is tightly constrained, because the parton-photon pair exactly balance in momentum at leading order in perturbative quantum chromodynamics, making such correlations a powerful probe of the in-medium parton energy loss. The away-side nuclear suppression factor, I-AA, in central Au+Au collisions, is 0.32 +/- 0.12(stat)+/- 0.09(syst) for hadrons of 3 < p(T)(h)< 5 in coincidence with photons of 5 < p(T)(gamma)< 15 GeV/c. The suppression is comparable to that observed for high-p(T) single hadrons and dihadrons. The direct photon associated yields in p+p collisions scale approximately with the momentum balance, z(T)equivalent to p(T)(h)/p(T)(gamma), as expected for a measurement of the away-side parton fragmentation function. We compare to Au+Au collisions for which the momentum balance dependence of the nuclear modification should be sensitive to the path-length dependence of parton energy loss.
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| 21. |
- Adare, A., et al.
(author)
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Production of omega mesons in p plus p, d plus Au, Cu plus Cu, and Au plus Au collisions at root s(NN)=200 GeV
- 2011
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:4
-
Journal article (peer-reviewed)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has measured omega meson production via leptonic and hadronic decay channels in p + p, d + Au, Cu+ Cu, and Au + Au collisions at root s(NN) = 200 GeV. The invariant transverse momentum spectra measured in different decay modes give consistent results. Measurements in the hadronic decay channel in Cu Cu and Au + Au collisions show that. production has a suppression pattern at high transverse momentum, similar to that of pi(0) and eta in central collisions, but no suppression is observed in peripheral collisions. The nuclear modification factors, R-AA, are consistent in Cu + Cu and Au + Au collisions at similar numbers of participant nucleons.
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| 22. |
- Anderson, J. L., et al.
(author)
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The Fishery Performance Indicators: A Management Tool for Triple Bottom Line Outcomes
- 2015
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
-
Journal article (peer-reviewed)abstract
- Pursuit of the triple bottom line of economic, community and ecological sustainability has increased the complexity of fishery management; fisheries assessments require new types of data and analysis to guide science-based policy in addition to traditional biological information and modeling. We introduce the Fishery Performance Indicators (FPIs), a broadly applicable and flexible tool for assessing performance in individual fisheries, and for establishing cross-sectional links between enabling conditions, management strategies and triple bottom line outcomes. Conceptually separating measures of performance, the FPIs use 68 individual outcome metrics-coded on a 1 to 5 scale based on expert assessment to facilitate application to data poor fisheries and sectors-that can be partitioned into sectorbased or triple-bottom-line sustainability-based interpretative indicators. Variation among outcomes is explained with 54 similarly structured metrics of inputs, management approaches and enabling conditions. Using 61 initial fishery case studies drawn from industrial and developing countries around the world, we demonstrate the inferential importance of tracking economic and community outcomes, in addition to resource status.
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| 23. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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| 24. |
- Borgquist, Signe, et al.
(author)
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Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study
- 2017
-
In: Journal of Clinical Oncology. - 0732-183X. ; 35:11, s. 1179-1188
-
Journal article (peer-reviewed)abstract
- Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor-positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-freesurvival, breast cancer-free interval, and distant recurrence-free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer-free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence-free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor-positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.
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| 25. |
- Chasman, Daniel I., et al.
(author)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
-
Journal article (peer-reviewed)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 26. |
- Cochemé, Helena M, et al.
(author)
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Mitochondrial targeting of quinones: therapeutic implications.
- 2007
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In: Mitochondrion. - : Elsevier BV. - 1567-7249. ; 7 Suppl
-
Research review (peer-reviewed)abstract
- Mitochondrial oxidative damage contributes to a range of degenerative diseases. Ubiquinones have been shown to protect mitochondria from oxidative damage, but only a small proportion of externally administered ubiquinone is taken up by mitochondria. Conjugation of the lipophilic triphenylphosphonium cation to a ubiquinone moiety has produced a compound, MitoQ, which accumulates selectively into mitochondria. MitoQ passes easily through all biological membranes and, because of its positive charge, is accumulated several hundred-fold within mitochondria driven by the mitochondrial membrane potential. MitoQ protects mitochondria against oxidative damage in vitro and following oral delivery, and may therefore form the basis for mitochondria-protective therapies.
