| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Khatri, C, et al.
(författare)
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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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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Abe, H., et al.
(författare)
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Gamma-ray observations of MAXI J1820+070 during the 2018 outburst
- 2022
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 517:4, s. 4736-4751
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Tidskriftsartikel (refereegranskat)abstract
- MAXIJ1820+070 is a low-mass X-ray binary with a black hole (BH) as a compact object. This binary underwent an exceptionally bright X-ray outburst from 2018 March to October, showing evidence of a non-thermal particle population through its radio emission during this whole period. The combined results of 59.5 h of observations of the MAXI J1820+070 outburst with the H.E.S.S., MAGIC and VERITAS experiments at energies above 200 GeV are presented, together with Fermi-LAT data between 0.1 and 500 GeV, and multiwavelength observations from radio to X-rays. Gamma-ray emission is not detected from MAXI J1820+070, but the obtained upper limits and the multiwavelength data allow us to put meaningful constraints on the source properties under reasonable assumptions regarding the non-thermal particle population and the jet synchrotron spectrum. In particular, it is possible to show that, if a high-energy (HE) gamma-ray emitting region is present during the hard state of the source, its predicted flux should be at most a factor of 20 below the obtained Fermi-LAT upper limits, and closer to them for magnetic fields significantly below equipartition. During the state transitions, under the plausible assumption that electrons are accelerated up to similar to 500 GeV, the multiwavelength data and the gamma-ray upper limits lead consistently to the conclusion that a potential HE and very-HE gamma-ray emitting region should be located at a distance from the BH ranging between 10(11) and 10(13) cm. Similar outbursts from low-mass X-ray binaries might be detectable in the near future with upcoming instruments such as CTA.
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| 6. |
- Mullins, N., et al.
(författare)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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| 7. |
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| 11. |
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| 12. |
- Hamilton, B. R., et al.
(författare)
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Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement
- 2021
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Ingår i: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 51:7, s. 1401-1415
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Tidskriftsartikel (refereegranskat)abstract
- Sport is historically designated by the binary categorization of male and female that conflicts with modern society. Sport's governing bodies should consider reviewing rules determining the eligibility of athletes in the female category as there may be lasting advantages of previously high testosterone concentrations for transwomen athletes and currently high testosterone concentrations in differences in sex development (DSD) athletes. The use of serum testosterone concentrations to regulate the inclusion of such athletes into the elite female category is currently the objective biomarker that is supported by most available scientific literature, but it has limitations due to the lack of sports performance data before, during or after testosterone suppression. Innovative research studies are needed to identify other biomarkers of testosterone sensitivity/responsiveness, including molecular tools to determine the functional status of androgen receptors. The scientific community also needs to conduct longitudinal studies with specific control groups to generate the biological and sports performance data for individual sports to inform the fair inclusion or exclusion of these athletes. Eligibility of each athlete to a sport-specific policy needs to be based on peer-reviewed scientific evidence made available to policymakers from all scientific communities. However, even the most evidence-based regulations are unlikely to eliminate all differences in performance between cisgender women with and without DSD and transwomen athletes. Any remaining advantage held by transwomen or DSD women could be considered as part of the athlete's unique makeup.
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| 13. |
- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 14. |
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| 17. |
- Mansouri, L, et al.
(författare)
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Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY
- 2023
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 37:2, s. 339-347
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3–9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Bethlehem, RAI, et al.
(författare)
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Brain charts for the human lifespan
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
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Tidskriftsartikel (refereegranskat)abstract
- Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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| 22. |
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| 23. |
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| 24. |
- Eriksson, L. S.E., et al.
(författare)
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Ultrasound-based risk model for preoperative prediction of lymph-node metastases in women with endometrial cancer : model-development study
- 2020
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:3, s. 443-452
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. Methods: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). Results: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68–0.78), the calibration slope was 1.06 (95% CI, 0.79–1.34) and the calibration intercept was 0.06 (95% CI, –0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. Conclusions: Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound.
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| 25. |
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| 26. |
- Harmsen, M. J., et al.
