Коментарі Валерія Шевчука в літописі Самійла Величка як позатекстова інтерпретація давньоукраїнської пам'ятки

У статті розглядаються різновиди коментарів як позатекстової інтерпретації Валерієм Шевчуком барокової пам’ятки – Літопису Самійла Величка.The article deals with Valery Shevchuk’s way of varieties of the commentaries as out-of-text interpretation of Baroque remembrance of Chronicle of Samiylo Velitchko

Searching for Planets in the Hyades II: Some Implications of Stellar Magnetic Activity

The Hyades constitute a homogeneous sample of stars ideal for investigating the dependence of planet formation on the mass of the central star. Due to their youth, Hyades members are much more chromospherically active than stars traditionally surveyed for planets using high precision radial velocity (RV) techniques. Therefore, we have conducted a detailed investigation of whether magnetic activity of our Hyades target stars will interfere with our ability to make precise RV searches for substellar companions. We measure chromospheric activity (which we take as a proxy for magnetic activity) by computing the equivalent of the R'HK activity index from the Ca II K line. is not constant in the Hyades: we confirm that it decreases with increasing temperature in the F stars, and also find it decreases for stars cooler than mid-K. We examine correlations between simultaneously measured R'HK and RV using both a classical statistical test and a Bayesian odds ratio test. We find that there is a significant correlation between R'HK and the RV in only 5 of the 82 stars in this sample. Thus, simple Rprime HK-RV correlations will generally not be effective in correcting the measured RV values for the effects of magnetic activity in the Hyades. We argue that this implies long timescale activity variations (of order a few years; i.e., magnetic cycles or growth and decay of plage regions) will not significantly hinder our search for planets in the Hyades if the stars are closely monitored for chromospheric activity. The trends in the RV scatter (sigma'_v) with , vsini, and P_rot for our stars is generally consistent with those found in field stars in the Lick planet search data, with the notable exception of a shallower dependence of sigma'_v on for F stars.Comment: 15 pages, 7 figures, 3 tables; To appear in the July 2002 issue of The Astronomical Journa

Critical design considerations for time-to-event endpoints in amyotrophic lateral sclerosis clinical trials

Background: Funding and resources for low prevalent neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) are limited, and optimising their use is vital for efficient drug development. In this study, we review the design assumptions for pivotal ALS clinical trials with time-to-event endpoints and provide optimised settings for future trials. Methods: We extracted design settings from 13 completed placebo-controlled trials. Optimal assumptions were estimated using parametric survival models in individual participant data (n=4991). Designs were compared in terms of sample size, trial duration, drug use and costs. Results: Previous trials overestimated the hazard rate by 18.9% (95% CI 3.4% to 34.5%, p=0.021). The median expected HR was 0.56 (range 0.33–0.66). Additionally, we found evidence for an increasing mean hazard rate over time (Weibull shape parameter of 2.03, 95% CI 1.93 to 2.15, p<0.001), which affects the design and planning of future clinical trials. Incorporating accrual time and assuming an increasing hazard rate at the design stage reduced sample size by 33.2% (95% CI 27.9 to 39.4), trial duration by 17.4% (95% CI 11.6 to 23.3), drug use by 14.3% (95% CI 9.6 to 19.0) and follow-up costs by 21.2% (95% CI 15.6 to 26.8). Conclusions: Implementing distributional knowledge and incorporating accrual at the design stage could achieve large gains in the efficiency of ALS clinical trials with time-to-event endpoints. We provide an open-source platform that helps investigators to make more accurate sample size calculations and optimise the use of their available resources

Impact of climate change on hydrological regimes and water resource management in the Rhine basin”,