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| 27. |
- Dall'Ora, C, et al.
(author)
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Nurses' 12-hour shifts and missed or delayed vital signs observations on hospital wards: retrospective observational study
- 2019
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In: BMJ open. - : BMJ. - 2044-6055. ; 9:1, s. e024778-
-
Journal article (peer-reviewed)abstract
- 12-hour shifts worked by nurses on acute hospital wards have been associated with increased rates of missed care reported by nurses. This study aimed to measure the association between nurses working shifts of at least 12 hours and an objective measure of missed care: vital signs observations taken on time according to an acuity-based surveillance protocol.DesignA retrospective observational study using routinely collected data from March 2012 to March 2015.Setting32 general inpatient wards at a large acute hospital in England.Participants658 628 nursing shifts nested in 24 069 ward days.Outcome measuresThe rate of daily delayed and missed vital signs observations. We focused on situations where vital signs observations were required at least every 4 hours and measured the number of instances where observations were delayed or missed, per 24-hour period. For each ward and each day, shift patterns were characterised in terms of proportion of care hours per patient day deriving from ‘long’ shifts (≥12 hours) for both registered nurses and healthcare assistants.ResultsOn 99 043 occasions (53%), observations were significantly delayed, and on 81 568 occasions (44%), observations were missed. Observations were more likely to be delayed when a higher proportion of the hours worked by healthcare assistants were part of long shifts (IRR=1.05; 95% CI 1.00 to 1.10). No significant association was found in relation to the proportion of hours registered nurses worked as long shifts.ConclusionOn days when a higher proportion of hours worked by healthcare assistants are from long shifts, the risk of delaying vital signs observations is higher, suggesting lower job performance. While longer shifts are thought to require fewer staff resources to maintain nurse-to-patient ratios, any benefits may be lost if staff become less productive.
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| 28. |
- Diermeier, T., et al.
(author)
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Patient-Reported and Quantitative Outcomes of Anatomic Anterior Cruciate Ligament Reconstruction With Hamstring Tendon Autografts
- 2020
-
In: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 8:7
-
Journal article (peer-reviewed)abstract
- Background: The pivot-shift test has become more consistent and reliable and is a meaningful outcome measurement after anterior cruciate ligament reconstruction (ACLR). Purpose/Hypothesis: The purpose of this investigation was to assess patient-reported outcomes (PROs) and the quantitative pivot shift (QPS) preoperatively, at time zero immediately after anatomic ACLR, and after 24 months as well as the relationship between PROs and the QPS. It was hypothesized that anatomic ACLR would restore rotatory stability measured by the pivot-shift test and that QPS measurements would be positively correlated with PROs. Study Design: Cohort study; Level of evidence, 2. Methods: The ACL-injured and contralateral uninjured knees from 89 of 107 (83.2%) enrolled patients at 4 international centers were evaluated using a standardized pivot-shift test. Tibial acceleration was assessed with an inertial sensor, and lateral compartment translation was measured using an image analysis system preoperatively, at time zero immediately postoperatively, and at follow-up after 2 years. PROs were assessed at 12 and 24 months postoperatively with the International Knee Documentation Committee (IKDC) subjective knee form, Cincinnati Knee Rating System (CKRS), Marx activity rating scale, and activity of daily living score (ADLS). Results: The mean patient age at surgery was 27 years (range, 15-45 years). A positive pivot shift preoperatively (side-to-side difference in tibial acceleration, 2.6 +/- 4.0 m/s(2); side-to-side difference in anterior tibial translation, 2.0 +/- 2.0 mm) was reduced at time zero postoperatively (side-to-side difference in tibial acceleration, -0.5 +/- 1.3 m/s(2); side-to-side difference in anterior tibial translation, -0.1 +/- 1.0 mm). All PROs improved from preoperatively to final follow-up at 24 months: from 56.5 to 85.5 points for the IKDC (P= .0001), from 28.8 to 32.4 points for the CKRS (P= .04), from 11.2 to 7.9 points for the Marx (P< .0001), and from 75.7 to 91.6 points for the ADLS (P< .0001). Neither preoperative nor time zero postoperative rotatory laxity assessed by the pivot-shift test correlated with PROs at 24-month follow-up. A graft retear was observed in 4 patients (4.5%) within 2 years of follow-up. Conclusion: Anatomic ACLR resulted in significantly improved and acceptable PROs at 2-year follow-up and a low failure rate. Anatomic ACLR restored QPS measurements of anterior tibial translation and tibial acceleration to those of the contralateral knee immediately after surgery while still under anesthesia, but there was no correlation between the QPS preoperatively or at time zero after ACLR and PROs at 2-year follow-up.
