| 1. |
- Barucca, G., et al.
(författare)
-
The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
-
Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
|
|
| 2. |
- Barucca, G., et al.
(författare)
-
Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
-
Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
-
Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
|
|
| 3. |
|
|
| 4. |
- Menkveld, Albert J., et al.
(författare)
-
Nonstandard Errors
- 2024
-
Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
-
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.
|
|
| 5. |
- Windhorst, Rogier A., et al.
(författare)
-
JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
- 2023
-
Ingår i: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
-
Tidskriftsartikel (refereegranskat)abstract
- We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
|
|
| 6. |
- Mansoor, Rashid, et al.
(författare)
-
Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
- 2022
-
Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Diego, Jose M., et al.
(författare)
-
JWST's PEARLS : Mothra, a new kaiju star at z=2.091 extremely magnified by MACS0416, and implications for dark matter models
- 2023
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of Mothra, an extremely magnified monster star, likely a binary system of two supergiant stars, in one of the strongly lensed galaxies behind the galaxy cluster MACS J0416.1-2403. Mothra is in a galaxy with spectroscopic redshift z = 2.091 in a portion of the galaxy that is parsecs away from the cluster caustic. The binary star is observed only on the side of the critical curve with negative parity but has been detectable for at least eight years, implying the presence of a small lensing perturber. Microlenses alone cannot explain the earlier observations of this object made with the Hubble Space Telescope. A larger perturber with a mass of at least 10(4 )M(circle dot) offers a more satisfactory explanation. Based on the lack of perturbation on other nearby sources in the same arc, the maximum mass of the perturber is 2.5 x 10(6) M-circle dot, making this the smallest substructure constrained by lensing at z > 0.3. The existence of this millilens is fully consistent with expectations from standard cold dark matter cosmology. On the other hand, the existence of such a small substructure in a cluster environment has implications for other dark matter models. In particular, warm dark matter models with particle masses below 8.7 keV are excluded by our observations. Similarly, axion dark matter models are consistent with the observations only if the axion mass is in the range 0.5 x 10(-22) eV < m(a )< 5 x 10(-22) eV.
|
|
| 10. |
- Nabizadeh, Armin, et al.
(författare)
-
A search for high-redshift direct-collapse black hole candidates in the PEARLS north ecliptic pole field
- 2024
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 683
-
Tidskriftsartikel (refereegranskat)abstract
- Direct-collapse black holes (DCBHs) of mass ∼ 104-105 M⊙ that form in HI-cooling halos in the early Universe are promising progenitors of the greater than or similar to 109 M⊙ supermassive black holes that fuel observed z greater than or similar to 7 quasars. Efficient accretion of the surrounding gas onto such DCBH seeds may render them sufficiently bright for detection with the JWST up to z ≈ 20. Additionally, the very steep and red spectral slope predicted across the ≈ 1-5 μm wavelength range of the JWST/NIRSpec instrument during their initial growth phase should make them photometrically identifiable up to very high redshifts. In this work, we present a search for such DCBH candidates across the 34 arcmin2 in the first two spokes of the JWST cycle-1 PEARLS survey of the north ecliptic pole time-domain field covering eight NIRCam filters down to a maximum depth of ∼ 29 AB mag. We identify two objects with spectral energy distributions consistent with the Pacucci et al. (2016) DCBH models. However, we also note that even with data in eight NIRCam filters, objects of this type remain degenerate with dusty galaxies and obscured active galactic nuclei over a wide range of redshifts. Follow-up spectroscopy would be required to pin down the nature of these objects. Based on our sample of DCBH candidates and assumptions on the typical duration of the DCBH steep-slope state, we set a conservative upper limit of less than or similar to 5x10-4 comoving Mpc-3 (cMpc-3) on the comoving density of host halos capable of hosting DCBHs with spectral energy distributions similar to the Pacucci et al. (2016) models at z ≈ 6-14.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Viljur, Mari-Liis, et al.
(författare)
-
The effect of natural disturbances on forest biodiversity : an ecological synthesis
- 2022
-
Ingår i: Biological Reviews. - : Wiley. - 1464-7931 .- 1469-185X. ; 97:5, s. 1930-1947
-
Tidskriftsartikel (refereegranskat)abstract
- Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human-induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land-use change. Conversely, the suppression of natural disturbances threatens disturbance-dependent biota. Using a meta-analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α-diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground-dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α-diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55% of trees killed by disturbance. We further extended our meta-analysis by applying a unified diversity concept based on Hill numbers to estimate α-diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity–disturbance relationships are shaped by species relative abundances. Our synthesis of α-diversity was extended by a synthesis of disturbance-induced change in species assemblages, and revealed that disturbance changes the β-diversity of multiple taxonomic groups, including some groups that were not affected at the α-diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α-diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes.
|
|
| 14. |
- Carleo, Ilaria, et al.
(författare)
-
The Multiplanet System TOI-421*
- 2020
-
Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 160:3
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations-comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echelle Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution echelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements-and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of P-b = 5.19672 +/- 0.00049 days, a mass of M-b = 7.17 +/- 0.66 M-circle plus, and a radius of R-b = R-circle plus, whereas the outer warm Neptune, TOI-421 c, has a period of P-c = 16.06819 +/- 0.00035 days, a mass of M-c = 16.42(-1.04)(+1.06)M(circle plus), a radius of R-c = 5.09(-0.15)(+0.16)R(circle plus), and a density of rho(c) = 0.685(-0.072)(+0.080) cm(-3). With its characteristics, the outer planet (rho(c) = 0.685(-0.0072)(+0.080) cm(-3)) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Ly alpha transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed.
|
|
| 15. |
- Kamoun, Aurélie, et al.
(författare)
-
A Consensus Molecular Classification of Muscle-invasive Bladder Cancer
- 2020
-
Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 77:4, s. 420-433
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. Objective: To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. Design, setting, and participants: We used 1750 MIBC transcriptomic profiles from 16 published datasets and two additional cohorts. Outcome measurements and statistical analysis: We performed a network-based analysis of six independent MIBC classification systems to identify a consensus set of molecular classes. Association with survival was assessed using multivariable Cox models. Results and limitations: We report the results of an international effort to reach a consensus on MIBC molecular subtypes. We identified a consensus set of six molecular classes: luminal papillary (24%), luminal nonspecified (8%), luminal unstable (15%), stroma-rich (15%), basal/squamous (35%), and neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics, including outcomes. We provide a single-sample classifier that assigns a consensus class label to a tumor sample's transcriptome. Limitations of the work are retrospective clinical data collection and a lack of complete information regarding patient treatment. Conclusions: This consensus system offers a robust framework that will enable testing and validation of predictive biomarkers in future prospective clinical trials. Patient summary: Bladder cancers are heterogeneous at the molecular level, and scientists have proposed several classifications into sets of molecular classes. While these classifications may be useful to stratify patients for prognosis or response to treatment, a consensus classification would facilitate the clinical use of molecular classes. Conducted by multidisciplinary expert teams in the field, this study proposes such a consensus and provides a tool for applying the consensus classification in the clinical setting.
|
|
| 16. |
- Li, Jian-Yang, et al.
(författare)
-
Ejecta from the DART-produced active asteroid Dimorphos
- 2023
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 616, s. 452-456
-
Tidskriftsartikel (refereegranskat)abstract
- Some active asteroids have been proposed to be formed as a result of impact events1. Because active asteroids are generally discovered by chance only after their tails have fully formed, the process of how impact ejecta evolve into a tail has, to our knowledge, not been directly observed. The Double Asteroid Redirection Test (DART) mission of NASA2, in addition to having successfully changed the orbital period of Dimorphos3, demonstrated the activation process of an asteroid resulting from an impact under precisely known conditions. Here we report the observations of the DART impact ejecta with the Hubble Space Telescope from impact time T + 15 min to T + 18.5 days at spatial resolutions of around 2.1 km per pixel. Our observations reveal the complex evolution of the ejecta, which are first dominated by the gravitational interaction between the Didymos binary system and the ejected dust and subsequently by solar radiation pressure. The lowest-speed ejecta dispersed through a sustained tail that had a consistent morphology with previously observed asteroid tails thought to be produced by an impact4,5. The evolution of the ejecta after the controlled impact experiment of DART thus provides a framework for understanding the fundamental mechanisms that act on asteroids disrupted by a natural impact1,6.
|
|
| 17. |
- Bakari, Catherine, et al.
(författare)
-
Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021
- 2024
-
Ingår i: MALARIA JOURNAL. - 1475-2875. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. Methods A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). Results Sequencing success was >= 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. Conclusion This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.
|
|
| 18. |
- Ebrahimi-Fakhari, Darius, et al.
(författare)
-
Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
-
Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
-
Tidskriftsartikel (refereegranskat)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
|
|
| 19. |
- Kabath, Petr, et al.
(författare)
-
TOI-2046b, TOI-1181b, and TOI-1516b, three new hot Jupiters from TESS: planets orbiting a young star, a subgiant, and a normal star
- 2022
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5955-5972
-
Tidskriftsartikel (refereegranskat)abstract
- We present the confirmation and characterization of three hot Jupiters, TOI-118 lb, TOI-1516b, and TOI-2046b, discovered by the "NESS space mission. The reported hot Jupiters have orbital periods between 1.4 and 2.05 d. The masses of the three planets are 1.18 +/- 0.14 Mj, 3.16 +/- 0.12 Mj, and 2.30 +/- 0.28 Mj, for TOI-1181b, TOI-1516b, and TOI-2046b, respectively. The stellar host of TOI-1181b is a F9IV star, whereas TOI-1516b and TOI-2046b orbit F main sequence host stars. The ages of the first two systems are in the range of 2-5 Gyrs. However, TOI-2046 is among the few youngest known planetary systems hosting a hot Jupiter, with an age estimate of 100-400 Myrs. The main instruments used for the radial velocity follow-up of these three planets are located at OndIejov, Tautenburg, and McDonald Observatory, and all three are mounted on 2-3 m aperture telescopes, demonstrating that mid-aperture telescope networks can play a substantial role in the follow-up of gas giants discovered by TESS and in the future by PLATO.
|
|
| 20. |
- Le Guen, Yann, et al.
(författare)
-
Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
-
Tidskriftsartikel (refereegranskat)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
|
|
| 21. |
- Polyakov,, et al.
(författare)
-
Borealization of the Arctic Ocean in Response to Anomalous Advection From Sub-Arctic Seas
- 2020
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- An important yet still not well documented aspect of recent changes in the Arctic Ocean is associated with the advection of anomalous sub-Arctic Atlantic- and Pacific-origin waters and biota into the polar basins, a process which we refer to as borealization. Using a 37-year archive of observations (1981-2017) we demonstrate dramatically contrasting regional responses to atlantification (that part of borealization related to progression of anomalies from the Atlantic sector of sub-Arctic seas into the Arctic Ocean) and pacification (the counterpart of atlantification associated with influx of anomalous Pacific waters). Particularly, we show strong salinification of the upper Eurasian Basin since 2000, with attendant reductions in stratification, and potentially altered nutrient fluxes and primary production. These changes are closely related to upstream conditions. In contrast, pacification is strongly manifested in the Amerasian Basin by the anomalous influx of Pacific waters, creating conditions favorable for increased heat and freshwater content in the Beaufort Gyre halocline and expansion of Pacific species into the Arctic interior. Here, changes in the upper (overlying) layers are driven by local Arctic atmospheric processes resulting in stronger wind/ice/ocean coupling, increased convergence within the Beaufort Gyre, a thickening of the fresh surface layer, and a deepening of the nutricline and deep chlorophyll maximum. Thus, a divergent (Eurasian Basin) gyre responds altogether differently than does a convergent (Amerasian Basin) gyre to climate forcing. Available geochemical data indicate a general decrease in nutrient concentrations Arctic-wide, except in the northern portions of the Makarov and Amundsen Basins and northern Chukchi Sea and Canada Basin. Thus, changes in the circulation pathways of specific water masses, as well as the utilization of nutrients in upstream regions, may control the availability of nutrients in the Arctic Ocean. Model-based evaluation of the trajectory of the Arctic climate system into the future suggests that Arctic borealization will continue under scenarios of global warming. Results from this synthesis further our understanding of the Arctic Ocean's complex and sometimes non-intuitive Arctic response to climate forcing by identifying new feedbacks in the atmosphere-ice-ocean system in which borealization plays a key role.
|
|
| 22. |
- Subjak, Jan, et al.
(författare)
-
TOI-503: The First Known Brown-dwarf Am-star Binary from the TESS Mission
- 2020
-
Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 159:4
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of an intermediate-mass transiting brown dwarf (BD), TOI-503b, from the TESS mission. TOI-503b is the first BD discovered by TESS, and it has circular orbit around a metallic-line A-type star with a period of P.=.3.6772.+/-.0.0001 days. The light curve from TESS indicates that TOI-503b transits its host star in a grazing manner, which limits the precision with which we measure the BD's radius ( = R 1.34+ R b 0.150.26 J). We obtained highresolution spectroscopic observations with the FIES, Ondr.ejov, PARAS, Tautenburg, and TRES spectrographs, and measured the mass of TOI-503b to be Mb.=.53.7.+/-.1.2 MJ. The host star has a mass of Ma.=.1.80.+/-.0.06Me, a radius of Ra.=.1.70.+/-.0.05Re, an effective temperature of Teff.=.7650.+/-.160 K, and a relatively high metallicity of 0.61.+/-.0.07 dex. We used stellar isochrones to derive the age of the system to be 180 Myr, which places its age between that of RIK 72b (a 10 Myr old BD in the Upper Scorpius stellar association) and AD 3116b (a 600 Myr old BD in the Praesepe cluster). Given the difficulty in measuring the tidal interactions between BDs and their host stars, we cannot precisely say whether this BD formed in situ or has had its orbit circularized by its host star over the relatively short age of the system. Instead, we offer an examination of plausible values for the tidal quality factor for the star and BD. TOI-503b joins a growing number of known short-period, intermediate-mass BDs orbiting mainsequence stars, and is the second such BD known to transit an A star, after HATS-70b. With the growth in the population in this regime, the driest region in the BD desert (35-55MJ sin i) is reforesting.
|
|
| 23. |
|
|
| 24. |
- Zhou, Jinyuan, et al.
(författare)
-
Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T : Application to brain tumors
- 2022
-
Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 88:2, s. 546-574
-
Tidskriftsartikel (refereegranskat)abstract
- Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.
|
|
| 25. |
- Alfaro-Cuello, M., et al.
