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This editorial discusses the expanding role of paper as a platform on which to build new point-of-care assays, particularly those intended for use in resource-limited settings. Successful diagnostics for use in these environments require a low-cost platform (possibly paper) as well as new assay strategies, reagents and materials for achieving selectivity and sensitivity. Paper provides a common platform for bringing these components together and serves as a low-cost medium for prototyping new point-of-care assays. [ABSTRACT FROM AUTHOR]

Modern manufacturing systems are often installed with sensor networks which generate high-dimensional data at high velocity. These data streams offer valuable information about the industrial system's real-time performance. If a shift occurs in the manufacturing process, fault diagnosis based on the data streams becomes a fundamental task as it identifies the affected data streams and provides insights into the root cause. Existing fault diagnostic methods either ignore the correlation between different streams or fail to determine the shift directions. In this paper, we propose a directional fault classification procedure that incorporates the between-stream correlations. We suggest a three-state hidden Markov model that captures the correlation structure and enables inference about the shift direction. We show that our procedure is optimal in the sense that it minimizes the expected number of false discoveries while controlling the proportion of missed signals at a desired level. We also propose a deconvolution-expectation-maximization (DEM) algorithm for estimating the model parameters and establish the asymptotic optimality for the data-driven version of our procedure. Numerical comparisons with an existing approach and an application to a semiconductor production study show that the proposed procedure works well in practice. [ABSTRACT FROM AUTHOR]

Introduction: Globally, both communicable and non-communicable diseases pose a serious threat to populations in developed as well as developing countries. Access to reliable diagnostic testing along with qualified health practitioners is severely limited in low resource and very remote areas and following natural catastrophes. Areas covered: This paper provides an overview of the challenges involved and suggests strategies to address them. The emergence of more robust, user-friendly, cost-effective and ‘sample-to-result’ point-of-care (POC) tools, along with the proliferation of mobile technologies, may provide a practical approach in addressing some of the challenges. Expert commentary: The successful implementation of POC testing requires the availability of versatile diagnostic technologies, improved platforms and back-up infrastructure, successful leveraging of human resources through training and, finally, engagement/coordination of associated stakeholders, including public health agencies, diagnostics companies, healthcare practitioners and local rural authorities. [ABSTRACT FROM PUBLISHER]

Introduction: Sensorineural hearing impairment (SNHI), a common childhood disorder with heterogeneous genetic causes, can lead to delayed language development and psychosocial problems. Next-generation sequencing (NGS) offers high-throughput screening and high-sensitivity detection of genetic etiologies of SNHI, enabling clinicians to make informed medical decisions, provide tailored treatments, and improve prognostic outcomes. Areas covered: This review covers the diverse etiologies of HHI and the utility of different NGS modalities (targeted sequencing and whole exome/genome sequencing), and includes HHI-related studies on newborn screening, genetic counseling, prognostic prediction, and personalized treatment. Challenges such as the trade-off between cost and diagnostic yield, detection of structural variants, and exploration of the non-coding genome are also highlighted. Expert opinion: In the current landscape of NGS-based diagnostics for HHI, there are both challenges (e.g. detection of structural variants and non-coding genome variants) and opportunities (e.g. the emergence of medical artificial intelligence tools). The authors advocate the use of technological advances such as long-read sequencing for structural variant detection, multi-omics analysis for non-coding variant exploration, and medical artificial intelligence for pathogenicity assessment and outcome prediction. By integrating these innovations into clinical practice, precision medicine in the diagnosis and management of HHI can be further improved. [ABSTRACT FROM AUTHOR]

Generally, the primary structures of buildings perform well throughout their lifetime. However, there is still considerable expenditure on both building maintenance and the consequential damage caused by failures associated with building envelopes. This paper presents the main causal factors of building envelope defects and the forensic process used to investigate these defects. It then explores a number of case studies where forensic investigation, along with an in-depth understanding of the building envelope, its materials and the interaction of the building envelope with the supporting structure, was key in determining the cause of the underlying defects. [ABSTRACT FROM AUTHOR]

Introduction:Polymerase chain reaction (PCR) has emerged as a promising technology for the rapid and reliable detection and identification of medical mycoses. Recent technological advancements – including microarray, multiplex PCR with magnetic resonance, and beacon probes – have mitigated the technical difficulties of performing nucleic amplification in fungi, thereby improving the sensitivity and specificity of PCR-based assays. In this paper, we examine current applications of PCR in the diagnosis of human fungal infections and look ahead to emerging techniques that may play a larger role in molecular diagnostics in the future. Areas covered:This review includes a brief overview of the advantages and disadvantages of PCR using various clinical specimens, manual versus automated DNA extraction procedures, panfungal versus specific targets, and spectrum of pathogens detected. This is followed by a brief synopsis of species-specific PCR approaches and a more in-depth look at the obstacles to widespread implementation. Expert commentary:The review concludes with a short perspective for the next five years, including the hurdles to standardization and validation, as well as the role of PCR coupled with electrospray-ionization mass spectrometry (PCR/ESI-MS) or nuclear magnetic resonance for the diagnosis of medical mycoses. [ABSTRACT FROM PUBLISHER]

The striking prevalence of HIV, TB and malaria, as well as outbreaks of emerging infectious diseases, such as influenza A (H7N9), Ebola and MERS, poses great challenges for patient care in resource-limited settings (RLS). However, advanced diagnostic technologies cannot be implemented in RLS largely due to economic constraints. Simple and inexpensive point-of-care (POC) diagnostics, which rely less on environmental context and operator training, have thus been extensively studied to achieve early diagnosis and treatment monitoring in non-laboratory settings. Despite great input from material science, biomedical engineering and nanotechnology for developing POC diagnostics, significant technical challenges are yet to be overcome. Summarized here are the technical challenges associated with POC diagnostics from a RLS perspective and the latest advances in addressing these challenges are reviewed. [ABSTRACT FROM PUBLISHER]

In recent years, exciting developments in disease modifying treatments for Alzheimer's disease (AD) have made accurate and timely diagnosis of this disease a priority. Blood biomarkers (BBMs) for amyloid pathology using improved immunoassay and mass spectrometry techniques have been an area of intense research for the last 10 years and are coming to the fore, as a real prospect to be used in the clinical diagnostics of the disease. The following review will update and discuss blood biomarkers that will be most useful in diagnosing AD and the context necessary for their implementation. It is clear we now have BBMs, and technology to measure them, that are capable of detecting amyloid pathology in AD. The challenge is to validate them across platforms and populations to incorporate them into clinical practice. It is important that implementation comes with education, we need to give clinicians the tools for appropriate use and interpretation. It is feasible that BBMs will be used to screen populations, initially for clinical trial entry but also therapeutic intervention in the foreseeable future. We now need to focus BBM research on other pathologies to ensure we accelerate the development of therapeutics for all neurodegenerative diseases [ABSTRACT FROM AUTHOR]

Copyright of Automatika: Journal for Control, Measurement, Electronics, Computing & Communications is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present editorial introduces selected research for a special issue covering the 15th Annual Meeting of the European Society for Traumatic Stress Studies (ESTSS) 2017, 'Child Maltreatment across the Lifespan'. Unfortunately, childhood maltreatment is highly prevalent around the world. Exposure to child maltreatment is associated with a considerable risk of developing a wide range of psychopathologies. Thus, preventing child maltreatment and offering early treatment to victims is an important and promising area in reducing the risk of psychopathology. The 10 articles included in the special issue focus on different important areas related to the topic of child maltreatment. These include a biological and systemic understanding of maltreatment, a globalization perspective, and contributions on diagnosis and treatment, with implications for clinical practice. Furthermore, the special issue includes an update on ICD-11 and implications associated with the implementation of ICD-11. Future research recommendations are provided to underline the enduring need to promote and undertake research into all aspects of child maltreatment. [ABSTRACT FROM AUTHOR]

As data acquisition and processing technologies continue to advance rapidly, new challenges emerge for statistical process monitoring. One such challenge, especially in the era of big data analytics, is monitoring multivariate processes involving a mixture of continuous, categorical, and discrete quality variables. The existing multivariate control charts focus mostly on monitoring correlated variables of the same type. We propose a new Phase II control chart that is based on a modified Holm's step-down multiple testing procedure (Holm 1979) which achieves two important goals at the same time: (1) it simultaneously monitors correlated variables of different types, while keeping the probability of false alarm under desirable level, and (2) when the process is determined to be out of control, it further provides, without any additional efforts, diagnostics to pinpoint which parameters are out of control. The proposed chart is shown to outperform the existing charts particularly in its ability to provide more accurate diagnostics. [ABSTRACT FROM AUTHOR]

Decades of ongoing research has established that oral microbial communities play a role in oral diseases such as periodontitis and caries. Yet the detection of oral bacteria and the profiling of oral polymicrobial communities currently rely on methods that are costly, slow, and technically complex, such as qPCR or next-generation sequencing. For the widescale screening of oral microorganisms suitable for point-of-care settings, there exists the need for a low-cost, rapid detection technique. Here, we tailored the novel CRISPR-Cas-based assay SHERLOCK for the species-specific detection of oral bacteria. We developed a computational pipeline capable of generating constructs suitable for SHERLOCK and experimentally validated the detection of seven oral bacteria. We achieved detection within the single-molecule range that remained specific in the presence of off-target DNA found within saliva. Further, we adapted the assay for detecting target sequences directly from unprocessed saliva samples. The results of our detection, when tested on 30 healthy human saliva samples, fully aligned with 16S rRNA sequencing. Looking forward, this method of detecting oral bacteria is highly scalable and can be easily optimized for implementation at point-of-care settings. [ABSTRACT FROM AUTHOR]

Profiling of circulating cell-free DNA (cfDNA) by tissue-specific base modifications, such as 5-methylcytosines (5mC), may enable the monitoring of ongoing pathophysiological processes. Nanopore sequencing allows genome-wide 5mC detection in cfDNA without bisulphite conversion. The aims of this study were: i) to find differentially methylated regions (DMRs) of cfDNA associated with obesity in Göttingen minipigs using Nanopore sequencing, ii) to validate a subset of the DMRs using methylation-specific PCR (MSP-PCR), and iii) to compare the cfDNA DMRs with those from whole blood genomic DNA (gDNA). Serum cfDNA and gDNA were obtained from 10 lean and 7 obese Göttingen Minipigs both with experimentally induced myocardial infarction and sequenced using Oxford Nanopore MinION. A total of 1,236 cfDNA DMRs (FDR<0.01) were associated with obesity. In silico analysis showed enrichment of the adipocytokine signalling, glucagon signalling, and cellular glucose homoeostasis pathways. A strong cfDNA DMR was discovered in PPARGC1B, a gene linked to obesity and type 2 diabetes. The DMR was validated using MSP-PCR and correlated significantly with body weight (P < 0.05). No DMRs intersected between cfDNA and gDNA, suggesting that cfDNA originates from body-wide shedding of DNA. In conclusion, nanopore sequencing detected differential methylation in minute quantities (0.1-1 ng/µl) of cfDNA. Future work should focus on translation into human and comparing 5mC from somatic tissues to pinpoint the exact location of pathology. KEY POLICY HIGHLIGHTS Oxford nanopore sequencing can reveal changes in methylation patterns associated with obesity in minute quantities of cell-free DNA from serum. Bisulphite conversion and methylation-specific PCR can be used to validate differentially methylated regions in cell-free DNA. A differentially methylated region in an intronic region of the PPARGC1B gene was found associated with obesity. Differentially methylated regions in cell-free DNA could be useful as early risk markers of certain diseases and pathologies. [ABSTRACT FROM AUTHOR]

Copyright of Automatika: Journal for Control, Measurement, Electronics, Computing & Communications is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The high-dimensionality and volume of large-scale streaming data has inhibited significant research progress in developing an integrated monitoring and diagnostics (M&D) approach. Such data streams are becoming common in various applications including manufacturing, healthcare, and web mining. In this article, we propose an integrated M&D approach for large-scale streaming data. Using principal component analysis (PCA), we first develop a new monitoring method that adaptively chooses principal components that are most likely to be affected by the process change. Furthermore, we propose a novel diagnostic approach, seamlessly integrated with the proposed monitoring method to enable a streamlined SPC. This diagnostics approach draws inspiration from compressed sensing and uses adaptive lasso for identifying the sparse sources of the process change. We theoretically motivate our method and evaluate our integrated M&D method through simulations and case studies. [ABSTRACT FROM AUTHOR]

Lassa fever (LF) is a deadly viral hemorrhagic disease that is endemic to West Africa. The causative agent of LF is Lassa virus (LASV), which causes approximately 300,000 infections and 5,000 deaths annually. There are currently no approved therapeutics or FDA-approved vaccines against LASV. The high genetic variability between LASV strains and immune evasion mediated by the virus complicate the development of effective therapeutics and vaccines. Here, we aim to provide a comprehensive review of the basic biology of LASV and its mechanisms of disease pathogenesis and virulence in various animal models, as well as an update on prospective vaccines, therapeutics, and diagnostics for LF. Until effective vaccines and/or therapeutics are available for use to prevent or treat LF, a better level of understanding of the basic biology of LASV, its natural genetic variations and immune evasion mechanisms as potential pathogenicity factors, and of the rodent reservoir-vector populations and their geographical distributions, is necessary for the development of accurate diagnostics and effective therapeutics and vaccines against this deadly human viral pathogen. [ABSTRACT FROM AUTHOR]

An influential observation is any point that has a huge effect on the coefficients of a regression line fitting the data. The presence of such observations in the data set reduces the sensitivity and validity of the statistical analysis. In the literature there are many methods used for identifying influential observations. However, many of those methods are highly influenced by masking and swamping effects and require distributional assumptions. Especially in the presence of influential subsets most of these methods are insufficient to detect these observations. This study aims to develop a new diagnostic tool for identifying influential observations using the meta-heuristic binary particle swarm optimization algorithm. This proposed approach does not require any distributional assumptions and also not affected by masking and swamping effects as the known methods. The performance of the proposed method is analyzed via simulations and real data set applications. [ABSTRACT FROM AUTHOR]

Metabolomics is rapidly evolving omics technology in personalized medicine, it offers a new avenue for identification of multiple novel metabolic mediators of impaired glucose tolerance and dysglycemia. Liquid chromatography–mass spectrometry, gas chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy are most commonly used analytical methods in the field of metabolomics. Recent evidences showed that metabolomic profiles are link to the incidence of diabetes. In this review, an overview of metabolomics studies in diabetes revealed several diabetes-associated metabolites including 1,5-anhydroglycitol, branch chain amino acids, glucose, α-hydroxybutyric acid, 3-hydroundecanoyl-carnitine and phosphatidylcholine that could be potential biomarkers associated with diabetes. These identified metabolites can be used to develop personalized prognostics and diagnostic, and help in diabetes management. [ABSTRACT FROM AUTHOR]

Rapid and accurate diagnostic approaches are essential for impeding the spread of infectious diseases. This review aims to summarize current progress of clustered regularly interspaced short palindromic repeats (CRISPR)‐associated (Cas) systems in the applications for diagnostics of infectious diseases including the ongoing COVID-19 epidemic. In this review, we discuss class 2 CRISPR-Cas biosensing systems-based diagnostics in various emerging and reemerging infectious diseases, CRISPR-Cas systems have created a new era for early diagnostics of infectious diseases, especially with the discovery of the collateral cleavage activity of Cas12 and Cas13. We mainly focus on different CRISPR-Cas effectors for the detection of pathogenic microorganisms as well as provide a detailed explanation of the pros and cons of CRISPR-Cas biosensing systems. In addition, we also introduce future research perspectives. However, further improvement of newly discovered systems and engineering existing ones should be developed to increase the specificity, sensitivity or stability of the diagnostic tools. It may be a long journey to finish the clinical transition from research use. CRISPR-Cas approaches will emerge as more promising and robust tools for infectious disease diagnosis in the future. [ABSTRACT FROM AUTHOR]

