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- Pierel, J. D. R., et al.
(author)
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LensWatch. I. Resolved HST Observations and Constraints on the Strongly Lensed Type Ia Supernova 2022qmx (SN Zwicky)
- 2023
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 948:2
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Journal article (peer-reviewed)abstract
- Supernovae (SNe) that have been multiply imaged by gravitational lensing are rare and powerful probes for cosmology. Each detection is an opportunity to develop the critical tools and methodologies needed as the sample of lensed SNe increases by orders of magnitude with the upcoming Vera C. Rubin Observatory and Nancy Grace Roman Space Telescope. The latest such discovery is of the quadruply imaged Type Ia SN 2022qmx (aka, SN Zwicky) at z = 0.3544. SN Zwicky was discovered by the Zwicky Transient Facility in spatially unresolved data. Here we present follow-up Hubble Space Telescope observations of SN Zwicky, the first from the multicycle LensWatch (www.lenswatch.org) program. We measure photometry for each of the four images of SN Zwicky, which are resolved in three WFC3/UVIS filters (F475W, F625W, and F814W) but unresolved with WFC3/IR F160W, and present an analysis of the lensing system using a variety of independent lens modeling methods. We find consistency between lens-model-predicted time delays (less than or similar to 1 day), and delays estimated with the single epoch of Hubble Space Telescope colors (less than or similar to 3.5 days), including the uncertainty from chromatic microlensing (similar to 1-1.5 days). Our lens models converge to an Einstein radius of theta(E) = 0.168 (+0.009)(-0.005) the smallest yet seen in a lensed SN system. The standard candle nature of SN Zwicky provides magnification estimates independent of the lens modeling that are brighter than predicted by similar to 1.7 (-0.6) (+0.8) mag and similar to 0.9 (-0.6) (+0.8) mag for two of the four images, suggesting significant microlensing and/or additional substructure beyond the flexibility of our image-position mass models.
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- Winkler, M., et al.
(author)
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The rich sides of mountain summits - a pan-European view on aspect preferences of alpine plants
- 2016
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In: Journal of Biogeography. - : Wiley. - 0305-0270. ; 43:11, s. 2261-2273
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Journal article (peer-reviewed)abstract
- Aim In the alpine life zone, plant diversity is strongly determined by local topography and microclimate. We assessed the extent to which aspect and its relatedness to temperature affect plant species diversity, and the colonization and disappearance of species on alpine summits on a pan-European scale. Methods Vascular plant species and their percentage cover were recorded in permanent plots in each cardinal direction on 123 summits in 32 regions across Europe. For a subset from 17 regions, resurvey data and 6-year soil temperature series were available. Differences in temperature sum and Shannon index as well as species richness, colonization and disappearance of species among cardinal directions were analysed using linear mixed-effects and generalised mixed-effects models, respectively. Results Temperature sums were higher in east-and south-facing aspects than in the north-facing ones, while the west-facing ones were intermediate; differences were smallest in northern Europe. The patterns of temperature sums among aspects were consistent among years. In temperate regions, thermal differences were reflected by plant diversity, whereas this relationship was weaker or absent on Mediterranean and boreal mountains. Colonization of species was positively related to temperature on Mediterranean and temperate mountains, whereas disappearance of species was not related to temperature. Main conclusions Thermal differences caused by solar radiation determine plant species diversity on temperate mountains. Advantages for plants on eastern slopes may result from the combined effects of a longer diurnal period of radiation due to convection cloud effects in the afternoon and the sheltered position against the prevailing westerly winds. In northern Europe, long summer days and low sun angles can even out differences among aspects. On Mediterranean summits, summer drought may limit species numbers on the warmer slopes. Warmer aspects support a higher number of colonization events. Hence, aspect can be a principal determinant of the pace of climate-induced migration processes.
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- Ercan, Ayse Bahar, et al.
(author)
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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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In: The Lancet Oncology. - 1470-2045. ; 25:5, s. 668-682
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Journal article (peer-reviewed)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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- Kober, L., et al.
(author)
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Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction
- 2006
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In: European journal of heart failure. - 1388-9842. ; 8:6, s. 591-8
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Journal article (peer-reviewed)abstract
- AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). METHODS: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. RESULTS: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03-1.52; p=0.03) for prior AF and 1.32 (1.20-1.45; p<0.0001) for current AF. HR for major CV events was 1.15 (0.98-1.35; p=0.08) and 1.21 (1.12-1.31; p<0.0001). CONCLUSION: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.
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- Cerna, Katerina, 1986, et al.
(author)
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Transformation of HCI co-research with older adults: researchers' positionality in the COVID-19 pandemic
- 2021
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In: Interaction Design and Architecture(s). - 1826-9745. ; :50, s. 27-47
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Journal article (peer-reviewed)abstract
- In the time of COVID-19, many measurements to contain the pandemic contributed to social isolation and loneliness. Older adults in particular experience various forms of ageism in this regard, for example by being stereotyped as digitally illiterate. Hence, we need to learn more about the aging discourse in the context of participatory approaches, as it is currently lacking. This article presents the results from two participatory research projects that were significantly affected by the 1st COVID-19 lockdown. We specifically focus on the ways the relationships and modes of cooperation with our older research partners, i.e. the positionalities, have been impacted. We draw on the projects' results, reflecting on the possible implications for the involvement of older adults in design and HCI research and specifically, technologies that are supportive and empowering for the individuals against the background of the pandemic situation. © 2021. All Rights Reserved.
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- Das, Anirban, et al.
(author)
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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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In: Cancer discovery. - 2159-8290. ; 14:2, s. 258-273
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Journal article (peer-reviewed)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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