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| 29. |
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| 30. |
- Janssens, Rosanne, et al.
(author)
-
Key Determinants of Health-Related Quality of Life Among Advanced Lung Cancer Patients: A Qualitative Study in Belgium and Italy
- 2021
-
In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12
-
Journal article (peer-reviewed)abstract
- Background: The lung cancer (LC) treatment landscape has drastically expanded with the arrival of immunotherapy and targeted therapy. This new variety of treatment options, each with its own characteristics, raises uncertainty regarding the key aspects affecting patients’ health-related quality of life (HRQL). The present qualitative study aimed to investigate how LC patients perceive their HRQL and the factors that they consider to be most influential in determining their HRQL.Methods: This qualitative research incorporates four focus group discussions, with six LC patients in each group. In total, 24 stage III and IV LC patients were included in the discussions, with Italian (n = 12) and Belgian (n = 12) patients, age range: 42–78, median age = 62 (IQR = 9.3 years), SD = 8.5; 62% men. Using thematic analysis, transcripts and notes from the FGDs were analyzed using NVivo software (edition 12).Results: Three main themes capturing determinants of HRQL were identified. First, patients agreed on the importance of physical aspects (symptoms and side-effects) in determining their HRQL. In particular, skin conditions, nausea, fatigue, risk of infections, sensory abnormalities, pain, and changes in physical appearance were highlighted. Second, patients worried about psychological aspects, negatively impacting their wellbeing such as uncertainties regarding their future health state, and a lower degree of autonomy and independence. Third, patients underlined the importance of social aspects, such as communication with healthcare providers and social interaction with friends, family and peers.Conclusion: This study demonstrates that physical, psychological, and social aspects are key factors driving LC patients’ HRQL. Gaining a better understanding of how LC patients perceive their HRQL and how it is affected by their illness and therapy will aid patient-centric decision-making across the drug life cycle, by providing stakeholders (drug developers, regulators, reimbursement bodies, and clinicians) insights about the treatment and disease aspects of importance to LC patients as well as the unmet needs LC patients may have regarding available treatment modalities. Finally, this study underscores a need for individual treatment decision-making that is considerate of uncertainties among LC patients about their future health state, and ways for improving communication between healthcare providers and patients to do so.
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| 31. |
- Janssens, Rosanne, et al.
(author)
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Opportunities and challenges for the inclusion of patient preferences in the medical product life cycle: a systematic review
- 2019
-
In: BMC Medical Informatics and Decision Making. - : Springer Science and Business Media LLC. - 1472-6947.
-
Journal article (peer-reviewed)abstract
- Background: The inclusion of patient preferences (PP) in the medical product life cycle is a topic of growing interest to stakeholders such as academics, Health Technology Assessment (HTA) bodies, reimbursement agencies, industry, patients, physicians and regulators. This review aimed to understand the potential roles, reasons for using PP and the expectations, concerns and requirements associated with PP in industry processes, regulatory benefitrisk assessment (BRA) and marketing authorization (MA), and HTA and reimbursement decision-making. Methods: A systematic review of peer-reviewed and grey literature published between January 2011 and March 2018 was performed. Consulted databases were EconLit, Embase, Guidelines International Network, PsycINFO and PubMed. A two-step strategy was used to select literature. Literature was analyzed using NVivo (QSR international). Results: From 1015 initially identified documents, 72 were included. Most were written from an academic perspective (61%) and focused on PP in BRA/MA and/or HTA/reimbursement (73%). Using PP to improve understanding of patients’ valuations of treatment outcomes, patients’ benefit-risk trade-offs and preference heterogeneity were roles identified in all three decision-making contexts. Reasons for using PP relate to the unique insights and position of patients and the positive effect of including PP on the quality of the decision-making process. Concerns shared across decision-making contexts included methodological questions concerning the validity, reliability and cognitive burden of preference methods. In order to use PP, general, operational and quality requirements were identified, including recognition of the importance of PP and ensuring patient understanding in PP studies. Conclusions: Despite the array of opportunities and added value of using PP throughout the different steps of the MPLC identified in this review, their inclusion in decision-making is hampered by methodological challenges and lack of specific guidance on how to tackle these challenges when undertaking PP studies. To support the development of such guidance, more best practice PP studies and PP studies investigating the methodological issues identified in this review are critically needed.
