A HYBRID DIFFERENTIAL EVOLUTION FOR NON-SMOOTH OPTIMIZATION PROBLEMS

Solving high dimentional, multimodal, non-smooth global optimization problems faces challenges concerning quality of solution, computational costs or even the impossibility of solving the problem. Evolutionary algorithms, in particular, differential evolution algorithm proved itself as good method of global optimization. On the other side, approach based on subgradient methods are good for optimizing non-smooth functions. Combination of these two approaches enables to improve the quality of the algorithm, using the best features of both methods. In this paper, a new hybrid evolutionary approach based on differential evolution and subgradient algorithm as the local search procedure is proposed. Behavior of the proposed SSGDE algorithm was studied in a numerical experiment on three groups of generated tests. Comparison of the new hybrid algorithm with the pure DE approach showed the advantage of the SSGDE. It has been experimentally established that the proposed method finds the global minimum in the best way for all considered dimensions of the problem with respect to the differential evolution method. The SSGDE algorithm showed the best results with a significant increase in the number of functions

КОРРЕКЦИЯ ИММУНОЛОГИЧЕСКИХ НАРУШЕНИЙ У БЕРЕМЕННЫХ С ХРОНИЧЕСКИМ ПИЕЛОНЕФРИТОМ

Дослідження проведено з метою оцінки ефективності пребіотика лактулози як імунокорегуючого засобу при загостренні хронічного пієлонефриту у вагітних із функціональними запорами. Матеріал та методи дослідження. Проведено обстеження та лікування 37 вагітних жінок із загостренням хронічного пієлонефриту, які страждають функціональними закрепами. Тривалість спостереження склала 28 діб. У всіх вагітних вивчали показники антиендотоксинового імунітету, фагоцитарну активність клітин крові та рівень цитокінів. Результати дослідження. Виявлено, що у пацієнток, які отримували лактулозу в комплексному лікуванні пієлонефриту, нормалізуються такі показники антиендотоксінових імунітету як Ig класів А, M і G до ліпополісахариду кишкової палички та рівень експресії ліпополісахаридзв’язуючих рецепторів гранулоцитами і моноцитами периферичної крові, а також підвищується фагоцитарна активність гранулоцитів периферичної крові, як фактор неспецифічного захисту, при достовірно якнайшвидшому зниженні активності запальних реакцій. Висновки. Використання пребіотика лактулози у комплексному лікуванні загострення хронічного пієлонефриту у вагітних з функціональними закрепами веде до нормалізації вказаних показників антиендотоксинового імунітету, а також до підвищення фагоцитарної активності гранулоцитів периферичної крові

The diagnostic performance of novel skin-based in-vivo tests for tuberculosis infection compared with purified protein derivative tuberculin skin tests and blood-based in vitro interferon-γ release assays: a systematic review and meta-analysis