Abstract. The International Commission for the Hydrology of the Rhine basin (CHR) has carried out a research project to assess the impact of climate change on the river flow conditions in the Rhine basin. Along a bottom-up line, different detailed hydrological models with hourly and daily time steps have been developed for representative sub-catchments of the Rhine basin. Along a topdown line, a water balance model for the entire Rhine basin has been developed, which calculates monthly discharges and which was tested on the scale of the major tributaries of the Rhine. Using this set of models, the effects of climate change on the discharge regime in different parts of the Rhine basin were calculated using the results of UKHI and XCCC GCM-experiments. All models indicate the same trends in the changes: higher winter discharge as a result of intensified snow-melt and increased winter precipitation, and lower summer discharge due to the reduced winter snow storage and an increase of evapotranspiration. When the results are considered in more detail, however, several differences show up. These can firstly be attributed to different physical characteristics of the studied areas, but different spatial and temporal scales used in the modelling and different representations of several hydrological processes (e.g., evapotranspiration, snow melt) are responsible for the differences found as well. Climate change can affect various socio-economic sectors. Higher temperatures may threaten winter tourism in the lower winter sport areas. The hydrological changes will increase flood risk during winter, whilst low flows during summer will adversely affect inland navigation, and reduce water availability for agriculture and industry. Balancing the required actions against economic cost and the existing uncertainties in the climate change scenarios, a policy of &apos;noregret and flexibility&apos; in water management planning and design is recommended, where anticipatory adaptive measures in response to climate change impacts are undertaken in combination with ongoing activities. Present address

Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria

BACKGROUND: Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection. METHODS: LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay. RESULTS: 32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and < 50 cells/μl, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls. CONCLUSIONS: Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection

The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study

Background and objectives: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral glucosamine sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2×2 factorial design. Methods: A total of 407 overweight (BMI ≥ 27 kg/m2) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) glucosamine sulfate + no DEP (GS, N = 102), and (4) DEP + glucosamine sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero-anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline glucosamine sulfate 1500 mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of ≥1 mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. Results: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with glucosamine sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2×2 factorial design allowed analysis of patients receiving glucosamine sulfate (= 204) vs. those not receiving it (= 203), similarly for those on the DEP (= 203) or not (= 204). Glucosamine sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. Conclusions: Glucosamine sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss

The discontinuous nature of chromospheric activity evolution

Chromospheric activity has been thought to decay smoothly with time and, hence, to be a viable age indicator. Measurements in solar type stars in open clusters seem to point to a different conclusion: chromospheric activity undergoes a fast transition from Hyades level to that of the Sun after about 1 Gyr of main--sequence lifetime and any decaying trend before or after this transition must be much less significant than the short term variations.Comment: 6 pages, 1 figure, to be published in Astrophysics and Space Scienc

Plasma proteome profiling identifies changes associated to AD but not to FTD

Background Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. Methods Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 +/- 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 +/- 7.9; 45% female), AD patients (n = 57; age = 65.5 +/- 8.0; 39% female), and non-demented controls (n = 148; 61.3 +/- 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 +/- 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 +/- 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 +/- 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. Results Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. Conclusions We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts

Polarised Quark Distributions in the Nucleon from Semi-Inclusive Spin Asymmetries

We present a measurement of semi-inclusive spin asymmetries for positively and negatively charged hadrons from deep inelastic scattering of polarised muons on polarised protons and deuterons in the range $0.003$1 GeV$^2$. Compared to our previous publication on this subject, with the new data the statistical errors have been reduced by nearly a factor of two. From these asymmetries and our inclusive spin asymmetries we determine the polarised quark distributions of valence quarks and non-strange sea quarks at $Q^2$=10 GeV$^2$. The polarised $u$ valence quark distribution, $\Delta u_v(x)$, is positive and the polarisation increases with $x$. The polarised $d$ valence quark distribution, $\Delta d_v(x)$, is negative and the non-strange sea distribution, $\Delta \bar q(x)$, is consistent with zero over the measured range of $x$. We find for the first moments $\int_0^1 \Delta u_v(x) dx = 0.77 \pm 0.10 \pm 0.08$, $\int_0^1 \Delta d_v(x) dx = -0.52 \pm 0.14 \pm 0.09$ and $\int_0^1 \Delta \bar q(x) dx= 0.01 \pm 0.04 \pm 0.03$, where we assumed $\Delta \bar u(x) = \Delta \bar d(x)$. We also determine for the first time the second moments of the valence distributions $\int_0^1 x \Delta q_v(x) dx$.Comment: 17 page