Towards Good Statistical Practice. CORSTAN Validated Questionnaire for Assessing the Correctness of Statistical Analysis in Medical Research.

BACKGROUND: In evidence-based medicine, the research methodology is determined by the risks of systematic biases and incorrect data analysis. Minimizing both risks increases the internal validity of the study. There are numerous recommendations and guidelines for data analysis and reporting, but the international community has not yet developed a questionnaire for reviewers to assess the quality of statistical analysis. AIM: To develop a tool for formalized assessment of the quality of statistical analysis presented in scientific medical publications. MATERIALS AND METHODS: The questionnaire was developed based on the authors' decades of experience in statistical data analysis and reviewing the statistical aspects of biomedical articles and dissertations. The SAMPL guidelines, ICH E9, and other guidelines were taken into account when developing the questionnaire. Internal validation of the questionnaire was based on an independent assessment by two experts of 20 randomly selected articles on randomized controlled trials (RCTs) from elibrary.ru, and further statistical analysis of the agreement of experts' conclusions. RESULTS: The CORSTAN (CORrect STatistical ANalysis) questionnaire was developed, which consists of two parts: the first part (10 questions) is intended for evaluating studies of any designs, while the second (following eight questions) is for additional assessment of RCTs. A stratification of the risk of incorrect statistical analysis is proposed. The evaluation of the questionnaire's internal validity showed its substantial and almost perfect agreement for each question and each article both in the sum of points and risk level. CONCLUSION: The use of the questionnaire will simplify and harmonize the statistical review of publications and manuscripts in various institutions - scientific journals, dissertation boards, etc. The questionnaire can also be helpful for authors during preparing manuscripts; it will also help improve the quality of publications and research itself. We plan to improve the questionnaire as we gain experience in its application.

Vitamin D Deficiency as an Independent Predictor of Myocardial Infarction in the Elderly.

Cardiovascular diseases are among the most common causes of disability and death in the world, and the number of patients with this category of diseases is increasing every year. This study aimed to investigate the role of vitamin D and the problems caused by its deficiency on the cardiovascular system. Level of D-(25(OH]D) in blood was studied by enzyme immunoassay in 95 elderly patients with myocardial infarction (MI) (the main group) and 92 elderly patients with no history of MI. The level of lipid metabolism as an indicator was determined using a KoneLab 300 auto-analyzer. Based on the results of this study, it was found that the elderly group without MI had the highest amount of D-(25(OH]D)(24.5±1.2), compared to the elderly group with MI (14.8±1.3). The rates of expressed deficiency, deficiency, and insufficiency in the group of elderly with MI were 53.6±5.1, 23.2±4.4, and 12.6±3.4%, respectively. This experiment has shown that D-(25(OH]D) is involved in lipid metabolism and reduces the accumulation of cholesterol by macrophages. The content of vitamin D in blood plasma was a prognostic predictor of MI, which improved MI in the elderly. Regardless of pathological changes, the deficit level of D-(25(OH]D) should be considered a laboratory predictor of MI in the elderly.

Spectral detection of spin-polarized ultra low-energy electrons in semiconductor heterostructures.

The circularly polarized cathodoluminescence (CL) technique has been used to study the free spin-polarized electron injection in semiconductor heterostructures with quantum wells (QWs). A polarized electron beam was created by the emission of optically oriented electrons from the p-GaAs(Cs,O) negative electron affinity (NEA) photocathode. The prepared beam was injected in a semiconductor QW target, which was activated by cesium and oxygen to reduce the work function. To study the spin-dependent injection, we developed a spin-detector prototype, which consists of a compact proximity focused vacuum tube with the source and target placed parallel to each other on the opposite ends of the vacuum tube (photodiode). The injection of polarized low-energy electrons into the target by varying the kinetic energy in the range of 0.5-5.0 eV and temperature in the range of 90-300 K was studied. The CL was polarized to 2 % by the injection of 20 % spin-polarized electron beam with the energy of 0.5 eV at room temperature. The asymmetry (Sherman function) of spin detection was estimated. It was shown that the dependence of the CL polarization degree on the injected electron energy is satisfactory described by the model that considers the electron spin relaxation in the heterostructure matrix and QWs. The results demonstrate that semiconductor detectors are promising for the spin-polarimetry applications based on the optical detection of free-electron spin polarization.