(författare)
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Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis : results of modified Delphi procedure
- 2022
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 60:1, s. 118-131
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate whether the Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis need to be better defined and, if deemed necessary, to reach consensus on the updated definitions. Methods: A modified Delphi procedure was performed among European gynecologists with expertise in ultrasound diagnosis of adenomyosis. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings also included three-dimensional (3D) still images) of transvaginal ultrasound (TVS) examinations of the uterus were presented in the first Delphi round (online questionnaire). Experts were asked to confirm or refute the presence of each of the nine MUSA features of adenomyosis (described in the original MUSA consensus statement) in each of the 15 videoclips and to provide comments. In the second Delphi round (online questionnaire), the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVS examinations and to provide feedback on the proposed revisions. A third Delphi round (virtual group meeting) was conducted to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts. Results: Of 18 invited experts, 16 agreed to participate in the Delphi procedure. Eleven experts completed and four experts partly finished the first round. The experts identified a need for more detailed definitions of some MUSA features. They recommended use of 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts participated in the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most of the still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the online meeting, in which they discussed and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct features of adenomyosis, i.e. features indicating presence of ectopic endometrial tissue in the myometrium, and indirect features, i.e. features reflecting changes in the myometrium secondary to presence of endometrial tissue in the myometrium. Myometrial cysts, hyperechogenic islands and echogenic subendometrial lines and buds were classified unanimously as direct features of adenomyosis. Globular uterus, asymmetrical myometrial thickening, fan-shaped shadowing, translesional vascularity, irregular junctional zone and interrupted junctional zone were classified as indirect features of adenomyosis. Conclusion: Consensus between gynecologists with expertise in ultrasound diagnosis of adenomyosis was achieved regarding revised definitions of the MUSA features of adenomyosis and on the classification of MUSA features as direct or indirect signs of adenomyosis.
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| 27. |
- Heard, J. M., et al.
(författare)
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Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network
- 2020
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The European Medicine Agency granted marketing approval to 164 orphan medicinal products for rare diseases, among which 28 products intended for the treatment of hereditary metabolic diseases. Taking advantage of its privileged connection with 69 healthcare centres of excellence in this field, MetabERN, the European Reference Network for hereditary metabolic diseases, performed a survey asking health care providers from 18 European countries whether these products are available on the market, reimbursed and therefore accessible for prescription, and actually delivered in their centre. Results Responses received from 52 centres (75%) concerned the design of treatment plans, the access to marketed products, and the barriers to delivery. Treatment options are always discussed with patients, who are often involved in their treatment plan. Most products (26/28) are available in most countries (15/18). Among the 15 broadly accessible products (88.5% of the centres), 9 are delivered to most patients (mean 70.1%), and the others to only few (16.5%). Among the 10 less accessible products (40.2% of the centres), 6 are delivered to many patients (66.7%), and 4 are rarely used (6.3%). Information was missing for 3 products. Delay between prescription and delivery is on average one month. Beside the lack of availability or accessibility, the most frequent reasons for not prescribing a treatment are patients' clinical status, characteristic, and personal choice. Conclusions Data collected from health care providers in the MetabERN network indicate that two-third of the orphan medicines approved by EMA for the treatment of hereditary metabolic diseases are accessible to treating patients, although often less than one-half of the patients with the relevant conditions actually received the approved product to treat their disease. Thus, in spite of the remarkable achievement of many products, patients concerned by EMA-approved orphan medicinal products have persistent unmet needs, which deserve consideration. The enormous investments made by the companies to develop products, and the high financial burden for the Member States to purchase these products emphasize the importance of a scrupulous appreciation of treatment value involving all stakeholders at early stage of development, before marketing authorization, and during follow up.
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| 28. |
- Heremans, R., et al.
(författare)
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Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA-1 multinomial regression model : validation study
- 2023
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Ingår i: Ultrasound in Obstetrics and Gynecology. - 0960-7692.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. Methods: This was a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). The IETA-3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow-up of non-endometrial pathology, in the work-up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow-up of at least 1 year if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver-operating-characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). Results: The median age of the women in the IETA-3 cohort was 51 (range, 20–85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI, 0.73–0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32–0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62–0.73) (n = 1532). The IETA-1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95–0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75–0.91), compared with 0.62 (95% CI, 0.52–0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08–0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI, 0.71–0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60–0.81) (difference in AUC, 0.11; 95% CI, 0.01–0.20). Conclusion: The IETA-1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories.
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| 29. |
- Heremans, R., et al.
(författare)
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Ultrasound features of endometrial pathology in women without abnormal uterine bleeding : results from the International Endometrial Tumor Analysis study (IETA3)
- 2022
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Ingår i: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 60:2, s. 243-255
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB. METHODS: This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology. RESULTS: In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized. CONCLUSIONS: We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts.
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| 30. |
- Hidalgo, F, et al.
(författare)
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How do coffee farmers engage with digital technologies? A capabilities perspective
- 2024
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Ingår i: Agriculture and Human Values. - 0889-048X.
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Tidskriftsartikel (refereegranskat)abstract
- A reality-design gap in the conceptualization and practice of digital agriculture has been systematically reported in the literature. This condition is favored by the lack of understanding and inclusion of local worldviews around digital technologies. Informed by Amartya Sen’s capabilities approach, this study looks to bring stories of local appropriation to the spotlight. Based on a qualitative approach that included data collected through interviews with 73 households, the authors explored the way in which two selected communities of Colombian coffee growers are engaged in the use of digital technologies in material and symbolic ways. Three emergent themes—a relational way of farming, (dis)connected machines, and nurtured families and communities – articulate multiple interactions between farmers, farms, institutional programs, and technologies, that originate local forms of digitalization (and non-digitalization). This study points out the relevant role of situated ideas of development in positioning technologies in or out of the farm, and broader digitalization agendas in or out of farmers’ life projects. At the same time, it presents a critique of notions of universality that drive unquestioned quests for technification. In contrast, building on a relational perspective, this study calls for embracing a perspective of multiplicity within notions of development and innovation.
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| 31. |
- Jordans, I. P.M., et al.
(författare)
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Definition and sonographic reporting system for Cesarean scar pregnancy in early gestation : modified Delphi method
- 2022
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 59:4, s. 437-449
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop a standardized sonographic evaluation and reporting system for Cesarean scar pregnancy (CSP) in the first trimester, for use by both general gynecology and expert clinics. Methods: A modified Delphi procedure was carried out, in which 28 international experts in obstetric and gynecological ultrasonography were invited to participate. Extensive experience in the use of ultrasound to evaluate Cesarean section (CS) scars in early pregnancy and/or publications concerning CSP or niche evaluation was required to participate. Relevant items for the detection and evaluation of CSP were determined based on the results of a literature search. Consensus was predefined as a level of agreement of at least 70% for each item, and a minimum of three Delphi rounds were planned (two online questionnaires and one group meeting). Results: Sixteen experts participated in the Delphi study and four Delphi rounds were performed. In total, 58 items were determined to be relevant. We differentiated between basic measurements to be performed in general practice and advanced measurements for expert centers or for research purposes. The panel also formulated advice on indications for referral to an expert clinic. Consensus was reached for all 58 items on the definition, terminology, relevant items for evaluation and reporting of CSP. It was recommended that the first CS scar evaluation to determine the location of the pregnancy should be performed at 6–7 weeks' gestation using transvaginal ultrasound. The use of magnetic resonance imaging was not considered to add value in the diagnosis of CSP. A CSP was defined as a pregnancy with implantation in, or in close contact with, the niche. The experts agreed that a CSP can occur only when a niche is present and not in relation to a healed CS scar. Relevant sonographic items to record included gestational sac (GS) size, vascularity, location in relation to the uterine vessels, thickness of the residual myometrium and location of the pregnancy in relation to the uterine cavity and serosa. According to its location, a CSP can be classified as: (1) CSP in which the largest part of the GS protrudes towards the uterine cavity; (2) CSP in which the largest part of the GS is embedded in the myometrium but does not cross the serosal contour; and (3) CSP in which the GS is partially located beyond the outer contour of the cervix or uterus. The type of CSP may change with advancing gestation. Future studies are needed to validate this reporting system and the value of the different CSP types. Conclusion: Consensus was achieved among experts regarding the sonographic evaluation and reporting of CSP in the first trimester.
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| 32. |
- Loibl, S., et al.
