Correlation between the parameters of ion and X-ray emissions from the plasma of a micropinch discharge

Ion emission from the plasma of a micropinch discharge is studied by analyzing the plasma flow from the discharge region with the help of time-of-flight technique and probe diagnostics. Concurrently, soft Xray emission from the micropinch is recorded. The experimental data are interpreted using the radiative contraction model.     

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.     

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.     

Overcoming regulatory and economic challenges facing pharmacogenomics

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place.     

Experimental technique of passive optical diagnostics of plasma

An experimental technique of passive optical diagnostics of plasma is proposed. The equipment complex designed for its practical implementation is described. The technique is based on the simultaneous recording of self-radiation spectra and images of plasma with the subsequent analysis of the recorded data. This technique can be applied for diagnosing plasmas generated by various means, such as a gas discharge, laser radiation, a shock wave, an explosion, and so on.     

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.     

Problems of epidemiology and diagnostics of leptospiroses in Siberia and Far East

Multi-year literature data as well as materials of the Reference centre of monitoring of natural foci infections of Irkutsk Research Institute of Plague Control of Siberia and the Far East regarding epidemiology, epizootology and laboratory diagnostics of leptospiroses in Siberia and the Far East are analyzed and summarized in the review. Situation on leptospiroses in the region has changed significantly. In 50 - 70s of the 20th century diseases were registered ubiquitously in the form of outbreaks, group and single cases. Currently a low level of sporadic morbidity is noted in separate subjects of the Russian Federation. The contemporary state of the problem remains insufficiently clear, this demands the expansion of studies, creation of modern databases, as well as introduction into the practice of highly sensitive methods of express diagnostics in a complex with bacteriologic and serologic methods.     

Liposomes and diagnostic imaging: the potential to visualize both structure and function

Abstract

Liposomes have been studied over the past several decades because of their usefulness as a model membranes. The knowledge gained in these studies has been applied in the design of liposomes for use as therapeutic drug carriers. Currently, several liposome-based therapeutics are in the final stages of clinical trials. The field of liposome-based diagnostics is less advanced. For liposome-based materials to reach the clinic, it wIII be necessary for them to show significant advantages over currently employed diagnostic agents. It is the thesis of this review that the major advantage of liposomes is their ability to deliver agents in a manner that makes it possible to image and/or quantitate physiological processes. This ability, along with the demonstrated ability of liposomes to target or constrain contrast agents to specific tissues or structures, constitute the chief advantages of liposome-based diagnostics. Several examples of how these characteristics are being exploited in animal studies are given. It is postulated that continued refinement of liposome carriers and further increases in the ability to control the interactions of liposomes with the in vivo environment wIII allow liposome-based diagnostics to assume a place in the clinic with liposome-based therapeutic agents.     

Determination of the fraction composition of blood lipoproteins by the small-angle X-ray scattering technique.

A new method for analyzing the fraction composition of blood lipoproteins (LP) was developed based on the small-angle X-ray scattering (SAXS) technique. The method allows quantitative determination of the contents of basic LP fractions (high-density LP, low-density LP, very low-density LP and their subfractions) in the blood plasma or serum. The results of LP analysis by the new method were compared with electron microscopy, ultracentrifugation and gel electrophoresis data. The results obtained by SAXS correlated with those obtained by traditional methods. The new method for the determination of the LP fraction composition in the blood is rapid (1-1.5 h), uses only one reagent (e.g., sucrose) and features a high accuracy and resolution up to LP subfractions. A total of 0.05 ml of the blood plasma or serum is required for an assay. The assays can be carried out in purified preparations or in the blood plasma or serum. The method developed can be used in clinical practice for diagnostics and in scientific research.     

Data management in the cell therapy production facility: the batch process record (BPR)

The activities of cell therapy establishments are associated with substantial amounts of information. For reasons of best practice, regulation and adherence to prevailing standards, the data generated in the course of cell therapy product processing must be recorded and retained in an organized manner. Because cell therapy products are functionally pharmaceuticals, the paradigm of the pharmaceutical manufacturing batch process record (BPR) is proposed as a unit for collecting the data resulting from processing. Considerations for cell-processing facilities for the design of BPR and possible selection of electronic data-recording tools are reviewed, including data to collect in response to regulatory or accreditation mandates and different types of electronic data management tools that may be employed. Additionally, considerations for selection, qualification and validation of computer software for maintenance of the BPR are addressed.     

DNA microarrays in the clinic: how soon,how extensively?

