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2.
  • Rauer, H., et al. (author)
  • The PLATO 2.0 mission
  • 2014
  • In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 38:1-2, s. 249-330
  • Journal article (peer-reviewed)abstract
    • PLATO 2.0 has recently been selected for ESA's M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s cadence) providing a wide field-of-view (2232 deg(2)) and a large photometric magnitude range (4-16 mag). It focuses on bright (4-11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4-10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2-3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e. g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such a low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmospheres. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA's Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.
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  • Gaulton, Kyle J, et al. (author)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Journal article (peer-reviewed)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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5.
  • Razavi, Homie A., et al. (author)
  • Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
  • 2023
  • In: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
  • Journal article (peer-reviewed)abstract
    • Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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6.
  • Razavi-Shearer, Devin M., et al. (author)
  • Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
  • 2024
  • In: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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  • Rieke, Johanna Magdalena, et al. (author)
  • SLC20A1Is Involved in Urinary Tract and Urorectal Development
  • 2020
  • In: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
  • Journal article (peer-reviewed)abstract
    • Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
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  • Spiro, S., et al. (author)
  • Low luminosity Type II supernovae - II. Pointing towards moderate mass precursors
  • 2014
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 439:3, s. 2873-2892
  • Journal article (peer-reviewed)abstract
    • We present new data for five underluminous Type II-plateau supernovae (SNe IIP), namely SN 1999gn, SN 2002gd, SN 2003Z, SN 2004eg and SN 2006ov. This new sample of low-luminosity SNe IIP (LL SNe IIP) is analysed together with similar objects studied in the past. All of them show a flat light-curve plateau lasting about 100 d, an underluminous late-time exponential tail, intrinsic colours that are unusually red, and spectra showing prominent and narrow P Cygni lines. A velocity of the ejected material below 10(3) km s(-1) is inferred from measurements at the end of the plateau. The Ni-56 masses ejected in the explosion are very small (< 10(-2) M-circle dot). We investigate the correlations among Ni-56 mass, expansion velocity of the ejecta and absolute magnitude in the middle of the plateau, confirming the main findings of Hamuy, according to which events showing brighter plateau and larger expansion velocities are expected to produce more Ni-56. We propose that these faint objects represent the LL tail of a continuous distribution in parameters space of SNe IIP. The physical properties of the progenitors at the explosion are estimated through the hydrodynamical modelling of the observables for two representative events of this class, namely SN 2005cs and SN 2008in. We find that the majority of LL SNe IIP, and quite possibly all, originate in the core collapse of intermediate-mass stars, in the mass range 10-15 M-circle dot.
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  • Balato, A., et al. (author)
  • The role of the dermatologist in the immune-mediated/allergic diseases – position statement of the EADV task force on contact dermatitis, EADV task force on occupational skin diseases, UEMS-EBDV subcommission allergology and European Dermatology Forum
  • 2019
  • In: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 33:8, s. 1459-1464
  • Journal article (peer-reviewed)abstract
    • Background: The members of the Task Force on Contact Dermatitis and the Task Force on Occupational Dermatoses of the European Academy of Dermatology and Venereology (EADV), of the European Dermatology Forum (EDF), and the members of the UEMS Section of Dermatology-Venereology (UEMS-EBDV) we want to vindicate the fundamental role that the specialist in Dermatology has in the diagnosis and management of Immuno-mediated /allergic Diseases. Objective: In disagreement with the blueprint paper of the UEMS section of Allergology (2013), in which dermatologists are excluded from one of their core activities it was decided to write this consensus paper. Discussion: The skin occupies a crucial place in the broad spectrum of allergic diseases; there is no other organ with such a multitude of different clinical conditions mediated by so many pathogenetic immune mechanisms. Subsequently, dermatologists play a fundamental role in the management of immune-mediated diseases including among others contact dermatitis, atopic dermatitis, urticaria and angioedema or cutaneous adverse drug, food and arthropod reactions. The essential role of dermatology in the diagnostic, therapeutic and preventive management of immune mediated /allergic diseases which is crucial for patient management is justified from both the academic and professional point of view. Conclusion: Based on the best care of the patient with cutaneous immune allergic disease a multidisciplinary approach is desirable and the dermatologist has a pivotal role in patient management. Be so good and no one will not ignore you, dermatologist. Ideally Dermatology should be governed according the following Henry Ford statement: “Arriving together is the beginning; keeping together is progress; working together is success.”.
