Molecular subtyping of bladder cancer using Kohonen self-organizing maps

Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with a SOM to stratify tumors according to the risk of progression to more advanced disease. In univariable analysis, tumor stage (log rank P = 0.006) and grade (P < 0.001), HPV DNA (P < 0.004), Chromosome 9 loss (P = 0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (P = 0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, P = 0.001, OR.2.9 (95% CI 1.6–5.2)) and the presence of HPV DNA (P = 0.017, OR 3.8 (95% CI 1.3–11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank P = 0.39). These genetic variables were presented to SOM input neurons. SOMs are suitable for complex data integration, allow easy visualization of outcomes, and may stratify BC progression more robustly than hierarchical clustering

Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland and the Baltic States.

Peer reviewe

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

EQ-5D in Central and Eastern Europe : 2000-2015

Objective: Cost per quality-adjusted life year data are required for reimbursement decisions in many Central and Eastern European (CEE) countries. EQ-5D is by far the most commonly used instrument to generate utility values in CEE. This study aims to systematically review the literature on EQ-5D from eight CEE countries. Methods: An electronic database search was performed up to July 1, 2015 to identify original EQ-5D studies from the countries of interest. We analysed the use of EQ-5D with respect to clinical areas, methodological rigor, population norms and value sets. Results: We identified 143 studies providing 152 country-specific results with a total sample size of 81,619: Austria (n=11), Bulgaria (n=6), Czech Republic (n=18), Hungary (n=47), Poland (n=51), Romania (n=2), Slovakia (n=3) and Slovenia (n=14). Cardiovascular (20%), neurologic (16%), musculoskeletal (15%) and endocrine/nutritional/metabolic diseases (14%) were the most frequently studied clinical areas. Overall 112 (78%) of the studies reported EQ VAS results and 86 (60%) EQ-5D index scores, of which 27 (31%) did not specify the applied tariff. Hungary, Poland and Slovenia have population norms. Poland and Slovenia also have a national value set. Conclusions: Increasing use of EQ-5D is observed throughout CEE. The spread of health technology assessment activities in countries seems to be reflected in the number of EQ-5D studies. However, improvement in informed use and methodological quality of reporting is needed. In jurisdictions where no national value set is available, in order to ensure comparability we recommend to apply the most frequently used UK tariff. Regional collaboration between CEE countries should be strengthened

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Deficits and excess of precipitation for rye crops in northeastern Poland in the years 1971-2000

W pracy przedstawiono częstości występowania niekorzystnych sytuacji opadowych (do których zaliczono nadmiary i niedobory opadów większe od podwójnego odchylenia standardowego) obliczonych w procentach lat z okresu 30-lecia 1971-2000, w Polsce Północno-Wschodniej, w stosunku do zapotrzebowania żyta na wodę na glebach lekkich oraz pszenicy ozimej na glebach średnich i ciężkich. Na wszystkich badanych glebach najmniej korzystne warunki opadowe dla badanych roślin występowały w maju, przy czym na glebach lekkich, na większości badanego obszaru, częstości występowania niekorzystnych sytuacji opadowych dla żyta wynosiły od 45% do ponad 60%. Na glebach średnich w tym miesiącu (dla pszenicy ozimej) niekorzystne sytuacje opadowe o częstości występowania od ponad 35% do ponad 40% wystąpiły w zachodniej i północnej części obszaru. Na glebach ciężkich średnie wieloletnie częstości występowania niekorzystnych opadów dla pszenicy ozimej były o około 5-10% mniejsze niż na analogicznych obszarach na glebach średnich.The paper presents results of analysis of the effects of water supply on rye (light soils) and winter wheat (medium heavy and heavy soils) in northeastern Poland based on meteorological dataset (monthly sums of precipitation) covering the period from 1971 to 2000. The highest risk of extreme situations (total surplus of precipitation and its deficits) with respect to cereal species demands occurred in May irrespective of the soil type. The frequency of occurrence of extreme situation was estimated at 45-60 % on light soils. For winter wheat, cultivated on medium soils, unfavorable precipitation values of the frequency from over 35 % to over 40 % were noticed in northwestern and western part of the study area. Long term mean frequencies of unfavourable precipitation were lower by 5-10% on heavy than on medium soils

The excesses and deficits of precipitation for pea and horse bean cultivated in Northeastern Poland in the years 1971-2000