(författare)
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ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC)
- 2023
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Ingår i: Annals of Oncology. - 0923-7534. ; 34:10, s. 849-866
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Tidskriftsartikel (refereegranskat)abstract
- The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: 1. PrBC: incidence, epidemiology, biology and pathology, diagnostic work-up, staging and risk assessment, prognosis (Chairs: Vincent Vandecaveye, Fedro Peccatori). 2. Clinical pharmacology of systemic agents during pregnancy: management of localized disease and (neo) adjuvant therapies, management of systemic disease (Chairs: Giuseppe Curigliano, Peter Schmid). 3. Obstetric care and fetal/newborn follow-up and outcomes: metastases to fetus, management of pregnancy during anticancer therapy, lactation, psychological support (Chairs: Elyce Cardonick, Mathilde van Gerwen). Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.
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| 33. |
- Mangano, M. C., et al.
(författare)
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The aquaculture supply chain in the time of covid-19 pandemic : Vulnerability, resilience, solutions and priorities at the global scale
- 2022
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Ingår i: Environmental Science and Policy. - : Elsevier. - 1462-9011 .- 1873-6416. ; 127, s. 98-110
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 global pandemic has had severe, unpredictable and synchronous impacts on all levels of perishable food supply chains (PFSC), across multiple sectors and spatial scales. Aquaculture plays a vital and rapidly expanding role in food security, in some cases overtaking wild caught fisheries in the production of high quality animal protein in this PFSC. We performed a rapid global assessment to evaluate the effects of the COVID19 pandemic and related emerging control measures on the aquaculture supply chain. Socio-economic effects of the pandemic were analysed by surveying the perceptions of stakeholders, who were asked to describe potential supply-side disruption, vulnerabilities and resilience patterns along the production pipeline with four main supply chain components: a) hatchery, b) production/processing, c) distribution/logistics and d) market. We also assessed different farming strategies, comparing land-vs. sea-based systems; extensive vs. intensive methods; and with and without integrated multi-trophic aquaculture, IMTA. In addition to evaluating levels and sources of economic distress, interviewees were asked to identify mitigation solutions adopted at local / internal (i.e., farm site) scales, and to express their preference on national / external scale mitigation measures among a set of a priori options. Survey responses identified the potential causes of disruption, ripple effects, sources of food insecurity, and socio-economic conflicts. They also pointed to various levels of mitigation strategies. The collated evidence represents a first baseline useful to address future disaster-driven responses, to reinforce the resilience of the sector and to facilitate the design reconstruction plans and mitigation measures, such as financial aid strategies.
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| 34. |
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| 35. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 36. |
- Mullins, Niamh, et al.
(författare)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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| 37. |
- Nelson, G., et al.
(författare)
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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
- 2021
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
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Tidskriftsartikel (refereegranskat)abstract
- A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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| 38. |
- Reinke, Beth A, et al.
(författare)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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| 39. |
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| 40. |
- Verbakel, J. Y., et al.
(författare)
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Validation of ultrasound strategies to assess tumor extension and to predict high-risk endometrial cancer in women from the prospective IETA (International Endometrial Tumor Analysis)-4 cohort
- 2020
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 55:1, s. 115-124
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). Methods: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The ‘subjective prediction model’ included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the ‘objective prediction model’ included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. Results: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver–operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. Conclusions: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%.
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| 41. |
- Alves, Carla L., et al.
(författare)
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Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have shown impressive efficacy in estrogen receptor-positive advanced breast cancer. However, most patients will eventually experience disease progression on this combination, underscoring the need for effective subsequent treatments or better initial therapies. Here, we show that triple inhibition with fulvestrant, CDK4/6i and AKT inhibitor (AKTi) durably impairs growth of breast cancer cells, prevents progression and reduces metastasis of tumor xenografts resistant to CDK4/6i-fulvestrant combination or fulvestrant alone. Importantly, switching from combined fulvestrant and CDK4/6i upon resistance to dual combination with AKTi and fulvestrant does not prevent tumor progression. Furthermore, triple combination with AKTi significantly inhibits growth of patient-derived xenografts resistant to combined CDK4/6i and fulvestrant. Finally, high phospho-AKT levels in metastasis of breast cancer patients treated with a combination of CDK4/6i and endocrine therapy correlates with shorter progression-free survival. Our findings support the clinical development of ER, CDK4/6 and AKT co-targeting strategies following progression on CDK4/6i and endocrine therapy combination, and in tumors exhibiting high phospho-AKT levels, which are associated with worse clinical outcome.