Introduction: Molecular technology has played an important role in arboviruses diagnostics. PCR-based methods stand out in terms of sensitivity, specificity, cost, robustness, and accessibility, and especially the isothermal amplification (IA) method is ideal for field-adaptable diagnostics in resource-limited settings (RLS). Areas covered: In this review, we provide an overview of the various molecular methods for West Nile, Zika, Dengue and Chikungunya. We summarize literature works reporting the assessment and use of in house and commercial assays. We describe limitations and challenges in the usage of methods and opportunities for novel approaches such as NNext-GenerationSequencing (NGS). Expert opinion: The rapidity and accuracy of differential diagnosis is essential for a successful clinical management, particularly in co-circulation area of arboviruses. Several commercial diagnostic molecular assays are available, but many are not affordable by RLS and not usable as Point-of-care/Point-of-need (POC/PON) such as RReal-TimeRT-PCR, Array-based methods and NGS. In contrast, the IA-based system fits better for POC/PON but it is still not ideal for the multiplexing detection system. Improvement in the characterization and validation of current molecular assays is needed to optimize their translation to the point of care. [ABSTRACT FROM AUTHOR]

Background: Rapid Lateral Flow Test (LFT) has been broadly utilized in detection or diagnosis of numerous disease-related antigens and antibodies. It is the most popular format of point-of-care test (POCT) and quickest and easiest way to detect a targeted molecule. In the combat against COVID-19 pandemic, hundreds of POCTs have been developed and are commercially available now. They are designed to detect either a SARS-CoV-2 viral antigen or IgG and IgM antibodies binding to it. Among the binding antibodies, a special type of functional antibodies that block the interaction between SARS-CoV-2 virus and its human receptor, neutralizing antibodies (NAbs), are of particular interest to public as well as in vaccination management. However as of today, POCTs for the detection of SARS-CoV-2 NAbs remain under late stage of development. Scope and method:In this review, we first summarize the importance of awareness and monitoring of SARS-CoV-2 NAbs in the combat against COVID-19 pandemic. Secondly, we compare the available methods for the detection of SARS-CoV-2 NAbs. Next, we describe challenges in the development of a rapid lateral flow test for the detection of SARS-CoV-2 NAbs. Finally, we outline its product formats and applications in research and in disease management. Conclusion:Vaccine effectiveness is unknown for an individual unless measured. NAb level is the most viable measurement for vaccine effectiveness or immunity. A broadly accessible NAb POCT is urgently needed. [ABSTRACT FROM AUTHOR]

Introduction: SARS-CoV-2, the new coronavirus that originated in 2019, continues to impact every aspect of society in a profound manner. Testing will remain an important tool to mitigate the effects of this pandemic as early and accurate diagnosis can lead to appropriate countermeasures to reduce mortality and morbidity. However, testing isn't a simple yes/no answer as the target and host are complex, the virus is a moving target, there is a plethora of tests that identify different parts of the virus and have their own limits and range of detection, and when prevalence is low, false positives and negatives can be very high. Areas covered: This article covers all the major questions related to COVID-19 diagnostics, the why, when, where, who, what and how of testing, the different types of tests, interpretation of results and the ideal ASSURED-SQVM diagnostic. A comprehensive literature review using all the publicly available databases and government websites and reports was performed. Expert opinion: Diagnostics that meet the 'ASSURED-SQVM' (Affordable, Selective and Sensitive, User-friendly, Rapid and Robust, Equipment-free, Deliverable to end-users and additionally, allows for Self-testing, Quantifiable, detects if pathogens are Viable and can detect Multiple pathogens) would make a major impact in our fight against the current pandemic. While a significant majority of researchers focus on developing novel diagnostics that are highly selective and sensitive, it is the opinion of these authors that other aspects of the ASSURED-SQVM principles also be considered early in the development process for widespread use. [ABSTRACT FROM AUTHOR]

Global health security is constantly under threat from infectious diseases. Despite advances in biotechnology that have improved diagnosis and treatment of such diseases, delays in detecting outbreaks and the lack of countermeasures for some biological agents continue to pose severe challenges to global health security. In this review, we describe some of the challenges facing global health security and how genome editing technologies can help overcome them. We provide specific examples of how the genome-editing tool CRISPR is being used to develop new tools to characterize pathogenic agents, diagnose infectious disease, and develop vaccines and therapeutics to mitigate the effects of an outbreak. The article also discusses some of the challenges associated with genome-editing technologies and the efforts that scientists are undertaking to mitigate them. Overall, CRISPR and genome-editing technologies are poised to have a significant positive influence on global health security over the years to come. [ABSTRACT FROM AUTHOR]

Important information about medical laboratory providers is not readily available to all patients, clinicians nor regulators in Kenya. This study was conducted as part of a wider project aiming to improve access to high quality diagnostics by addressing information asymmetries in the Kenyan market for laboratory services. The purpose of this study was to: 1) Gather pricing information for 49 common laboratory tests from medical laboratories in Nairobi, Kenya, noting where these prices were publicly available or withheld. 2) Assess patients' knowledge of testing information including: turnaround time, price, and test availability. This was a cross-sectional study where a mystery caller approach was used to survey 49 tests for turnaround time, price, and availability across 13 laboratories selected purposively. The mystery shopper survey was complemented by 251 patient exit interviews at two Kenyan hospitals to understand whether patients seeking laboratory tests in Nairobi had access to such information. All 251 patients were selected by convenience sampling. We noted that 85% of the private laboratories did not disclose test prices and turnaround times to their patients. There was a wide range of prices on several key tests, with private in-facility laboratories charging an average test price of 468% of the average test price in public laboratories across all the 49 tests. We also found that many patients lacked key information regarding the tests they needed: 65% did not know the purpose of the test while 41% did not know the test price at all. Under the current system, patients have limited access to information regarding the key criteria required to make a rational decision. This has a significant impact on the quality, price, and turnaround time (TAT) offered by the medical laboratories that operate in this dysfunctional market. [ABSTRACT FROM AUTHOR]

Introduction: Over the past decade, loop-mediated isothermal amplification (LAMP) technology has played an important role in molecular diagnostics. Amongst numerous nucleic acid amplification assays, LAMP stands out in terms of sample-to-answer time, sensitivity, specificity, cost, robustness, and accessibility, making it ideal for field-deployable diagnostics in resource-limited regions. Areas covered: In this review, we outline the front-end LAMP design practices for point-of-care (POC) applications, including sample handling and various signal readout methodologies. Next, we explore existing LAMP technologies that have been validated with clinical samples in the field. We summarize recent work that utilizes reverse transcription (RT) LAMP to rapidly detect SARS-CoV-2 as an alternative to standard PCR protocols. Finally, we describe challenges in translating LAMP from the benchtop to the field and opportunities for future LAMP assay development and performance reporting. Expert opinion: Despite the popularity of LAMP in the academic research community and a recent surge in interest in LAMP due to the COVID-19 pandemic, there are numerous areas for improvement in the fundamental understanding of LAMP, which are needed to elevate the field of LAMP assay development and characterization. [ABSTRACT FROM AUTHOR]

Objectives: A growing number of studies demonstrate that long noncoding RNAs (lncRNAs) could act as biomarkers to determine the prognosis of acute myeloid leukemia (AML) patients. Nonetheless, the significance of lncRNAs in AML prognosis remains unclear. We conducted a meta-analysis to assess the prognostic indicators of abnormally expressed lncRNAs in AML. Methods: Literature was searched using PubMed, EMBASE, and Web of Science databases up to November 10, 2018. Results: Thirteen studies with 2755 individuals were included. The abnormal expression of lncRNAs was associated with worse overall survival (OS) in AML patients, especially in cytogenetically normal AML (CN-AML), and was associated with shorter disease-free survival and event-free survival. Subgroup analysis showed that high levels of HOTAIR and TUG1 were associated with poor OS. Discussion: Overexpression of lncRNA HOTAIR and TUG1 were reported in two separate studies, and correlated with worse AML prognoses. Conclusion: Abnormally expressed lncRNAs are significantly related to worse prognoses of AML patients and might serve as potential prognostic markers to predict the prognosis of AML patients. [ABSTRACT FROM AUTHOR]

A pandemic is the worst-case scenario in the field of infectious diseases. Innovative technologies have the potential to address the challenges associated with the manufacture of personalized drug delivery systems, biosensors, and medical devices during a pandemic. 3D-Printing, microfluidics, and Microelectromechanical systems (MEMS) can provide an important part on this fight, as are cheap, easy to be operated, capable to provide rapid detection and monitoring of a disease, and deliver medicines. This manuscript answers the question of how these emerging technologies can save lives during a pandemic by avoiding supply chain delays and also by providing rapid diagnostics, disease monitoring, or by offering personalized treatments. The manuscript covers recent approaches in the topic with a focus in manuscripts published in the last year and by emphasising recent regulatory considerations by regulatory agencies in the manufacturing of 3DP systems or other medical devices during COVID. New manufacturing techniques are emerging with the ability to address the challenges associated with the development of medical devices or diagnostics, during a pandemic. Are many challenges in order to achieve this and especially in short times that are required under a pandemic attack, which will also be covered in this manuscript. [ABSTRACT FROM AUTHOR]

Different upper tail indicators exist to characterize heavy tail phenomena, but no comparative study has been carried out so far. We evaluate the shape parameter (GEV), obesity index, Gini index and upper tail ratio (UTR) against a novel benchmark of tail heaviness – the surprise factor. Sensitivity analyses to sample size and changes in scale-to-location ratio are carried out in bootstrap experiments. The UTR replicates the surprise factor best but is most uncertain and only comparable between records of similar length. For samples with symmetric Lorenz curves, shape parameter, obesity and Gini indices provide consistent indications. For asymmetric Lorenz curves, however, the first two tend to overestimate, whereas Gini index tends to underestimate tail heaviness. We suggest the use of a combination of shape parameter, obesity and Gini index to characterize tail heaviness. These indicators should be supported with calculation of the Lorenz asymmetry coefficients and interpreted with caution. [ABSTRACT FROM AUTHOR]

Point-of-care (POC) tests for Neisseria gonorrhoeae (Ng) are urgently needed to control the gonorrhea epidemic, so patients can receive immediate diagnoses and treatment. While the advent of nucleic acid amplification tests (NAATs) has improved the accuracy of Ng identification, very few POC assays are able to provide results of such tests at the clinical visit. Additionally, antimicrobial resistance (AMR) presents a unique treatment challenge for Ng. This review notes that older POC tests have lower sensitivity for Ng, compared to the currently-available NAATs, and are not adequate for the current demand for high sensitivity. Promising newer assays, which can be used at the POC are covered. This review also includes data about clinicians' and patients' acceptability and expectations of POC tests for Ng, testing of extragenital specimens, pooling studies, as well as their impact clinically, and use in low-resource settings. The ability to use POC tests to identify and immediately treat Ng infections at the patient encounter offers many benefits and opportunities. POC tests for Ng are currently available, but not widely used especially in low-resource settings. Further development of POC tests with AMR testing capacity is needed to help guide antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Epilepsy is a disease group that encompasses numerous brain pathologies, all leading to spontaneous seizures. Several diagnostic needs in the area of epilepsy diagnostics remain unmet. MicroRNAs (miRNAs) have emerged as potential biomarkers of disease. We review clinical trials in epilepsy patients that investigated circulating miRNAs (CmiRNAs) as diagnostic biomarkers. The surveyed trial results are highly discordant and do not confidently support the identification of definite diagnostic biomarkers yet. Important progress comes from studies that identified measures to increase the discriminatory power of CmiRNAs, such as an investigation of specific miRNA compartments (e.g. exosomal vs. Argonaute-bound) or a study that developed point-of-care detection devices for CmiRNAs. No sufficient data elucidating the validity of CmiRNAs as biomarkers for monitoring disease status, the responses to treatment, the likelihood of treatment effects, prognosis, or safety or susceptibility are available. Further studies should adopt standardized designs and in-depth phenotyping to improve their validity. One of the most important and promising future research topics will be the identification of biomarkers for epileptogenesis in humans. [ABSTRACT FROM AUTHOR]

Companion diagnostics (CDx) are important in oncology therapeutic decision-making, but specific regulatory-approved CDx for infectious disease treatment are officially lacking. While not approved as CDx, several ID diagnostics are used as CDx. The diagnostics community, manufacturers, and regulatory agencies have made major efforts to ensure that diagnostics for new antimicrobials are available at or near release of new agents. This review highlights the status of Complementary and companion diagnostic (c/CDx) in the infectious disease literature, with a focus on genotypic antimicrobial resistance testing against pathogens as a class of diagnostic tests. CRISPR, sepsis markers, and narrow spectrum antimicrobials, in addition to current and emerging technologies, present opportunities for infectious disease c/CDx. Challenges include slow guideline revision, high costs for regulatory approval, lengthy buy in by agencies, discordant pharmaceutical/diagnostic partnerships, and higher treatment costs. The number of patients and available medications used to treat different infectious diseases is well suited to support competing diagnostic tests. However, newer approaches to treatment (for example, narrow spectrum antibiotics), may be well suited for a small number of patients, i.e. a niche market in support of a CDx. The current emphasis is rapid and point-of-care (POC) diagnostic platforms as well as changes in treatment. [ABSTRACT FROM AUTHOR]

Introduction: The use of Virtual Reality (VR) in neurology mainly concerns motor solutions. Such an approach is cost-effective and resource-effective. The aim of this work is to review and assess the effectiveness of proposed VR systems in order to diagnose and rehabilitate neurological patients with cognitive disorders. Areas covered: The existing analog neuropsychological tests lack ecological validity. The literature review revealed that VR solutions' biggest advantage is the possibility of assessing patients in everyday situations. Specific tasks (e.g. spatial, verbal, adaptive) could be focused on examining the exact types of memory disabilities in the heterogeneous group of cognitive impairments. There is a visible promise for further development in this area and a good basis for personalized and remote use. While different methodology is set in the analyzed articles the improvement in neurological functions is seen in all of them. Expert opinion: VR is still a relatively new and understudied solution, but there is a visible progress in its research. This trend could lead to more specific and tailored methods for therapy and diagnostics. [ABSTRACT FROM AUTHOR]

Introduction: The 2014-16 outbreak of ebola virus disease (EVD) in West Africa resulted in 11,308 deaths. During the outbreak only 60% of patients were laboratory confirmed and global health authorities have identified the need for accurate and readily deployable molecular diagnostics as an important component of the ideal response to future outbreaks, to quickly identify and isolate patients. Areas covered: Currently PCR-based techniques and rapid diagnostic tests (RDTs) that detect antigens specific to EVD infections dominate the diagnostic landscape, but recent advances in biosensor technologies have led to novel approaches for the development of EVD diagnostics. This review summarises the literature and available performance data of currently available molecular diagnostics for ebolavirus, identifies knowledge gaps and maps out future priorities for research in this field. Expert opinion: While there are now a plethora of diagnostic tests for EVD at various stages of development, there is an acute need for studies to compare their clinical performance, but the sporadic nature of EVD outbreaks makes this extremely challenging, demanding pragmatic new modalities of research funding and ethical/institutional approval, to enable responsive research in outbreak settings. Retrospective head-to-head diagnostic comparisons could also be implemented using biobanked specimens, providing this can be done safely. [ABSTRACT FROM AUTHOR]

The aim of our study was to find the most appropriate way of sample collection from cattle feet as well as to assess simple and effective sample processing, including DNA extraction for reliable diagnosis of bacteria Dichelobacter nodosus and Fusobacterium necrophorum. 11 clinically healthy cows were included in the study, from which swabbing samples (2 types: surface swab and deep swab) were taken. Two isolation methods were used for DNA extraction: 1. freezing and boiling the samples, 2. commercial kit (Roche). PCR analysis of the samples has not shown any variations in the detection ratio of D. nodosus and F. necrophorum at different swabbing methods. The highest sensitivity of the detection of both bacteria was reached with a cultivation of samples in AB with subsequent extraction of DNA with freezing and boiling. The cultivation in anaerobic broth resulted in the detection rate of D. nodosus and F. necrophorum in over 95% and 27%, respectively. To conclude, the simple 'surface' swab is sufficient to detect studied pathogens, the most appropriate method of DNA extraction has proven to be freezing and boiling of the sample. [ABSTRACT FROM AUTHOR]

The European Commission released €130 million over 2014, 2015 and 2017 under the EU Framework Program for Research and Innovation, Horizon 2020, to support innovative small and medium-sized enterprises in the diagnostic area. The call topic focused on ‘Clinical research for the validation of biomarkers and/or diagnostic medical devices’. It attracted 1194 applicants from all over Europe. The quality of the proposals was high and a large proportion of them were eligible for funding. In the majority, proposals were about in vitro diagnostics and tackled both clinical validation of new biomarkers and device optimization. The proposals dealt with various advanced technologies. One third of the proposers gave priority to the new and promising field of personalized medicine. [ABSTRACT FROM AUTHOR]

