In patients with chronic myeloid leukemia (CML), first-line imatinib treatment leads to 8-year overall survival (OS) probabilities above 80%. Many patients die of reasons unrelated to CML. This work ...tackled the reassessment of prognosis under particular consideration of the probabilities of dying of CML. Analyses were based on 2290 patients with chronic phase CML treated with imatinib in six clinical trials. 'Death due to CML' was defined by death after disease progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML. Higher age, more peripheral blasts, bigger spleen and low platelet counts were significantly associated with increased probabilities of dying of CML and determined a new long-term survival score with three prognostic groups. Compared with the low-risk group, the patients of the intermediate- and the high-risk group had significantly higher probabilities of dying of CML. The score was successfully validated in an independent sample of 1120 patients. In both samples, the new score differentiated probabilities of dying of CML better than the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The new score identified 61% low-risk patients with excellent long-term outcome and 12% high-risk patients. The new score supports the prospective assessment of long-term antileukemic efficacy and risk-adapted treatment.
This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed ...Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.
Summary Background In many Demodex‐associated skin diseases Demodex mites are present in abundance and seem to be at least partially pathogenic. So far all diagnostic approaches such as scraping or ...standardized superficial skin biopsy are (semi‐)invasive and may cause discomfort to the patient.
Objectives To see whether confocal laser scanning microscopy (CLSM) – a noninvasive method for the visualization of superficial skin layers – is able to detect and quantify D. folliculorum in facial skin of patients with rosacea.
Methods Twenty‐five patients (34–72 years of age) with facial rosacea and 25 age‐ and sex‐matched normal controls were examined by CLSM. Mosaics of 8 × 8 mm and 5 × 5 mm were created by scanning horizontal layers of lesional skin and quantification of mites per follicle and per area as well as follicles per area was performed.
Results In all patients D. folliculorum could be detected by CLSM and presented as roundish or lengthy cone‐shaped structures. CLSM allowed the quantification of Demodex mites and revealed significant differences (P < 0·0001): the mean number of mites was 165·4 per 8 × 8 mm area and 94·2 per 5 × 5 mm area in the patients compared with 34·7 and 22·4, respectively, in the controls. The corresponding mean number of mites per follicle was 0·7 and 0·8, respectively, in the patients and 0·1 and 0·2, respectively, in the controls.
Conclusions With the help of CLSM it is possible to detect, image and quantify Demodex mites noninvasively in facial skin of patients with rosacea.
We present a combined experimental and theoretical study of the mineral atacamite Cu2Cl(OH)3. Density-functional theory yields a Hamiltonian describing anisotropic sawtooth chains with weak 3D ...connections. Experimentally, we fully characterize the antiferromagnetically ordered state. Magnetic order shows a complex evolution with the magnetic field, while, starting at 31.5 T, we observe a plateaulike magnetization at about Msat/2. Based on complementary theoretical approaches, we show that the latter is unrelated to the known magnetization plateau of a sawtooth chain. Instead, we provide evidence that the magnetization process in atacamite is a field-driven canting of a 3D network of weakly coupled sawtooth chains that form giant moments.
Fluorine-18 labelled N,N-diethyl-2-(2-4-(2-fluoroethoxy)phenyl-5,7-dimethylpyrazolo1,5-αpyrimidine-3-yl)acetamide (18F DPA-714) binds to the 18-kDa translocator protein (TSPO) with high affinity. The ...aim of this initial methodological study was to develop a plasma input tracer kinetic model for quantification of 18FDPA-714 binding in healthy subjects and Alzheimer's disease (AD) patients, and to provide a preliminary assessment whether there is a disease-related signal. Ten AD patients and six healthy subjects underwent a dynamic positron emission tomography (PET) study along with arterial sampling and a scan protocol of 150 minutes after administration of 250 ± 10 MBq 18FDPA-714. The model that provided the best fits to tissue time activity curves (TACs) was selected based on Akaike Information Criterion and F-test. The reversible two tissue compartment plasma input model with blood volume parameter was the preferred model for quantification of 18FDPA-714 kinetics, irrespective of scan duration, volume of interest, and underlying volume of distribution (VT). Simplified reference tissue model (SRTM)-derived binding potential (BPND) using cerebellar gray matter as reference tissue correlated well with plasma input-based distribution volume ratio (DVR). These data suggest that 18FDPA-714 cannot be used for separating individual AD patients from heathy subjects, but further studies including TSPO binding status are needed to substantiate these findings.
This work stresses on damage at the molecular level caused by ultraviolet radiation (UV) in the range from 3.5 to 8 eV, deoxyribonucleic acid (DNA) films observed by X-ray photoelectron spectroscopy ...(XPS). Detailed quantitative XPS analysis, in which all the amounts are relative to sodiumassumed not to be released from the samples, of the carbon, oxygen, and particularly, nitrogen components, reveals that irradiation leads to sugar degradation with CO-based compounds release for energies above 6.9 eV and decrease of nitrogen groups which are not involved in hydrogen bonding at energies above 4.2 eV. Also the phosphate groups are seen to decrease to energies above 4.2 eV. Analysis of XPS spectra allowed to conclude that the damage on bases peripheral nitrogen atoms are following the damage on phosphates. It suggests that very low kinetic energy photoelectrons are ejected from the DNA bases, as a result of UV light induced breaking of the phosphate ester groups which forms a transient anion with resonance formation and whereby most of the nitrogen DNA peripheral groups are removed. The degree of ionization of DNA was observed to increase with radiation energy, indicating that the ionized phosphate groups are kept unchanged. This result was interpreted by the shielding of phosphate groups caused by water molecules hydration near sodium atoms.
Electronic State Spectroscopy of Nitromethane and Nitroethane Dalagnol, Luiz V. S.; Bettega, Márcio H. F.; Jones, Nykola C. ...
The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory,
02/2023, Letnik:
127, Številka:
6
Journal Article
Recenzirano
Odprti dostop
High-resolution photoabsorption cross-sections in the 3.7–10.8 eV energy range are reinvestigated for nitromethane (CH3NO2), while for nitroethane (C2H5NO2), they are reported for the first time. New ...absorption features are observed for both molecules which have been assigned to vibronic excitations of valence, Rydberg, and mixed valence-Rydberg characters. In comparison with nitromethane, nitroethane shows mainly broad absorption bands with diffuse structures, which can be interpreted as a result of the side-chain effect contributing to an increased number of internal degrees of freedom. New theoretical quantum chemical calculations performed at the time-dependent density functional theory (TD-DFT) level were used to qualitatively help interpret the recorded photoabsorption spectra. From the photoabsorption cross-sections, photolysis lifetimes in the terrestrial atmosphere have been obtained for both compounds. Relevant internal conversion from Rydberg to valence character is noted for both molecules, while the nuclear dynamics of CH3NO2 and C2H5NO2 along the C–N reaction coordinate have been evaluated through potential energy curves at the TD-DFT level of theory, showing that the pre-dissociative character is more prevalent in nitromethane than in nitroethane.
The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid ...leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.
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