(författare)
-
A Deep View into the Nucleus of the Sagittarius Dwarf Spheroidal Galaxy with MUSE. II. Kinematic Characterization of the Stellar Populations
- 2020
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 892:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Sagittarius dwarf spheroidal galaxy is in an advanced stage of disruption but still hosts its nuclear star cluster (NSC), M54, at its center. In this paper, we present a detailed kinematic characterization of the three stellar populations present in M54: Young metal-rich (YMR); intermediate-age metal-rich (IMR); and old metal-poor (OMP), based on the spectra of 6500 individual M54 member stars extracted from a large Multi-Unit Spectroscopic Explorer (MUSE)/Very Large Telescope data set. We find that the OMP population is slightly flattened with a low amount of rotation (0.8 km s-1) and with a velocity dispersion that follows a Plummer profile. The YMR population displays a high amount of rotation (5 km s-1) and a high degree of flattening, with a lower and flat velocity dispersion profile. The IMR population shows a high but flat velocity dispersion profile, with some degree of rotation (2 km s-1). We complement our MUSE data with information from Gaia DR2 and confirm that the stars from the OMP and YMR populations are comoving in 3D space, suggesting that they are dynamically bound. While dynamical evolutionary effects (e.g., energy equipartition) are able to explain the differences in velocity dispersion between the stellar populations, the strong differences in rotation indicate different formation paths for the populations, as supported by an N-body simulation tailored to emulate the YMR-OMP system. This study provides additional evidence for the M54 formation scenario proposed in our previous work, where this NSC formed via GC accretion (OMP) and in situ formation from gas accretion in a rotationally supported disk (YMR).
|
|
| 26. |
|
|
| 27. |
- Benson, Tyler W, et al.
(författare)
-
Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms.
- 2023
-
Ingår i: bioRxiv : the preprint server for biology.
-
Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (J) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.KEY POINTS: Soluble glycoprotein VI, which is a platelet-derived blood biomarker, predicts a diagnosis of AAA, with high sensitivity and specificity in distinguishing patients with fast from slow-growing AAA.Blockade of glycoprotein VI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential.
|
|
| 28. |
|
|
| 29. |
- Dandoy, Christopher E., et al.
(författare)
-
Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplant
- 2020
-
Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other).Objective: To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT.Design, Setting, and Participants: A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018.Main Outcomes and Measures: Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups.Results: Of the 16875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 [99% CI, 1.38-2.48]). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% CI, 2.17-3.24]) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4740 [11.9%]).Conclusions and Relevance: In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population. This cohort study examines the incidence, timing, risk factors, and outcomes of patients who develop mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI) in the first 100 days after hematopoietic stem cell transplant (HSCT).
|
|
| 30. |
- Fimbo, AM, et al.
(författare)
-
Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania
- 2020
-
Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:5
-
Tidskriftsartikel (refereegranskat)abstract
- Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1–6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.
|
|
| 31. |
- Hopper, Rachel K, et al.
(författare)
-
International practice heterogeneity in pre-transplant management of pulmonary hypertension related to pediatric left heart disease
- 2023
-
Ingår i: Pediatric Transplantation. - : Wiley. - 1399-3046 .- 1397-3142. ; 27:2, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elevated pulmonary vascular resistance (PVR) in the setting of left heart failure may contribute to poor outcomes after pediatric heart transplant (HTx), but peri-transplant management is variable.METHODS: We sought to characterize international practice by surveying physicians at pediatric HTx centers.RESULTS: We received 49 complete responses from 39 centers in 16 countries. Most respondents are pediatric cardiologists (90%), practice at centers offering heart (86%) and lung (55%) transplant, and perform pre-HTx acute vasoreactivity testing (AVT, 88%) in patients with elevated PVR. Half (51%) reported defining a PVR cutoff for HTx eligibility as ≤6 WU m 2 (56%) post-AVT (84%). The highest post-AVT PVR ever accepted for HTx ranged from 3-14.4 (median 6) WU m 2 . To treat elevated pre-transplant PVR, phosphodiesterase type 5 inhibitors are most common (65%) followed by oxygen (31%), nitric oxide (14%), endothelin receptor antagonists (11%), and prostacyclins (6%). Nearly a third (31%) do not routinely use pulmonary vasodilators without implantation of a left ventricular assist device (LVAD). Case scenarios highlight treatment variability: in a restrictive cardiomyopathy scenario, HTx listing with post-transplant vasodilator therapy was favored, whereas in a Shone's complex patient with fixed PVR, LVAD ± pulmonary vasodilators followed by repeat catheterization was most common. Management of dilated cardiomyopathy with reactive PVR was variable. Most continue vasodilator therapy until HTx (16%), PVR normalizes (16%) or ≤6 months. CONCLUSIONS: Management of elevated PVR in children awaiting HTx is heterogenous. Evidence-based guidelines are needed to allow for longitudinal determination of optimal outcomes and standardized care.
|
|
| 32. |
- Jakobsson, Martin, et al.
