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| 2. |
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| 3. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 5. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
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| 7. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 12. |
- Dixon-Suen, Suzanne C, et al.
(author)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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In: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 13. |
- Ovadia, C., et al.
(author)
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Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis
- 2021
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In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 6:7
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Journal article (peer-reviewed)abstract
- Background Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes. Methods In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 mu mol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495. Findings The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67.8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0.7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0.6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1.04, 95% CI 0.35-3.07; p=0.95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0.29, 95% CI 0.04-2.42; p=0.25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1.28, 95% CI 0.86-1.91; p=0.22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0.60, 0.39-0.91; p=0.016). Interpretation Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment. Copyright (C) 2021 The Authors(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 14. |
- Sanchez, Erlan, et al.
(author)
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Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative
- 2024
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In: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1753-1770
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Journal article (peer-reviewed)abstract
- INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ42/40. DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.
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| 15. |
- Dixon, P. H., et al.
(author)
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GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility. Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.
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| 16. |
- Ovadia, C., et al.
(author)
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Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher’s exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19. © 2020, The Author(s).
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| 17. |
- Bell, Taylor, et al.
(author)
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Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b
- 2024
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In: Nature Astronomy. - 2397-3366. ; 8:7, s. 879-898
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Journal article (peer-reviewed)abstract
- Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 μm to 12 μm with the JWST’s Mid-Infrared Instrument. The spectra reveal a large day–night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1–6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet’s nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models.
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| 18. |
- Akdemir, KC, et al.
(author)
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Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
- 2020
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 294-
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Journal article (peer-reviewed)abstract
- Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.
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| 19. |
- de Vries, Claire E. E., et al.
(author)
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Outcomes of the first global multidisciplinary consensus meeting including persons living with obesity to standardize patient-reported outcome measurement in obesity treatment research
- 2022
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In: Obesity Reviews. - : John Wiley & Sons. - 1467-7881 .- 1467-789X. ; 23:8
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Journal article (peer-reviewed)abstract
- Quality of life is a key outcome that is not rigorously measured in obesity treatment research due to the lack of standardization of patient-reported outcomes (PROs) and PRO measures (PROMs). The S.Q.O.T. initiative was founded to Standardize Quality of life measurement in Obesity Treatment. A first face-to-face, international, multidisciplinary consensus meeting was conducted to identify the key PROs and preferred PROMs for obesity treatment research. It comprised of 35 people living with obesity (PLWO) and healthcare providers (HCPs). Formal presentations, nominal group techniques, and modified Delphi exercises were used to develop consensus-based recommendations. The following eight PROs were considered important: self-esteem, physical health/functioning, mental/psychological health, social health, eating, stigma, body image, and excess skin. Self-esteem was considered the most important PRO, particularly for PLWO, while physical health was perceived to be the most important among HCPs. For each PRO, one or more PROMs were selected, except for stigma. This consensus meeting was a first step toward standardizing PROs (what to measure) and PROMs (how to measure) in obesity treatment research. It provides an overview of the key PROs and a first selection of the PROMs that can be used to evaluate these PROs.
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| 20. |
- Markmann, James F., et al.
(author)
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Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes
- 2021
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In: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 21:4, s. 1477-1492
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Journal article (peer-reviewed)abstract
- Allogeneic islet transplant offers a minimally invasive option for beta cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and HbA(1c) <= 6.5% or reduced by >= 1 percentage point at 1 year posttransplant. Median HbA(1c)declined from 8.1% before to 6.0% at 1 year and 6.3% at 2 and 3 years following transplant (P < .001 for all vs baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality of life. The procedure was safe and kidney allograft function remained stable after 3 years. These results add to evidence establishing allogeneic islet transplant as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post-renal transplant setting.
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| 21. |
- Peters, Ruth, et al.
(author)
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An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.
- 2020
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In: Neurology. - 1526-632X. ; 94:3
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Journal article (peer-reviewed)abstract
- High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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| 22. |
- Turro, Ernest, et al.