Introduction: Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome prognosis and possible identification of post-TBI neurodegernative diseases (e.g. chronic traumatic encephalopathy and Alzheimer’s disease), and as theranostic tools in pre-clinical and clinical settings. Expert commentary: A spectrum of biomarkers is now at or near the stage of formal clinical validation of their diagnostic and prognostic utilities in the management of TBI of varied severities including concussions. TBI biomarkers could serve as a theranostic tool in facilitating drug development and treatment monitoring. [ABSTRACT FROM PUBLISHER]

Introduction: Successful treatment outcomes for viral respiratory tract infections presenting from primary health care to quaternary hospitals will only be achieved with rapid, sensitive and specific identification of pathogens to allow effective pathogen-specific antiviral therapy and infection control measures. Areas covered: This review aims to explore the different point-of-care tests currently available to diagnose viral respiratory tract infections, discuss the advantages and limitations of point-of-care testing, and provide insights into the future of point-of-care tests. The following databases were searched: Medline (January 1996 to 30 September 2017) and Embase (1988 to 30 September 2017), using the following keywords: ‘point of care’, ‘respiratory virus’, ‘influenza’, ‘RSV’, ‘diagnostics’, ‘nucleic acid test’ and ‘PCR’. Expert commentary: Viral respiratory tract infections cause significant morbidity and mortality worldwide, and point-of-care tests are facilitating the rapid identification of the pathogen responsible given the similarities in clinical presentation. [ABSTRACT FROM PUBLISHER]

Introduction: The availability of simple, tolerable, therapies for hepatitis C virus (HCV) infection with responses >95% is one of the greatest medical advances in decades, offering an opportunity to reverse the rising burden due to HCV and strive towards HCV elimination. A key challenge moving forward will be to ensure that those who are undiagnosed are made aware of their infection, receive HCV therapy and achieve viral cure. The availability of point-of-care tests for HCV infection has the potential to simplify testing algorithms, increase diagnoses, and facilitate linkage to treatment. Areas covered: This commentary explores why point-of-care tests for HCV are needed, what markers of HCV can be measured, methods for sample collection, where HCV testing can occur, and the remaining challenges for HCV point-of-care testing. Expert commentary: Currently, we have reached an era where there are now several commercial assays to detect HCV RNA (active HCV infection) in 60–90 min, and have reached a single visit HCV diagnosis. In the future, it is hoped that further technological advances will enable access to low-cost, rapid, and accurate assays for HCV RNA detection, improving the number of people diagnosed with HCV infection and contributing to global elimination efforts. [ABSTRACT FROM PUBLISHER]

To develop accurate diagnostic techniques, this study examines the dynamic responses of spur gear transmission system with including frictional effects on a tooth mesh process. An 8-degree-of-freedom model is developed to include the effects of supporting bearings, a driving motor and a loading system. Moreover, it takes into account not only the time-varying stiffness, but also the time-varying forces and moments due to the frictional effect. The latter causes additional vibration responses in the direction of the off-line-of-action (OLOA). To show the quantitative effect of the friction, vibration responses are simulated under different friction coefficients. It shows that an increase in friction coefficient value causes a nearly linear increase in the vibration features of diagnostics. However, features from torsional responses and the principal responses in the line-of-action show less changes in the vibration level, whereas the most significant increasing is in the OLOA direction. Furthermore, the spectral peaks at the rotational and sideband frequencies are influenced significantly by small breakage defects, especially when the friction effect is taken into account. In addition, the second and third harmonics of the mesh frequency are more influenced than the first harmonic component for all motions, which can be effective features for both indicating lubrication deterioration and improving conventional diagnostic features. [ABSTRACT FROM AUTHOR]

The Influenza virus is a leading cause of respiratory disease in the United States each year. While the virus normally causes mild to moderate disease, hospitalization and death can occur in many cases. There are several methodologies that are used for detection; however problems such as decreased sensitivity and high rates of false-negative results may arise. There is a crucial need for an effective sample preparation technology that concentrates viruses at low abundance while excluding resident analytes that may interfere with detection. Nanotrap particles are hydrogel particles that are coupled to chemical dye affinity baits that bind a broad range of proteins and virions. Within minutes (<30 minutes), Nanotrap particles concentrate low abundant proteins and viruses from clinically complex matrices. Nanotrap particles with reactive red baits concentrated numerous respiratory viruses including various strains and subtypes of Influenza virus, Coronavirus, and Respiratory Syncytial Virus from saliva, nasal fluid swab specimens, and nasal aspirates. Detection was enhanced more than 10-foldwhen coupled to plaque assays and qRT-PCR. Importantly, Nanotrap particle can efficiently capture and concentrate multiple viral pathogens during a coinfection scenario. These results collectively demonstrate that Nanotrap particles are an important tool that can easily be integrated into various detectionmethodologies. [ABSTRACT FROM AUTHOR]