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| 32. |
- Johansson, Mattias, et al.
(author)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
-
In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
-
Journal article (peer-reviewed)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 33. |
- Kelly, Meredith A., et al.
(author)
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Late glacial fluctuations of Quelccaya Ice Cap, southeastern Peru
- 2012
-
In: Geology. - 0091-7613 .- 1943-2682. ; 40:11, s. 991-994
-
Journal article (peer-reviewed)abstract
- The last glacial-interglacial transition (ca. 18-11 ka) was interrupted by abrupt climate events that differed in each hemisphere. During the Antarctic Cold Reversal (ca. 14.5-12.9 ka), the Southern Hemisphere high and mid latitudes cooled, while the Northern Hemisphere warmed. The pattern of change then reversed during the Younger Dryas (ca. 12.9-11.7 ka), which was characterized by cold conditions in much of the Northern Hemisphere. Well-dated paleoclimate records serve to reveal the possible mechanisms for these events. Here we present a reconstruction of the late glacial fluctuations of Quelccaya Ice Cap, located in the southern tropics, based on 38 new radiocarbon ages. Quelccaya was retreating from its Last Glacial Maximum (ca. 21 ka) extent by ca. 17.2 ka, and was located upvalley from its late glacial moraines by 13.6-12.8 ka. Quelccaya experienced a significant readvance that culminated at 12.5-12.4 ka, and then receded several kilometers to near, or within, its late Holocene extent by ca. 11.6 ka. This record provides the most detailed evidence yet of glacier fluctuations in the southern tropics during late glacial time.
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| 34. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
-
In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
-
Research review (peer-reviewed)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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| 35. |
- Mitsiadis, Thimios A., et al.
(author)
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The Notch-mediated circuitry in the evolution and generation of new cell lineages: the tooth model
- 2023
-
In: Cellular and Molecular Life Sciences (CMLS). - : SPRINGER BASEL AG. - 1420-682X .- 1420-9071. ; 80:7
-
Journal article (peer-reviewed)abstract
- The Notch pathway is an ancient, evolutionary conserved intercellular signaling mechanism that is involved in cell fate specification and proper embryonic development. The Jagged2 gene, which encodes a ligand for the Notch family of receptors, is expressed from the earliest stages of odontogenesis in epithelial cells that will later generate the enamel-producing ameloblasts. Homozygous Jagged2 mutant mice exhibit abnormal tooth morphology and impaired enamel deposition. Enamel composition and structure in mammals are tightly linked to the enamel organ that represents an evolutionary unit formed by distinct dental epithelial cell types. The physical cooperativity between Notch ligands and receptors suggests that Jagged2 deletion could alter the expression profile of Notch receptors, thus modifying the whole Notch signaling cascade in cells within the enamel organ. Indeed, both Notch1 and Notch2 expression are severely disturbed in the enamel organ of Jagged2 mutant teeth. It appears that the deregulation of the Notch signaling cascade reverts the evolutionary path generating dental structures more reminiscent of the enameloid of fishes rather than of mammalian enamel. Loss of interactions between Notch and Jagged proteins may initiate the suppression of complementary dental epithelial cell fates acquired during evolution. We propose that the increased number of Notch homologues in metazoa enabled incipient sister cell types to form and maintain distinctive cell fates within organs and tissues along evolution.
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| 36. |
- Murray, Conor, et al.