(author)
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Whole-genome sequencing of patients with rare diseases in a national health system.
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 583:7814, s. 96-102
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Journal article (peer-reviewed)abstract
- Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065extensively phenotypedparticipants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data ofUK Biobankparticipants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
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| 23. |
- Beitchman, Joshua A. A., et al.
(author)
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Spatial Distribution of Neuropathology and Neuroinflammation Elucidate the Biomechanics of Fluid Percussion Injury
- 2021
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In: NEUROTRAUMA REPORTS. - : Mary Ann Liebert. - 2689-288X. ; 2:1, s. 59-75
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Journal article (peer-reviewed)abstract
- Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. We hypothesized that local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology. We demonstrated local thickening of the skull at the temporal ridges using contour analysis on magnetic resonance imaging. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, and 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge before injury reduced injury-induced inflammation in the sensorimotor cortex. These data build evidence for temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy.
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| 24. |
- Cassetta, L, et al.
(author)
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Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation
- 2020
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In: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:2
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Journal article (peer-reviewed)abstract
- Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells.MethodsWe developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders.ResultsWe observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC.ConclusionsThis study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation.
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| 25. |
- Di Sacco, A., et al.
(author)
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Ten golden rules for reforestation to optimize carbon sequestration, biodiversity recovery and livelihood benefits
- 2021
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 27:7, s. 1328-1348
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Journal article (peer-reviewed)abstract
- Urgent solutions to global climate change are needed. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon to partly compensate for anthropogenic CO2 emissions, which are a major cause of rising global temperatures. However, tree planting that is poorly planned and executed could actually increase CO2 emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose 10 golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery while improving livelihoods. These are as follows: (1) Protect existing forest first; (2) Work together (involving all stakeholders); (3) Aim to maximize biodiversity recovery to meet multiple goals; (4) Select appropriate areas for restoration; (5) Use natural regeneration wherever possible; (6) Select species to maximize biodiversity; (7) Use resilient plant material (with appropriate genetic variability and provenance); (8) Plan ahead for infrastructure, capacity and seed supply; (9) Learn by doing (using an adaptive management approach); and (10) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities as sources of indigenous knowledge, and the benefits they could derive from successful reforestation that restores ecosystem functioning and delivers a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is crucial to build upon the currently growing public and private interest in this topic, to ensure interventions provide effective, long-term carbon sinks and maximize benefits for biodiversity and people.
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| 26. |
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| 27. |
- Léget, P-F, et al.
(author)
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SUGAR : An improved empirical model of Type Ia supernovae based on spectral features
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
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Journal article (peer-reviewed)abstract
- Context. Type Ia supernovae (SNe Ia) are widely used to measure the expansion of the Universe. Improving distance measurements of SNe Ia is one technique to better constrain the acceleration of expansion and determine its physical nature.Aims. This document develops a new SNe Ia spectral energy distribution (SED) model, called the SUpernova Generator And Reconstructor (SUGAR), which improves the spectral description of SNe Ia, and consequently could improve the distance measurements.Methods. This model was constructed from SNe Ia spectral properties and spectrophotometric data from the Nearby Supernova Factory collaboration. In a first step, a principal component analysis-like method was used on spectral features measured at maximum light, which allowed us to extract the intrinsic properties of SNe Ia. Next, the intrinsic properties were used to extract the average extinction curve. Third, an interpolation using Gaussian processes facilitated using data taken at different epochs during the lifetime of an SN Ia and then projecting the data on a fixed time grid. Finally, the three steps were combined to build the SED model as a function of time and wavelength. This is the SUGAR model.Results. The main advancement in SUGAR is the addition of two additional parameters to characterize SNe Ia variability. The first is tied to the properties of SNe Ia ejecta velocity and the second correlates with their calcium lines. The addition of these parameters, as well as the high quality of the Nearby Supernova Factory data, makes SUGAR an accurate and efficient model for describing the spectra of normal SNe Ia as they brighten and fade.Conclusions. The performance of this model makes it an excellent SED model for experiments like the Zwicky Transient Facility, the Large Synoptic Survey Telescope, or the Wide Field Infrared Survey Telescope.
