Landscape analysis of NTD diagnostics and considerations on the development of a strategy for regulatory pathways

Access to quality-assured, accurate diagnostics is critical to ensure that the 2021–2030 neglected tropical disease (NTD) road map targets can be achieved. Currently, however, there is limited regulatory oversight and few quality assurance mechanisms for NTD diagnostic tools. In attempting to address such challenges and the changing environment in regulatory requirements for diagnostics, a landscape analysis was conducted, to better understand the availability of NTD diagnostics and inform future regulatory frameworks. The list of commercially available diagnostics was compiled from various sources, including WHO guidance, national guidelines for case detection and management, diagnostic target product profiles and the published literature. The inventory was analyzed according to diagnostic type, intended use, regulatory status, and risk classification. To estimate the global need and size of the market for each type of diagnostic, annual procurement data were collected from WHO, procurement agencies, NGOs and international organizations, where available and global disease prevalence. Expert interviews were also conducted to ensure a better understanding of how diagnostics are procured and used. Of 125 diagnostic tools included in this analysis, rapid diagnostic tools accounted for 33% of diagnostics used for NTDs and very few diagnostics had been subjected to regulatory assessment. The number of tests needed for each disease was less than 1 million units per annum, except in the case of two diseases, suggesting limited commercial value. Despite the nature of the market, and presumed insufficient return on commercial investment, acceptable levels of assurance on performance, quality and safety of diagnostics are still required. Priority actions include setting up an agile, interim, stepwise risk assessment mechanism, in particular for diagnostics of lower risk, in order to support national NTD programmes and their partners with the selection and procurement of the diagnostics needed to control, eliminate and eradicate NTDs.     

On the reliability of probe diagnostics in RF plasma

The errors of probe diagnostics of the resting or slow-moving plasma of Q-machines or dc discharges are shown to lie typically within a range of ±(20–30)%. Problems of probe diagnostics of RF plasma and modern approaches to their solving are considered. The objectivity of probe diagnostics of RF plasma is established by the mutual agreement between the electron energy distribution functions measured in the same experiment using the Langmuir probes and the method of relative intensities of spectral lines.     

Immunologic methods in the diagnostics and treatment of nosocomial cases of pneumonia

The publications on the etiology, bacteriological and immunochemical diagnostics of pneumonia, as well as on the role of immunotherapy and prophylaxis in the treatment of this disease, are analyzed. The importance of immunological methods in the diagnostics of pneumonia is pointed out. Approaches to the immunotherapy and immunoprophylaxis of pneumonia are updated.     

The possibility of increasing the precision of biochemical diagnostics of Gaucher disease

Estimation of chitotriosidase activity is proposed for final diagnostics of Gaucher disease. Using this method the diagnosis has not been confirmed in one patient of 25 ones with this preliminary diagnosis. The problems of complex diagnostics of Gaucher disease are discussed.     

The contact-free control of the functional state: the experience of its practical use]

Application of contactless control method does not create any psychological or physical discomfort for a man and allows to realize diagnostics continuously for a long time, evidently or secretly. These properties of the control determine its effective application in practice. In the paper the data are given of the studies of the functional state of a man-operator using the parameters of the eyelids movements contactlessly recorded in infra-red rays, and the results of diagnostics of patients with depression by the characteristics of their speech, recorded from the microphone. The above data are obtained in practice.     

Charge-exchange recombination spectroscopy of the plasma ion temperature at the T-10 tokamak

Charge-exchange recombination spectroscopy (CXRS) based on a diagnostic neutral beam has been developed at the T-10 tokamak. The diagnostics allows one to measure the ion temperature profile in the cross section of the plasma column. In T-10 experiments, the measurement technique was adjusted and the elements of the CXRS diagnostics for ITER were tested. The used spectroscopic equipment makes it possible to reliably determine the ion temperature from the Doppler broadening of impurity lines (helium, carbon), as well as of the spectral lines of the working gas. The profiles of the plasma ion temperature in deuterium and helium discharges were measured at different plasma currents and densities, including with the use of active Doppler measurements of lines of different elements. The validity and reliability of ion temperature measurements performed by means of the developed CXRS diagnostics are analyzed.     

Spectroscopic diagnostics of the solar coronal plasma

The review is addressed to problems of spectroscopic diagnostics of the solar coronal plasma by its radiation in the X-ray and extreme ultraviolet (EUV) bands. Physical conditions in the corona, elementary processes and mechanisms of radiation formation, and methods and results of the temperature and density diagnostics of diverse coronal structures (such as active and quiet solar regions, coronal holes, and the extended corona) are considered. The types and main parameters of instruments for investigation of the corona by its X-ray and EUV emission in space experiments are given.     

Deletion diagnostics for alternating logistic regressions

Deletion diagnostics are introduced for the regression analysis of clustered binary outcomes estimated with alternating logistic regressions, an implementation of generalized estimating equations (GEE) that estimates regression coefficients in a marginal mean model and in a model for the intracluster association given by the log odds ratio. The diagnostics are developed within an estimating equations framework that recasts the estimating functions for association parameters based upon conditional residuals into equivalent functions based upon marginal residuals. Extensions of earlier work on GEE diagnostics follow directly, including computational formulae for one‐step deletion diagnostics that measure the influence of a cluster of observations on the estimated regression parameters and on the overall marginal mean or association model fit. The diagnostic formulae are evaluated with simulations studies and with an application concerning an assessment of factors associated with health maintenance visits in primary care medical practices. The application and the simulations demonstrate that the proposed cluster‐deletion diagnostics for alternating logistic regressions are good approximations of their exact fully iterated counterparts.     

Nonstationarity and duration of the R-R-segment in the diagnostics of functional states of operators

The effect of the nonstationarity of R-R interval series on the diagnostics of functional states of operators has been analyzed. The functional states were diagnosed by means of a factor model of heart rate variability. The heart rate was recorded in the supine position, before the performance of an important task, and after its completion. A high resistance of the diagnostics of functional states to nonstationarity was found for all periods. Indices of heart rate variability resistant to nonstationarity were defined. Also, the effect of R-R segment duration on functional states diagnostics was explored. The results obtained allow one to conclude that the diagnostics of functional states based on the three-factor model of heart rate variability can be used on short segments within a range of 256 divided 32 R-R intervals. The indices of the factor model of heart rate variability must be normalized for corresponding R-R segment duration before diagnostics. In addition, the effect of the duration of R-R segment on the indices of heart rate variability was analyzed for different functional states. The indices resistant to the duration of R-R segments and conditions necessary for heart rate recording were defined.     

Rectal Swabs for Analysis of the Intestinal Microbiota

The composition of the gut microbiota is associated with various disease states, most notably inflammatory bowel disease, obesity and malnutrition. This underlines that analysis of intestinal microbiota is potentially an interesting target for clinical diagnostics. Currently, the most commonly used sample types are feces and mucosal biopsy specimens. Because sampling method, storage and processing of samples impact microbiota analysis, each sample type has its own limitations. An ideal sample type for use in routine diagnostics should be easy to obtain in a standardized fashion without perturbation of the microbiota. Rectal swabs may satisfy these criteria, but little is known about microbiota analysis on these sample types. In this study we investigated the characteristics and applicability of rectal swabs for gut microbiota profiling in a clinical routine setting in patients presenting with various gastro-intestinal disorders. We found that rectal swabs appeared to be a convenient means of sampling the human gut microbiota. Swabs can be performed on demand, whenever a patient presents; swab-derived microbiota profiles are reproducible, whether they are gathered at home by patients or by medical professionals in an outpatient setting and may be ideally suited for clinical diagnostics and large-scale studies.     

Proteome profiling for the identification of lung cancer signatures

Comprehensive and in-depth discovery of the disease proteome is an important issue in recent proteomics developments. Previous studies have shown a number of biomarkers discovered in various diseases, including lung cancer. Some of them are potentially useful in lung cancer diagnostics and prognostics. However, few of them can act as organ-specific biomarkers to extensively compare multiple cancer models. This article evaluates a recently published study employing comparative proteomics on multiple genetically engineered mouse models and sheds light on the usefulness and application of the discovered marker panel for human lung cancer diagnostics.     

Molekularzytogenetische Methoden und Array-Diagnostik in der Pr?natalmedizin

In addition to the widely used cytogenetic standard approaches, molecular methods are being increasingly used in prenatal diagnostics. While molecular cytogenetics, e.g., fluorescence in situ hybridization (FISH), has been used for many years in invasive prenatal diagnostics, array-based diagnostics are only now being implemented in this field. FISH is prenatally applied for determination of size of a mosaic cell clone, for exclusion of a microdeletion, or for further clarification of structural chromosomal aberrations. Array CGH (comparative genomic hybridization) is used more conservatively in prenatal diagnostics, mostly for further clarification in sonographically abnormal fetuses and to diagnose breakpoints in cases with proven chromosomal changes. In the future, array CGH will gain further importance, but already provides a valuable supplement to the diagnostic approaches of the cytogenetic and the molecular-based methods.     

The current composition of the subfamily Encotyllabinae (Monogenoidea: Capsalidae)

The historical account and recent taxonomic consideration of the monogenean subfamily Encotyllabinae are given. Main criteria used for diagnostics of the subfamily and its genera are discussed.     

Neuroendocrine tumors of the small intestine and the appendix - management guidelines (recommended by The Polish Network of Neuroendocrine Tumors)

Polish recommendations regarding management of patients suffering from neuroendocrine tumors of small intestine and appendix are presented. Small intestine, especially ileum represent most common origin of these tumors. Majority of them are well differentiated and grow slowly. Rarely, they are less differentiated with fast growth and poor prognosis. Symptoms are atypical, diagnosis could be often accidental. In 4-10% of patients typical symptoms of carcinoid syndrome are present. Chromogranin A is useful in the laboratory diagnostics, and urinary excretion of 5-hydroxyindoloacetic acid is helpful for the diagnostics and monitoring of the disease. Histopathological diagnostics was extensively described. Ultrasound, colonoscopy, capsule endoscopy, baloon enteroscopy, computed tomography, magnetic resonance and somatostatin analogs scintigraphy could be used for the visualization. The treatment of choice in the neuroendocrine tumors of small intestine and appendix is radical or palliative surgery, if possible using endoscopy. Pharmacotherapy consists of biotherapy and chemotherapy. The crucial in biotherapy is somatostatin analogs application, possible in symptomatic treatment of hormonally functioning tumors. This is treatment of choice in carcinoid crisis. Interferon alfa could be applied because of the same indications as somatostatin analogs, except for carcinoid crisis. Chemotherapy is less successful in disseminated or locally advanced intestinal neuroendocrine tumors, so radioisotope therapy should be considered in each case of unresectable tumor.     

Integrated Artificial Intelligence Approaches for Disease Diagnostics

Mechanocomputational techniques in conjunction with artificial intelligence (AI) are revolutionizing the interpretations of the crucial information from the medical data and converting it into optimized and organized information for diagnostics. It is possible due to valuable perfection in artificial intelligence, computer aided diagnostics, virtual assistant, robotic surgery, augmented reality and genome editing (based on AI) technologies. Such techniques are serving as the products for diagnosing emerging microbial or non microbial diseases. This article represents a combinatory approach of using such approaches and providing therapeutic solutions towards utilizing these techniques in disease diagnostics.     

Differential rotation of plasma in the GOL-3 multiple-mirror trap during injection of a relativistic electron beam

Results of spectral and magnetic diagnostics of plasma differential rotation in the GOL-3 multiplemirror trap are presented. It is shown that the maximum frequency of plasma rotation about the longitudinal axis reaches 0.5 MHz during the injection of a relativistic electron beam into the plasma. The data of two diagnostics agree if there is a region with a higher rotation frequency near the boundary of the electron beam. Plasma differential rotation can be an additional factor stabilizing interchange modes in the GOL-3 facility.     

Critical remarks on the monocyte test]

The application of the monocyte test in the diagnostics of drug allergy is considered from a critical point of view. Further hospital application of the test and its evaluation are discussed.     

Massive parallele Sequenzierung in der Diagnostik hereditärer BRCA1-/-2-Mutationen

During the past few years, application of massively-parallel sequencing (MPS) in molecular diagnostics of hereditary cancer has increased significantly. The potential advantages of MPS, compared for example to Sanger sequencing-based methods, are higher sample capacities, shorter turnaround times, and decreased costs. Adoption in routine diagnostics is simplified due to the availability of certified kits for sample preparation. Here, the validation of two MPS systems for routine BRCA1/2 sequencing diagnostics are describe. Users should keep in mind the technical advantages and disadvantages of the individual sequencing machines. The results achieved with MPS are equal to those from Sanger sequencing.     

Dissecting the role of peptides in the immune response: theory, practice and the application to vaccine design.

Analytical biochemistry and synthetic peptide based chemistry have helped to reveal the pivotal role that peptides play in determining the specificity, magnitude and quality of both humoral (antibody) and cellular (cytotoxic and helper T cell) immune responses. In addition, peptide based technologies are now at the forefront of vaccine design and medical diagnostics. The chemical technologies used to assemble peptides into immunogenic structures have made great strides over the past decade and assembly of highly pure peptides which can be incorporated into high molecular weight species, multimeric and even branched structures together with non-peptidic material is now routine. These structures have a wide range of applications in designer vaccines and diagnostic reagents. Thus the tools of the peptide chemist are exquisitely placed to answer questions about immune recognition and along the way to provide us with new and improved vaccines and diagnostics.