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| 42. |
- Bergström, Sofia, et al.
(författare)
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Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease
- 2021
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:7, s. 1456-1470
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Decreased amyloid beta (A beta) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of A beta 42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.
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| 43. |
- Borne, Kurtis D., et al.
(författare)
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Ultrafast electronic relaxation pathways of the molecular photoswitch quadricyclane
- 2024
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Ingår i: NATURE CHEMISTRY. - 1755-4330 .- 1755-4349. ; 16, s. 499-505
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Tidskriftsartikel (refereegranskat)abstract
- The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.
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| 44. |
- Del Palacio, Santiago, 1990, et al.
(författare)
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Evidence for non-thermal X-ray emission from the double Wolf-Rayet colliding-wind binary Apep
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 672
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Tidskriftsartikel (refereegranskat)abstract
- Context. Massive colliding-wind binaries (CWBs) can be non-thermal sources. The emission produced in their wind-collision region (WCR) encodes information of both the shock properties and the relativistic electrons accelerated in them. The recently discovered system Apep, a unique massive system hosting two Wolf-Rayet stars, is the most powerful synchrotron radio emitter among the known CWBs. It is an exciting candidate in which to investigate the non-thermal processes associated with stellar wind shocks. Aims. We intend to break the degeneracy between the relativistic particle population and the magnetic field strength in the WCR of Apep by probing its hard X-ray spectrum, where inverse-Compton (IC) emission is expected to dominate. Methods. We observed Apep with NuSTAR for 60 ks and combined this with a reanalysis of a deep archival XMM-Newton observation to better constrain the X-ray spectrum. We used a non-thermal emission model to derive physical parameters from the results. Results. We detect hard X-ray emission consistent with a power-law component from Apep. This is compatible with IC emission produced in the WCR for a magnetic field of ≈ 105-190 mG, corresponding to a magnetic-to-thermal pressure ratio in the shocks of ≈ 0.007-0.021, and a fraction of ∼1.5 × 10-4 of the total wind kinetic power being transferred to relativistic electrons. Conclusions. The non-thermal emission from a CWB is detected for the first time in radio and at high energies. This allows us to derive the most robust constraints so far for the particle acceleration efficiency and magnetic field intensity in a CWB, reducing the typical uncertainty of a few orders of magnitude to just within a factor of a few. This constitutes an important step forward in our characterisation of the physical properties of CWBs.
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| 45. |
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| 46. |
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| 47. |
- Fukui, A., et al.
(författare)
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TOI-1749: an M dwarf with a Trio of Planets including a Near-resonant Pair
- 2021
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 162:4
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of one super-Earth- (TOI-1749b) and two sub-Neptune-sized planets (TOI-1749c and TOI-1749d) transiting an early M dwarf at a distance of 100 pc, which were first identified as planetary candidates using data from the TESS photometric survey. We have followed up this system from the ground by means of multiband transit photometry, adaptive optics imaging, and low-resolution spectroscopy, from which we have validated the planetary nature of the candidates. We find that TOI-1749b, c, and d have orbital periods of 2.39, 4.49, and 9.05 days, and radii of 1.4, 2.1, and 2.5 R (circle plus), respectively. We also place 95% confidence upper limits on the masses of 57, 14, and 15 M (circle plus) for TOI-1749b, c, and d, respectively, from transit timing variations. The periods, sizes, and tentative masses of these planets are in line with a scenario in which all three planets initially had a hydrogen envelope on top of a rocky core, and only the envelope of the innermost planet has been stripped away by photoevaporation and/or core-powered mass-loss mechanisms. These planets are similar to other planetary trios found around M dwarfs, such as TOI-175b,c,d and TOI-270b,c,d, in the sense that the outer pair has a period ratio within 1% of 2. Such a characteristic orbital configuration, in which an additional planet is located interior to a near 2:1 period-ratio pair, is relatively rare around FGK dwarfs.
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| 48. |
- Galosi, Serena, et al.