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| 28. |
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| 29. |
- Rigault, M., et al.
(author)
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Strong dependence of Type Ia supernova standardization on the local specific star formation rate
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644
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Journal article (peer-reviewed)abstract
- As part of an on-going effort to identify, understand and correct for astrophysics biases in the standardization of Type Ia supernovae (SN Ia) for cosmology, we have statistically classified a large sample of nearby SNe Ia into those that are located in predominantly younger or older environments. This classification is based on the specific star formation rate measured within a projected distance of 1 kpc from each SN location (LsSFR). This is an important refinement compared to using the local star formation rate directly, as it provides a normalization for relative numbers of available SN progenitors and is more robust against extinction by dust. We find that the SNe Ia in predominantly younger environments are ΔY = 0.163 ± 0.029 mag (5.7σ) fainter than those in predominantly older environments after conventional light-curve standardization. This is the strongest standardized SN Ia brightness systematic connected to the host-galaxy environment measured to date. The well-established step in standardized brightnesses between SNe Ia in hosts with lower or higher total stellar masses is smaller, at ΔM = 0.119 ± 0.032 mag (4.5σ), for the same set of SNe Ia. When fit simultaneously, the environment-age offset remains very significant, with ΔY = 0.129 ± 0.032 mag (4.0σ), while the global stellar mass step is reduced to ΔM = 0.064 ± 0.029 mag (2.2σ). Thus, approximately 70% of the variance from the stellar mass step is due to an underlying dependence on environment-based progenitor age. Also, we verify that using the local star formation rate alone is not as powerful as LsSFR at sorting SNe Ia into brighter and fainter subsets. Standardization that only uses the SNe Ia in younger environments reduces the total dispersion from 0.142 ± 0.008 mag to 0.120 ± 0.010 mag. We show that as environment-ages evolve with redshift, a strong bias, especially on the measurement of the derivative of the dark energy equation of state, can develop. Fortunately, data that measure and correct for this effect using our local specific star formation rate indicator, are likely to be available for many next-generation SN Ia cosmology experiments.
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| 30. |
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| 31. |
- Dixon, A., et al.
(author)
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PRESERVING BRIGHT ELECTRON BEAMS : DISTORTED CSR KICKS
- 2022
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In: LINAC 2022 - International Linear Accelerator Conference, Proceedings. - 2226-0366. - 9783954502158 ; , s. 91-94
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Conference paper (peer-reviewed)abstract
- Short pulse, low emittance electron beams are necessary to drive bright FEL X-rays, for this reason it is important to preserve and limit emittance growth. The strong bunch compression required to achieve the short bunches, can lead to coherent synchrotron radiation (CSR)-induced emittance growth, and while there are some methods of CSR cancellation, these methods may be less effective when the CSR kicks are distorted. In an attempt to understand why CSR kicks become distorted, we compare the CSR kicks calculated using the whole beam parameters to the CSR kicks calculated using the longitudinally sliced beam parameters, when propagated to the end of the bunch compressor. We find that CSR kicks can become distorted when calculated with non-uniform slice beam parameters. While slice beam parameters that are uniform along the centre of the bunch, do not result in distorted CSR kicks.
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| 32. |
- Hayes, Steven C., et al.