(author)
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International consensus statement on the design, delivery and evaluation of sport-based interventions aimed at promoting social, psychological and physical well-being in prison
- 2024
-
In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:1
-
Journal article (peer-reviewed)abstract
- Objective: To develop an international consensus statement to advise on designing, delivering and evaluating sport-based interventions (SBIs) aimed at promoting social, psychological and physical well-being in prison.Design: Modified Delphi using two rounds of survey questionnaires and two consensus workshops.Participants: A multidisciplinary panel of more than 40 experts from 15 international jurisdictions was formed, including representation from the following groups and stakeholders: professionals working in the justice system; officials from sport federations and organisations; academics with research experience of prisons, secure forensic mental health settings and SBIs; and policy-makers in criminal justice and sport.Results: A core research team and advisory board developed the initial rationale, statement and survey. This survey produced qualitative data which was analysed thematically. The findings were presented at an in-person workshop. Panellists discussed the findings, and, using a modified nominal group technique, reached a consensus on objectives to be included in a revised statement. The core research team and advisory board revised the statement and recirculated it with a second survey. Findings from the second survey were discussed at a second, virtual, workshop. The core research team and advisory board further revised the consensus statement and recirculated it asking panellists for further comments. This iterative process resulted in seven final statement items; all participants have confirmed that they agreed with the content, objectives and recommendations of the final statement.Conclusions: The statement can be used to assist those that design, deliver and evaluate SBIs by providing guidance on: (1) minimum levels of competence for those designing and delivering SBIs; (2) the design and delivery of inclusive programmes prioritising disadvantaged groups; and (3) evaluation measures which are carefully calibrated both to capture proposed programme outcomes and to advance an understanding of the systems, processes and experiences of sport engagement in prison.
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| 37. |
- Newman, Louise, et al.
(author)
-
Delivering sustained, coordinated and integrated observations of the Southern Ocean for global impact
- 2019
-
In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
-
Research review (peer-reviewed)abstract
- The Southern Ocean is disproportionately important in its effect on the Earth system, impacting climatic, biogeochemical and ecological systems, which makes recent observed changes to this system cause for global concern. The enhanced understanding and improvements in predictive skill needed for understanding and projecting future states of the Southern Ocean require sustained observations. Over the last decade, the Southern Ocean Observing System (SOOS) has established networks for enhancing regional coordination and research community groups to advance development of observing system capabilities. These networks support delivery of the SOOS 20-year vision, which is to develop a circumpolar system that ensures time series of key variables, and deliver the greatest impact from data to all key end-users. Although the Southern Ocean remains one of the least-observed ocean regions, enhanced international coordination and advances in autonomous platforms have resulted in progress towards addressing the need for sustained observations of this region. Since 2009, the Southern Ocean community has deployed over 5700 observational platforms south of 40°S. Large-scale, multi-year or sustained, multidisciplinary efforts have been supported and are now delivering observations of essential variables at space and time scales that enable assessment of changes being observed in Southern Ocean systems. The improved observational coverage, however, is predominantly for the open ocean, encompasses the summer, consists of primarily physical oceanographic variables and covers surface to 2000 m. Significant gaps remain in observations of the ice-impacted ocean, the sea ice, depths more than 2000 m, the air-sea-ice interface, biogeochemical and biological variables, and for seasons other than summer. Addressing these data gaps in a sustained way requires parallel advances in coordination networks, cyberinfrastructure and data management tools, observational platform and sensor technology, platform interrogation and data-transmission technologies, modeling frameworks, and internationally agreed sampling requirements of key variables. This paper presents a community statement on the major scientific and observational progress of the last decade, and importantly, an assessment of key priorities for the coming decade, towards achieving the SOOS vision and delivering essential data to all end users.
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| 38. |
- Parsa, Afshin, et al.
(author)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
-
In: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
-
Journal article (peer-reviewed)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 39. |
- Pattaro, Cristian, et al.
(author)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
-
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
-
Journal article (peer-reviewed)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 40. |
- Petrocchi, Serena, et al.