(författare)
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De novo DHDDS variants cause a neurodevelopmental and neurodegenerative disorder with myoclonus
- 2022
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:1, s. 208-223
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Tidskriftsartikel (refereegranskat)abstract
- Subcellular membrane systems are highly enriched in dolichol, whose role in organelle homeostasis and endosomal-lysosomal pathway remains largely unclear besides being involved in protein glycosylation. DHDDS encodes for the catalytic subunit (DHDDS) of the enzyme cis-prenyltransferase (cis-PTase), involved in dolichol biosynthesis and dolichol-dependent protein glycosylation in the endoplasmic reticulum. An autosomal recessive form of retinitis pigmentosa (retinitis pigmentosa 59) has been associated with a recurrent DHDDS variant. Moreover, two recurring de novo substitutions were detected in a few cases presenting with neurodevelopmental disorder, epilepsy, and movement disorder. We evaluated a large cohort of patients (n=25) with de novo pathogenic variants in DHDDS and provided the first systematic description of the clinical features and long-term outcome of this new neurodevelopmental and neurodegenerative disorder. The functional impact of the identified variants was explored by yeast complementation system and enzymatic assay. Patients presented during infancy or childhood with a variable association of neurodevelopmental disorder, generalized epilepsy, action myoclonus/cortical tremor, and ataxia. Later in the disease course they experienced a slow neurological decline with the emergence of hyperkinetic and/or hypokinetic movement disorder, cognitive deterioration, and psychiatric disturbances. Storage of lipidic material and altered lysosomes were detected in myelinated fibers and fibroblasts, suggesting a dysfunction of the lysosomal enzymatic scavenger machinery. Serum glycoprotein hypoglycosylation was not detected and, in contrast to retinitis pigmentosa and other congenital disorders of glycosylation involving dolichol metabolism, the urinary dolichol D18/D19 ratio was normal. Mapping the disease-causing variants into the protein structure revealed that most of them clustered around the active site of the DHDDS subunit. Functional studies using yeast complementation assay and in vitro activity measurements confirmed that these changes affected the catalytic activity of the cis-PTase and showed growth defect in yeast complementation system as compared with the wild-type enzyme and retinitis pigmentosa-associated protein. In conclusion, we characterized a distinctive neurodegenerative disorder due to de novo DHDDS variants, which clinically belongs to the spectrum of genetic progressive encephalopathies with myoclonus. Clinical and biochemical data from this cohort depicted a condition at the intersection of congenital disorders of glycosylation and inherited storage diseases with several features akin to of progressive myoclonus epilepsy such as neuronal ceroid lipofuscinosis and other lysosomal disorders.
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| 49. |
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| 50. |
- Hale, S. E., et al.
(författare)
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Evaluating Nature-Based Solutions for Water Management in Peri-Urban Areas
- 2023
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Ingår i: Water. - : MDPI. - 2073-4441. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- The term nature-based solutions (NBS) has gained traction in recent years and has been applied in many settings. There are few comprehensive assessment frameworks available that can guide NBS planning and implementation while at the same time capturing the short- and long-term impacts and benefits of the NBS. Here a recently presented framework, which builds on the theory of change and was developed to assess NBS at different phases of the project cycle, was applied to seven diverse case studies. The case studies addressed water quality and quantity issues in peri-urban areas across the global north and south. Framework indicators covering the sustainability dimensions (environmental, social and economic) were assessed at three stages of the framework: context, process and results. The work sought to investigate the following research objectives: (1) Can this framework be robust and yet flexible enough to be applied across a diverse selection of NBS projects that are at different phases of the project cycle and address different kinds of water challenges within varied ecological, social and economic contexts? (2) Is it possible to draw generalisations from a comparative analysis of the application of the framework to the case studies? Results showed that the framework was able to be applied to the case studies; however, their diversity showed that NBS projects designed in one context, for a specific purpose in a specific location, can not necessarily be transferred easily to another location. There were several process-based indicators that were universally significant for the case studies, including expertise, skills and knowledge of the involved actors, roles and responsibilities of involved actors and political support. The result-based indicators were case study-specific when environmental indicators were case study-specific, and important social indicators were environmental identity and recreational values. Overall, the use of the framework benefits the recognition of the implementation’s advances, such as the change in context, the processes in place and the results obtained.
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