(författare)
-
The International Bathymetric Chart of the Arctic Ocean Version 4.0
- 2020
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean (IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 x 200m versus 500 x 500m) and with individual depth soundings constraining three times more area of the Arctic Ocean (similar to 19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises similar to 14.3% in Ver. 4.0 compared to similar to 5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet. Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12369314
|
|
| 33. |
- Kahn, Justine M., et al.
(författare)
-
Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases
- 2020
-
Ingår i: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 4:9, s. 2084-2094
-
Tidskriftsartikel (refereegranskat)abstract
- We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). Weincluded 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.
|
|
| 34. |
- Lee, Catherine J., et al.
(författare)
-
Late effects after ablative allogeneic stem cell transplantation for adolescent and young adult acute myeloid leukemia
- 2020
-
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:6, s. 983-992
-
Tidskriftsartikel (refereegranskat)abstract
- There is marked paucity of data regarding late effects in adolescents and young adults (AYAs) who undergo myeloablative conditioning (MAC) allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). We evaluated late effects and survival in 826 1-year disease-free survivors of MAC HCT for AYA AML, with an additional focus on comparing late effects based upon MAC type (total body irradiation [TBI] vs high-dose chemotherapy only). The estimated 10-year cumulative incidence of subsequent neoplasms was 4% (95% confidence interval [CI], 2%-6%); 10-year cumulative incidence of nonmalignant late effects included gonadal dysfunction (10%; 95% CI, 8%-13%), cataracts (10%; 95% CI, 7%-13%), avascular necrosis (8%; 95% CI, 5%-10%), diabetes mellitus (5%; 95% CI, 3%-7%), and hypothyroidism (3%; 95% CI, 2%-5%). Receipt of TBI was independently associated with a higher risk of cataracts only (hazard ratio [HR], 4.98; P < .0001) whereas chronic graft-versus-host disease (cGVHD) was associated with an increased risk of cataracts (HR, 3.22; P = .0006), avascular necrosis (HR, 2.49; P = .006), and diabetes mellitus (HR, 3.36; P = .03). Estimated 10-year overall survival and leukemia-free survival were 73% and 70%, respectively, and did not differ on the basis of conditioning type. In conclusion, late effects among survivors of MAC HCT for AYA AML are frequent and are more closely linked to cGVHD than type of conditioning.
|
|
| 35. |
|
|
| 36. |
- Muncke, Jane, et al.
(författare)
-
Impacts of food contact chemicals on human health : a consensus statement
- 2020
-
Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Food packaging is of high societal value because it conserves and protects food, makes food transportable and conveys information to consumers. It is also relevant for marketing, which is of economic significance. Other types of food contact articles, such as storage containers, processing equipment and filling lines, are also important for food production and food supply. Food contact articles are made up of one or multiple different food contact materials and consist of food contact chemicals. However, food contact chemicals transfer from all types of food contact materials and articles into food and, consequently, are taken up by humans. Here we highlight topics of concern based on scientific findings showing that food contact materials and articles are a relevant exposure pathway for known hazardous substances as well as for a plethora of toxicologically uncharacterized chemicals, both intentionally and non-intentionally added. We describe areas of certainty, like the fact that chemicals migrate from food contact articles into food, and uncertainty, for example unidentified chemicals migrating into food. Current safety assessment of food contact chemicals is ineffective at protecting human health. In addition, society is striving for waste reduction with a focus on food packaging. As a result, solutions are being developed toward reuse, recycling or alternative (non-plastic) materials. However, the critical aspect of chemical safety is often ignored. Developing solutions for improving the safety of food contact chemicals and for tackling the circular economy must include current scientific knowledge. This cannot be done in isolation but must include all relevant experts and stakeholders. Therefore, we provide an overview of areas of concern and related activities that will improve the safety of food contact articles and support a circular economy. Our aim is to initiate a broader discussion involving scientists with relevant expertise but not currently working on food contact materials, and decision makers and influencers addressing single-use food packaging due to environmental concerns. Ultimately, we aim to support science-based decision making in the interest of improving public health. Notably, reducing exposure to hazardous food contact chemicals contributes to the prevention of associated chronic diseases in the human population.
|
|
| 37. |
- Seth, Sudipta, et al.
(författare)
-
Presence of Maximal Characteristic Time in Photoluminescence Blinking of MAPbI3 Perovskite
- 2021
-
Ingår i: Advanced Energy Materials. - : Wiley. - 1614-6832 .- 1614-6840. ; 11:44
-
Tidskriftsartikel (refereegranskat)abstract
- Photoluminescence (PL) blinking is a common phenomenon in nanostructured semiconductors associated with charge trapping and defect dynamics. PL blinking kinetics exhibit very broadly distributed timescales. The traditionally employed analysis of probability distribution of ON and OFF events suffers from ambiguities in their determination in complex PL traces making its suitability questionable. Here, the statistically correct power spectral density (PSD) estimation method applicable for fluctuations of any complexity is employed. PSDs of the blinking traces of submicrometer MAPbI3 crystals at high frequencies follow power law with excitation power density dependent parameters. However, at frequencies less than 0.3 Hz, the majority of the PSDs saturate revealing the presence of a maximal characteristic timescale of blinking in the range of 0.5–10 s independently of the excitation power density. Super-resolution optical microscopy shows the characteristic timescale to be an inherent material property independent of polycrystallinity. Thus, for the first time the maximum timescale of the multiscale blinking behavior of nanoparticles is observed demonstrating that the power law statistics are not universal for semiconductors. It is proposed that the viscoelasticity of metal-halide perovskites can limit the maximum timescale for the PL fluctuations by limiting the memory of preceded deformations/re-arrangements of the crystal lattice.
|
|
| 38. |
- Seth-Smith, Helena M. B., et al.