BACKGROUND: Novel skin-based tests for tuberculosis infection might present suitable alternatives to current tests; however, diagnostic performance of new tests compared with the purified protein derivative-tuberculin skin test (TST) or interferon-γ release assays (IGRA) needs systematic assessment. METHODS: In this systematic review and meta-analysis, we searched English (Medline OVID), Chinese (Chinese Biomedical Literature Database and the China National Knowledge Infrastructure), and Russian (e-library) databases from the inception of each database to May 15, 2019, (with updated search of the Russian and English databases on Oct, 20 2020) using terms "ESAT6" OR "CFP10" AND "skin test" AND "Tuberculosis" OR "C-Tb" OR "Diaskintest". We included studies reporting on the performance of index tests alone or compared with a comparator. Inclusion criteria varied according to review objectives and performance outcome, but reporting of test cut-offs for positivity applied to study population was required from all studies. We used a hierarchy of reference standards for tuberculosis infection consistent with the 2020 WHO framework to evaluate diagnostic performance. Two authors independently reviewed the titles and abstracts for English and Chinese (LF and MK) and Russian studies (MK and VN). Study quality was assessed with QUADAS-2. Pooled random-effects estimates are presented when appropriate for total agreement proportion, sensitivity in microbiologically confirmed tuberculosis and specificity in cohorts with low risk of tuberculosis infection. This study is registered with PROSPERO, CRD42019135572. FINDINGS: We identified 1466 original articles, of which 37 (2·5%) studies, including 10 915 individuals (7111 Diaskintest, 2744 C-Tb, 887 EC, 173 DPPD), were included in the qualitative analysis (29 [78%] studies of Diaskintest, five [15%] studies of C-Tb, two [5%] studies of EC-skintest, and one [3%] study of DPPD). 22 (1·5%) studies including 5810 individuals (3143 Diaskintest, 2129 C-Tb, 538 EC-skintest) were included in the quantitative analysis: 15 (68%) of Diaskintest, five (23%) of C-Tb, and two (9%) of EC-skintest. Tested sub-populations included individuals with HIV, children (0-18 years), and individuals exposed to tuberculosis. Studies were heterogeneous with moderate to high risk of bias. Nine head-to-head studies of index test versus TST and IGRA permitted direct comparisons and pooling. In a mixed cohort of people with and without tuberculosis, Diaskintest pooled agreement with IGRA was 87·16% (95% CI 79·47-92·24) and 55·45% (46·08-64·45) with TST-5 mm cut-off (TST5 mm). Diaskintest sensitivity was 91·18% (95% CI 81·72-95·98) compared with 88·24% (78·20-94·01) for TST5 mm, 89·66 (78·83-95·28) for IGRA QuantiFERON, and 90·91% (79·95-96·16) for TSPOT.TB. C-Tb agreement with IGRA in individuals with active tuberculosis was 79·80% (95% CI 76·10-83·07) compared with 78·92% (74·65-82·63) for TST5 mm/15 mm cut-off (TST5 mm/15 mm). TST5/15mm reflects threshold in cohorts that applied stratified cutoffs: 5 mm for HIV-infected, immunocompromised, or BCG-naive individuals, and 15mm for BCG-vaccinated immunocompetent individuals. C-Tb sensitivity was 74·52% (95% CI 70·39-78·25) compared with a sensitivity of 78·18% (67·75-85·94) for TST5 mm/15 mm, and 71·67% (63·44-78·68) for IGRA. Specificity was 97·85% (95% CI 93·96-99·25) for C-Tb versus 93·31% (90·22-95·48) for TST 15 mm cut-off and 99·15% (79·66-99·97) for IGRA. EC-skintest sensitivity was 86·06% (95% CI 82·39-89·07). INTERPRETATION: Novel skin-based tests for tuberculosis infection appear to perform similarly to IGRA or TST; however, study quality varied. Evaluation of test performance, patient-important outcomes, and diagnostic use in current clinical algorithms will inform implementation in key populations. FUNDING: StopTB (New Diagnostics Working Group) and FIND. TRANSLATIONS: For the Chinese and Russian translations of the abstract see Supplementary Materials section

Spectral studies of the dithiacrown ether derivative in the presence of metal cations and modeling their possible complexes