Although DNA microarrays are now widely used in research settings, they have been slow to penetrate clinical practice in spite of their apparent advantages. This is due to the very different requirements for a clinical test in contrast to a research tool, and to a strict necessity for demonstrated clinical utility. There is a clear differentiation between two types of DNA array tests: "genomic" diagnostics, developed to ascertain the presence or absence of mutations, deletions or duplications, and for which clinical evidence is already established, and tests using expression profiling for prognosis or predictive purposes, in which case the clinical correlate must be proven. Most array diagnostics currently used belong, understandably, to the "genomic" variety. It is to be expected that future improvements in tailored technology, as well as a logical trend towards measuring an ever-increasing number of parameters, will ensure an important diagnostic role for DNA arrays in the coming decade.     

A Systematic Review of the Mortality from Untreated Leptospirosis

BackgroundLeptospirosis occurs worldwide, but the global incidence of human disease and its mortality are not well understood. Many patients are undiagnosed and untreated due to its non-specific symptoms and a lack of access to diagnostics. This study systematically reviews the literature to clarify the mortality from untreated leptospirosis. Results will help quantify the global burden of disease and guide health policies.ConclusionsThis systematic review contributes to our understanding of the mortality of untreated leptospirosis and provides data for the estimation of DALYs attributable to this disease. We show that mortality is significantly higher in older patients with icteric disease or renal failure but is lower in younger, anicteric patients. Increased surveillance and accurate point-of-care diagnostics are required to better understand the incidence and improve diagnosis of disease. Empirical treatment strategies should prioritize early treatment to improve outcomes from leptospirosis.     

Personalised Medicine in 2012: Editorial to the Special Issue of New Biotechnology on "MOLECULAR DIAGNOSTICS & PERSONALISED MEDICINE"

This special issue of New Biotechnology is focused on molecular diagnostics and personalised medicine and appears at an epochal moment in the development of the field. The practice of medicine is taking a significant and irrevocable turn towards personalisation, due to the great progress in areas such as genomics, pharmacogenomics and molecular diagnosis. It becomes increasingly apparent that to deliver the promise of personalised treatments, more and more novel medicines discovered today will be presented together with innovative companion diagnostics. The contributions to this volume touch on many disciplines, ranging from cell biology to genetics, immunology, molecular diagnostics, pharmaceutics and economic issues. The contributions of clinicians and basic scientists are synergistically presented to underline better the wide spectrum of studies that can contribute to the new field of personalised medicine. The promising perspectives of individualised treatments are related not only to higher effectiveness, but also to increased efficiency. This is relevant not only for the individual patient, but even more so for the general public, within a wider economical perspective where resources are limited and it becomes more and more mandatory to close the gap between social costs and benefits. This approach follows the steps of a stratified and individualised medicine and finds its final goal in an individualised healthcare.     

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.     

Abnormally high digestive enzyme activity and gene expression explain the contemporary evolution of a Diabrotica biotype able to feed on soybeans

Western corn rootworm (Diabrotica virgifera) (WCR) depends on the continuous availability of corn. Broad adoption of annual crop rotation between corn (Zea mays) and nonhost soybean (Glycine max) exploited WCR biology to provide excellent WCR control, but this practice dramatically reduced landscape heterogeneity in East-central Illinois and imposed intense selection pressure. This selection resulted in behavioral changes and "rotation-resistant" (RR) WCR adults. Although soybeans are well defended against Coleopteran insects by cysteine protease inhibitors, RR-WCR feed on soybean foliage and remain long enough to deposit eggs that will hatch the following spring and larvae will feed on roots of planted corn. Other than documenting changes in insect mobility and egg laying behavior, 15 years of research have failed to identify any diagnostic differences between wild-type (WT)- and RR-WCR or a mechanism that allows for prolonged RR-WCR feeding and survival in soybean fields. We documented differences in behavior, physiology, digestive protease activity (threefold to fourfold increases), and protease gene expression in the gut of RR-WCR adults. Our data suggest that higher constitutive activity levels of cathepsin L are part of the mechanism that enables populations of WCR to circumvent soybean defenses, and thus, crop rotation. These new insights into the mechanism of WCR tolerance of soybean herbivory transcend the issue of RR-WCR diagnostics and management to link changes in insect gut proteolytic activity and behavior with landscape heterogeneity. The RR-WCR illustrates how agro-ecological factors can affect the evolution of insects in human-altered ecosystems.     

