31 research outputs found
Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study
Background: The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods: From January 2014 to January 2018, 100 men aged 50-63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss' kappa (kappa) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results: Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD +/- 10%, range 62-96%), and mean specificity 60% (SD +/- 22%, range 27-82%). For csPCa (Gleason Grade 2-5) MRI was equally sensitive (mean 82%, SD +/- 9%, range 67-97%) but less specific (mean 47%, SD +/- 20%, range 21-75%). Interreader agreement for any lesion was fair (kappa 0.40) and for PI-RADS 4-5 lesions it was moderate (kappa 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions: Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.Peer reviewe
Expected impact of MRI-related interreader variability on ProScreen prostate cancer screening trial: a pre-trial validation study
Background: The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods: From January 2014 to January 2018, 100 men aged 50-63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss' kappa (kappa) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results: Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD +/- 10%, range 62-96%), and mean specificity 60% (SD +/- 22%, range 27-82%). For csPCa (Gleason Grade 2-5) MRI was equally sensitive (mean 82%, SD +/- 9%, range 67-97%) but less specific (mean 47%, SD +/- 20%, range 21-75%). Interreader agreement for any lesion was fair (kappa 0.40) and for PI-RADS 4-5 lesions it was moderate (kappa 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions: Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.Peer reviewe
Simultaneous Planck, Swift, and Fermi observations of X-ray and gamma-ray selected blazars
We present simultaneous Planck, Swift, Fermi, and ground-based data for 105
blazars belonging to three samples with flux limits in the soft X-ray, hard
X-ray, and gamma-ray bands. Our unique data set has allowed us to demonstrate
that the selection method strongly influences the results, producing biases
that cannot be ignored. Almost all the BL Lac objects have been detected by
Fermi-LAT, whereas ~40% of the flat-spectrum radio quasars (FSRQs) in the
radio, soft X-ray, and hard X-ray selected samples are still below the
gamma-ray detection limit even after integrating 27 months of Fermi-LAT data.
The radio to sub-mm spectral slope of blazars is quite flat up to ~70GHz, above
which it steepens to ~-0.65. BL Lacs have significantly flatter spectra
than FSRQs at higher frequencies. The distribution of the rest-frame
synchrotron peak frequency (\nupS) in the SED of FSRQs is the same in all the
blazar samples with =10^13.1 Hz, while the mean inverse-Compton peak
frequency, , ranges from 10^21 to 10^22 Hz. The distributions of \nupS
and of \nupIC of BL Lacs are much broader and are shifted to higher energies
than those of FSRQs and strongly depend on the selection method. The Compton
dominance of blazars ranges from ~0.2 to ~100, with only FSRQs reaching values
>3. Its distribution is broad and depends strongly on the selection method,
with gamma-ray selected blazars peaking at ~7 or more, and radio-selected
blazars at values ~1, thus implying that the assumption that the blazar power
is dominated by high-energy emission is a selection effect. Simple SSC models
cannot explain the SEDs of most of the gamma-ray detected blazars in all
samples. The SED of the blazars that were not detected by Fermi-LAT may instead
be consistent with SSC emission. Our data challenge the correlation between
bolometric luminosity and \nupS predicted by the blazar sequence.Comment: Version accepted by A&A. Joint Planck, Swift, and Fermi
collaborations pape
Kansallinen allergiaohjelma 2008-2018 muutti asenteita ja vähensi sairastavuutta
Lähtökohdat : Allergiaohjelma 2008–2018 on kansallinen kansanterveysohjelma, jonka avulla välttöstrategia on käännetty sietostrategiaksi ja painotettu allergiaterveyttä. Raportoimme 10 vuoden tulokset.Menetelmät : Ohjelmalla oli kuusi tavoitetta, joiden toteuttamiseksi määriteltiin tehtävät, työkalut ja mittarit. Ohjelmaa toteutettiin kouluttamalla terveydenhuoltoa ja viestimällä väestölle.Tulokset : Astman ja allergisen nuhan esiintyvyys tasoittui asevelvollisissa ja Helsingin aikuisväestössä. Helsingin aikuisista astmaatikoista 41 % oli ollut vuoden 2016 kyselyä edeltäneen vuoden oireettomia (31 % 2006). Lasten allergiaruokavaliot vähenivät koko maassa noin puoleen. Työperäiset allergiset sairaudet vähenivät 45 %. Astman sairaalahoidon tarve puolittui, mutta päivystyskäynnit vähenivät oleellisesti vain lapsilla. Anafylaksia aiheutti aiempaa enemmän päivystyskäyntejä. Allergiasta ja astmasta aiheutuvat vuosittaiset suorat ja epäsuorat kustannukset vähenivät 200 miljoonaa euroa (30 %) verrattaessa vuosia 2007 ja 2018.Päätelmät : Allergian ja astman aiheuttama sairastavuus ja niistä koituvat kustannukset vähenivät merkittävästi. Haitat vähenivät aluksi nopeasti, myöhemmin hitaammin. Ammattilaiset ja suuri yleisö hyväksyivät uuden suunnan, jossa painottuivat sietokyky ja terveys allergiasta huolimatta. Tietoon perustuvat systemaattiset ohjelmat ovat vahva keino parantaa kansanterveyttä
Planck early results. XV. Spectral energy distributions and radio continuum spectra of northern extragalactic radio sources
Spectral energy distributions (SEDs) and radio continuum spectra are presented for a northern sample of 104 extragalactic radio sources, based
on the Planck Early Release Compact Source Catalogue (ERCSC) and simultaneous multifrequency data. The nine Planck frequencies, from 30
to 857 GHz, are complemented by a set of simultaneous observations ranging from radio to gamma-rays. This is the first extensive frequency
coverage in the radio and millimetre domains for an essentially complete sample of extragalactic radio sources, and it shows how the individual
shocks, each in their own phase of development, shape the radio spectra as they move in the relativistic jet. The SEDs presented in this paper
were fitted with second and third degree polynomials to estimate the frequencies of the synchrotron and inverse Compton (IC) peaks, and the
spectral indices of low and high frequency radio data, including the Planck ERCSC data, were calculated. SED modelling methods are discussed,
with an emphasis on proper, physical modelling of the synchrotron bump using multiple components. Planck ERCSC data also suggest that the
original accelerated electron energy spectrum could be much harder than commonly thought, with power-law index around 1.5 instead of the
canonical 2.5. The implications of this are discussed for the acceleration mechanisms effective in blazar shocks. Furthermore in many cases the
Planck data indicate that gamma-ray emission must originate in the same shocks that produce the radio emission
A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes
dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe