НАУКОВО-МЕТОДИЧНЕ ЗАБЕЗПЕЧЕННЯ ДІАГНОСТИКИ КРИЗОВИХ ЯВИЩ В БАНКІВСЬКІЙ СИСТЕМІ

Summary of publications allowed the researchers to determine that the crisis in the banking sector at the micro level there (at the level of individual elements of the banking system) and macro level (at the level of the banking system). This stipulates that the causal relationship between them is difficult to establish clear. It was established that this necessitates the formation of specific mechanisms and choice of instruments of crisis regulation. Diagnosis in the public crisis management – is a set of actions aimed at identifying the sources and symptoms of the crisis, as well as the identification of the factors activating the banking crisis. The main purpose of this process is to neutralize the negative impact of factors and prevent the crisis unfolding banking crisis. To achieve diagnostic purposes must be the formation of analytical tools, taking into account the features of the objects of crisis management.В статье определена сущность диагностики как составляющей механизма государственного антикризисного регулирования банковской системы. Установлено, что объектами диагностики является микроуровень (уровень отдельных элементов банковской системы) и макроуровень (уровень банковской системы). Целью применения диагностического инструментария является выявление источников, факторов и симптомов кризисных явлений для формирования комплекса превентивных антикризисных мер. Автором охарактеризованы инструментарий, который целесообразно использовать для диагностики банковского кризиса на микро- и макроуровне. В статті визначено сутність діагностики як складової механізму державного антикризового регулювання банківської системи. Визначено, що об’єктами діагностики є мікрорівень (рівень окремих елементів банківської системи) та макрорівень (рівень банківської системи). Метою діагностичних заходів є виявлення джерел, факторів та симптомів кризових явищ задля формування комплексу превентивних антикризових заходів. Автором надано характеристику інструментарію, що можу бути використаний для діагностики банківської кризи на мікро- та макрорівнях

Improved method for assessing iron stores in the bone marrow

Background: Bone marrow iron microscopy has been the "gold standard'' method of assessing iron deficiency. However, the commonly used method of grading marrow iron remains highly subjective. Aim: To improve the bone marrow grading method by developing a detailed protocol that assesses iron in fragments, in macrophages around fragments and in erythroblasts. Methods: A descriptive study of marrow aspirates of 303 children (aged 6-60 months) with severe anaemia and 22 controls (children undergoing elective surgery) was conducted at hospitals in southern Malawi (2002-04). Results: Using an intensive marrow iron grading method, 22% and 39% of cases and controls had deficient iron stores, and 40% and 46% had functional iron deficiency, respectively. Further evaluation of the iron status classification by the intensive method showed that functional iron deficiency was associated with significantly increased C-reactive protein concentrations (126.7 (85.6) mg/l), and iron stores deficiency with significantly increased soluble transferrin receptor concentrations (21.7 (12.5) mg/ml). Conclusions: Iron assessment can be greatly improved by a more intense marrow examination. This provides a useful iron status classification which is of particular importance in areas where there is a high rate of inflammatory conditions

Hepatitis B vaccination impact and the unmet need for antiviral treatment in Blantyre, Malawi

BACKGROUND: Hepatitis B is the leading cause of cirrhosis and liver cancer in sub-Saharan Africa. To reduce hepatitis-associated mortality, antiviral treatment programmes are needed. We estimated prevalence, vaccine impact and need for antiviral treatment in Blantyre, Malawi to inform an effective public health response. METHODS: We conducted a household study in Blantyre in 2016-2018. We selected individuals from a census using random sampling and estimated age-sex-standardised HBsAg seroprevalence. Impact of infant hepatitis B vaccination, which began in 2002, was estimated by binomial log-linear regression comparing individuals born before and after vaccine implementation. In HBsAg-positive adults, eligibility for antiviral therapy was assessed. RESULTS: Of 97,386 censused individuals, 6,073 (median age 18 years; 56.7% female) were sampled. HBsAg seroprevalence was 5.1% (95% CI 4.3-6.1) among adults and 0.3% (0.1-0.6) among children born after vaccine introduction. Estimated vaccine impact was 95.8% (70.3-99.4). Of HBsAg-positive adults, 26% were HIV-positive. Among HIV-negative individuals, 3%, 6% and 9% were eligible for hepatitis B treatment by WHO, European and American hepatology association criteria, respectively. CONCLUSIONS: Infant HBV vaccination has been highly effective in reducing HBsAg prevalence in urban Malawi. Up to 9% of HBsAg-positive HIV-negative adults are eligible, but have an unmet need, for antiviral therapy

A pragmatic health centre-based evaluation comparing the effectiveness of a PCV13 schedule change from 3+0 to 2+1 in a high pneumococcal carriage and disease burden setting in Malawi: a study protocol

INTRODUCTION: Streptococcus pneumoniae (the pneumococcus) is commonly carried as a commensal bacterium in the nasopharynx but can cause life-threatening disease. Transmission occurs by human respiratory droplets and interruption of this process provides herd immunity. A 2017 WHO Consultation on Optimisation of pneumococcal conjugate vaccines (PCV) Impact highlighted a substantial research gap in investigating why the impact of PCV vaccines in low-income countries has been lower than expected. Malawi introduced the 13-valent PCV (PCV13) into the national Expanded Programme of Immunisations in 2011, using a 3+0 (3 primary +0 booster doses) schedule. With evidence of greater impact of a 2+1 (2 primary +1 booster dose) schedule in other settings, including South Africa, Malawi's National Immunisations Technical Advisory Group is seeking evidence of adequate superiority of a 2+1 schedule to inform vaccine policy. METHODS: A pragmatic health centre-based evaluation comparing impact of a PCV13 schedule change from 3+0 to 2+1 in Blantyre district, Malawi. Twenty government health centres will be randomly selected, with ten implementing a 2+1 and 10 to continue with the 3+0 schedule. Health centres implementing 3+0 will serve as the direct comparator in evaluating 2+1 providing superior direct and indirect protection against pneumococcal carriage. Pneumococcal carriage surveys will evaluate carriage prevalence among children 15-24 months, randomised at household level, and schoolgoers 5-10 years of age, randomly selected from school registers. Carriage surveys will be conducted 18 and 33 months following 2+1 implementation. ANALYSIS: The primary endpoint is powered to detect an effect size of 50% reduction in vaccine serotype (VT) carriage among vaccinated children 15-24 months old, expecting a 14% and 7% VT carriage prevalence in the 3+0 and 2+1 arms, respectively. ETHICS AND DISSEMINATION: The study has been approved by the Malawi College of Medicine Research Ethics Committee (COMREC; Ref: P05.19.2680), the University College London Research Ethics Committee (Ref: 8603.002) and the University of Liverpool Research Ethics Committee (Ref: 5439). The results from this study will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04078997

Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer

Background Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains. Methods We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo. Results We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice. Conclusion The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice

Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies

Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outcome of P. falciparum infection. Here we report an analysis of multiple allelic forms of G6PD deficiency in a large multi-centre case-control study of severe malaria, using the WHO classification of G6PD mutations to estimate each individual's level of enzyme activity from their genotype. Aggregated across all genotypes, we find that increasing levels of G6PD deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia. Models of balancing selection based on these findings indicate that an evolutionary trade-off between different clinical outcomes of P. falciparum infection could have been a major cause of the high levels of G6PD polymorphism seen in human populations

Severe anaemia is not associated with HIV-1 env gene characteristics in Malawian children

Background Anaemia is the most common haematological complication of HIV and associated with a high morbidity and a poor prognosis. The pathogenesis of HIV-associated anaemia is poorly understood and may include a direct effect of HIV on erythropoiesis. In vitro studies have suggested that specific HIV strains, like X4 that uses the CXCR4 co-receptor present on erythroid precursors, are associated with diminished erythropoiesis. This co-receptor affinity is determined by changes in the hypervariable loop of the HIV-1 envelope genome. In a previous case-control study we observed an association between HIV and severe anaemia in Malawian children that could not be fully explained by secondary infections and micronutrient deficiencies alone. We therefore explored the possibility that alterations in the V1-V2-V3 fragment of HIV-1 were associated with severe anaemia. Methods Using peripheral blood nucleic acid isolates of HIV-infected children identified in the previous studied we assessed if variability of the V1-V2-V3 region of HIV and the occurrence of X4 strains were more common in HIV-infected children with (cases, n = 29) and without severe anaemia (controls, n = 30). For 15 cases bone marrow isolates were available to compare against peripheral blood. All children were followed for 18 months after recruitment. Results Phylogenetic analysis showed that HIV-1 subtype C was present in all but one child. All V1-V2-V3 characteristics tested: V3 charge, V1-V2 length and potential glycosylation sites, were not found to be different between cases and controls. Using a computer model (C-PSSM) four children (7.8%) were identified to have an X4 strain. This prevalence was not different between study groups (p = 1.00). The V3 loop characteristics for bone marrow and peripheral blood isolates in the case group were identical. None of the children identified as having an X4 strain developed a (new) episode of severe anaemia during follow up. Conclusion The prevalence of X4 strains in these young HIV-1-subtype-C-infected children that were most likely vertically infected and nave to anti-retroviral therapy can be considered high compared to previous results from Malawi. It is unlikely that V1-V2-V3 fragment characteristics and HIV co-receptor affinity is an important feature in the development of severe anaemia in Malawian children

Measuring the use of information and communication technologies (ICTs) in the classroom

In 2003, the “ICT Curriculum Integration Performance Measurement Instrument” was developed froman extensive review ofthe contemporary international and Australian research pertaining to the definition and measurement of ICT curriculum integration in classrooms (Proctor, Watson, & Finger, 2003). The 45-item instrument that resulted was based on theories and methodologies identified by the literature review. This paper describes psychometric results from a large-scale evaluation of the instrument subsequently conducted, as recommended by Proctor, Watson, and Finger (2003). The resultant 20-item, two-factor instrument, now called “Learning with ICTs: Measuring ICT Use in the Curriculum,” is both statistically and theoretically robust. This paper should be read in association with the original paper published in Computers in the Schools(Proctor, Watson, & Finger, 2003) that described in detail the theoretical framework underpinning the development of the instrument