(författare)
-
Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum : exploring the genomic diversity of circulating strains
- 2021
-
Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 7:6
-
Tidskriftsartikel (refereegranskat)abstract
- Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA- genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV- positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA- genotype L2b. However, analysis of the ompA gene shows ompA- genotype L2b (n=83), ompA- genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA- genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA- genotypes derive from an ompA- genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrep-resented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA- genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA- genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA- genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.
|
|
| 39. |
- von Clarmann, Thomas, et al.
(författare)
-
Overview: Estimating and reporting uncertainties in remotely sensed atmospheric composition and temperature
- 2020
-
Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 13:8, s. 4393-4436
-
Tidskriftsartikel (refereegranskat)abstract
- Remote sensing of atmospheric state variables typically relies on the inverse solution of the radiative transfer equation. An adequately characterized retrieval provides information on the uncertainties of the estimated state variables as well as on how any constraint or a priori assumption affects the estimate. Reported characterization data should be intercomparable between different instruments, empirically validatable, grid-independent, usable without detailed knowledge of the instrument or retrieval technique, traceable and still have reasonable data volume. The latter may force one to work with representative rather than individual characterization data. Many errors derive from approximations and simplifications used in real-world retrieval schemes, which are reviewed in this paper, along with related error estimation schemes. The main sources of uncertainty are measurement noise, calibration errors, simplifications and idealizations in the radiative transfer model and retrieval scheme, auxiliary data errors, and uncertainties in atmospheric or instrumental parameters. Some of these errors affect the result in a random way, while others chiefly cause a bias or are of mixed character. Beyond this, it is of utmost importance to know the influence of any constraint and prior information on the solution. While different instruments or retrieval schemes may require different error estimation schemes, we provide a list of recommendations which should help to unify retrieval error reporting.
|
|
| 40. |
- Widemann, Thomas, et al.
(författare)
-
Venus Evolution Through Time : Key Science Questions, Selected Mission Concepts and Future Investigations
- 2023
-
Ingår i: Space Science Reviews. - : SPRINGER. - 0038-6308 .- 1572-9672. ; 219:7
-
Forskningsöversikt (refereegranskat)abstract
- In this work we discuss various selected mission concepts addressing Venus evolution through time. More specifically, we address investigations and payload instrument concepts supporting scientific goals and open questions presented in the companion articles of this volume. Also included are their related investigations (observations & modeling) and discussion of which measurements and future data products are needed to better constrain Venus' atmosphere, climate, surface, interior and habitability evolution through time. A new fleet of Venus missions has been selected, and new mission concepts will continue to be considered for future selections. Missions under development include radar-equipped ESA-led EnVision M5 orbiter mission (European Space Agency 2021), NASA-JPL's VERITAS orbiter mission (Smrekar et al. 2022a), NASA-GSFC's DAVINCI entry probe/flyby mission (Garvin et al. 2022a). The data acquired with the VERITAS, DAVINCI, and EnVision from the end of this decade will fundamentally improve our understanding of the planet's long term history, current activity and evolutionary path. We further describe future mission concepts and measurements beyond the current framework of selected missions, as well as the synergies between these mission concepts, ground-based and space-based observatories and facilities, laboratory measurements, and future algorithmic or modeling activities that pave the way for the development of a Venus program that extends into the 2040s (Wilson et al. 2022).
|
|
| 41. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 42. |
|
|
| 43. |
- Bowman, Chelsie N., et al.