Introduction: Nanoparticle-based disease diagnostics harness a range of unique physical and chemical phenomena for the detection of biomarkers at exceedingly low levels. This capability potentially enables the diagnosis of disease earlier in its progression and improves the likelihood of positive treatment outcomes. This review highlights recent work in this area, and then projects the next steps needed to move this emerging capability beyond the research laboratory. Areas covered: This review examines the advantages and limitations of in vitro health care diagnostic tests that utilize nanoparticles (e.g. noble metal, quantum dot, and magnetic). It includes a brief overview of their unique properties, syntheses, and applicable readout strategies. This is followed by a brief synopsis of the obstacles faced when attempting to translate nanoparticle-based diagnostics from the R&D laboratory to the clinic and other arenas (i.e. the difficulties common to in vitro diagnostics), and then by a much more in-depth examination of the need to control and characterize a range of nanoparticle properties (e.g. size, shape, surface composition, and stability) when making this transition. Expert commentary: The review wraps up with a short commentary and perspective for the next five years, focusing on possible guidelines for nanoparticle characterization. [ABSTRACT FROM AUTHOR]

Introduction: Advances in the biology of non-small-cell lung cancer, especially adenocarcinoma, reveal multiple molecular subtypes driving oncogenesis. Accordingly, individualized targeted therapeutics are based on mutational diagnostics. Areas covered: Advances in strategies and techniques for individualized treatment, particularly of adenocarcinoma, are described through literature review. Approved therapies are established for some molecular subsets, with new driver mutations emerging that represent increasing proportions of patients. Actionable mutations aredenovooncogenic drivers or acquired resistance mediators, and mutational profiling is important for directing therapy. Patients should be monitored for emerging actionable resistance mutations. Liquid biopsy and associated multiplex diagnostics will be important means to monitor patients during treatment. Expert commentary: Outcomes with targeted agents may be improved by integrating mutation screens during treatment to optimize subsequent therapy. In order for this to be translated into impactful patient benefit, appropriate platforms and strategies need to be optimized and then implemented universally. [ABSTRACT FROM PUBLISHER]

Pancreatic cancer (Pa) is generally a very aggressive disease, with few effective approaches available for early diagnosis or therapy. These factors, combined with the aggressiveness and chemoresistance of Pa, results in a bleak outcome post-diagnosis. Cancer-related biomarkers have established capabilities for diagnosis, prognosis and screening and can be exploited to aid in earlier less-invasive diagnosis and optimization of targeted therapies. Pa has only one US FDA-approved biomarker, CA19-9, which has significant limitations. Hence, it is vital that novel biomarkers are identified and validated to diagnose, treat, control and monitor Pa. This review focuses on existing and potential Pa-associated markers and discusses how they may be applied in cohort for improved management of Pa. [ABSTRACT FROM PUBLISHER]

The effective management of infectious diseases depends on the early detection of the microbes responsible, since pathogens are most effectively eliminated in the initial stages of infection. Current immunodiagnostic methods lack the sensitivity for earliest possible diagnosis. Nucleic acid-based tests (NATs) are more sensitive, but the detection of microbial DNA does not definitively prove the presence of a viable microorganism capable of causing a given infection. Proximity assays combine the specificity of antibody-based detection of proteins with the sensitivity and dynamic range of NATs, and their use may allow earlier as well as more clinically relevant detection than is possible with current NATs or immunoassays. However, the full potential of proximity assays for pathogen detection remains to be fulfilled, mainly due to the challenges associated with identifying suitable antibodies and antibody combinations, sensitivity issues arising from non-specific interactions of proximity probes and the longer incubation times required to carry out the assays. [ABSTRACT FROM AUTHOR]

Interview with Professor Madhukar Pai, MD, PhD by Claire Raison (Commissioning Editor) Professor Madhukar Pai did his medical training and community medicine residency in Vellore, India. He completed his PhD in epidemiology at the University of California, Berkeley (CA, USA) and a postdoctoral fellowship at the University of California, San Francisco (CA, USA). He is currently an associate professor of epidemiology at McGill University in Montreal (Canada). He serves as the Director of Global Health Programs, and as an Associate Director of the McGill International Tuberculosis Centre. In addition, he serves as a Consultant for the Bill & Melinda Gates Foundation. He also serves on the Scientific Advisory Committee of the Foundation for Innovative New Diagnostics, Geneva, Switzerland. His research is focused on improving the diagnosis and treatment of tuberculosis, especially in high-burden countries such as India and South Africa. His research is supported by grant funding from the Gates Foundation, Grand Challenges Canada and Canadian Institutes of Health Research. He has more than 200 peer-reviewed publications. He is recipient of the Union Scientific Prize, Chanchlani Global Health Research Award and Stars in Global Health award from Grand Challenges Canada, and is a member of the Royal Society of Canada. [ABSTRACT FROM PUBLISHER]

The article provides an overview on the of two trends of biosensor research, the move towards high-density biosensor arrays and the development of multimodal biosensor technologies. Topics including the fabrication of high-density biosensor arrays for multiplexed diagnostics, the multimodal, label-free biosensors, and the enzyme-linked immunosorbent assay are discussed.

Personalized medicine - healthcare based on individual genetic variation - has the potential to transform the way healthcare is delivered to patients. The promise of personalized medicine has been predicated on the predictive and diagnostic power of genomic and proteomic biomarkers. Biomarker screening may help improve health outcomes, for example, by identifying individuals' susceptibility to diseases and predicting how patients will respond to drugs. Microfluidic droplet technology offers an exciting opportunity to revolutionize the accessibility of personalized medicine. A framework for the role of droplet microfluidics in biomarker detection can be based on two main themes. Emulsion-based microdroplet platforms can provide new ways to measure and detect biomolecules. In addition, microdroplet platforms facilitate high-throughput screening of biomarkers. Meanwhile, surface-based droplet platforms provide an opportunity to develop miniaturized diagnostic systems. These platforms may function as portable benchtop environments that dramatically shorten the transition of a benchtop assay into a point-of-care format. [ABSTRACT FROM AUTHOR]