Probability distribution of intensity fluctuations of arbitrary-type laser beams in the turbulent atmosphere.

Statistical characteristics of radiation intensity in the cross section of laser beams propagating in the turbulent atmosphere are analyzed by using numerical simulations. It is shown that for arbitrary values of the propagation distance, Rytov parameter, beam type, and position of the analyzed point in the beam cross section, the probability density function (PDF) of radiation intensity is fully determined by the scintillation index and the average intensity. In the case of moderate and weak intensity fluctuations characterized by the scintillation index smaller than unity, the probability density function is determined by the gamma distribution. For the case of strong fluctuations (with the scintillation index larger than unity), a new analytical expression for PDF is proposed, which well approximates PDFs obtained in numerical experiments under different conditions of propagation of different-type beams.

[The prognostication of development of peri-apical abscess under chronic periodontitis by blood parameters and cell immunity in children].

The chronic periodontitis in children is frequently complicated by development of periapical abscess under inadequate conservative therapy. However, prognostic models of estimation of probability of its development are lacking. The purpose of study is to develop regression models of prognostication of periapical abscess under chronic periodontitis in children according indices of peripheral blood and systemic cellular immunity. The chronic periodontitis complicated with periapical abscess is analyzed in 120 children aged from 8 to 15 years. The prognostication of periapical abscess was implemented by stepwise regression technique using parameters of blood and systemic cellular immunity. The mathematical models are developed for prognostication of periapical abscess in children with chronic periodontitis on the basis of indices of peripheral blood and systemic cellular immunity permitting to prognosticate development of the given complication with needed quality. The prognostication periapical abscess requires using the given models, absolute number of lymphocytes, percentage of stab bond neutrophils, ESR, absolute number of T-lymphocytes in blood, T-helpers, T-suppressors and relative content of T-suppressors.

[The prognostication of acute myocardium infarction according biochemical indices of blood.]

In actual conditions, the acute myocardium infarction is a main cause of population mortality factually in all countries. The purpose of study is to establish a prognostic significance of biochemical cardio-markers of blood and to develop prognostic models for acute myocardium infarction. The sampling included 157 patients with acute myocardium infarction and 138 healthy individuals. The cardio-markers in blood were analyzed using immune chromatographic and spectrometric techniques and also applying portable biochemical analyzer MultiCareIn (Italy). It is demonstrated that the highest prognostic value for development of acute myocardium infarction is increasing of level of creatine kinase in blood more than 25 ME/l, troponin - more than 0.5 mkg/l, lactate dehydrogenase 1 - more than 200 ME/l and lactate dehydrogenase 2 - more than 180 ME/l. The developed regression model for prognosis of acute myocardium infarction according the indices mentioned above has a high sensitivity and specificity. Conclusion. The application of prognostically significant cardio-markers of blood and developed regression model permits to forecast development of acute myocardium infarction and to implement prevention and treatment in earlier period.

[The development of diagnostic of acute endometritis on the basis of modeling and cluster analysis of parameters of local immunity.]

The acute endometritis provoking expressed disorders of local immunity is considered as one of the prevalent complications of postnatal period and abortions. The purpose of study is to develop diagnostic of acute endometritis on the basis of applied correlation modeling and cluster analysis techniques diagnostically priority-driven immunological indices of vaginal cervical mucus. The sample included main group (154 patients with acute endometritis) and control group (103 patients with uncomplicated post-natal period). Both groups were subjected to enzyme-linked immunosorbent assay to analyze content of immunoglobulins, components of complement and lysozyme in vaginal cervical mucus. The sampling of diagnostically significant indices was implemented using correlation and cluster analysis techniques. It is established that chief diagnostic indices of local immunity in case of acute endometritis are IG M, sIg A, С4 components of complement and lysozyme. The established diagnostically significant parameters of local immunity provide development of detection of acute endometritis according less number of indices.

Solar energy converters based on multi-junction photoemission solar cells.

Multi-junction solar cells with multiple p-n junctions made of different semiconductor materials have multiple bandgaps that allow reducing the relaxation energy loss and substantially increase the power-conversion efficiency. The choice of materials for each sub-cell is very limited due to the difficulties in extracting the current between the layers caused by the requirements for lattice- and current-matching. We propose a new vacuum multi-junction solar cell with multiple p-n junctions separated by vacuum gaps that allow using different semiconductor materials as cathode and anode, both activated to the state of effective negative electron affinity (NEA). In this work, the compact proximity focused vacuum tube with the GaAs(Cs,O) photocathode and AlGaAs/GaAs-(Cs,O) anode with GaAs quantum wells (QWs) is used as a prototype of a vacuum single-junction solar cell. The photodiode with the p-AlGaAs/GaAs anode showed the spectral power-conversion efficiency of about 1% at V bias = 0 in transmission and reflection modes, while, at V bias = 0.5 V, the efficiency increased up to 10%. In terms of energy conservation, we found the condition at which the energy cathode-to-anode transition was close to 1. Considering only the energy conservation part, the NEA-cell power-conversion efficiency can rich a quantum yield value which is measured up to more than 50%.

[The application of flow cytometry technique and diagnostically significant indices of systemic cellular immunity for diagnostic of acute endometritis.]

The acute endometritis is a the most widespread pathology among women of reproductive age.The immune system plays a leading role in its development. However, there is no data concerning the most informative parameters of cell immunity. The purpose of study is to enhance diagnostic of acute endometritis using immunologic technique with objective evaluation of diagnostic value of indices of systemic cell immunity. The indices of cell immunity are analyzed on sampling of 78 patients with postnatal acute endometritis and 54 healthy women. The technique of flow cytometry was applied with subsequent calculation of index of informativeness and disintegration objectifying selection of diagnostically significant parameters. It is demonstrated that full-fledged diagnostic of acute endometritis requires detection of absolute and relative content of T-helpers and natural killers having high value of informativeness and disintegration. Hence an opportunity to reduce number of analyzed parameters of systemic cell immunity and financial costs of diagnostic of acute endometritis.

[The differentiated diagnostic of chronic salpingoophoritis and ovary cancer on the basis of immunologic and discriminant techniquea.]

The ovary cancer and chronic salpingoophoritis are among leading pathologies of female's sexual sphere and a main cause of morbidity and mortality of female population. The purpose of study was to select leading differential diagnostic indices of systemic cellular immunity and to carry out a differentiation of patients with ovary cancer and chronic salpingoophoritis using discriminant technique. The differentiated diagnostic of ovary cancer and chronic salpingoophoritis was applied to 92 and 87 patients correspondingly to indices of systemic cellular immunity and analyzed by flow cytometry technique. It is demonstrated that the main differential diagnostic indices of systemic cellular immunity in case of ovary cancer and chronic salpingoophoritis are decreasing of relative content of natural killers, absolute number of B-lymphocytes and T-helpers. The developed discriminant models permit to carry out in 91.8%-92.1% cases a faultless differentiated diagnostic of ovary cancer and chronic salpingoophoritis. The approach like that increases quality of differentiated diagnostic of ovary cancer and chronic salpingoophoritis.

[The application of the lyophilized xenodermoimplants for the plastic correction of the external auditory canal and nasal septum perforation].

The objective of the present work was to improve the effectiveness of the treatment of atresia of the external auditory canal (EAC). Atresia of external acoustic meatus is a result of a mechanical or thermal injury but can also develop after a surgical intervention for the removal of foreign bodies, benign and malignant tumours. This condition is frequently associated with the narrowing and obliteration of EAC leading to the marked impairment of hearing despite preservation of the middle ear structures. Plastic correction of the external auditory canal for the purpose of its broadening does not always produce the desired result. To improve the efficiency of such intervention, we made use of the lyophilized xenodermoimplants based on porcine skin. Such preparation were applied in 19 patients; patency of the external auditory canal was restored in 16 cases.

[Etiology and pathogenesis of glomus tumours (chemodectomas) of the base of the skull].

The objective of the present work was to describe the poorly known history of the development of the nomenclature of glomus tumours (chemodectomas) of the base of the skull, elucidate etiology and pathogenesis of these neoplasms. The authors present a chronological table illustrating the progress of etiological and pathogenetic studies as well as the surgical treatment of the tumours. The results of analysis and discussion of the controversial issues of the nomenclature are reported.

A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc.

Application of small-angle X-ray scattering to the characterization and quantification of the drug transport nanosystem based on the soybean phosphatidylcholine.