(författare)
-
Integrated sedimentary, biotic, and paleoredox dynamics from multiple localities in southern Laurentia during the late Silurian (Ludfordian) extinction event
- 2020
-
Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier BV. - 0031-0182. ; 553
-
Tidskriftsartikel (refereegranskat)abstract
- The Silurian was a time of major climatic transition punctuated by multiple biotic crises and global carbon cycle perturbations. The most severe of these biotic events was the late Silurian (Ludfordian) Lau/Kozlowskii extinction event (LKE) and the associated Lau carbon isotope excursion (CIE). Although the extinction event and Lau CIE are globally documented, the only records thus far of local and global marine paleoredox conditions through this interval are from a single region in Scandinavia. Here we examine four sections along a bathymetric transect of mixed carbonate-siliciclastic sediments from western Tennessee, USA. A novel approach using a multi-proxy dataset combining high-resolution geochemical data and microfacies analyses from multiple localities explores the possibilities of local/regional-scale redox heterogeneities during a time of widespread environmental upheaval on a global scale. Paired positive excursions recorded in carbonate carbon isotopes and carbonate-associated sulfate sulfur isotopes support recent work from carbonate and siliciclastic successions from Scandinavia, suggesting a global enhancement of organic carbon and pyrite burial driven by an expansion of euxinic (anoxic and sulfidic water column) conditions in the oceans during the mid-Ludfordian. Furthermore, positive excursions in organic carbon isotopes and pyrite sulfur isotopes reflect the global changes in redox. Stratigraphic trends in I/Ca ratios imply a local expansion of low-oxygen conditions, with low, but non-zero values during the rising limb and peak of the CIE. The fossil assemblages vary across the shelf and through the CIE interval. Stratigraphic changes in fossil assemblages and I/Ca are closely associated with local and global changes in oxygenation and sea level during the mid-Ludfordian. The collective data indicate significant biotic reorganization in response to changes in marine redox conditions and in conjunction with sea-level variation during the LKE interval, but detailed macroscopic biodiversity is currently unconstrained for this region.
|
|
| 44. |
- Bulovaite, Edita, et al.
(författare)
-
A brain atlas of synapse protein lifetime across the mouse lifespan
- 2022
-
Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 110:24, s. 4057-
-
Tidskriftsartikel (refereegranskat)abstract
- The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, and for memory duration. We quantified the lifetime of endogenous PSD95, an abundant postsynaptic protein in excitatory synapses, at single-synapse resolution across the mouse brain and lifespan, generating the Protein Lifetime Synaptome Atlas. Excitatory synapses have a wide range of PSD95 lifetimes extending from hours to several months, with distinct spatial distributions in dendrites, neurons, and brain regions. Synapses with short protein lifetimes are enriched in young animals and in brain regions controlling innate behaviors, whereas synapses with long protein lifetimes accumulate during development, are enriched in the cortex and CA1 where memories are stored, and are preferentially preserved in old age. Synapse protein lifetime increases throughout the brain in a mouse model of autism and schizophrenia. Protein lifetime adds a further layer to synapse diversity and enriches prevailing concepts in brain development, aging, and disease.
|
|
| 45. |
- Castner, Ashleigh T., et al.
(författare)
-
Mimicking the Electron Transport Chain and Active Site of [FeFe] Hydrogenases in One Metal-Organic Framework : Factors That Influence Charge Transport
- 2021
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:21, s. 7991-7999
-
Tidskriftsartikel (refereegranskat)abstract
- [FeFe] hydrogenase (H2ase) enzymes are effective proton reduction catalysts capable of forming molecular dihydrogen with a high turnover frequency at low overpotential. The active sites of these enzymes are buried within the protein structures, and substrates required for hydrogen evolution (both protons and electrons) are shuttled to the active sites through channels from the protein surface. Metal–organic frameworks (MOFs) provide a unique platform for mimicking such enzymes due to their inherent porosity which permits substrate diffusion and their structural tunability which allows for the incorporation of multiple functional linkers. Herein, we describe the preparation and characterization of a redox-active PCN-700-based MOF (PCN = porous coordination network) that features both a biomimetic model of the [FeFe] H2ase active site as well as a redox-active linker that acts as an electron mediator, thereby mimicking the function of [4Fe4S] clusters in the enzyme. Rigorous studies on the dual-functionalized MOF by cyclic voltammetry (CV) reveal similarities to the natural system but also important limitations in the MOF-enzyme analogy. Most importantly, and in contrast to the enzyme, restrictions apply to the total concentration of reduced linkers and charge-balancing counter cations that can be accommodated within the MOF. Successive charging of the MOF results in nonideal interactions between linkers and restricted mobility of charge-compensating redox-inactive counterions. Consequently, apparent diffusion coefficients are no longer constant, and expected redox features in the CVs of the materials are absent. Such nonlinear effects may play an important role in MOFs for (electro)catalytic applications.
|
|
| 46. |
- Cataldi, Gianni, et al.
(författare)
-
Primordial or Secondary? Testing Models of Debris Disk Gas with ALMA*
- 2023
-
Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 951:2
-
Tidskriftsartikel (refereegranskat)abstract
- The origin and evolution of gas in debris disks are still not well understood. Secondary gas production from cometary material or a primordial origin have been proposed. So far, observations have mostly concentrated on CO, with only a few C observations available. We overview the C and CO content of debris disk gas and test state-of-the-art models. We use new and archival Atacama Large Millimeter/submillimeter Array (ALMA) observations of CO and C i emission, complemented by C ii data from Herschel, for a sample of 14 debris disks. This expands the number of disks with ALMA measurements of both CO and C i by 10 disks. We present new detections of C i emission toward three disks: HD 21997, HD 121191, and HD 121617. We use a simple disk model to derive gas masses and column densities. We find that current state-of-the-art models of secondary gas production overpredict the C-0 content of debris disk gas. This does not rule out a secondary origin, but might indicate that the models require an additional C removal process. Alternatively, the gas might be produced in transient events rather than a steady-state collisional cascade. We also test a primordial gas origin by comparing our results to a simplified thermochemical model. This yields promising results, but more detailed work is required before a conclusion can be reached. Our work demonstrates that the combination of C and CO data is a powerful tool to advance our understanding of debris disk gas.
|
|
| 47. |
- Cataldi, Gianni, et al.