(author)
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What Matters Most to Lung Cancer Patients? A Qualitative Study in Italy and Belgium to Investigate Patient Preferences
- 2021
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12
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Journal article (peer-reviewed)abstract
- Background: The potential value of patient preference studies has been recognized in clinical individual treatment decision-making between clinicians and patients, as well as in upstream drug decision-making. Drug developers, regulators, reimbursement and Health Technology Assessment (HTA) bodies are exploring how the use of patient preference studies could inform drug development, regulatory benefit risk-assessment and reimbursement decisions respectively. Understanding patient preferences may be especially valuable in decisions regarding Non-Small Cell Lung Cancer (NSCLC) treatment options, where a variety of treatment options with different characteristics raise uncertainty about which features are most important to NSCLC patients. As part of the Innovative Medicines Initiative PREFER project, this qualitative study aimed to identify patient-relevant lung cancer treatment characteristics.Methods: This study consisted of a scoping literature review and four focus group discussions, 2 in Italy and 2 in Belgium, with a total of 24 NSCLC patients (Stages III-IV). The focus group discussions sought to identify which treatment characteristics patients find most relevant. The discussions were analyzed thematically using a thematic inductive analysis.Results: Patients highlighted themes reflecting: 1) positive effects or expected gains from treatment such as greater life expectancy and maintenance of daily functioning, 2) negative effects or adverse events related to therapy that negatively impact patients’ daily functioning such as fatigue and 3) uncertainty regarding the duration and type of treatment effects. These overarching themes were consistent among patients from Belgium and Italy, suggesting that treatment aspects related to efficacy and safety as well as the psychological impact of lung cancer treatment are common areas of concern for patients, regardless of cultural background or country.Discussion: Our findings illustrate the value of using qualitative methods with patients to identify preferred treatment characteristics for advanced lung cancer. These could inform a subsequent quantitative preference survey that assesses patient trade-offs regarding treatment options.
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| 41. |
- Rambaree, Komalsingh, 1970-, et al.
(author)
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Ecosocial work and social change in community practice
- 2019
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In: Journal of Community Practice. - : Taylor & Francis. - 1070-5422 .- 1543-3706. ; 27:3-4, s. 205-212
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Journal article (other academic/artistic)abstract
- An introduction is presented in which the editor discusses articles in the issue on topics including focuses on contexts, policies, practices, and challenges for successes related to an emerging vision for eco social work; and considered that eco social work are inclusive of structural social work
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Reilly, Colin, 1977, et al.
(author)
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Scoping review and expert-based consensus recommendations for assessment and management of psychogenic non-epileptic (functional) seizures (PNES) in children: A report from the Pediatric Psychiatric Issues Task Force of the International League Against Epilepsy
- 2023
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In: EPILEPSIA. - 0013-9580 .- 1528-1167. ; 64:12, s. 3160-3195
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Journal article (peer-reviewed)abstract
- Limited guidance exists regarding the assessment and management of psychogenic non-epileptic seizures (PNES) in children. Our aim was to develop consensus-based recommendations to fill this gap. The members of the International League Against Epilepsy (ILAE) Task Force on Pediatric Psychiatric Issues conducted a scoping review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-SR) standards. This was supplemented with a Delphi process sent to pediatric PNES experts. Consensus was defined as >= 80% agreement. The systematic search identified 77 studies, the majority (55%) of which were retrospective (only one randomized clinical trial). The primary means of PNES identification was video electroencephalography (vEEG) in 84% of studies. Better outcome was associated with access to counseling/psychological intervention. Children with PNES have more frequent psychiatric disorders than controls. The Delphi resulted in 22 recommendations: Assessment-There was consensus on the importance of (1) taking a comprehensive developmental history; (2) obtaining a description of the events; (3) asking about potential stressors; (4) the need to use vEEG if available parent, self, and school reports and video recordings can contribute to a "probable" diagnosis; and (5) that invasive provocation techniques or deceit should not be employed. Management-There was consensus about the (1) need for a professional with expertise in epilepsy to remain involved for a period after PNES diagnosis; (2) provision of appropriate educational materials to the child and caregivers; and (3) that the decision on treatment modality for PNES in children should consider the child's age, cognitive ability, and family factors. Comorbidities-There was consensus that all children with PNES should be screened for mental health and neurodevelopmental difficulties. Recommendations to facilitate the assessment and management of PNES in children were developed. Future directions to fill knowledge gaps were proposed.
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| 46. |
- Rodriguez-Palmero, Agusti, et al.
(author)
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DLG4-related synaptopathy : a new rare brain disorder
- 2021
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In: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 23:5, s. 888-899
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Journal article (peer-reviewed)abstract
- PurposePostsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.MethodsThe clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing.ResultsThe clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit–hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies.ConclusionThe present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.
