Familiáris myelodysplasiás szindróma és akut myeloid leukaemia klinikai és genetikai háttere

Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT. Furthermore, there are new, emerging syndromes associated with germline mutations in novel genes including ANKRD26, ETV6, SRP72 or DDX41. This review will discuss the current understanding of the genetic basis and clinical presentation of familial leukemia and myelodysplasia. Orv. Hetil., 2016, 157(8), 283-289

Narrowing of EIT resonance in a Doppler Broadened Medium

We derive an analytic expression for the linewidth of EIT resonance in a Doppler broadened system. It is shown here that for relatively low intensity of the driving field the EIT linewidth is proportional to the square root of intensity and is independent of the Doppler width, similar to the laser induced line narrowing effect by Feld and Javan. In the limit of high intensity we recover the usual power broadening case where EIT linewidth is proportional to the intensity and inversely proportional to the Doppler width.Comment: 4 pages, 2 figure

High degree of mitochondrial gene heterogeneity in the bat tick species Ixodes vespertilionis, I. ariadnae and I. simplex from Eurasia

Background: Phylogeographical studies allow precise genetic comparison of specimens, which were collected over large geographical ranges and belong to the same or closely related animal species. These methods have also been used to compare ticks of veterinary-medical importance. However, relevant data are missing in the case of ixodid ticks of bats, despite (1) the vast geographical range of both Ixodes vespertilionis and Ixodes simplex, and (2) the considerable uncertainty in their taxonomy, which is currently unresolvable by morphological clues. Methods: In the present study 21 ticks were selected from collections or were freshly removed from bats or cave walls in six European and four Asian countries. The DNA was extracted and PCRs were performed to amplify part of the cytochrome oxidase I (COI), 16S and 12S rDNA genes, followed by sequencing for identification and molecular-phylogenetic comparison. Results: No morphological differences were observed between Ixodes vespertilionis specimens from Spain and from other parts of Europe, but corresponding genotypes had only 94.6 % COI sequence identity. An I. vespertilionis specimen collected in Vietnam was different both morphologically and genetically (i.e. with only 84.1 % COI sequence identity in comparison with I. vespertilionis from Europe). Two ticks (collected in Vietnam and in Japan) formed a monophyletic clade and shared morphological features with I. ariadnae, recently described and hitherto only reported in Europe. In addition, two Asiatic specimens of I. simplex were shown to differ markedly from European genotypes of the same species. Phylogenetic relationships of ticks showed similar clustering patterns with those of their associated bat host species. Conclusions: Although all three ixodid bat tick species evaluated in the present study appear to be widespread in Eurasia, they exhibit pronounced genetic differences. Data of this study also reflect that I. vespertilionis may represent a species complex

HPV type-specific risks of high-grade CIN during 4 years of follow-up: A population-based prospective study

We followed a population-based cohort of 5696 women, 32–38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2+ development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2+ than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2+. In summary, the different HPV types found in cervical cancer show distinctly different CIN2+ risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B = −0.12, 95% C.I. −0.18, −0.06, p < 0.001) and depressive (B = −0.09, 95% C.I. −0.15, −0.03, p = 0.032), and more manic (B = 0.07, 95% C.I. 0.01, 0.14, p = 0.023) symptoms. Patients with a lower IQ presented with slightly more negative and positive, and fewer manic, symptoms. Secondary analysis on IQ subdomains revealed associations between better perceptual reasoning and fewer negative (B = −0.09, 95% C.I. −0.17, −0.01, p = 0.023) and more manic (B = 0.10, 95% C.I. 0.02, 0.18, p = 0.014) symptoms. Fewer positive symptoms were associated with better processing speed (B = −0.12, 95% C.I. −0.02, −0.004, p = 0.003) and working memory (B = −0.10, 95% C.I. −0.18, −0.01, p = 0.024). These findings suggest that the negative and manic symptom dimensions may serve as clinical proxies of different neurodevelopmental predisposition in psychosis

CHEOPS: a space telescope for ultra-high precision photometry of exoplanet transits

The CHaracterising ExOPlanet Satellite (CHEOPS) is a joint ESA-Switzerland space mission dedicated to search for exoplanet transits by means of ultra-high precision photometry whose launch readiness is expected end 2017. The CHEOPS instrument will be the first space telescope dedicated to search for transits on bright stars already known to host planets. By being able to point at nearly any location on the sky, it will provide the unique capability of determining accurate radii for a subset of those planets for which the mass has already been estimated from ground-based spectroscopic surveys. CHEOPS will also provide precision radii for new planets discovered by the next generation ground-based transits surveys (Neptune-size and smaller). The main science goals of the CHEOPS mission will be to study the structure of exoplanets with radii typically ranging from 1 to 6 Earth radii orbiting bright stars. With an accurate knowledge of masses and radii for an unprecedented sample of planets, CHEOPS will set new constraints on the structure and hence on the formation and evolution of planets in this mass range. To reach its goals CHEOPS will measure photometric signals with a precision of 20 ppm in 6 hours of integration time for a 9th magnitude star. This corresponds to a signal to noise of 5 for a transit of an Earth-sized planet orbiting a solar-sized star (0.9 solar radii). This precision will be achieved by using a single frame-transfer backside illuminated CCD detector cool down at 233K and stabilized within {10 mK . The CHEOPS optical design is based on a Ritchey-Chretien style telescope with 300 mm effective aperture diameter, which provides a defocussed image of the target star while minimizing straylight using a dedicated field stop and baffle system. As CHEOPS will be in a LEO orbit, straylight suppression is a key point to allow the observation of faint stars. The telescope will be the only payload on a spacecraft platform providing pointing stability of < 8 arcsec rms, power of 60W for instrument operations and downlink transmission of at least 1.2GBit/day. Both CHEOPS paylaod and platform will rely mainly on components with flight heritage. The baseline CHEOPS mission fits within the technical readiness requirements, short development time and the cost envelope defined by ESA in its first call for S-missions. It represents a breakthrough opportunity in furthering our understanding of the formation and evolution of planetary systems

Jumping to conclusions, general intelligence, and psychosis liability: Findings from the multi-centre EU-GEI case-control study

BackgroundThe 'jumping to conclusions' (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.MethodsA total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI-0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25-0.76, p &lt; 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B =-1.7, 95% CI-2.8 to-0.5, p = 0.006), but did not relate to delusions in patients.ConclusionsOur findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders