Demystifying a Q-Matrix for Making Diagnostic Inferences about L2 Reading Skills: The Author Responds

ERIC Educational Resources Information Center

Jang, Eunice Eunhee

2010-01-01

This article presents the author's response to the commentary essays by Charles Alderson and Fred Davidson on "Demystifying a Q-matrix for making diagnostic inferences about L2 reading skills" (Jang, 2009). The author stresses that their commentaries provides vital perspectives on the challenges to pushing the boundaries of current testing…

Melioidosis Diagnostic Workshop, 20131

PubMed Central

AuCoin, David; Baccam, Prasith; Baggett, Henry C.; Baird, Rob; Bhengsri, Saithip; Blaney, David D.; Brett, Paul J.; Brooks, Timothy J.G.; Brown, Katherine A.; Chantratita, Narisara; Cheng, Allen C.; Dance, David A.B.; Decuypere, Saskia; Defenbaugh, Dawn; Gee, Jay E.; Houghton, Raymond; Jorakate, Possawat; Lertmemongkolchai, Ganjana; Limmathurotsakul, Direk; Merlin, Toby L.; Mukhopadhyay, Chiranjay; Norton, Robert; Peacock, Sharon J.; Rolim, Dionne B.; Simpson, Andrew J.; Steinmetz, Ivo; Stoddard, Robyn A.; Stokes, Martha M.; Sue, David; Tuanyok, Apichai; Whistler, Toni; Wuthiekanun, Vanaporn; Walke, Henry T.

2015-01-01

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions. PMID:25626057

Challenging clinical presentations of pernicious anemia.

PubMed

Oo, Thein Hlaing; Rojas-Hernandez, Cristhiam Mauricio

2017-09-01

Pernicious anemia (PA) is an autoimmune disease of multifactorial etiologies characterized by autoimmune chronic atrophic gastritis, cobalamin deficiency (CD) due to defective absorption of dietary cobalamin from the terminal ileum, and by the presence of intrinsic factor and parietal cell antibodies. PA is a very common cause of CD-related anemia worldwide. Despite advances in the understanding molecular biology and pathophysiology of PA, the diagnosis of PA remains challenging in many circumstances for many clinicians because of its diverse clinical manifestations and the limitations of currently available diagnostic tools. Diagnostic dilemmas could occur when patients with PA present with spuriously normal or high cobalamin levels, normocytic or microcytic anemia, non-anemic macrocytosis, autoimmune hemolytic anemia, pseudo-thrombotic microangiopathy, hyperhomocysteinemia-associated thromboembolism, pseudoleu-kemia, bone marrow failure, bone marrow ring sideroblasts, and neurologic manifestations without anemia or macrocytosis. Herein, we provide an overview of the challenging clinical presentations of PA, diagnostic approach, and management.

Paper-based sample-to-answer molecular diagnostic platform for point-of-care diagnostics.

PubMed

Choi, Jane Ru; Tang, Ruihua; Wang, ShuQi; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

2015-12-15

Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

Current challenges in diagnostic imaging of venous thromboembolism.

PubMed

Huisman, Menno V; Klok, Frederikus A

2015-01-01

Because the clinical diagnosis of deep-vein thrombosis and pulmonary embolism is nonspecific, integrated diagnostic approaches for patients with suspected venous thromboembolism have been developed over the years, involving both non-invasive bedside tools (clinical decision rules and D-dimer blood tests) for patients with low pretest probability and diagnostic techniques (compression ultrasound for deep-vein thrombosis and computed tomography pulmonary angiography for pulmonary embolism) for those with a high pretest probability. This combination has led to standardized diagnostic algorithms with proven safety for excluding venous thrombotic disease. At the same time, it has become apparent that, as a result of the natural history of venous thrombosis, there are special patient populations in which the current standard diagnostic algorithms are not sufficient. In this review, we present 3 evidence-based patient cases to underline recent developments in the imaging diagnosis of venous thromboembolism. © 2015 by The American Society of Hematology. All rights reserved.

Prostate cancer diagnostics: Clinical challenges and the ongoing need for disruptive and effective diagnostic tools.

PubMed

Sharma, Shikha; Zapatero-Rodríguez, Julia; O'Kennedy, Richard

The increased incidence and the significant health burden associated with carcinoma of the prostate have led to substantial changes in its diagnosis over the past century. Despite technological advancements, the management of prostate cancer has become progressively more complex and controversial for both early and late-stage disease. The limitations and potential harms associated with the use of prostate-specific antigen (PSA) as a diagnostic marker have stimulated significant investigation of numerous novel biomarkers that demonstrate varying capacities to detect prostate cancer and can decrease unnecessary biopsies. However, only a few of these markers have been approved for specific clinical settings while the others have not been adequately validated for use. This review systematically and critically assesses ongoing issues and emerging challenges in the current state of prostate cancer diagnostic tools and the need for disruptive next generation tools based on analysis of combinations of these biomarkers to enhance predictive accuracy which will benefit clinical diagnostics and patient welfare. Copyright © 2016. Published by Elsevier Inc.

A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.

PubMed

Orr, Miranda E; Sullivan, A Campbell; Frost, Bess

2017-07-01

There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predictive and prognostic biomarkers in colorectal cancer: A systematic review of recent advances and challenges.

PubMed

Das, Vishal; Kalita, Jatin; Pal, Mintu

2017-03-01

Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. Since CRC is largely asymptomatic until alarm features develop to advanced stages, the implementation of the screening programme is very much essential to reduce cancer incidence and mortality rates. CRC occurs predominantly from accumulation of genetic and epigenetic changes in colon epithelial cells, which later gets transformed into adenocarcinomas. The current challenges of screening paradigm and diagnostic ranges are from semi-invasive methods like colonoscopy to non-invasive stool-based test, have resulted in over-diagnosis and over-treatment of CRC. Hence, new screening initiatives and deep studies are required for early diagnosis of CRC. In this regard, we not only summarise current predictive and prognostic biomarkers with their potential for diagnostic and therapeutic applications, but also describe current limitations, future perspectives and challenges associated with the progression of CRC. Currently many potential biomarkers have already been successfully translated into clinical practice eg. Fecal haemoglobin, Carcinoembryonic antigen (CEA) and CA19.9, although these are not highly promising diagnostic target for personalized medicine. So there is a critical need for reliable, minimally invasive, highly sensitive and specific genetic markers of an individualised and optimised patient treatment at the earliest disease stage possible. Identification of a new biomarker, or a set of biomarkers to the development of a valid, and clinical sensible assay that can be served as an alternative tool for early diagnosis of CRC and open up promising new targets in therapeutic intervention strategies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

PSMA Theranostics: Current Status and Future Directions

PubMed Central

Afshar-Oromieh, Ali; Jadvar, Hossein; Ahmadzadehfar, Hojjat

2018-01-01

Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT. Challenges and opportunities of PSMA theranostics are discussed. PMID:29873291

Major regulatory changes and the impact on diagnostic imaging in the United States 2005 to 2012∗: ∗effective May 15, 2013.

PubMed

Relyea-Chew, Annemarie

2013-09-01

Federal regulation of diagnostic imaging in the United States has increased dramatically in recent years. The primary statutes aimed at curbing escalating costs and reorienting the national priorities of health care have a direct effect on the specialty of diagnostic imaging. This paper surveys the major regulations and current issues that pose challenges to the practice of diagnostic imaging in the United States, from the Deficit Reduction Act of 2005 through the American Taxpayer Relief Act of 2012. Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.

The Problem of Rarity: Estimation of Prevalence in Rare Disease.

PubMed

Auvin, Stéphane; Irwin, John; Abi-Aad, Paul; Battersby, Alysia

2018-05-01

From a disease's first description to its wider recognition, factors such as changes over time in diagnostic criteria, available therapies, and subsequent mortality rates may influence diagnosed prevalence of rare diseases. To propose a novel methodology for estimating the true prevalence of rare diseases using current incidence adjusted to changing diagnostic practice over time. This article focuses on rare diseases whose diagnosis may have changed over time, and raises the hypothesis that prevalence calculated from current incidence may be higher than diagnosed prevalence, which may lag behind the current disease definition and diagnostic methods. A rare epileptic encephalopathy, Dravet syndrome (DS), is explored as an illustrative example. A targeted literature review was performed for DS to identify all reported incidence, prevalence, and mortality and depict how diagnostic practice has evolved over time. A conceptual model was developed to calculate prevalence derived from current incidence figures alone (incidence-derived prevalence) or incidence adjusted with factors that cause a diagnostic drag (diagnostic awareness-adjusted prevalence). We identified sufficient publications of incidence and prevalence to test the conceptual model. For pediatric patients with DS, diagnosed prevalence in the field (as reported in current literature) matches incidence-derived prevalence, whereas for adult patients, it is overestimated by incidence-derived prevalence, but not by diagnostic awareness-adjusted prevalence. Care should be taken with current incidence-derived prevalence figures to not overstate the prevalence in rare diseases, as methodological challenges in counting small populations, coupled with advances in rare disease discovery, may cause discrepancies. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Challenges in Diagnosing Narcolepsy without Cataplexy: A Consensus Statement

PubMed Central

Baumann, Christian R.; Mignot, Emmanuel; Lammers, Gert Jan; Overeem, Sebastiaan; Arnulf, Isabelle; Rye, David; Dauvilliers, Yves; Honda, Makoto; Owens, Judith A.; Plazzi, Giuseppe; Scammell, Thomas E.

2014-01-01

Background: Diagnosing narcolepsy without cataplexy is often a challenge as the symptoms are nonspecific, current diagnostic tests are limited, and there are no useful biomarkers. In this report, we review the clinical and physiological aspects of narcolepsy without cataplexy, the limitations of available diagnostic procedures, and the differential diagnoses, and we propose an approach for more accurate diagnosis of narcolepsy without cataplexy. Methods: A group of clinician-scientists experienced in narcolepsy reviewed the literature and convened to discuss current diagnostic tools, and to map out directions for research that should lead to a better understanding and more accurate diagnosis of narcolepsy without cataplexy. Recommendations: To aid in the identification of narcolepsy without cataplexy, we review key indicators of narcolepsy and present a diagnostic algorithm. A detailed clinical history is mainly helpful to rule out other possible causes of chronic sleepiness. The multiple sleep latency test remains the most important measure, and prior sleep deprivation, shift work, or circadian disorders should be excluded by actigraphy or sleep logs. A short REM sleep latency (≤ 15 minutes) on polysomnography can aid in the diagnosis of narcolepsy without cataplexy, although sensitivity is low. Finally, measurement of hypocretin levels can helpful, as levels are low to intermediate in 10% to 30% of narcolepsy without cataplexy patients. Citation: Baumann CR, Mignot E, Lammers GJ, Overeem S, Arnulf I, Rye D, Dauvilliers Y, Honda M, Owens JA, Plazzi G, Scammell TE. Challenges in diagnosing narcolepsy without cataplexy: a consensus statement. SLEEP 2014;37(6):1035-1042. PMID:24882898

Upper Extremity Injuries in Tennis Players: Diagnosis, Treatment, and Management

PubMed Central

Chung, Kevin C.; Lark, Meghan E.

2016-01-01

Synopsis Upper extremity tennis injuries are most commonly characterized as overuse injuries to the wrist, elbow and shoulder. The complex anatomy of these structures and their interaction with biomechanical properties of tennis strokes contributes to the diagnostic challenges. A thorough understanding of tennis kinetics, in combination with the current literature surrounding diagnostic and treatment methods, will improve clinical decision-making. PMID:27886833

Diagnosing cystic fibrosis-related diabetes: current methods and challenges.

PubMed

Prentice, Bernadette; Hameed, Shihab; Verge, Charles F; Ooi, Chee Y; Jaffe, Adam; Widger, John

2016-07-01

Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms "Cystic Fibrosis Related Diabetes", "Cystic Fibrosis" AND "glucose", "Cystic Fibrosis" AND "insulin", "Cystic Fibrosis" AND "Diabetes". Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute sampled oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF.

Nanostructured sensors for biomedical applications--a current perspective.

PubMed

Krishnamoorthy, Sivashankar

2015-08-01

Nanostructured sensors have unique capabilities that can be tailored to advantage in advancing the diagnosis, monitoring and cure of several diseases and health conditions. This report aims at providing a current perspective on, (a) the emerging clinical needs that defines the challenges to be addressed by nanostructured sensors, with specific emphasis on early stage diagnosis, drug-diagnostic combinations, and predictive models to design therapy, (b) the emerging industry trends in in vitro diagnostics, mobile health care, high-throughput molecular and cell-based diagnostic platforms, and (c) recent instances of nanostructured biosensors, including promising sensing concepts that can be enhanced using nanostructures that carry high promise towards catering to the emerging clinical needs, as well as the market/industry trends. Copyright © 2014 Elsevier Ltd. All rights reserved.

The challenge of Propionibacterium acnes and revision shoulder arthroplasty: a review of current diagnostic options.

PubMed

Shields, Margaret V; Abdullah, Leath; Namdari, Surena

2016-06-01

Propionibacterium acnes is the most common cause of infection after shoulder arthroplasty. Whereas there are several methods that can aid in the diagnosis of P. acnes infection, there is not a single "gold standard" because of the difficulties inherent in identifying this bacterium. We present an evidence-based discussion of the demographic, clinical, and radiographic predictors of P. acnes infection and review the current options for diagnosis. This review was written after a comprehensive analysis of the current literature related to shoulder periprosthetic joint infection and P. acnes identification. Of the techniques reviewed, α-defensin had the highest sensitivity in detecting P. acnes infection (63%). C-reactive protein level and erythrocyte sedimentation rate were often normal in cases of infection. Whereas P. acnes can be challenging to successfully diagnose, there are several options that are considered preferable because of their higher sensitivities and specificities. The current gold standard is intraoperative culture, but major advances in molecular techniques may provide future improvements in diagnostic accuracy. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Upper Extremity Injuries in Tennis Players: Diagnosis, Treatment, and Management.

PubMed

Chung, Kevin C; Lark, Meghan E

2017-02-01

Upper extremity tennis injuries are most commonly characterized as overuse injuries to the wrist, elbow, and shoulder. The complex anatomy of these structures and their interaction with biomechanical properties of tennis strokes contributes to the diagnostic challenges. A thorough understanding of tennis kinetics, in combination with the current literature surrounding diagnostic and treatment methods, will improve clinical decision-making. Copyright © 2016 Elsevier Inc. All rights reserved.

Challenges in diagnosing narcolepsy without cataplexy: a consensus statement.

PubMed

Baumann, Christian R; Mignot, Emmanuel; Lammers, Gert Jan; Overeem, Sebastiaan; Arnulf, Isabelle; Rye, David; Dauvilliers, Yves; Honda, Makoto; Owens, Judith A; Plazzi, Giuseppe; Scammell, Thomas E

2014-06-01

Diagnosing narcolepsy without cataplexy is often a challenge as the symptoms are nonspecific, current diagnostic tests are limited, and there are no useful biomarkers. In this report, we review the clinical and physiological aspects of narcolepsy without cataplexy, the limitations of available diagnostic procedures, and the differential diagnoses, and we propose an approach for more accurate diagnosis of narcolepsy without cataplexy. A group of clinician-scientists experienced in narcolepsy reviewed the literature and convened to discuss current diagnostic tools, and to map out directions for research that should lead to a better understanding and more accurate diagnosis of narcolepsy without cataplexy. To aid in the identification of narcolepsy without cataplexy, we review key indicators of narcolepsy and present a diagnostic algorithm. A detailed clinical history is mainly helpful to rule out other possible causes of chronic sleepiness. The multiple sleep latency test remains the most important measure, and prior sleep deprivation, shift work, or circadian disorders should be excluded by actigraphy or sleep logs. A short REM sleep latency (≤ 15 minutes) on polysomnography can aid in the diagnosis of narcolepsy without cataplexy, although sensitivity is low. Finally, measurement of hypocretin levels can helpful, as levels are low to intermediate in 10% to 30% of narcolepsy without cataplexy patients.

Schizoaffective disorder--an ongoing challenge for psychiatric nosology.

PubMed

Jäger, M; Haack, S; Becker, T; Frasch, K

2011-04-01

Schizoaffective disorder is a common diagnosis in mental health services. The present article aims to provide an overview of diagnostic reliability, symptomatology, outcome, neurobiology and treatment of schizoaffective disorder. Literature was identified by searches in "Medline" and "Cochrane Library". The diagnosis of schizoaffective disorder has a low reliability. There are marked differences between the current diagnostic systems. With respect to psychopathological symptoms, no clear boundaries were found between schizophrenia, schizoaffective disorder and affective disorders. Common neurobiological factors were found across the traditional diagnostic categories. Schizoaffective disorder according to ICD-10 criteria, but not to DSM-IV criteria, shows a more favorable outcome than schizophrenia. With regard to treatment, only a small and heterogeneous database exists. Due to the low reliability and questionable validity there is a substantial need for revision and unification of the current diagnostic concepts of schizoaffective disorder. If future diagnostic systems return to Kraepelin's dichotomous classification of non-organic psychosis or adopt a dimensional diagnostic approach, schizoaffective disorder will disappear from the psychiatric nomenclature. A nosological model with multiple diagnostic entities, however, would be compatible with retaining the diagnostic category of schizoaffective disorder. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

The Effects of Diagnostic Group and Gender on Challenging Behaviors in Infants and Toddlers with Cerebral Palsy, Down Syndrome or Seizures

ERIC Educational Resources Information Center

Hattier, Megan A.; Matson, Johnny L.; Belva, Brian; Kozlowski, Ali

2012-01-01

Challenging behaviors are frequently studied in individuals with various developmental disabilities, although specific conditions are rarely compared to one another. Such data would be informative to clinicians who assess and develop treatment plans for children with these disabilities. For that reason, the current study's aim was to analyze…

The next organizational challenge: finding and addressing diagnostic error.

PubMed

Graber, Mark L; Trowbridge, Robert; Myers, Jennifer S; Umscheid, Craig A; Strull, William; Kanter, Michael H

2014-03-01

Although health care organizations (HCOs) are intensely focused on improving the safety of health care, efforts to date have almost exclusively targeted treatment-related issues. The literature confirms that the approaches HCOs use to identify adverse medical events are not effective in finding diagnostic errors, so the initial challenge is to identify cases of diagnostic error. WHY HEALTH CARE ORGANIZATIONS NEED TO GET INVOLVED: HCOs are preoccupied with many quality- and safety-related operational and clinical issues, including performance measures. The case for paying attention to diagnostic errors, however, is based on the following four points: (1) diagnostic errors are common and harmful, (2) high-quality health care requires high-quality diagnosis, (3) diagnostic errors are costly, and (4) HCOs are well positioned to lead the way in reducing diagnostic error. FINDING DIAGNOSTIC ERRORS: Current approaches to identifying diagnostic errors, such as occurrence screens, incident reports, autopsy, and peer review, were not designed to detect diagnostic issues (or problems of omission in general) and/or rely on voluntary reporting. The realization that the existing tools are inadequate has spurred efforts to identify novel tools that could be used to discover diagnostic errors or breakdowns in the diagnostic process that are associated with errors. New approaches--Maine Medical Center's case-finding of diagnostic errors by facilitating direct reports from physicians and Kaiser Permanente's electronic health record--based reports that detect process breakdowns in the followup of abnormal findings--are described in case studies. By raising awareness and implementing targeted programs that address diagnostic error, HCOs may begin to play an important role in addressing the problem of diagnostic error.

Current role of multidetector computed tomography in imaging of wrist injuries.

PubMed

Syed, Mohd Arif; Raj, Vimal; Jeyapalan, Kanagaratnam

2013-01-01

Imaging of the wrist is challenging to both radiologists and orthopedic surgeons. This is primarily because of the complex anatomy/functionality of the wrist and also the fact that many frequent injuries are sustained to the hands. On going developments in multidetector computed tomography (MDCT) technology with its "state of the art" postprocessing capabilities have revolutionized this field. Apart from routine imaging of wrist trauma, it is now possible to assess intrinsic ligaments with MDCT arthrography, thereby avoiding invasive diagnostic arthroscopies. Postoperative wrist imaging can be a diagnostic challenge, and MDCT can be helpful in assessment of these cases because volume acquisition and excellent postprocessing abilities help to evaluate these wrists in any desired plane and thinner slices. This article pictorially reviews the current clinical role of MDCT imaging of wrist in our practice. It also describes arthrography technique and scanning parameters used at our center. Copyright © 2013 Mosby, Inc. All rights reserved.

Pink-pigmented non-fermentative gram-negative rods associated with human infections: a clinical and diagnostic challenge.

PubMed

Hogue, R; Graves, M; Moler, S; Janda, J M

2007-06-01

Over the past several decades, the appearance of pink-pigmented bacteria in clinical specimens has gone from being a microbiologic curiosity in the clinical laboratory to the recognition of these aerobic microorganisms as etiologic agents of human disease, most notably bloodstream infections. Advances in the fields of molecular taxonomy and phylogenetics indicate that at least four distinct genera and eight different species are associated with clinical infections in susceptible patient populations. However, these bacteria are slow growing and present multiple diagnostic challenges to the microbiology laboratory including culture, isolation, and identification to species rank. This article provides a current review of these unusual non-fermentative chromogenic bacteria including their disease spectrum, taxonomy, and laboratory identification. The review also highlights the pitfalls or shortcomings we currently have in our knowledge of these microbes and their disease-producing capabilities.

Sesame allergy: current perspectives.

PubMed

Adatia, Adil; Clarke, Ann Elaine; Yanishevsky, Yarden; Ben-Shoshan, Moshe

2017-01-01

Sesame is an important global allergen affecting ~0.1% of the North American population. It is a major cause of anaphylaxis in the Middle East and is the third most common food allergen in Israel. We conducted a systematic review of original articles published in the last 10 years regarding the diagnosis and management of sesame allergy. Skin prick testing appears to be a useful predictor of sesame allergy in infants, although data are less consistent in older children and adults. The diagnostic capacity of serum-specific immunoglobulin E is poor, especially in studies that used oral food challenges to confirm the diagnosis. Double-blind, placebo-controlled food challenge thus remains the diagnostic gold standard for sesame allergy. The cornerstone of sesame allergy management is allergen avoidance, though accidental exposures are common and patients must be prepared to treat the consequent reactions with epinephrine. Novel diagnostic and treatment options such as component-resolved diagnostics, basophil activation testing, and oral immunotherapy are under development but are not ready for mainstream clinical application.

Next-Generation Climate Modeling Science Challenges for Simulation, Workflow and Analysis Systems

NASA Astrophysics Data System (ADS)

Koch, D. M.; Anantharaj, V. G.; Bader, D. C.; Krishnan, H.; Leung, L. R.; Ringler, T.; Taylor, M.; Wehner, M. F.; Williams, D. N.

2016-12-01

We will present two examples of current and future high-resolution climate-modeling research that are challenging existing simulation run-time I/O, model-data movement, storage and publishing, and analysis. In each case, we will consider lessons learned as current workflow systems are broken by these large-data science challenges, as well as strategies to repair or rebuild the systems. First we consider the science and workflow challenges to be posed by the CMIP6 multi-model HighResMIP, involving around a dozen modeling groups performing quarter-degree simulations, in 3-member ensembles for 100 years, with high-frequency (1-6 hourly) diagnostics, which is expected to generate over 4PB of data. An example of science derived from these experiments will be to study how resolution affects the ability of models to capture extreme-events such as hurricanes or atmospheric rivers. Expected methods to transfer (using parallel Globus) and analyze (using parallel "TECA" software tools) HighResMIP data for such feature-tracking by the DOE CASCADE project will be presented. A second example will be from the Accelerated Climate Modeling for Energy (ACME) project, which is currently addressing challenges involving multiple century-scale coupled high resolution (quarter-degree) climate simulations on DOE Leadership Class computers. ACME is anticipating production of over 5PB of data during the next 2 years of simulations, in order to investigate the drivers of water cycle changes, sea-level-rise, and carbon cycle evolution. The ACME workflow, from simulation to data transfer, storage, analysis and publication will be presented. Current and planned methods to accelerate the workflow, including implementing run-time diagnostics, and implementing server-side analysis to avoid moving large datasets will be presented.

Warfighter Neuroendocrinology: Modeling Stress Response, PTSD, and TBI

DTIC Science & Technology

studies are challenged by incongruent diagnostic criteria and confounding treatment protocols. Understanding PTSD is not a simple task as there is no...reliable biological predictor or marker for PTSD and diagnoses are heavily reliant on self-reporting. Current treatments include psychotherapy and...pharmacotherapy: it is not very clear how the two intervention methods inform each other and they are not always very successful. In part, these challenges

Pancreatic cystic neoplasms: Review of current knowledge, diagnostic challenges, and management options

PubMed Central

Jana, Tanima; Shroff, Jennifer; Bhutani, Manoop S.

2015-01-01

Pancreatic cystic lesions are being detected with increasing frequency, largely due to advances in cross-sectional imaging. The most common neoplasms include serous cystadenomas, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms, and cystic pancreatic endocrine neoplasms. Computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) are currently used as imaging modalities. EUS-guided fine needle aspiration has proved to be a useful diagnostic tool, and enables an assessment of tumor markers, cytology, chemistries, and DNA analysis. Here, we review the current literature on pancreatic cystic neoplasms, including classification, diagnosis, treatment, and recommendations for surveillance. Data for this manuscript was acquired via searching the literature from inception to December 2014 on PubMed and Ovid MEDLINE. PMID:25821410

Ankle ligament injuries.

PubMed

Abbassian, Ali; Thomas, Rhidian

2008-06-01

Ankle ligament injuries in the presence or in the absence of fractures are common. They often present a diagnostic challenge, and their management is poorly understood and subject to debate. This article reviews and discusses the current literature on the management and diagnosis of these injuries.

Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier?

PubMed Central

2012-01-01

Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection. PMID:22647543

Challenges to Global Implementation of Infrared Thermography Technology: Current Perspective

PubMed Central

Shterenshis, Michael

2017-01-01

Medical infrared thermography (IT) produces an image of the infrared waves emitted by the human body as part of the thermoregulation process that can vary in intensity based on the health of the person. This review analyzes recent developments in the use of infrared thermography as a screening and diagnostic tool in clinical and nonclinical settings, and identifies possible future routes for improvement of the method. Currently, infrared thermography is not considered to be a fully reliable diagnostic method. If standard infrared protocol is established and a normative database is available, infrared thermography may become a reliable method for detecting inflammatory processes. PMID:29138741

Challenges to Global Implementation of Infrared Thermography Technology: Current Perspective.

PubMed

Shterenshis, Michael

2017-01-01

Medical infrared thermography (IT) produces an image of the infrared waves emitted by the human body as part of the thermoregulation process that can vary in intensity based on the health of the person. This review analyzes recent developments in the use of infrared thermography as a screening and diagnostic tool in clinical and nonclinical settings, and identifies possible future routes for improvement of the method. Currently, infrared thermography is not considered to be a fully reliable diagnostic method. If standard infrared protocol is established and a normative database is available, infrared thermography may become a reliable method for detecting inflammatory processes.

De-escalating Antibiotic Use in the Inpatient Setting: Strategies, Controversies, and Challenges.

PubMed

Daniel Markley, J; Bernard, Shaina; Bearman, Gonzalo; Stevens, Michael P

2017-04-01

Antibiotic de-escalation (ADE) is widely accepted as an integral strategy to curtail the global antibiotic resistance crisis. However, there is significant uncertainty regarding the ideal ADE strategy and its true impact on antibiotic resistance. Rapid diagnostic testing has the potential to enhance ADE strategies. Herein, we aim to discuss the current strategies, controversies, and challenges of ADE in the inpatient setting. A consensus definition of ADE remains elusive at this time. Preliminary studies utilizing rapid diagnostic tests including matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), procalcitonin, and other molecular techniques have demonstrated the potential to support ADE strategies. In the absence of evidence-based, highly specific ADE protocols, the likelihood that individual providers will make consistent, often challenging, decisions to de-escalate antibiotic therapy is low. Antimicrobial stewardship programs should support local physicians with ADE and develop innovative ways to integrate ADE into the broader construct of antimicrobial stewardship programs. The evolving field of rapid diagnostics has significant potential to improve ADE strategies, but more research is needed to fully realize this goal.

Air Breathing Propulsion Controls and Diagnostics Research at NASA Glenn Under NASA Aeronautics Research Mission Programs

NASA Technical Reports Server (NTRS)

Garg, Sanjay

2014-01-01

This lecture will provide an overview of the aircraft turbine engine control research at NASA (National Aeronautics and Space Administration) Glenn Research Center (GRC). A brief introduction to the engine control problem is first provided with a description of the current state-of-the-art control law structure. A historical aspect of engine control development since the 1940s is then provided with a special emphasis on the contributions of GRC. The traditional engine control problem has been to provide a means to safely transition the engine from one steady-state operating point to another based on the pilot throttle inputs. With the increased emphasis on aircraft safety, enhanced performance and affordability, and the need to reduce the environmental impact of aircraft, there are many new challenges being faced by the designers of aircraft propulsion systems. The Controls and Dynamics Branch (CDB) at GRC is leading and participating in various projects in partnership with other organizations within GRC and across NASA, other government agencies, the U.S. aerospace industry, and academia to develop advanced propulsion controls and diagnostics technologies that will help meet the challenging goals of NASA programs under the Aeronautics Research Mission. The second part of the lecture provides an overview of the various CDB technology development activities in aircraft engine control and diagnostics, both current and some accomplished in the recent past. The motivation for each of the research efforts, the research approach, technical challenges and the key progress to date are summarized. The technologies to be discussed include system level engine control concepts, gas path diagnostics, active component control, and distributed engine control architecture. The lecture will end with a futuristic perspective of how the various current technology developments will lead to an Intelligent and Autonomous Propulsion System requiring none to very minimum pilot interface, interfacing directly with the flight management system to determine its mode of operation, and providing personalized engine control to optimize its performance given the current condition and mission objectives.

Personalized medicine in psychiatry.

PubMed

Wium-Andersen, Ida Kim; Vinberg, Maj; Kessing, Lars Vedel; McIntyre, Roger S

2017-01-01

Personalized medicine is a model in which a patient's unique clinical, genetic, and environmental characteristics are the basis for treatment and prevention. Aim, method, and results: This review aims to describe the current tools, phenomenological features, clinical risk factors, and biomarkers used to provide personalized medicine. Furthermore, this study describes the target areas in which they can be applied including diagnostics, treatment selection and response, assessment of risk of side-effects, and prevention. Personalized medicine in psychiatry is challenged by the current taxonomy, where the diagnostic categories are broad and great biological heterogeneity exists within each category. There is, thus, a gap between the current advanced research prospects and clinical practice, and the current taxonomy is, thus, a poor basis for biological research. The discussion proposes possible solutions to narrow this gap and to move psychiatric research forward towards personalized medicine.

Technical challenges in the construction of the steady-state stellarator Wendelstein 7-X

NASA Astrophysics Data System (ADS)

Bosch, H.-S.; Wolf, R. C.; Andreeva, T.; Baldzuhn, J.; Birus, D.; Bluhm, T.; Bräuer, T.; Braune, H.; Bykov, V.; Cardella, A.; Durodié, F.; Endler, M.; Erckmann, V.; Gantenbein, G.; Hartmann, D.; Hathiramani, D.; Heimann, P.; Heinemann, B.; Hennig, C.; Hirsch, M.; Holtum, D.; Jagielski, J.; Jelonnek, J.; Kasparek, W.; Klinger, T.; König, R.; Kornejew, P.; Kroiss, H.; Krom, J. G.; Kühner, G.; Laqua, H.; Laqua, H. P.; Lechte, C.; Lewerentz, M.; Maier, J.; McNeely, P.; Messiaen, A.; Michel, G.; Ongena, J.; Peacock, A.; Pedersen, T. S.; Riedl, R.; Riemann, H.; Rong, P.; Rust, N.; Schacht, J.; Schauer, F.; Schroeder, R.; Schweer, B.; Spring, A.; Stäbler, A.; Thumm, M.; Turkin, Y.; Wegener, L.; Werner, A.; Zhang, D.; Zilker, M.; Akijama, T.; Alzbutas, R.; Ascasibar, E.; Balden, M.; Banduch, M.; Baylard, Ch.; Behr, W.; Beidler, C.; Benndorf, A.; Bergmann, T.; Biedermann, C.; Bieg, B.; Biel, W.; Borchardt, M.; Borowitz, G.; Borsuk, V.; Bozhenkov, S.; Brakel, R.; Brand, H.; Brown, T.; Brucker, B.; Burhenn, R.; Buscher, K.-P.; Caldwell-Nichols, C.; Cappa, A.; Cardella, A.; Carls, A.; Carvalho, P.; Ciupiński, Ł.; Cole, M.; Collienne, J.; Czarnecka, A.; Czymek, G.; Dammertz, G.; Dhard, C. P.; Davydenko, V. I.; Dinklage, A.; Drevlak, M.; Drotziger, S.; Dudek, A.; Dumortier, P.; Dundulis, G.; Eeten, P. v.; Egorov, K.; Estrada, T.; Faugel, H.; Fellinger, J.; Feng, Y.; Fernandes, H.; Fietz, W. H.; Figacz, W.; Fischer, F.; Fontdecaba, J.; Freund, A.; Funaba, T.; Fünfgelder, H.; Galkowski, A.; Gates, D.; Giannone, L.; García Regaña, J. M.; Geiger, J.; Geißler, S.; Greuner, H.; Grahl, M.; Groß, S.; Grosman, A.; Grote, H.; Grulke, O.; Haas, M.; Haiduk, L.; Hartfuß, H.-J.; Harris, J. H.; Haus, D.; Hein, B.; Heitzenroeder, P.; Helander, P.; Heller, R.; Hidalgo, C.; Hildebrandt, D.; Höhnle, H.; Holtz, A.; Holzhauer, E.; Holzthüm, R.; Huber, A.; Hunger, H.; Hurd, F.; Ihrke, M.; Illy, S.; Ivanov, A.; Jablonski, S.; Jaksic, N.; Jakubowski, M.; Jaspers, R.; Jensen, H.; Jenzsch, H.; Kacmarczyk, J.; Kaliatk, T.; Kallmeyer, J.; Kamionka, U.; Karaleviciu, R.; Kern, S.; Keunecke, M.; Kleiber, R.; Knauer, J.; Koch, R.; Kocsis, G.; Könies, A.; Köppen, M.; Koslowski, R.; Koshurinov, J.; Krämer-Flecken, A.; Krampitz, R.; Kravtsov, Y.; Krychowiak, M.; Krzesinski, G.; Ksiazek, I.; Kubkowska, M.; Kus, A.; Langish, S.; Laube, R.; Laux, M.; Lazerson, S.; Lennartz, M.; Li, C.; Lietzow, R.; Lohs, A.; Lorenz, A.; Louche, F.; Lubyako, L.; Lumsdaine, A.; Lyssoivan, A.; Maaßberg, H.; Marek, P.; Martens, C.; Marushchenko, N.; Mayer, M.; Mendelevitch, B.; Mertens, Ph.; Mikkelsen, D.; Mishchenko, A.; Missal, B.; Mizuuchi, T.; Modrow, H.; Mönnich, T.; Morizaki, T.; Murakami, S.; Musielok, F.; Nagel, M.; Naujoks, D.; Neilson, H.; Neubauer, O.; Neuner, U.; Nocentini, R.; Noterdaeme, J.-M.; Nührenberg, C.; Obermayer, S.; Offermanns, G.; Oosterbeek, H.; Otte, M.; Panin, A.; Pap, M.; Paquay, S.; Pasch, E.; Peng, X.; Petrov, S.; Pilopp, D.; Pirsch, H.; Plaum, B.; Pompon, F.; Povilaitis, M.; Preinhaelter, J.; Prinz, O.; Purps, F.; Rajna, T.; Récsei, S.; Reiman, A.; Reiter, D.; Remmel, J.; Renard, S.; Rhode, V.; Riemann, J.; Rimkevicius, S.; Riße, K.; Rodatos, A.; Rodin, I.; Romé, M.; Roscher, H.-J.; Rummel, K.; Rummel, Th.; Runov, A.; Ryc, L.; Sachtleben, J.; Samartsev, A.; Sanchez, M.; Sano, F.; Scarabosio, A.; Schmid, M.; Schmitz, H.; Schmitz, O.; Schneider, M.; Schneider, W.; Scheibl, L.; Scholz, M.; Schröder, G.; Schröder, M.; Schruff, J.; Schumacher, H.; Shikhovtsev, I. V.; Shoji, M.; Siegl, G.; Skodzik, J.; Smirnow, M.; Speth, E.; Spong, D. A.; Stadler, R.; Sulek, Z.; Szabó, V.; Szabolics, T.; Szetefi, T.; Szökefalvi-Nagy, Z.; Tereshchenko, A.; Thomsen, H.; Thumm, M.; Timmermann, D.; Tittes, H.; Toi, K.; Tournianski, M.; Toussaint, U. v.; Tretter, J.; Tulipán, S.; Turba, P.; Uhlemann, R.; Urban, J.; Urbonavicius, E.; Urlings, P.; Valet, S.; Van Eester, D.; Van Schoor, M.; Vervier, M.; Viebke, H.; Vilbrandt, R.; Vrancken, M.; Wauters, T.; Weissgerber, M.; Weiß, E.; Weller, A.; Wendorf, J.; Wenzel, U.; Windisch, T.; Winkler, E.; Winkler, M.; Wolowski, J.; Wolters, J.; Wrochna, G.; Xanthopoulos, P.; Yamada, H.; Yokoyama, M.; Zacharias, D.; Zajac, J.; Zangl, G.; Zarnstorff, M.; Zeplien, H.; Zoletnik, S.; Zuin, M.

2013-12-01

The next step in the Wendelstein stellarator line is the large superconducting device Wendelstein 7-X, currently under construction in Greifswald, Germany. Steady-state operation is an intrinsic feature of stellarators, and one key element of the Wendelstein 7-X mission is to demonstrate steady-state operation under plasma conditions relevant for a fusion power plant. Steady-state operation of a fusion device, on the one hand, requires the implementation of special technologies, giving rise to technical challenges during the design, fabrication and assembly of such a device. On the other hand, also the physics development of steady-state operation at high plasma performance poses a challenge and careful preparation. The electron cyclotron resonance heating system, diagnostics, experiment control and data acquisition are prepared for plasma operation lasting 30 min. This requires many new technological approaches for plasma heating and diagnostics as well as new concepts for experiment control and data acquisition.

A systematic review and checklist presenting the main challenges for health economic modeling in personalized medicine: towards implementing patient-level models.

PubMed

Degeling, Koen; Koffijberg, Hendrik; IJzerman, Maarten J

2017-02-01

The ongoing development of genomic medicine and the use of molecular and imaging markers in personalized medicine (PM) has arguably challenged the field of health economic modeling (HEM). This study aims to provide detailed insights into the current status of HEM in PM, in order to identify if and how modeling methods are used to address the challenges described in literature. Areas covered: A review was performed on studies that simulate health economic outcomes for personalized clinical pathways. Decision tree modeling and Markov modeling were the most observed methods. Not all identified challenges were frequently found, challenges regarding companion diagnostics, diagnostic performance, and evidence gaps were most often found. However, the extent to which challenges were addressed varied considerably between studies. Expert commentary: Challenges for HEM in PM are not yet routinely addressed which may indicate that either (1) their impact is less severe than expected, (2) they are hard to address and therefore not managed appropriately, or (3) HEM in PM is still in an early stage. As evidence on the impact of these challenges is still lacking, we believe that more concrete examples are needed to illustrate the identified challenges and to demonstrate methods to handle them.

Comparison of Ear-Canal Reflectance and Umbo Velocity in Patients with Conductive Hearing Loss

NASA Astrophysics Data System (ADS)

Merchant, Gabrielle R.; Nakajima, Hideko H.; Pisano, Dominic V.; Röösli, Christof; Hamade, Mohamad A.; Mafoud, Lorice; Halpin, Christopher F.; Merchant, Saumil N.; Rosowski, John J.

2011-11-01

Patients who present at hearing clinics with a conductive hearing loss (CHL) in the presence of an intact, healthy tympanic membrane create a unique challenge for otologists. While patient counseling, treatment options, and outcome vary with differing middle-ear pathologies, a non-invasive diagnostic that can differentiate between these pathologies does not currently exist. We evaluated the clinical utility and diagnostic accuracy of two non-invasive measures of middle-ear mechanics: ear-canal reflectance (ECR) and umbo velocity (VU).

Cancer Diagnosis Using a Liquid Biopsy: Challenges and Expectations.

PubMed

Castro-Giner, Francesc; Gkountela, Sofia; Donato, Cinzia; Alborelli, Ilaria; Quagliata, Luca; Ng, Charlotte K Y; Piscuoglio, Salvatore; Aceto, Nicola

2018-05-09

The field of cancer diagnostics has recently been impacted by new and exciting developments in the area of liquid biopsy. A liquid biopsy is a minimally invasive alternative to surgical biopsies of solid tissues, typically achieved through the withdrawal of a blood sample or other body fluids, allowing the interrogation of tumor-derived material including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) fragments that are present at a given time point. In this short review, we discuss a few studies that summarize the state-of-the-art in the liquid biopsy field from a diagnostic perspective, and speculate on current challenges and expectations of implementing liquid biopsy testing for cancer diagnosis and monitoring in the clinical setting.

Clinical review: Current state and future perspectives in the diagnosis of diabetes insipidus: a clinical review.

PubMed

Fenske, Wiebke; Allolio, Bruno

2012-10-01

The differential diagnosis of diabetes insipidus (DI) is often challenging but essential, because treatment may vary substantially. This article analyzes the database and performance of currently used differential diagnostic tests for DI and discusses future perspectives for diagnostic improvement. A review of electronic and print data comprising original and review articles retrieved from the PubMed or Cochrane Library database up to January 2012 was conducted. The search term "polyuria polydipsia syndrome" was cross-referenced with underlying forms of disease and associated clinical, diagnostic, and therapeutic MeSH terms. In addition, references from review articles and textbook chapters were screened for papers containing original data. Search results were narrowed to articles containing primary data with a description of criteria for the differential diagnosis of DI. Fifteen articles on differential diagnosis of DI were identified, mainly consisting of small series of patients, and mostly covering only part of the differential diagnostic spectrum of DI. Test protocols differed, and prospective validation of diagnostic criteria was consistently missing. Inconsistent data were reported on the diagnostic superiority of direct plasma arginine vasopressin determination over the indirect water deprivation test. Both test methods revealed limitations, especially in the differentiation of disorders with a milder phenotype. The available data demonstrate limitations of current biochemical tests for the differential diagnosis of DI, potentially leading to incorrect diagnosis and treatment. The newly available assay for copeptin, the C terminus of the vasopressin precursor, holds promise for a higher diagnostic specificity and simplification of the differential diagnostic protocol in DI.

The clinical manifestations of vestibular migraine: A review.

PubMed

O'Connell Ferster, Ashley P; Priesol, Adrian J; Isildak, Huseyin

2017-06-01

To provide an overview of vestibular migraines presentation, pathology, and diagnosis, as well as an update on current diagnostic criteria. A review of the most recent literature on vestibular migraines was performed. Vestibular migraine is a process with significant impact on the quality of life for those afflicted with the disease, with attacks of spontaneous or positional vertigo and migraine symptoms lasting several minutes to 72h. Inner ear disease can co-exist with migraine and the vestibular symptoms occurring with vestibular migraine can mimic inner ear disorders providing a challenge for clinicians in establishing diagnosis. Recent diagnostic criteria for vestibular migraine proposed by a joint committee of the Bárány Society and the International Headache Society provide an important standard for clinical diagnosis and research endeavor. Vestibular migraine is a challenging disease process to both diagnose and treat. Proper diagnosis and treatment requires a thorough understanding of the current literature. Copyright © 2017 Elsevier B.V. All rights reserved.

Diagnosing Breast Cancer with Microwave Technology: remaining challenges and potential solutions with machine learning.

PubMed

Oliveira, Bárbara L; Godinho, Daniela; O'Halloran, Martin; Glavin, Martin; Jones, Edward; Conceição, Raquel C

2018-05-19

Currently, breast cancer often requires invasive biopsies for diagnosis, motivating researchers to design and develop non-invasive and automated diagnosis systems. Recent microwave breast imaging studies have shown how backscattered signals carry relevant information about the shape of a tumour, and tumour shape is often used with current imaging modalities to assess malignancy. This paper presents a comprehensive analysis of microwave breast diagnosis systems which use machine learning to learn characteristics of benign and malignant tumours. The state-of-the-art, the main challenges still to overcome and potential solutions are outlined. Specifically, this work investigates the benefit of signal pre-processing on diagnostic performance, and proposes a new set of extracted features that capture the tumour shape information embedded in a signal. This work also investigates if a relationship exists between the antenna topology in a microwave system and diagnostic performance. Finally, a careful machine learning validation methodology is implemented to guarantee the robustness of the results and the accuracy of performance evaluation.

Phenotypes of antibody-mediated rejection in organ transplants.

PubMed

Mengel, Michael; Husain, Sufia; Hidalgo, Luis; Sis, Banu

2012-06-01

Antibody-mediated hyperacute rejection was the first rejection phenotype observed in human organ transplants. This devastating phenotype was eliminated by reliable crossmatch technologies. Since then, the focus was on T-cell-mediated rejection and de novo donor-specific antibodies were considered an epiphenomenon of cognate T-cell activation. The immune theory was that controlling the T-cell response would entail elimination of antibody-mediated rejection (ABMR). With modern immunosuppressive drugs, T-cell-mediated rejection is essentially treatable. However, this did not prevent ABMR from emerging as a significant phenotype in all types of organ transplants. It became obvious that both rejection types require distinct treatment and thus reliable diagnosis. This is the current challenge. ABMR, depending on stage, grade, time course, organ type or prior treatment, can present with a wide spectrum of phenotypes. This review summarizes the current diagnostic consensus for ABMR, describes unmet needs and challenges in diagnostics, and proposes new approaches for consideration. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Aircraft Turbine Engine Control Research at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Garg, Sanjay

2014-01-01

This lecture will provide an overview of the aircraft turbine engine control research at NASA (National Aeronautics and Space Administration) Glenn Research Center (GRC). A brief introduction to the engine control problem is first provided with a description of the current state-of-the-art control law structure. A historical aspect of engine control development since the 1940s is then provided with a special emphasis on the contributions of GRC. The traditional engine control problem has been to provide a means to safely transition the engine from one steady-state operating point to another based on the pilot throttle inputs. With the increased emphasis on aircraft safety, enhanced performance and affordability, and the need to reduce the environmental impact of aircraft, there are many new challenges being faced by the designers of aircraft propulsion systems. The Controls and Dynamics Branch (CDB) at GRC is leading and participating in various projects in partnership with other organizations within GRC and across NASA, other government agencies, the U.S. aerospace industry, and academia to develop advanced propulsion controls and diagnostics technologies that will help meet the challenging goals of NASA programs under the Aeronautics Research Mission. The second part of the lecture provides an overview of the various CDB technology development activities in aircraft engine control and diagnostics, both current and some accomplished in the recent past. The motivation for each of the research efforts, the research approach, technical challenges and the key progress to date are summarized. The technologies to be discussed include system level engine control concepts, gas path diagnostics, active component control, and distributed engine control architecture. The lecture will end with a futuristic perspective of how the various current technology developments will lead to an Intelligent and Autonomous Propulsion System requiring none to very minimum pilot interface, interfacing directly with the flight management system to determine its mode of operation, and providing personalized engine control to optimize its performance given the current condition and mission objectives.

A review of mild traumatic brain injury diagnostics: current perspectives, limitations, and emerging technology.

PubMed

Cook, Glen A; Hawley, Jason S

2014-10-01

Mild traumatic brain injury (mTBI) or concussion is a common battlefield and in-garrison injury caused by transmission of mechanical forces to the head. The energy transferred in such events can cause structural and/or functional changes in the brain that manifest as focal neurological, cognitive, or behavioral dysfunction. Current diagnostic criteria for mTBI are highly limited, variable, and based on subjective self-report. The subjective nature of the symptoms, both in quantity and quality, together with their large overlap in other physical and behavioral maladies, limit the clinician's ability to accurately diagnose, treat, and make prognostic decisions after such injuries. These diagnostic challenges are magnified in an operational environment as well. The Department of Defense has invested significant resources into improving the diagnostic tools and accuracy for mTBI. This focus has been to supplement the clinician's examination with technology that is better able to objectify brain dysfunction after mTBI. Through this review, we discuss the current state of three promising technologies--soluble protein biomarkers, advanced neuroimaging, and quantitative electroencephalography--that are of particular interest within military medicine. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Dog and Cat Allergies: Current State of Diagnostic Approaches and Challenges

PubMed Central

Chan, Sanny K.

2018-01-01

Allergies to dogs and cats affect 10%–20% of the population worldwide and is a growing public health concern as these rates increase. Given the prevalence of detectable dog and cat allergens even in households without pets, there is a critical need to accurately diagnose and treat patients to reduce morbidity and mortality from exposure. The ability to diagnose cat sensitization is good, in contrast to dogs. Component resolved diagnostics of sensitization to individual allergenic proteins will dramatically improve diagnosis. This review focuses on the current state of knowledge regarding allergies to dogs and cats, recent advances, therapies such as subcutaneous immunotherapy, and discusses important areas to improve diagnosis and therapy. PMID:29411550

Extra-esophageal presentation of gastroesophageal reflux disease: new understanding in a new era.

PubMed

Martinucci, Irene; Albano, Eleonora; Marchi, Santino; Blandizzi, Corrado

2017-09-01

Associations of gastroesophageal reflux disease (GERD) with extraesophageal manifestations, such as chronic cough, asthma, and laryngitis, are reported frequently, and there is a strong evidence of biological plausibility in support of this relationship. On the other hand, extraesophageal reflux disease (EERD) is usually multifactorial in nature with reflux being just one of the several potential contributing cofactors. Moreover, the accuracy of currently available diagnostic tests for EERD is suboptimal, and therefore the causal relationship between GERD and EERD remains far from being conclusively proven. In addition, there is a general paucity of data supporting a beneficial effect of anti-reflux treatments on symptoms of patients with suspected EERD. Therefore, diagnostic as well as therapeutic management of EERD remains largely empirical. Current guidelines suggest an initial empiric trial of proton pump inhibitors in patients without alarm features, who present also typical GERD symptoms. For those patients who improve with PPIs, GERD is presumed to be the etiology. In patients with refractory reflux, combined impedance/pH monitoring might provide the single best strategy for evaluating reflux symptoms. In this context, as symptoms ascribable to GERD may depend on other causes, investigations that excludes GERD can help to redirect the diagnostic and treatment efforts to other pathological conditions. The present review intends to discuss the current state of knowledge regarding the challenging diagnostic and therapeutic management of patients with suspected EERD, emphasizing the points of strengths and limitations of currently available diagnostic options, and to provide an update on major diagnostic innovations in this area.

Diseases and Molecular Diagnostics: A Step Closer to Precision Medicine.

PubMed

Dwivedi, Shailendra; Purohit, Purvi; Misra, Radhieka; Pareek, Puneet; Goel, Apul; Khattri, Sanjay; Pant, Kamlesh Kumar; Misra, Sanjeev; Sharma, Praveen

2017-10-01

The current advent of molecular technologies together with a multidisciplinary interplay of several fields led to the development of genomics, which concentrates on the detection of pathogenic events at the genome level. The structural and functional genomics approaches have now pinpointed the technical challenge in the exploration of disease-related genes and the recognition of their structural alterations or elucidation of gene function. Various promising technologies and diagnostic applications of structural genomics are currently preparing a large database of disease-genes, genetic alterations etc., by mutation scanning and DNA chip technology. Further the functional genomics also exploring the expression genetics (hybridization-, PCR- and sequence-based technologies), two-hybrid technology, next generation sequencing with Bioinformatics and computational biology. Advances in microarray "chip" technology as microarrays have allowed the parallel analysis of gene expression patterns of thousands of genes simultaneously. Sequence information collected from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Further advances of genetic engineering have also revolutionized immunoassay biotechnology via engineering of antibody-encoding genes and the phage display technology. The Biotechnology plays an important role in the development of diagnostic assays in response to an outbreak or critical disease response need. However, there is also need to pinpoint various obstacles and issues related to the commercialization and widespread dispersal of genetic knowledge derived from the exploitation of the biotechnology industry and the development and marketing of diagnostic services. Implementation of genetic criteria for patient selection and individual assessment of the risks and benefits of treatment emerges as a major challenge to the pharmaceutical industry. Thus this field is revolutionizing current era and further it may open new vistas in the field of disease management.

Developing a tool to support diagnostic delivery of dementia.

PubMed

Bennett, Claire E; De Boos, Danielle; Moghaddam, Nima G

2018-01-01

It is increasingly recognised that there are challenges affecting the current delivery of dementia diagnoses. Steps are required to address this. Current good practice guidelines provide insufficient direction and interventions from other healthcare settings do not appear to fully translate to dementia care settings. This project has taken a sequential two-phase design to developing a tool specific to dementia diagnostic delivery. Interviews with 14 participants explored good diagnostic delivery. Thematic analysis produced key themes (overcoming barriers, navigation of multiple journeys and completing overt and covert tasks) that were used to inform the design of a tool for use by clinicians, patients and companions. The tool was evaluated for acceptability in focused group discussions with 13 participants, which indicated a desire to use the tool and that it could encourage good practice. Adaptations were highlighted and incorporated to improve acceptability. Future research is now required to further evaluate the tool.

Electromagnetic Navigational Bronchoscopy

PubMed Central

Port, Jeffrey; Harrison, Sebron

2013-01-01

Despite advances in technology and treatment options, lung cancer remains a deadly disease. National screening programs are being instituted in an attempt to discover lung cancer in high-risk individuals at an earlier stage. Such screening programs invariably discover small peripheral nodules that previously would not have been clinically apparent; the management of such lesions can be challenging. Current diagnostic options such as percutaneous biopsy are effective; however, they are hindered by their risk of morbidity such as pneumothorax. Electromagnetic bronchoscopy (ENB) is an emerging technology that allows the practitioner the ability to both sample and treat small peripheral pulmonary lesions. In experienced centers, ENB provides high rates of diagnostic yield for small lesions and a complication rate significantly lower than that of more conventional diagnostic modalities. Although there are current barriers to its widespread utilization (cost, specialized imaging, technical training), these obstacles will handled similarly to any other emerging technology and will likely not be long-term impediments to its use. PMID:24436528

Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brozik, Susan M; Manginell, Ronald P; Moorman, Matthew W

2013-09-01

Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the outbreak to identify since most outbreaks are only recognized through reportable diseases by health departments and reports of unusual diseases by clinicians. In recent decades, arthropod-borne viruses (arboviruses) have emerged as some of the most significant threats to human health. They emerge, often unexpectedly, from cryptic transmission foci causing localized outbreaks that can rapidly spread to multiple continents due to increased human travel and trade. Currently, diagnosis ofmore » acute infections requires amplification of viral nucleic acids, which can be costly, highly specific, technically challenging and time consuming. No diagnostic devices suitable for use at the bedside or in an outbreak setting currently exist. The original goals of this project were to 1) develop two highly sensitive and specific diagnostic assays for detecting RNA from a wide range of arboviruses; one based on an electrochemical approach and the other a fluorescent based assay and 2) develop prototype microfluidic diagnostic platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were developed for DNA-RNA hybridization detection and were implemented in microfluidic diagnostic sensing platforms that were developed in this project.« less

Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy: Progress and Pitfalls.

PubMed

Oomen, Ad W G J; Semsarian, Christopher; Puranik, Rajesh; Sy, Raymond W

2018-04-04

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that predominantly affects the right ventricle. With a prevalence in the range of 1:5000 to 1:2000 persons, ARVC is one of the leading causes of sudden cardiac death in young people and in athletes. Although early detection and treatment is important, the diagnosis of ARVC remains challenging. There is no single pathognomonic diagnostic finding in ARVC; rather, current international task force criteria specify diagnostic major and minor criteria in six categories: right ventricular imaging (including echocardiography and cardiac magnetic resonance imaging (MRI)), histology, repolarisation abnormalities, depolarisation and conduction abnormalities, arrhythmias and family history (including genetic testing). Combining findings from differing diagnostic modalities can establish a "definite", "borderline" or "possible" diagnosis of ARVC. However, there are limitations inherent in the current task force criteria, including the lack of specificity for ARVC; future iterations may be improved, for example, by enhanced imaging protocols able to detect subtle changes in the structure and function of the right ventricle, incorporation of electro-anatomical data, response to adrenergic challenge, and validated criteria for interpreting genetic variants. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

The challenges in defining and measuring diagnostic error.

PubMed

Zwaan, Laura; Singh, Hardeep

2015-06-01

Diagnostic errors have emerged as a serious patient safety problem but they are hard to detect and complex to define. At the research summit of the 2013 Diagnostic Error in Medicine 6th International Conference, we convened a multidisciplinary expert panel to discuss challenges in defining and measuring diagnostic errors in real-world settings. In this paper, we synthesize these discussions and outline key research challenges in operationalizing the definition and measurement of diagnostic error. Some of these challenges include 1) difficulties in determining error when the disease or diagnosis is evolving over time and in different care settings, 2) accounting for a balance between underdiagnosis and overaggressive diagnostic pursuits, and 3) determining disease diagnosis likelihood and severity in hindsight. We also build on these discussions to describe how some of these challenges can be addressed while conducting research on measuring diagnostic error.

Molecular pathology curriculum for medical laboratory scientists: A report of the association for molecular pathology training and education committee.

PubMed

Taylor, Sara; Bennett, Katie M; Deignan, Joshua L; Hendrix, Ericka C; Orton, Susan M; Verma, Shalini; Schutzbank, Ted E

2014-05-01

Molecular diagnostics is a rapidly growing specialty in the clinical laboratory assessment of pathology. Educational programs in medical laboratory science and specialized programs in molecular diagnostics must address the training of clinical scientists in molecular diagnostics, but the educational curriculum for this field is not well defined. Moreover, our understanding of underlying genetic contributions to specific diseases and the technologies used in molecular diagnostics laboratories change rapidly, challenging providers of training programs in molecular diagnostics to keep their curriculum current and relevant. In this article, we provide curriculum recommendations to molecular diagnostics training providers at both the baccalaureate and master's level of education. We base our recommendations on several factors. First, we considered National Accrediting Agency for Clinical Laboratory Sciences guidelines for accreditation of molecular diagnostics programs, because educational programs in clinical laboratory science should obtain its accreditation. Second, the guidelines of several of the best known certifying agencies for clinical laboratory scientists were incorporated into our recommendations. Finally, we relied on feedback from current employers of molecular diagnostics scientists, regarding the skills and knowledge that they believe are essential for clinical scientists who will be performing molecular testing in their laboratories. We have compiled these data into recommendations for a molecular diagnostics curriculum at both the baccalaureate and master's level of education. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Emerging Human Fetuin A Assays for Biomedical Diagnostics.

PubMed

Vashist, Sandeep Kumar; Schneider, E Marion; Venkatesh, A G; Luong, John H T

2017-05-01

Human fetuin A (HFA) plays a prominent pathophysiological role in numerous diseases and pathophysiological conditions with considerable biomedical significance; one example is the formation of calciprotein particles in osteoporosis and impaired calcium metabolisms. With impressive advances in in vitro diagnostic assays during the last decade, ELISAs have become a workhorse in routine clinical diagnostics. Recent diagnostic formats involve high-sensitivity immunoassay procedures, surface plasmon resonance, rapid immunoassay chemistries, signal enhancement, and smartphone detection. The current trend is toward fully integrated lab-on-chip platforms with smartphone readouts, enabling health-care practitioners and even patients to monitor pathological changes in biomarker levels. This review provides a critical analysis of advances made in HFA assays along with the challenges and future prospects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

PubMed

Dayton, Vanessa J; McKenna, Robert W; Yohe, Sophia L; Dolan, Michelle M; Courville, Elizabeth; Alvarez, Harold; Linden, Michael A

2017-01-01

Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Molecular diagnostics for low resource settings

NASA Astrophysics Data System (ADS)

Weigl, Bernhard H.