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| 47. |
- Smith, Meredith Y., et al.
(author)
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Patients as research partners in preference studies: learnings from IMI-PREFER
- 2023
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In: Research Involvement and Engagement. - 2056-7529. ; 9:1
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Journal article (peer-reviewed)abstract
- Background: There is growing recognition of the importance of patient and public stakeholder involvement (PPI) in patient preference research. However, limited evidence exists regarding the impact, barriers and enablers of PPI in preference studies. The Innovative Medicines Initiative (IMI)-PREFER project conducted a series of preference case studies which incorporated PPI.Objective: To describe: (1) how PPI was operationalized in the PREFER case studies, (2) the impact of PPI, and (3) factors that served to impede and facilitate PPI.Methods: We reviewed the PREFER final study reports to determine how patient partners were involved. We conducted a thematic framework analysis to characterize the impact of PPI and then administered a questionnaire to the PREFER study leads to identify barriers and facilitators to effective PPI.Results: Eight PREFER case studies involved patients as research partners. Patient partners were involved in activities spanning all phases of the patient preference research process, including in study design, conduct and dissemination. However, the type and degree of patient partner involvement varied considerably. Positive impacts of PPI included improvements in the: (1) quality of the research and research process; (2) patient partner empowerment; (3) study transparency and dissemination of results; (4) research ethics, and (5) trust and respect between the research team and the patient community. Of the 13 barriers identified, the 3 most frequently reported were inadequate resources, insufficient time to fully involve patient partners, and uncertainty regarding how to operationalize the role of ‘patient partner. Among the 12 facilitators identified, the two most frequently cited were (1) having a clearly stated purpose for involving patients as research partners; and (2) having multiple patient partners involved in the study.Conclusion: PPI had many positive impacts on the PREFER studies. Preference study leads with prior PPI experience reported a greater number of positive impacts than those with no such experience. In light of the numerous barriers identified, multi-faceted implementation strategies should be considered to support adoption, integration and sustainment of PPI within preference research. Additional case studies of patient partner involvement in preference research are needed as well to inform best practices in this area.
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| 48. |
- Wallgren, Arne, 1940, et al.
(author)
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Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer.
- 2009
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In: The New England journal of medicine. - 1533-4406. ; 361:8, s. 766-76
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS: In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS: At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P=0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)
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| 49. |
- Whichello, Chiara, et al.
(author)
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Factors and Situations Affecting the Value of Patient Preference Studies : Semi-Structured Interviews in Europe and the US
- 2019
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In: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 10
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Journal article (peer-reviewed)abstract
- Objectives: Patient preference information (PPI) is gaining recognition among the pharmaceutical industry, regulatory authorities, and health technology assessment (HTA) bodies/payers for use in assessments and decision-making along the medical product lifecycle (MPLC). This study aimed to identify factors and situations that influence the value of patient preference studies (PPS) in decision-making along the MPLC according to different stakeholders.Methods: Semi-structured interviews (n = 143) were conducted with six different stakeholder groups (physicians, academics, industry representatives, regulators, HTA/payer representatives, and a combined group of patients, caregivers, and patient representatives) from seven European countries (the United Kingdom, Sweden, Italy, Romania, Germany, France, and the Netherlands) and the United States. Framework analysis was performed using NVivo 11 software.Results: Fifteen factors affecting the value of PPS in the MPLC were identified. These are related to: study organization (expertise, financial resources, study duration, ethics and good practices, patient centeredness), study design (examining patient and/or other preferences, ensuring representativeness, matching method to research question, matching method to MPLC stage, validity and reliability, cognitive burden, patient education, attribute development), and study conduct (patients’ ability/willingness to participate and preference heterogeneity). Three types of situations affecting the use of PPS results were identified (stakeholder acceptance, market situations, and clinical situations).Conclusion: The factors and situation types affecting the value of PPS, as identified in this study, need to be considered when designing and conducting PPS in order to promote the integration of PPI into decision-making along the MPLC.
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| 50. |
- Zhang, Guojie, et al.
(author)
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Comparative genomics reveals insights into avian genome evolution and adaptation
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1311-1320
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Journal article (peer-reviewed)abstract
- Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
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