Charles University in Prague

About: Charles University in Prague is a education organization based out in Prague, Czechia. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 32392 authors who have published 74435 publications receiving 1804208 citations.

Carbon Paste Electrodes in Modern Electroanalysis

Abstract: Recent trends and advances in the electrochemistry with both unmodified and modified carbon paste electrodes are reviewed (247 refs.). Present day knowledge of their basic physico-chemical properties and characteristics is surveyed, including some specifics important in electrochemical measurements. Special attention is paid to the possibilities of carbon paste-based electrodes in electrochemical investigations and in modern electroanalysis of inorganic ions or molecules, organic substances, biologically important compounds, and pharmaceuticals.

Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial

Abstract: Summary Background Both single-agent ibrutinib and chlorambucil plus obinutuzumab have shown superior efficacy to chlorambucil monotherapy and are standard first-line treatments in chronic lymphocytic leukaemia. We compared the efficacy of the combination of ibrutinib plus obinutuzumab with chlorambucil plus obinutuzumab in first-line chronic lymphocytic leukaemia or small lymphocytic lymphoma. Methods iLLUMINATE is a multicentre, randomised, open-label, phase 3 trial done at 74 academic and community hospitals in Australia, Canada, Israel, New Zealand, Russia, Turkey, the EU, and the USA in patients with previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma, either aged 65 years or older or younger than 65 years with coexisting conditions. Patients were randomly assigned (1:1) using a blocked randomisation schedule, stratified by Eastern Cooperative Oncology Group performance status and cytogenetics, to receive ibrutinib plus obinutuzumab (oral ibrutinib [420 mg once daily continuously] combined with intravenous obinutuzumab [100 mg on day 1, 900 mg on day 2, 1000 mg on day 8, and 1000 mg on day 15 of cycle 1 and on day 1 of subsequent 28-day cycles, for a total of six cycles]) or chlorambucil plus obinutuzumab (oral chlorambucil [0·5 mg/kg bodyweight on days 1 and 15 of each 28-day cycle for six cycles] combined with the same obinutuzumab regimen). Allocation concealment was achieved using an interactive web response system. Patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival assessed by a masked independent review committee in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov (NCT02264574), and patient enrolment is complete. Findings Between Oct 6, 2014, and Oct 12, 2015, 229 patients were enrolled and randomly assigned to receive ibrutinib plus obinutuzumab (n=113) or chlorambucil plus obinutuzumab (n=116). After a median follow-up of 31·3 months (IQR 29·4–33·2), median progression-free survival was significantly longer in the ibrutinib plus obinutuzumab group (median not reached [95% CI 33·6–non-estimable]) than in the chlorambucil plus obinutuzumab group (19·0 months [15·1–22·1]; hazard ratio 0·23; 95% CI 0·15–0·37; p Interpretation Ibrutinib plus obinutuzumab is an efficacious and safe chemotherapy-free combination treatment in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma independent of high-risk features and provides an alternative first-line treatment option for these patients. Funding Pharmacyclics LLC, an AbbVie Company, and Janssen Research and Development.

Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy

Abstract: Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy-cataplexy cases [36 human leukocyte antigen (HLA)-DQB1*0602-positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin-1 was measurable (169 to 376 pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin-1 was dramatically decreased (<100 pg/ml) in 32 of 38 patients (all HLA-positive). Four patients had normal levels (2 HLA-negative). Two HLA-positive patients had high levels (609 and 637 pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.

Clinical findings with implications for genetic testing in families with clustering of colorectal cancer.

Abstract: Background Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PMS1, PMS2, and MSH6 ) cause susceptibility to hereditary nonpolyposis colorectal cancer. We assessed the prevalence of MSH2...

Spatio-temporal structure of storm-time chorus

Abstract: We discuss chorus emissions measured by the four Cluster spacecraft at close separations during a geomagnetically disturbed period on 18 April 2002. We analyze the lower band of chorus below one half of the electron cyclotron frequency, measured at a radial distance of 4.4 Earth's radii, within a 2000 km long source region located close to the equator. The characteristic wave vector directions in this region are nearly parallel to the field lines and the multipoint measurement demonstrates the dynamic character of the chorus source region, changing the Poynting flux direction at time scales shorter than a few seconds. The electric field waveforms of the chorus wave packets (forming separate chorus elements on power spectrograms) show a fine structure consisting of subpackets with a maximum amplitude above 30 mV/m. To study this fine structure we have used a sine-wave parametric model with a variable amplitude. The subpackets typically start with an exponential growth phase, and after reaching the saturation amplitude they often show an exponential decay phase. The duration of subpackets is variable from a few milliseconds to a few tens of milliseconds, and they appear in the waveform randomly, with no clear periodicity. The obtained growth rate (ratio of the imaginary part to the real part of the wave frequency) is highly variable from case to case with values obtained between a few thousandths and a few hundredths. The same chorus wave packets simultaneously observed on the different closely separated spacecraft appear to have a different internal subpacket structure. The characteristic scale of the subpackets can thus be lower than tens of kilometers in the plane perpendicular to the field line, or hundreds of kilometers parallel to the field line (corresponding to a characteristic time scale of few milliseconds during the propagation of the entire wave packet). Using delays of time-frequency curves obtained on different spacecraft, we have found the same propagation direction as obtained from the simultaneous Poynting flux calculations. The delays roughly correspond to the whistler-mode group velocity estimated from the cold plasma theory. We have also observed delays corresponding to antiparallel propagation directions for two neighboring chorus wave packets, less than 0.1 s apart.