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  • de Jong, Yde, et al. (author)
  • PESI - a taxonomic backbone for Europe
  • 2015
  • In: Biodiversity Data Journal. - 1314-2836 .- 1314-2828. ; 3, s. 1-51
  • Journal article (peer-reviewed)abstract
    • Reliable taxonomy underpins communication in all of biology, not least nature conservation and sustainable use of ecosystem resources. The flexibility of taxonomic interpretations, however, presents a serious challenge for end-users of taxonomic concepts. Users need standardised and continuously harmonised taxonomic reference systems, as well as high-quality and complete taxonomic data sets, but these are generally lacking for non-specialists. The solution is in dynamic, expertly curated web-based taxonomic tools.The Pan-European Species-directories Infrastructure (PESI) worked to solve this key issue by providing a taxonomic e-infrastructure for Europe. It strengthened the relevant social (expertise) and information (standards, data and technical) capacities of five major community networks on taxonomic indexing in Europe, which is essential for proper biodiversity assessment and monitoring activities. The key objectives of PESI were: 1) standardisation in taxonomic reference systems, 2) enhancement of the quality and completeness of taxonomic data sets and 3) creation of integrated access to taxonomic information.This paper describes the results of PESI and its future prospects, including the involvement in major European biodiversity informatics initiatives and programs.
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  • Zhang, Rong, et al. (author)
  • ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Journal article (peer-reviewed)abstract
    • Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 x 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 x 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.
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  • Dimopoulos, Meletios A., et al. (author)
  • Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010) : A phase 3b study in refractory multiple myeloma
  • 2016
  • In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:4, s. 497-503
  • Journal article (peer-reviewed)abstract
    • Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity. Safety was the primary end point; secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Among 682 patients enrolled, median age was 66 years, and median time since diagnosis was 5.3 years. Median number of prior regimens was 5. Most patients were refractory to both lenalidomide and bortezomib (80.2%). Median follow-up was 16.8 months; median duration of treatment was 4.9 months. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia [49.7%], anemia [33.0%], and thrombocytopenia [24.1%]). Most common grade 3/4 nonhematologic toxicities were pneumonia (10.9%) and fatigue (5.9%). Grade 3/4 venous thromboembolism and peripheral neuropathy were rare (1.6% each). The ORR was 32.6%, and the median DOR was 7.4 months. Median PFS and OS were 4.6 months and 11.9 months, respectively. We present the largest trial to date evaluating pomalidomide plus low-dose dexamethasone in patients with RRMM, further confirming that this regimen offers clinically meaningful benefit and is generally well tolerated. www.Clinicaltrials.gov identifier NCT01712789.
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  • Donati, Mauro, 1966, et al. (author)
  • Marginal Bone Preservation in Single-Tooth Replacement: A 5-Year Prospective Clinical Multicenter Study
  • 2015
  • In: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899. ; 17:3, s. 425-434
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Few long-term studies are available comparing immediate and conventional loading protocols of implant-supported single-tooth replacement. PURPOSE: The aim of the present randomized controlled clinical trial was to evaluate prospectively the 5-year clinical and radiological outcome of immediate functional loading implants used in single-tooth replacement. MATERIALS AND METHODS: One hundred fifty-one subjects, who required single-tooth rehabilitation in the area from position 15 to 25 and from 35 to 45, were enrolled in eight private clinics in Italy. A randomization protocol was applied to allocate the implants in three treatment groups: one control group and two test groups. In the control group, implant placement was performed according to a conventional drilling procedure, and the implants were submerged for 3 months before abutment connection and loading. Implants allocated in the test group 1 and 2 followed an immediate functional loading protocol. While in test group 1, implant placement was performed according to conventional drilling procedure, in test group 2, a modified implant installation procedure (osteotome technique) was applied. Clinical and radiographic examinations were performed during the 5-year follow-up, and technical and biological complications were registered. RESULTS: Although four implants (three in the test group 2 and one in the test group 1) were lost in the immediate functional loading groups in the first year of follow-up, no further implant loss occurred in any of the treatment groups in the following monitoring period up to 5 years. No significant differences on marginal bone level changes were observed between the treatment groups. About 52% of all implants showed bone gain in the period from 1-year to 5-year follow-up. The percentage of all implants that in the same interval of time showed bone loss was about 28%. Although few technical complications were recorded in the period of time up to 5 years, implants showing biological complication were 5.7%. CONCLUSION: It is suggested that implants installed with a conventional installation technique together with an immediate functional loading protocol may be considered as a valid treatment alternative in a long-term perspective when used in a single-tooth replacement in an esthetic area.