(författare)
-
The Surprisingly Low Carbon Mass in the Debris Disk around HD 32297
- 2020
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 892:2
-
Tidskriftsartikel (refereegranskat)abstract
- Gas has been detected in a number of debris disks. It is likely secondary, i.e., produced by colliding solids. Here, we report ALMA Band 8 observations of neutral carbon in the CO-rich debris disk around the 15-30 Myr old A-type star HD 32297. We find that C-0 is located in a ring at similar to 110 au with an FWHM of similar to 80 au and has a mass of (3.5 0.2) x 10(-3) M-circle plus. Naively, such a surprisingly small mass can be accumulated from CO photodissociation in a time as short as similar to 10(4) yr. We develop a simple model for gas production and destruction in this system, properly accounting for CO self-shielding and shielding by neutral carbon, and introducing a removal mechanism for carbon gas. We find that the most likely scenario to explain both C-0 and CO observations is one where the carbon gas is rapidly removed on a timescale of order a thousand years and the system maintains a very high CO production rate of similar to 15 M-circle plus Myr(-1), much higher than the rate of dust grind-down. We propose a possible scenario to meet these peculiar conditions: the capture of carbon onto dust grains, followed by rapid CO re-formation and rerelease. In steady state, CO would continuously be recycled, producing a CO-rich gas ring that shows no appreciable spreading over time. This picture might be extended to explain other gas-rich debris disks.
|
|
| 48. |
|
|
| 49. |
- Davis, Timothy A., et al.
(författare)
-
Revealing the intermediate-mass black hole at the heart of the dwarf galaxy NGC404 with sub-parsec resolution ALMA observations
- 2020
-
Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 496:4, s. 4061-4078
-
Tidskriftsartikel (refereegranskat)abstract
- We estimate the mass of the intermediate-mass black hole at the heart of the dwarf elliptical galaxy NGC 404 using Atacama Large Millimetre/submillimetre Array (ALMA) observations of the molecular interstellar medium at an unprecedented linear resolution of approximate to 0.5 pc, in combination with existing stellar kinematic information. These ALMA observations reveal a central disc/torus of molecular gas clearly rotating around the black hole. This disc is surrounded by a morphologically and kinematically complex flocculent distribution of molecular clouds, that we resolve in detail. Continuum emission is detected from the central parts of NGC 404, likely arising from the Rayleigh-Jeans tail of emission from dust around the nucleus, and potentially from dusty massive star-forming clumps at discrete locations in the disc. Several dynamical measurements of the black hole mass in this system have been made in the past, but they do not agree. We show here that both the observed molecular gas and stellar kinematics independently require a approximate to 5 x 10(5) M-circle dot black hole once we include the contribution of the molecular gas to the potential. Our best estimate comes from the high-resolution molecular gas kinematics, suggesting the black hole mass of this system is 5.5(-3.8)(+4.1) x 10(5) M-circle dot (at the 99 per cent confidence level), in good agreement with our revised stellar kinematic measurement and broadly consistent with extrapolations from the black hole mass-velocity dispersion and black hole massbulge mass relations. This highlights the need to accurately determine the mass and distribution of each dynamically important component around intermediate-mass black holes when attempting to estimate their masses.
|
|
| 50. |
- Dussex, Nicolas, et al.
(författare)
-
Population genomics of the critically endangered kākāpō
- 2021
-
Ingår i: Cell Genomics. - : Elsevier BV. - 2666-979X. ; 1:1
-
Tidskriftsartikel (refereegranskat)abstract
- Summary The kākāpō is a flightless parrot endemic to New Zealand. Once common in the archipelago, only 201 individuals remain today, most of them descending from an isolated island population. We report the first genome-wide analyses of the species, including a high-quality genome assembly for kākāpō, one of the first chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP). We also sequenced and analyzed 35 modern genomes from the sole surviving island population and 14 genomes from the extinct mainland population. While theory suggests that such a small population is likely to have accumulated deleterious mutations through genetic drift, our analyses on the impact of the long-term small population size in kākāpō indicate that present-day island kākāpō have a reduced number of harmful mutations compared to mainland individuals. We hypothesize that this reduced mutational load is due to the island population having been subjected to a combination of genetic drift and purging of deleterious mutations, through increased inbreeding and purifying selection, since its isolation from the mainland ∼10,000 years ago. Our results provide evidence that small populations can survive even when isolated for hundreds of generations. This work provides key insights into kākāpō breeding and recovery and more generally into the application of genetic tools in conservation efforts for endangered species.
|
|