Inferring maximum lifespan from maximum recorded longevity in the wild carries substantial risk of estimation bias

When comparing lifespan (longevity) between species, it is common practice to take the maximum recorded longevity value within each species as a proxy of maximum lifespan. Whether maximum recorded longevity is a reliable proxy of species' maximum longevity remains unclear. Some researchers correct for previously documented life history correlates of maximum recorded longevity before analysing new predictors of lifespan across species in the context of their current, specific hypotheses. At present there is no certainty that all relevant statistical, phenotypic, or ecological biases are accounted for by such corrective measures. Here, we employ Monte Carlo simulation to investigate the effect of differences in recapture numbers, recapture types (the point in life at which individuals are initially captured or recaptured), and actuarial population decay structure of simulated species on their maximum recorded longevities. We show that maximum recorded longevities differ in response to all three of these variables, as well as all of their two‐ and three‐way interactions. We then investigate empirical avian band‐recapture data for evidence of biases caused by recapture number and recapture type, predicted by the Monte Carlo analysis, and confirm the predicted biases as major sources of variance. Finally, we investigate the relationship between recapture type, recapture number, and a selection of ecological and life‐history variables previously documented to correlate with maximum recorded longevity, and find significant correlations between the biasing variables and those published correlates. Our results call into question the validity of using maximum recorded longevity as a proxy for different species' maximum longevities in comparative studies investigating the evolution of lifespan.     

Control of Mycobacterium bovis infections and the risk to human populations

Conventional control methods based on test-and-slaughter policies have, in several countries, led to the successful eradication of bovine tuberculosis in cattle. However, new approaches for control of bovine tuberculosis are required in developing countries and those with a wildlife reservoir of infection. Recent developments include improved diagnostics and evaluation of new vaccination strategies.     

X-ray backlighting of the periphery of an imploding multiwire array in the Angara-5-1 facility

Backlighting diagnostics for studying the peripheral region of an imploding liner in the Angara-5-1 facility by using X-ray emission from an X-pinch is described. The spatial resolution of the diagnostics was no worse than 4 µm. The X-pinch emission passed through the plasma was recorded with a photofilm. The plasma density was reconstructed from the photofilm blackening density with the help of a step attenuator made of the same material as the liner. Results are presented from experiments on X-ray backlighting of the peripheral region of a multiwire liner at the 70th ns after the beginning of the discharge. It was found that, by this time, the wire cores were depleted to different extent, their masses totalled 70% of the original wire mass, and their diameters had increased approximately threefold. The plasma ejected from the wire cores was found to be axially stratified with a spatial period of 200 µm. Sometimes the axial nonuniformity of the core material with a characteristic scale length of 20 µm was observed.     

Bayesian case influence diagnostics for survival models

We propose Bayesian case influence diagnostics for complex survival models. We develop case deletion influence diagnostics for both the joint and marginal posterior distributions based on the Kullback-Leibler divergence (K-L divergence). We present a simplified expression for computing the K-L divergence between the posterior with the full data and the posterior based on single case deletion, as well as investigate its relationships to the conditional predictive ordinate. All the computations for the proposed diagnostic measures can be easily done using Markov chain Monte Carlo samples from the full data posterior distribution. We consider the Cox model with a gamma process prior on the cumulative baseline hazard. We also present a theoretical relationship between our case-deletion diagnostics and diagnostics based on Cox's partial likelihood. A simulated data example and two real data examples are given to demonstrate the methodology.     

Integrating molecular and morphological approaches for characterizing parasite cryptic species: implications for parasitology

Herein we review theoretical and methodological considerations important for finding and delimiting cryptic species of parasites (species that are difficult to recognize using traditional systematic methods). Applications of molecular data in empirical investigations of cryptic species are discussed from an historical perspective, and we evaluate advantages and disadvantages of approaches that have been used to date. Developments concerning the theory and practice of species delimitation are emphasized because theory is critical to interpretation of data. The advantages and disadvantages of different molecular methodologies, including the number and kind of loci, are discussed relative to tree-based approaches for detecting and delimiting cryptic species. We conclude by discussing some implications that cryptic species have for research programmes in parasitology, emphasizing that careful attention to the theory and operational practices involved in finding, delimiting, and describing new species (including cryptic species) is essential, not only for fully characterizing parasite biodiversity and broader aspects of comparative biology such as systematics, evolution, ecology and biogeography, but to applied research efforts that strive to improve development and understanding of epidemiology, diagnostics, control and potential eradication of parasitic diseases.