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  • Goncalves, Nadia P., et al. (author)
  • Peripheral Nerve Regeneration Is Independent From Schwann Cell p75(NTR) Expression
  • 2019
  • In: Frontiers in Cellular Neuroscience. - : FRONTIERS MEDIA SA. - 1662-5102. ; 13
  • Journal article (peer-reviewed)abstract
    • Schwann cell reprogramming and differentiation are crucial prerequisites for neuronal regeneration and re-myelination to occur following injury to peripheral nerves. The neurotrophin receptor p75(NTR) has been identified as a positive modulator for Schwann cell myelination during development and implicated in promoting nerve regeneration after injury. However, most studies base this conclusion on results obtained from complete p75(NTR) knockout mouse models and cannot dissect the specific role of p75(NTR) expressed by Schwann cells. In this present study, a conditional knockout model selectively deleting p75(NTR) expression in Schwann cells was generated, where p75(NTR) expression is replaced with that of an mCherry reporter. Silencing of Schwann cell p75(NTR) expression was confirmed in the sciatic nerve in vivo and in vitro, without altering axonal expression of p75(NTR). No difference in sciatic nerve myelination during development or following sciatic nerve crush injury was observed, as determined by quantification of both myelinated and unmyelinated nerve fiber densities, myelinated axonal diameter and myelin thickness. However, the absence of Schwann cell p75(NTR) reduced motor nerve conduction velocity after crush injury. Our data indicate that the absence of Schwann cell p75(NTR) expression in vivo is not critical for axonal regrowth or remyelination following sciatic nerve crush injury, but does play a key role in functional recovery. Overall, this represents the first step in redefining the role of p75(NTR) in the peripheral nervous system, suggesting that the Schwann cell-axon unit functions as a syncytium, with the previous published involvement of p75(NTR) in remyelination most likely depending on axonal/neuronal p75(NTR) and/or mutual glial-axonal interactions.
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  • Hoffmann, V. S., et al. (author)
  • The EUTOS population-based registry : incidence and clinical characteristics of 2904 CML patients in 20 European Countries
  • 2015
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:6, s. 1336-1343
  • Journal article (peer-reviewed)abstract
    • This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100 000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.
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  • Hoffmann, V S, et al. (author)
  • Treatment and outcome of 2904 CML patients from the EUTOS population-based registry
  • 2017
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:3, s. 593-601
  • Journal article (peer-reviewed)abstract
    • The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.Leukemia advance online publication, 23 September 2016; doi:10.1038/leu.2016.246.
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23.
  • Raimondo, M, et al. (author)
  • A peaks over threshold model for change-point detection by wavelets
  • 2004
  • In: Statistica Sinica. - 1017-0405. ; 14:2, s. 395-412
  • Journal article (peer-reviewed)abstract
    • Newly available wavelet bases on multi-resolution analysis have exciting implications for detection of change-points. By checking the absolute value of wavelet coefficients one call detect discontinuities in ail otherwise smooth curve even in the presence of additive noise. In this paper, we combine wavelet methods and extreme value theory to test the presence of ail arbitrary number of discontinuities in an unknown function observed with noise. Our approach is based on a Peaks Over Threshold modelling of noisy wavelet transforms. Particular features of our method include the estimation of the extreme value index in the tail of the noise distribution. The critical region of our test is, derived using a Generalised Pareto Distribution approximation to normalised sums. Asymptotic results show that our method is powerful in a wide range of medium size wavelet frequencies. We compare our test with competing approaches on simulated examples and illustrate the method on Dow-Jones data.
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