(author)
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Report of the ACBS Task Force on the strategies and tactics of contextual behavioral science research
- 2021
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In: Journal of Contextual Behavioral Science. - : Elsevier. - 2212-1447. ; 20, s. 172-183
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Journal article (peer-reviewed)abstract
- Throughout its history the strategy and tactics of contextual behavioral science (CBS) research have had distinctive features as compared to traditional behavioral science approaches. Continued progress in CBS research can be facilitated by greater clarity about how its strategy and tactics can be brought to bear on current challenges. The present white paper is the result of a 2 1/2-year long process designed to foster consensus among representative producers and consumers of CBS research about the best strategic pathway forward. The Task Force agreed that CBS research should be multilevel, process-based, multidimensional, prosocial, and pragmatic, and provided 33 recommendations to the CBS community arranged across these characteristics. In effect, this report provides a detailed research agenda designed to maximize the impact of CBS as a field. Scientists and practitioners are encouraged to mount this ambitious agenda.
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| 33. |
- Kelley, Steven P., et al.
(author)
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Dehydration of UO2Cl2 center dot 3H(2)O and Nd(NO3)(3)center dot 6H(2)O with a Soft Donor Ligand and Comparison of Their Interactions through X-ray Diffraction and Theoretical Investigation
- 2020
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In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 59:5, s. 2861-2869
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Journal article (peer-reviewed)abstract
- We investigated whether the relatively Lewis basic imidazole-2-thiones could be used to substitute water ligands bound to f-element cations and generate f-element soft donor complexes. Reactions of 1,3-diethylimidazole-2-thione (C(2)C(2)ImT) with Nd(NO3)(3)center dot 6H(2)O and UO2Cl2 center dot 3H(2)O led to the isolation of the anhydrous thione complexes Nd(NO3)(3)(C(2)C(2)ImT)(3) and UO2Cl2(C(2)C(2)ImT)(2), characterized by single crystal X-ray diffraction. Differences in the strength of metal-thione interactions have been examined by means of the crystal structure analysis and density functional theory (DFT) calculations. The C(2)C(2)ImT ligands were found to be affected by both coordination and noncovalent interactions, making it impossible to deconvolute the effects of one from the other. Calculated partial atomic charges indicated greater ligand-to-metal charge transfer in the [UO2](2+) complex, indicative of a stronger interaction. The reactivity of C(2)C(2)ImT demonstrates its usefulness in the preparation of f-element soft donor complexes from readily available hydrates that could be useful intermediates for promoting the coordination and studying the effects of soft donor anions.
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| 34. |
- Mishra, Manish Kumar, et al.
(author)
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Crystallographic evidence of Watson-Crick connectivity in the base pair of anionic adenine with thymine
- 2020
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:31, s. 18224-18230
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Journal article (peer-reviewed)abstract
- Utilizing an ionic liquid strategy, we report crystal structures of salts of free anionic nucleobases and base pairs previously studied only computationally and in the gas phase. Reaction of tetrabutylammonium ([N-4444](+)) or tetrabutylphosphonium ([P-4444](+)) hydroxide with adenine (HAd) and thymine (HThy) led to hydrated salts of deprotonated adenine, [N-4444][Ad]center dot 2H(2)O, and thymine, [P4444][Thy]center dot 2H(2)O, as well as the double salt cocrystal, [P-4444](2)[Ad][Thy]center dot 3H(2)O center dot 2HThy. The cocrystal includes the anionic [Ad-(HThy)] base pair which is a stable formation in the solid state that has previously not even been suggested. It exhibits Watson-Crick connectivity as found in DNA but which is unusual for the free neutral base pairs. The stability of the observed anionic bases and their supramolecular formations and hydrates has also been examined by electronic structure calculations, contributing to more insight into how base pairs can bind when a proton is removed and highlighting mechanisms of stabilization or chemical transformation in the DNA chains.
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| 35. |
- Onerup, Aron, 1983, et al.