W pracy dokonano analizy warunków opadowych na obszarze Polski Północno-Wschodniej w aspekcie wymagań wodnych grochu (gleby lekkie) i bobiku (gleby średnie i ciężkie), wykorzystując dane meteorologiczne dotyczące miesięcznych sum opadów w latach 1971-2000. Generalnie, na całym obszarze, od kwietnia do czerwca notowano więcej sytuacji z ekstremalnymi niedoborami opadów w stosunku do zapotrzebowania bobiku i grochu, natomiast w lipcu - więcej przypadków z ekstremalnymi nadmiarami. W kwietniu i maju stopień ryzyka pojawienia się sytuacji z ekstremalnymi opadami był najwyższy w północno-zachodniej części regionu i malał w kierunku wschodu i południowego wschodu. W czerwcu i lipcu ryzyko występowania sytuacji ekstremalnych było w miarę równomiernie rozłożone w całym regionie i wynosiło od 20 do 40%.The paper presents results of analysis of the effects of water supply on pea (light soils) and horse bean (medium heavy and heavy soils) grown in northeastern Poland based on meteorological dataset (monthly sums of precipitation) covering the period from 1971 to 2000. The general findings suggest that the highest risks of extreme deficits of precipitation with respect to pea and horse bean demands occurred in the period from April to June, however, the extreme excesses occurred in July. The results also suggest that the distributions of precipitation from April to May were most unfavorable in the northern part of analyzed region and improved south-eastward, but in July the risk of the occurrence of extreme situation was even all over the region (20-40%)

The excesses and deficits of precipitations for potato and sugar beet cultivated in northeastern Poland in the years 1971-2000

W pracy zamieszczono analizę stopnia zaspokajania zapotrzebowania na wodę ziemniaka (gleby lekkie) i buraka cukrowego (gleby średnie i ciężkie) na obszarze Polski Północno-Wschodniej, wykonaną na podstawie danych meteorologicznych dotyczących miesięcznych sum opadu, w latach 1971-2000. Wykazano, iż największe ryzyko uprawy spowodowane znaczną częstością niedostosowania sum opadu do potrzeb ziemniaka i buraka cukrowego, występuje w północno-zachodniej części analizowanego obszaru. W wieloleciu w przypadku obydwu gatunków częste okazały się miesiące, w których występowały niedobory opadów, chociaż w przypadku buraka stwierdzono również dużą częstość miesięcy o znaczących nadmiarach w stosunku do potrzeb gatunku.The paper presents results of analysis of the effects of water supply on potato (light soils) and sugar beet (medium heavy and heavy soils) grown in northeastern Poland based on meteorological dataset (monthly sums of precipitation) covering the period from 1971 to 2000. The findings suggest that the highest risks of extreme situations (total excesses of precipitation and its deficits) with respect to potato and sugar beet demands occurred in northwestern part of analyzed region. Our analysis shows that precipitation deficits during critical periods of growing seasons were the main problem, though sugar beet was negatively affected by both excesses and deficits of precipitation

Warunki pluwiotermiczne w polnocno-wschodniej Polsce w wieloleciu 1971-2000

Niniejsze opracowanie stanowi kolejne uzupełnienie podstawowych charakterystyk klimatu północno-wschodniej Polski o elementy obliczone dla standardowego trzydziestolecia 1971-2000. Na obszarze tym średnia temperatura roczna wynosiła 7,1°C. Najwyższe temperatury średnie roczne notowano na północnym zachodzie regionu, najniższe zaś na południu i południowym wschodzie. Przeciętnie, najchłodniejszym miesiącem roku okazał się styczeń (-2,8°C), zaś najcieplejszym lipiec 17,1°C. Wartość średniej sumy opadów rocznych w regionie wyniosła 607,6 mm. W układzie rocznym przeważały opady letnie z najwyższymi wartościami odnotowanymi w czerwcu (80,6 mm) i lipcu (76,8 mm). Liczba miesięcy po- susznych okresu wegetacyjnego wynosiła od 25 - 40%, zaś skrajnie suchych od 4 do 11%. Średni okres wegetacyjny wynosił 199 dni.The paper presents expanded and complemented description of basic climate characteristics in north-eastern part of Poland. Average annual temperature in years 1971-2000 amounted to 7.1°C. The highest average annual temperatures occurred in north-western, while the lowest in southern and south-eastern parts of the area. On average, the coolest month turned out January (-2.8°C) and the warmest - July (17.1°C). Average annual sum of precipitation amounted to 607.6 mm. Summer precipitations prevailed within the years (80.6 mm in June and 76.8 in July). Percentage of the dry months (evaluated by Selianinov formula) oscillated from 25 to 40, while the extremely dry from 4 to 11. Average duration of growing seasons covered 199 days