© ISUCT Publishing. The preparation of compositions comprising multifunctional compound is one of the key directions for design of chemosensoring materials that are important for the determination of particular ions in solutions. These compounds are characterized by ionophoric and photosensitive parts with reliable optical response and ion-selectivity. Their structures suggest the possibility of the complex formation with particular metal cations. The main goals of this study are as following: a) to investigate the absorption spectra of the novel derivative of the dithiacrown ethers (DTCE), synthesized in the laboratory of Professor S.P. Gromov (Photochemistry Center RAS), both: in salt solutions and in monolayers; b) to study the DTCE interaction with various metal cations, including mercury, as well as to carry out quantum-chemical calculations of their possible complexes. Spectral characteristics were examined in the DTCE acetonitrile solutions and their changes in the presence of some cations were found. The pronounced changes were obtained in the case of Hg2+ which are expressed as a hypsochromic shift on 22 nm. Absorption spectra of aqueous solutions of DTCE and perchlorates of alkali, alkaline earth, and heavy metals (lithium, sodium, potassium, cesium, magnesium, calcium, strontium, barium, copper, zinc, lead, cadmium, and mercury) at various concentrations were obtained. When the DTCE concentration equals to 10–5 M, the absorption intensity is low, and DTCE absorption maximum shifts in the presence of all the salts are rather small. The greatest shift (by 6 nm) of the DTCE absorption maximum to shorter wavelengths was observed for the mercury(II) perchlorate only. In order to select the DTCE concentration for further research the spectral dependence of the optical density vs. DTCE concentration was obtained (10 M was the most appropriate value of the DTCE concentration). Based on these results the DTCE extinction coefficient in aqueous solutions was determined (ε = 9329 M–1cm–1). Assuming the formation of the DTCE-cation complexes as 1:1, the metal perchlorates with lack and excess of the cations in the aqueous solutions were chosen. The absorption spectra had minor differences at DTCE concentration of 10–4 M and metal perchlorates concentration of 10–5 M (lack of the metal cations). Maximum hypsochromic shift by 4 nm was observed in the presence of mercury(II) perchlorate. It appeared that the lack of concentration of the metal salt does not allow the formation of complexes between the crown ether ring and a cation. The absorption intensity in the presence of most of salts was slightly reduced up to 85–95 % from baseline. The absorption spectra showed significant shifts of the absorption maxima to shorter wavelengths by 29 nm only in the presence of mercury(II) perchlorate at high concentrations (10–3 M). This fact proves a DTCE selectivity for mercury(II) cation. Moreover, the value of the shift depends on the salt concentration. An additional confirmation of these results was obtained in the study of the absorption spectra of the DTCE monolayers transferred from bidistilled water and aqueous solutions of Hg(ClO4)2 at constant surface pressure (about 10 mN/m). In all cases, the broad absorption maxima in the region of 350–450 nm were found. The main feature was that the maximum absorption for DTCE monolayer transferred to 10–5 M solution of Hg(ClO4)2 was 0.00575 a.u. at 406 nm. This is by 209% higher than those for the DTCE monolayer transferred from the water. Thus, the shift of the absorption maximum of DTCE monolayer in the presence of mercury salt was 23 nm to shorter wavelengths. This is further evidence of complex formation between DTCE (in monolayer) and mercury(II) cations from the aqueous subphase. For visualization and confirmation of the possibility of complex formation between DTCE and mercury(II) cation the quantum-chemical calculations of their structural models were carried out. The total energy of the optimized structure of the complex between DTCE cation and mercury(II) (with 2 perchlorate counter-anions) is set to E0 = –565.1231 a.u. It can be compared with the energies of individual species: the DTCE cation (E0 = –250.5477 a.u.) and Hg(ClO4)2 (E0 = –314.4877 a.u.). Thus, the change in energy (ΔE) upon complex formation is about –0.0877 a.u. (–230 kJ/mol). High energy of complex formation and high covalency of the Hg–S bonds explain the significant blue shift of the maximum in the absorption spectra of the solutions of DTCE with Hg(ClO4)2

Study Protocol: Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI) [version 2; peer review: 2 approved]

Global infection and mortality rates from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are disproportionately high in certain populations, including amongst older people. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit 6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months. Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics. Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection

Модели сигналов импульсной РЛС, принимаемых однопозиционной станцией радиотехнической разведки на наземных трассах

Излагаются основы однопозиционного пассивного метода определения координат источника радиоизлучения путем использования множества отражений излученных сигналов от естественных и искусственных образований на трассе распространения радиоволн. Алгоритм основан на сравнении координат возможных отражателей, нанесенных на карту местности, с координатами, вычисленными по измеренным пеленгам источников отражений и задержек отраженных сигналов относительно прямого. Приводятся данные радиофизического эксперимента по изучению отражений, выполненного в трехсантиметровом диапазоне волн, позволяющие оценить пригодность принимаемых сигналов для реализации метода. Принимаемые сигналы представлены в виде простейших математических моделей. Показано, что их статистический характер не препятствует реализации метода

Extraspinal articular tuberculosis: An 11-year retrospective study of demographic features and clinical outcomes in East London