(author)
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Lifestyle and Subsequent Malignant Neoplasms in Childhood Cancer Survivors: A Report from the St. Jude Lifetime Cohort Study
- 2024
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In: CANCERS. - 2072-6694. ; 16:5
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Journal article (peer-reviewed)abstract
- Simple Summary It has been shown that lifestyle factors such as smoking, alcohol consumption, diet, and physical activity affect the risk of developing cancer in older adults. While this is not the case for childhood cancers, survivors of childhood cancer are at increased risk of developing cancer in adulthood, called subsequent malignant neoplasms, due to the cancer treatment they received in childhood. We aimed to assess whether the risk of developing subsequent malignant neoplasms in young adulthood was associated with lifestyle factors. We could not see any association between lifestyle factors and subsequent malignant neoplasms in young adult childhood cancer survivors. This suggests that while lifestyle has other health benefits, it is possible that the risk of subsequent malignant neoplasms in young adult childhood cancer survivors cannot be modified with lifestyle behaviors.Abstract Introduction: This study aimed to assess longitudinal associations between lifestyle and subsequent malignant neoplasms (SMNs) in young adult childhood cancer survivors. Methods: Members of the St. Jude Lifetime Cohort (SJLIFE) aged >= 18 years and surviving >= 5 years after childhood cancer diagnosis were queried and evaluated for physical activity, cardiorespiratory fitness (CRF), muscle strength, body mass index (BMI), smoking, risky drinking, and a combined lifestyle score. Time to first SMN, excluding nonmalignant neoplasms and nonmelanoma skin cancer, was the outcome of longitudinal analysis. Results: Survivors (n = 4072, 47% female, 29% smokers, 37% risky drinkers, 34% obese, and 48% physically inactive) had a mean (SD) time between baseline evaluation and follow-up of 7.0 (3.3) years, an age of 8.7 (5.7) years at diagnosis, and an age of 30 (8.4) years at baseline lifestyle assessment. Neither individual lifestyle factors nor a healthy lifestyle score (RR 0.8, 0.4-1.3, p = 0.36) were associated with the risk of developing an SMN. Conclusions: We did not identify any association between lifestyle factors and the risk of SMN in young adult childhood cancer survivors.
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| 36. |
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| 37. |
- Travaglini, Gabriele, et al.
(author)
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The SAGEX review on scattering amplitudes
- 2022
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In: Journal of Physics A. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 55:44
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Research review (peer-reviewed)abstract
- This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.
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| 38. |
- van Soest, Maud A. J., et al.
(author)
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Grazing and topography control nutrient pools in low Arctic soils of Southwest Greenland
- 2022
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In: European Journal of Soil Science. - : John Wiley & Sons. - 1351-0754 .- 1365-2389. ; 73:4
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Journal article (peer-reviewed)abstract
- Soil nutrient pools in the dry low Arctic are likely to be released under climatic change and this bioavailability has the potential to increase both terrestrial and aquatic productions. As well as the direct effect of warming, external disturbances such as nutrient deposition and grazing can also drive ecosystem change. This study in the low Arctic Kangerlussuaq area of southwest Greenland compared soil nutrient pools in terms of both topographic position on a catena and by soil depth in two small catchments with contrasting muskox abundance. We tested the hypotheses that there were differences between soil carbon (C), nitrogen (N) and phosphorus (P) across a soil catena (ridge - slope - valley) and by soil depth (litter - 0–5 cm - 25–30 cm) for the two sites (SS17b, muskox present, versus - SS85, no muskox). Total C and N concentrations of soils were on average lower at SS17b compared to SS85. Moreover, the soil N concentration increased downslope in the catena with higher amounts in the valleys compared to the slopes and ridges. Soil P concentration (0.70 g P kg−1) was similar between catchments; however, litter P content was substantially different. The difference in soil nutrients between the two catchments was most likely due to the presence of muskox at SS17b, and hence grazing associated processes (defecation, altered microbiology and nutrient cycling). This study emphasises the heterogeneity of arctic landscapes and need for ecosystem specific research.Highlights:Soil nutrient pools in two low-arctic catchments in Greenland were compared.Grazing and dung inputs by muskox affect soil nutrient pools in Greenland.Soil P stores in Kangerlussuaq are similar to intensively managed farmland in Europe.The heterogeneity of arctic landscapes and need for ecosystem-specific research are emphasised.
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