| 1. |
- Aharonian, F., et al.
(författare)
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TeV flaring activity of the AGN PKS 0625-354 in November 2018
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Most gamma-ray detected active galactic nuclei are blazars with one of their relativistic jets pointing towards the Earth. Only a few objects belong to the class of radio galaxies or misaligned blazars. Here, we investigate the nature of the object PKS 0625-354, its gamma-ray flux and spectral variability and its broad-band spectral emission with observations from H.E.S.S., Fermi-LAT, Swift-XRT, and UVOT taken in November 2018. The H.E.S.S. light curve above 200 GeV shows an outburst in the first night of observations followed by a declining flux with a halving time scale of 5.9 h. The gamma gamma-opacity constrains the upper limit of the angle between the jet and the line of sight to similar to 10 degrees. The broad-band spectral energy distribution shows two humps and can be well fitted with a single-zone synchrotron self Compton emission model. We conclude that PKS 0625-354, as an object showing clear features of both blazars and radio galaxies, can be classified as an intermediate active galactic nuclei. Multi-wavelength studies of such intermediate objects exhibiting features of both blazars and radio galaxies are sparse but crucial for the understanding of the broad-band emission of gamma-ray detected active galactic nuclei in general.
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| 2. |
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| 3. |
- Butterworth, Joshua, et al.
(författare)
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Molecular isotopologue measurements toward super star clusters and the relation to their ages in NGC 253 with ALCHEMI
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 686
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Tidskriftsartikel (refereegranskat)abstract
- Context. Determining the evolution of the CNO isotopes in the interstellar medium (ISM) of starburst galaxies can yield important constraints on the ages of super star clusters (SSCs), or on other aspects and factors contributing to their evolution, such as the initial mass function (IMF). Due to the time-dependent nature of the abundances of isotopes within the ISM -as they are supplied from processes such as nucleosynthesis or chemical fractionation -, this provides the opportunity to test whether or not isotope ratios trace the ages of highly star-forming regions, such as SSCs. Aims. The goal of this study is to investigate whether the isotopic variations in SSC regions within NGC 253 are correlated with their different ages as derived from stellar population modelling. Methods. We measured abundance ratios of CO, HCN, and HCO+ isotopologues in six regions containing SSCs within NGC 253 using high-spatial-resolution (1.6″, ~28 pc) data from the ALCHEMI (ALma Comprehensive High-resolution Extragalactic Molecular Inventory) ALMA Large program. We then analysed these ratios using RADEX radiative transfer modelling, with the parameter space sampled using the nested sampling Monte Carlo algorithm MLFriends. These abundance ratios were then compared to ages predicted in each region via the fitting of observed star-formation tracers (such as Brγ) to Starburst99 starburst stellar population evolution models. Results. We determined the isotopic column density ratios across multiple regions of SSC activity in NGC 253 using non-LTE radiative transfer modelling. We do not find any significant trend with age for the CO and HCN isotopologue ratios on timescales of the ages of the SSC∗ regions observed. However, HCO+ may show a correlation with age over these timescales in 12C/13C. Conclusions. The driving factors of these ratios within SSCs could be the IMF or fractionation effects. To further probe these effects in SSCs over time, a larger sample of SSCs must be observed spanning a larger age range.
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| 4. |
- Crowe, S., et al.
(författare)
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Near-infrared observations of outflows and young stellar objects in the massive star-forming region AFGL 5180
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Tidskriftsartikel (refereegranskat)abstract
- Context. Massive stars play important roles throughout the universe; however, their formation remains poorly understood. Observations of jets and outflows in high-mass star-forming regions, as well as surveys of young stellar object (YSO) content, can help test theoretical models of massive star formation. Aims. We aim at characterizing the massive star-forming region AFGL 5180 in the near-infrared (NIR), identifying outflows and relating these to sub-mm/mm sources, as well as surveying the overall YSO surface number density to compare to massive star formation models. Methods. Broad- and narrow-band imaging of AFGL 5180 was made in the NIR with the Large Binocular Telescope, in both seeing-limited (~0.5′) and high angular resolution (~0.09′) Adaptive Optics (AO) modes, as well as with the Hubble Space Telescope. Archival continuum data from the Atacama Millimeter/Submillimeter Array (ALMA) was also utilized. Results. At least 40 jet knots were identified via NIR emission from H2 and [FeII] tracing shocked gas. Bright jet knots outflowing from the central most massive protostar, S4 (estimated mass ~11 M⊙, via SED fitting), are detected towards the east of the source and are resolved in fine detail with the AO imaging. Additional knots are distributed throughout the field, likely indicating the presence of multiple driving sources. Sub-millimeter sources detected by ALMA are shown to be grouped in two main complexes, AFGL 5180 M and a small cluster ~15′ (0.15 pc in projection) to the south, AFGL 5180 S. From our NIR continuum images we identify YSO candidates down to masses of ~0.1 M⊙. Combined with the sub-mm sources, this yields a surface number density of such YSOs of N* ~ 103pc-2 within a projected radius of about 0.1 pc. Such a value is similar to those predicted by models of both core accretion from a turbulent clump environment and competitive accretion. The radial profile of N* is relatively flat on scales out to 0.2 pc, with only modest enhancement around the massive protostar inside 0.05 pc, which provides additional constraints on these massive star formation models. Conclusions. This study demonstrates the utility of high-resolution NIR imaging, in particular with AO, for detecting outflow activity and YSOs in distant regions. The presented images reveal the complex morphology of outflow-shocked gas within the large-scale bipolar flow of a massive protostar, as well as clear evidence for several other outflow driving sources in the region. Finally, this work presents a novel approach to compare the observed YSO surface number density from our study against different models of massive star formation.
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| 5. |
- Das, Anirban, et al.
(författare)
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Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: A report from the International RRD Consortium.
- 2024
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Ingår i: Cancer discovery. - 2159-8290. ; 14:2, s. 258-273
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Tidskriftsartikel (refereegranskat)abstract
- Immune-checkpoint inhibition (ICI) is effective for replication-repair deficient, high-grade gliomas (RRD-HGG). Clinical/biologic impact of immune-directed approaches after failing ICI-monotherapy are unknown. We performed an international study on 75 patients treated with anti-PD1; 20 are progression-free (median follow-up: 3.7-years). After 2nd-progression/recurrence (n=55), continuing ICI-based salvage prolonged survival to 11.6-months (n=38; p<0.001), particularly for those with extreme mutation burden (p=0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and immune-microenvironment. Response to re-irradiation was explained by an absence of deleterious post-radiation indel signatures (ID8). Increased CTLA4-expression over time, and subsequent CTLA4-inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to reinvigoration of peripheral immune and radiological responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/ synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology.
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| 6. |
- Ercan, Ayse Bahar, et al.
(författare)
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Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
- 2024
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Ingår i: The Lancet Oncology. - 1470-2045. ; 25:5, s. 668-682
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Tidskriftsartikel (refereegranskat)abstract
- Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
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| 7. |
- Harada, N., et al.
(författare)
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The ALCHEMI Atlas: Principal Component Analysis Reveals Starburst Evolution in NGC 253
- 2024
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Ingår i: Astrophysical Journal, Supplement Series. - 1538-4365 .- 0067-0049. ; 271:2
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Tidskriftsartikel (refereegranskat)abstract
- Molecular lines are powerful diagnostics of the physical and chemical properties of the interstellar medium (ISM). These ISM properties, which affect future star formation, are expected to differ in starburst galaxies from those of more quiescent galaxies. We investigate the ISM properties in the central molecular zone of the nearby starburst galaxy NGC 253 using the ultrawide millimeter spectral scan survey from the Atacama Large Millimeter/submillimeter Array Large Program ALCHEMI. We present an atlas of velocity-integrated images at a 1.″6 resolution of 148 unblended transitions from 44 species, including the first extragalactic detection of HCNH+ and the first interferometric images of C3H+, NO, and HCS+. We conduct a principal component analysis (PCA) on these images to extract correlated chemical species and to identify key groups of diagnostic transitions. To the best of our knowledge, our data set is currently the largest astronomical set of molecular lines to which PCA has been applied. The PCA can categorize transitions coming from different physical components in NGC 253 such as (i) young starburst tracers characterized by high-excitation transitions of HC3N and complex organic molecules versus tracers of on-going star formation (radio recombination lines) and high-excitation transitions of CCH and CN tracing photodissociation regions, (ii) tracers of cloud-collision-induced shocks (low-excitation transitions of CH3OH, HNCO, HOCO+, and OCS) versus shocks from star formation-induced outflows (high-excitation transitions of SiO), as well as (iii) outflows showing emission from HOC+, CCH, H3O+, CO isotopologues, HCN, HCO+, CS, and CN. Our findings show these intensities vary with galactic dynamics, star formation activities, and stellar feedback.
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| 8. |
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| 9. |
- Laguzzi, F., et al.
(författare)
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Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease : Pooled De Novo Results From 15 Observational Studies
- 2024
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 149:4, s. 305-316
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction.RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions.CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.
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| 10. |
- Lauper, Kim, et al.
(författare)
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Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept : Results from the international TOCERRA and PANABA observational collaborative studies
- 2024
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Ingår i: Joint Bone Spine. - 1297-319X. ; 91:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). Methods: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. Results: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48–0.87] for abatacept, and 1.04 [0.76–1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83–1.47] for abatacept, and 1.30 [0.96–1.78] for tocilizumab. Conclusion: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.
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