OBJECTIVES: To describe demographic features, clinical outcomes and diagnostic delay amongst patients with extra-spinal articular tuberculosis (TB) in a low-incidence setting. METHODS: Cases of TB treated at our institution between 2004 and 2014 were identified via the London TB register (LTBR). Demographic features of extra-spinal articular TB cases were compared to controls with TB at all other sites. For articular cases (excluding individuals <16 years or with spinal TB without peripheral joint involvement) clinical data were retrospectively collected. RESULTS: 6,146 TB patients were identified over the study period; 146 (2.4%) cases had extra-spinal articular infection. There was no difference in median age between extra-spinal articular TB cases and controls with TB at other sites (31 vs 32 years, p = 0.57). Articular cases were more likely to be male (70.6% vs 59.5%, p = 0.007), Bangladeshi (28.7% vs 18.0%) or Pakistani (24.0% vs 16.1%) and were less likely to be Black-African (9.5% vs 19.8%) (p < 0.001). 93 cases were included in the case series; 85 (88.5%) were migrants and 83 (89.2%) were South Asian. Knee and elbow joints were affected in 22 (23.7%) and 18 (19.4%) cases respectively. The median durations of pre-healthcare and healthcare associated delay were 16 and 6 weeks respectively. Where mycobacterial culture was performed, 57/75 (76%) were positive for Mycobacterium tuberculosis. 86 (92.5%) cases received standard quadruple therapy for a median of 6 months (IQR 6–9). Recurrence of TB infection occurred in 4 (4.3%) cases and there were no TB related deaths. Seven (7.6%) cases required surgical intervention. CONCLUSIONS: Extra-spinal articular TB more commonly affected men and people of South Asian ethnicity. Significant diagnostic delays were identified, including avoidable healthcare-associated delays

Study Protocol: Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI) [version 1; peer review: 1 approved, 1 approved with reservations]

Global infection and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are disproportionately high in certain populations, including the elderly. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit 6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months. Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics. Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection

OXIDATIVE STRESS IN THE PATIENTS WITH CKD V STAGE AND ANEMIA WHO RECEIVE REPLACEMENT HEMODIALYSIS THARAPY

The article presents research data of oxidative stress role in the pathogenesis of anemia in patients with CKD V stage, who receive hemodialysis replacement therapy. Background. Oxidative stress is a part of the pathogenesis of many complications in patients with CKD stage V on replacement therapy with hemodialysis. Anemia syndrome is the most frequent complication of this patient`s population. Aim. The aim of this study was to study indicators of oxidative stress in patients with            CKD stage V and anemia on replacement therapy with hemodialysis. Materials and methods. We studied laboratory parameters in 42 hemodialysis patients with CKD V stage. Biochemical methods are used for investigation of lipid peroxidation processes: studied diene conjugates (DC), malondialdehyde (MDA), total lipids and catalase, lipid’s structure of erythrocytes membranes and their osmotic resistance. Results. We found that in dialysis patients anemic syndrome was associated with high activity of oxidative stress. Also increased destruction of red blood cells depends from high activity of oxidative stress. In the blood of the patients concentration of DC was 1,12±0,26 opt.den.units/ mg of lipids (p<0,01), and MDA level 0,35±0,05 opt.den.units/ mg of lipids (p<0,01). Levels of catalase, decreased to 0,029±0,0019 mm/l*sec (p<0,001). Also osmotic resistance of erythrocytes significantly decreased. MDA has inverse correlation relationship with hemoglobin in the blood, with a correlation coefficient r=-0,36. Investigation of erythrocyte membrane lipid structure of patients by TLC showed a significant decrease of phospholipids and monoglycerides of higher fatty acids, and the increase of cholesterol fractions. Conclusions. In patients with chronic kidney disease on dialysis replacement therapy anemic syndrome is associated with high activity of oxidative stress, as there is an inverse relationship between the level of hemoglobin and the content of MDA in blood. As a consequence of oxidative stress changes the lipid composition of erythrocyte membranes of the patient, because some fraction of lipids are substrates for oxidative processes. Impairment of lipid membranes of red blood cells of hemodialysis patients is one of the probably causes of anemia