Phospholipid transport nanosystem (PTNS) for drug delivery is based on soybean phosphatidylcholine. The morphology of PTNS is investigated by means of small-angle X-ray scattering. The obtained results allow one to answer the key question from the viewpoint of organization of drug incorporation whether the PTNS nanoparticles have a structure of micelles or vesicles. It is demonstrated that PTNS is a vesicular system with an average vesicle radius of 160 ± 2Å.

On structural features of fullerene C60 dissolved in carbon disulfide: complementary study by small-angle neutron scattering and molecular dynamic simulations.

The parameters of fullerene C(60) dissolved in carbon disulfide CS(2) are analyzed by small-angle neutron scattering (SANS) in a wide interval of momentum transfer. To exclude the influence of nonequilibrium conditions, the solutions are prepared without applying shaking, stirring or ultrasound. No indication of the equilibrium cluster state of C(60) (with the cluster size below 60 nm) in the final solutions is revealed. Molecular dynamic simulations are complementary used to find out the partial volume of C(60) in CS(2) and the scattering contribution of the solvent organization at the interface with the fullerene molecule, which is shown to be small. Among several approaches for describing SANS data the preference is given to the model, which takes into account the presence of stable C(60) dimers (comprising 10% of the total particle number density) in the solution.

[Cardioprotective effect of cytoflavine on a model of doxorubicin-induced cardiomyopathy].

Experimental data on the influence of repeated administration of doxorubicin in a dose of 2.24 mg/kg on the glutathione exchange in heart tissues and erythrocytes of white outbred rats are presented. It was shown that disorders in the natural cytoprotection system caused by the introduction of this cardiotropic agent, can be corrected using a combined preparation of cytoflavin.

Study of α-crystallin structure by small angle neutron scattering with contrast variation.

The structure of the oligomeric protein α-crystallin from bovine eye lens was investigated by small-angle neutron scattering (SANS) with contrast variation. Based on the SANS curves, the match point for α-crystallin (43% D2O) and its average scattering length density at this point (2.4·10(10) cm(-2)) were evaluated. The radius of gyration and the distance distribution functions for α-crystallin were calculated. On the basis of these calculations, it was concluded that α-crystallin is characterized by homogeneous distribution of scattering density in the domains inaccessible for water penetration, and all polypeptide subunits in α-crystallin oligomers undergo equal deuteration. The latter indicates that all α-crystallin subunits are equally accessible for water and presumably for some other low molecular weight substances. These conclusions on the α-crystallin structure (homogeneous distribution of scattering density and equal accessibility of all subunits for low molecular weight substances) should be taken into account when elaborating α-crystallin quaternary structure models.

[Application of a hemostatic glue for the prevention of intra- and postoperative complications of septoplasty].

The authors describe the application of a hemostatic glue between the mucoperichondrial layers for the prevention of development of nasal septum hematoma and other possible complications of septoplasty. Analysis of the efficiency of the treatment of 30 patients by septoplasty with intraoperative application of the hemostatic glue has demonstrated the possibility of its use during surgery on the nasal septum.

Correction of vortex laser beam in a closed-loop adaptive system with bimorph mirror.

The phase correction of a vortex laser beam is undertaken in the closed-loop adaptive system including a Hartmann-Shack wavefront sensor with singular reconstruction technique and a bimorph piezoceramic mirror. After correction the vortex doughnutlike beam is focused into a beam with bright axial spot that considerably increases the Strehl ratio and optical system resolution. Since the phase break cannot be exactly reproduced on the flexible mirror surface, off-axis vortices appear in the far field at the beam periphery.

Comparative structure analysis of non-polar organic ferrofluids stabilized by saturated mono-carboxylic acids.

The structure of ferrofluids (magnetite in decahydronaphtalene) stabilized with saturated mono-carboxylic acids of different chain lengths (lauric, myristic, palmitic and stearic acids) is studied by means of magnetization analysis and small-angle neutron scattering. It is shown that in case of saturated acid surfactants, magnetite nanoparticles are dispersed in the carrier approximately with the same size distribution whose mean value and width are significantly less as compared to the classical stabilization with non-saturated oleic acid. The found thickness of the surfactant shell around magnetite is analyzed with respect to stabilizing properties of mono-carboxylic acids.