| 1. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Aprile, E., et al.
(författare)
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Double-weak decays of 124Xe and 136Xe in the XENON1T and XENONnT experiments
- 2022
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Ingår i: Physical Review C. - 2469-9985 .- 2469-9993. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- We present results on the search for two-neutrino double-electron capture (2νECEC) of 124Xe and neutrinoless double-β decay (0νββ) of 136Xe in XENON1T. We consider captures from the K shell up to the N shell in the 2νECEC signal model and measure a total half-life of T2νECEC1/2=(1.1±0.2stat±0.1sys)×1022yr with a 0.87 kg yr isotope exposure. The statistical significance of the signal is 7.0σ. We use XENON1T data with 36.16 kg yr of 136Xe exposure to search for 0νββ. We find no evidence of a signal and set a lower limit on the half-life of T0νββ1/2>1.2×1024 yr at 90%CL. This is the best result from a dark matter detector without an enriched target to date. We also report projections on the sensitivity of XENONnT to 0νββ. Assuming a 275 kg yr 136Xe exposure, the expected sensitivity is T0νββ1/2>2.1×1025 yr at 90%CL, corresponding to an effective Majorana mass range of ⟨mββ⟩<(0.19–0.59)eV/c2.
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| 4. |
- Aprile, E., et al.
(författare)
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Search for New Physics in Electronic Recoil Data from XENONnT
- 2022
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 129:16
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Tidskriftsartikel (refereegranskat)abstract
- We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3) events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.
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| 5. |
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| 6. |
- Biondi, Andrea, et al.
(författare)
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Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study
- 2012
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Ingår i: The Lancet Oncology. - 1474-5488. ; 13:9, s. 936-945
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Tidskriftsartikel (refereegranskat)abstract
- Background Trials of imatinib have provided evidence of activity in adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (ALL), but the drug's role when given with multidrug chemotherapy to children is unknown. This study assesses the safety and efficacy of oral imatinib in association with a Berlin-Frankfurt-Munster intensive chemotherapy regimen and allo geneic stem-cell transplantation for paediatric patients with Philadelphia-chromosome-positive ALL. Methods Patients aged 1-18 years recruited to national trials of front-line treatment for ALL were eligible if they had t(9;22)(q34;q11). Patients with abnormal renal or hepatic function, or an active systemic infection, were ineligible. Patients were enrolled by ten study groups between 2004 and 2009, and were classified as good risk or poor risk according to early response to induction treatment. Good-risk patients were randomly assigned by a web-based system with permuted blocks (size four) to receive post-induction imatinib with chemotherapy or chemotherapy only in a 1: 1 ratio, while all poor-risk patients received post-induction imatinib with chemotherapy. Patients were stratified by study group. The chemotherapy regimen was modelled on a Berlin-Frankfurt-Munster high-risk backbone; all received four post-induction blocks of chemotherapy after which they became eligible for stem-cell transplantation. The primary endpoints were disease-free survival at 4 years in the good-risk group and event-free survival at 4 years in the poor-risk group, analysed by intention to treat and a secondary analysis of patients as treated. The trial is registered with EudraCT (2004-001647-30) and ClinicalTrials.gov, number NCT00287105. Findings Between Jan 1, 2004, and Dec 31, 2009, we screened 229 patients and enrolled 178: 108 were good risk and 70 poor risk. 46 good-risk patients were assigned to receive imatinib and 44 to receive no imatinib. Median follow-up was 3.1 years (IQR 2.0-4.6). 4-year disease-free survival was 72.9% (95% CI 56.1-84.1) in the good-risk, imatinib group versus 61.7% (45.0-74.7) in the good-risk, no imatinib group (p=0.24). The hazard ratio (HR) for failure, adjusted for minimal residual disease, was 0.63 (0.28-1.41; p=0.26). The as-treated analysis showed 4-year disease-free survival was 75.2% (61.0-84.9) for good-risk patients receiving imatinib and 55.9% (36.1-71.7) for those who did not receive imatinib (p=0.06). 4-year event-free survival for poor-risk patients was 53.5% (40.4-65.0). Serious adverse events were much the same in the good-risk groups, with infections caused by myelosuppression the most common. 16 patients in the good-risk imatinib group versus ten in the good-risk, no imatinib group (p=0.64), and 24 in the poor-risk group, had a serious adverse event. Interpretation Our results suggests that imatinib in conjunction with intensive chemotherapy is well tolerated and might be beneficial for treatment of children with Philadelphia-chromosome-positive ALL.
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| 7. |
- Buitenkamp, Trudy D., et al.
(författare)
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Acute lymphoblastic leukemia in children with Down syndrome : a retrospective analysis from the Ponte di Legno study group
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 123:1, s. 70-77
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Tidskriftsartikel (refereegranskat)abstract
- Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Munster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% +/- 2% vs 15% +/- 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- < 1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P < .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 x 10(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups.
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| 8. |
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| 9. |
- Dirri, Fabrizio, et al.
(författare)
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VISTA instrument: a PCM-based sensor for organics and volatiles characterization by using Thermogravimetric technique
- 2018
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Konferensbidrag (refereegranskat)abstract
- VISTA (Volatile In Situ Thermogravimetry Analyser) is a µ-Thermogravimeter sensor developed by Consortium of Italian Institutes. ThermoGravimetric Analysis (TGA) is a widely used technique to monitor thermal processes involving volatile compounds, e.g. deposition/sublimation and absorption/ desorption. The instrument core is composed by a Piezoelectric Crystal Microbalance (PCM), equipped with built-in heater and built-in temperature sensor, and provided of its own Proximity Electronics (PE). The PCM oscillation frequency linearly depends on the mass deposited on its sensible area (according to Sauerbrey equation) while the PCM temperature can be increased by means of integrated heaters. Thus, mass and volatile composition can be inferred by the frequency change and by desorption temperature, respectively. The instrument is divided in two sensor heads: VISTA1, able to monitor outgassing processes in space, and VISTA2, able to reach higher temperatures, studying the dehydration and organics decomposition in minerals in different environmental conditions. An Engineering Model of VISTA1 and a laboratory breadboard of VISTA2 have been developed. Pure organic compounds and contaminant have been characterized by using deposition processes and TGA cycles obtaining some physical-chemical parameters, i.e. enthalpy of sublimation/evaporation, ΔHHsub,evap , deposition rates, kk and vapor pressures, Pvap . The instrument concept, the scientific objectives and the laboratory measurements are explained in this work.
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| 10. |
- Jankovic, Momcilo, et al.
(författare)
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Long-term survivors of childhood cancer : cure and care—the Erice Statement (2006) revised after 10 years (2016)
- 2018
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 12:5, s. 647-650
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The number of persons who have successfully completed treatment for a cancer diagnosed during childhood and who have entered adulthood is increasing over time, and former patients will become aging citizens. Methods: Ten years ago, an expert panel met in Erice, Italy, to produce a set of principles concerning the cure and care of survivors of childhood and adolescent cancer. The result was the Erice Statement (Haupt et al. Eur J Cancer 43(12):1778–80, 2007) that was translated into nine languages. Ten years on, it was timely to review, and possibly revise, the Erice Statement in view of the changes in paediatric oncology and the number and results of international follow-up studies conducted during the intervening years. Results: The long-term goal of the cure and care of a child with cancer is that he/she becomes a resilient and autonomous adult with optimal health-related quality of life, accepted in society at the same level as his/her age peers. “Cure” refers to cure from the original cancer, regardless of any potential for, or presence of, remaining disabilities or side effects of treatment. The care of a child with cancer should include complete and honest information for parents and the child. Conclusions and implication for cancer survivors: Some members of the previous expert panel, as well as new invited experts, met again in Erice to review the Erice Statement, producing a revised version including update and integration of each of the ten points. In addition, a declaration has been prepared, by the Childhood Cancer International Survivors Network in Dublin on October 2016 (see Annex 1).
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| 11. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 12. |
- Sepanlou, Sadaf G., et al.
(författare)
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The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2020
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Ingår i: The Lancet Gastroenterology & Hepatology. - 2468-1253. ; 5:3, s. 245-266
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Tidskriftsartikel (refereegranskat)abstract
- Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.
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| 13. |
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