2010-03-01

As traditional high quality diagnostic laboratories are not widely available or affordable in developing country health care settings, microfluidics-based point-of-care diagnostics may be able to address the need to perform complex assays in under-resourced areas. Many instrument-based as well as non-instrumented microfluidic prototype diagnostics are currently being developed. In addition to various engineering challenges, the greatest remaining issue is the search for truly low-cost disposable manufacturing methods. Diagnostics for global health, and specifically microfluidics and molecular-based low resource diagnostics, have become a very active research area over the last five years, thanks in part to new funding that became available from the Bill and Melinda Gates Foundation, the National Institutes of Health, and other sources. This has led to a number of interesting prototype devices that are now in advanced development or clinical validation. These devices include disposables and instruments that perform multiplexed PCR-based lab-on-a-chips for enteric, febrile, and vaginal diseases, as well as immunoassays for diseases such as malaria, HIV, and various sexually transmitted diseases. More recently, instrument-free diagnostic disposables based on isothermal nucleic acid amplification have been developed as well. Regardless of platform, however, the search for truly low-cost manufacturing methods that would result in cost of goods per disposable of around US1/unit at volume remains a big challenge. This talk will give an overview over existing platform development efforts as well as present some original research in this area at PATH.

Clinical and diagnostic aspects of lymphedema.

PubMed

Keo, Hong H; Gretener, Silvia B; Staub, Daniel

2017-07-01

Lymphedema is a chronic, progressive, and common but often unrecognized condition. The diagnosis of lymphatic disease on clinical grounds alone remains a challenge. Without proper diagnosis, therapy is often delayed, allowing disease progression. There is a need for a practical diagnostic algorithm and its imaging technique to guide clinical decision-making. The aim of this topical review is to provide a practical approach for assessing patients with suspected lymphedema and to give a critical appraisal of currently available imaging modalities that are applied in clinical practice to diagnose and map lymphatic disease.

Current and proposed molecular diagnostics in a genitourinary service line laboratory at a tertiary clinical institution.

PubMed

Udager, Aaron M; Alva, Ajjai; Mehra, Rohit

2014-01-01

The idea that detailed knowledge of molecular oncogenesis will drive diagnostic, prognostic, and therapeutic clinical decision making in an increasingly multidisciplinary practice of oncologic care has been anticipated for many years. With the recent rapid advancement in our understanding of the molecular underpinnings of genitourinary malignancies, this concept is now starting to take shape in the fields of prostate, kidney, bladder, testicular, and penile cancer. Such breakthroughs necessitate the development of robust clinical-grade assays that can be quickly made available for patients to facilitate diagnosis in challenging cases, risk-stratify patients for subsequent clinical management, select the appropriate targeted therapy from among increasingly diverse and numerous options, and enroll patients in advanced clinical trials. This rapid translation of basic and clinical cancer research requires a streamlined, multidisciplinary approach to clinical assay development, termed here the molecular diagnostics service line laboratory. In this review, we summarize the current state and explore the future of molecular diagnostics in genitourinary oncology to conceptualize a genitourinary service line laboratory at a tertiary clinical institution.

The changing face of hemostasis testing in modern laboratories: consolidation, automation, and beyond.

PubMed

Lippi, Giuseppe; Plebani, Mario; Favaloro, Emmanuel J

2015-04-01

The reality of laboratory diagnostics as a whole, and hemostasis testing in particular, is evolving under new paradigms of efficiency. The driving forces of health care and laboratory diagnostics in the third millennium are mainly represented by macro- and microeconomics. In a world with limited resources, shattered by an unprecedented economic crisis, laboratory diagnostics is undergoing a substantial reorganization, with emergence of new models under the imperative of terms, such as bedside testing, consolidation, and networking. The paradigms under which these changes are being developed include a variety of environment, preanalytical, technological, professional, and health-care aspects. The maintenance of continued quality is indeed the major challenge to be faced in the foreseeable future. In fact, some challenges prepotently emerge during a consolidation process, which basically involve delayed testing, centrifugation, transportation, and stability of the specimens, as well as the potential mismatch of sample matrix. This article is aimed to provide an overview of the current economic scenario of laboratory diagnostics and discuss the changing face of hemostasis testing in modern laboratories, providing a synthetic overview about potential drawbacks of actualized solutions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Addressing the Real-World Challenges in the Development of Propulsion IVHM Technology Experiment (PITEX)

NASA Technical Reports Server (NTRS)

Maul, William A.; Chicatelli, Amy; Fulton, Christopher E.; Balaban, Edward; Sweet, Adam; Hayden, Sandra Claire; Bajwa, Anupa

2005-01-01

The Propulsion IVHM Technology Experiment (PITEX) has been an on-going research effort conducted over several years. PITEX has developed and applied a model-based diagnostic system for the main propulsion system of the X-34 reusable launch vehicle, a space-launch technology demonstrator. The application was simulation-based using detailed models of the propulsion subsystem to generate nominal and failure scenarios during captive carry, which is the most safety-critical portion of the X-34 flight. Since no system-level testing of the X-34 Main Propulsion System (MPS) was performed, these simulated data were used to verify and validate the software system. Advanced diagnostic and signal processing algorithms were developed and tested in real-time on flight-like hardware. In an attempt to expose potential performance problems, these PITEX algorithms were subject to numerous real-world effects in the simulated data including noise, sensor resolution, command/valve talkback information, and nominal build variations. The current research has demonstrated the potential benefits of model-based diagnostics, defined the performance metrics required to evaluate the diagnostic system, and studied the impact of real-world challenges encountered when monitoring propulsion subsystems.

Engineering aspects of design and integration of ECE diagnostic in ITER

DOE PAGES

Udintsev, V. S.; Taylor, G.; Pandya, H. K.B.; ...

2015-03-12

ITER ECE diagnostic [1] needs not only to meet measurement requirements, but also to withstand various loads, such as electromagnetic, mechanical, neutronic and thermal, and to be protected from stray ECH radiation at 170 GHz and other millimeter wave emission, like Collective Thomson scattering which is planned to operate at 60 GHz. Same or similar loads will be applied to other millimetre-wave diagnostics [2], located both in-vessel and in-port plugs. These loads must be taken into account throughout the design phases of the ECE and other microwave diagnostics to ensure their structural integrity and maintainability. The integration of microwave diagnosticsmore » with other ITER systems is another challenging activity which is currently ongoing through port integration and in-vessel integration work. Port Integration has to address the maintenance and the safety aspects of diagnostics, too. Engineering solutions which are being developed to support and to operate ITER ECE diagnostic, whilst complying with safety and maintenance requirements, are discussed in this paper.« less

Current Concepts in Sports-related Concussion.

PubMed

Feden, Jeffrey P

2016-10-04

Increasing concern over the acute and long-term consequences of sports-related concussion has generated widespread interest and attention. This article provides an overview of concussion in athletes, including diagnostic and management considerations, and highlights the clinical challenges associated with repeated minor head trauma in sports. [Full article available at http://rimed.org/rimedicaljournal-2016-10.asp].

Transbronchial cryobiopsy for diffuse parenchymal lung disease: a state-of-the-art review of procedural techniques, current evidence, and future challenges.

PubMed

Lentz, Robert J; Argento, A Christine; Colby, Thomas V; Rickman, Otis B; Maldonado, Fabien

2017-07-01

Transbronchial lung biopsy with a cryoprobe, or cryobiopsy, is a promising new bronchoscopic biopsy technique capable of obtaining larger and better-preserved samples than previously possible using traditional biopsy forceps. Over two dozen case series and several small randomized trials are now available describing experiences with this technique, largely for the diagnosis of diffuse parenchymal lung disease (DPLD), in which the reported diagnostic yield is typically 70% to 80%. Cryobiopsy technique varies widely between centers and this predominantly single center-based retrospective literature heterogeneously defines diagnostic yield and complications, limiting the degree to which this technique can be compared between centers or to surgical lung biopsy (SLB). This review explores the broad range of cryobiopsy techniques currently in use, their rationale, the current state of the literature, and suggestions for the direction of future study into this promising but unproven procedure.

Disorders Related to Use of Psychoactive Substances in DSM-5: Changes and Challenges.

PubMed

Bhad, Roshan; Lal, Rakesh; Balhara, Yatan Pal Singh

2015-01-01

In the most recent edition of Diagnostic and Statistical Manual (DSM) that is DSM-5 many modifications have been made in substance use disorder section. These include changes in terminology; sections and categories; diagnostic criteria; threshold for diagnosis; severity; and specifier. Additionally, there have been certain additions and omissions from the earlier version. Critical evaluation of the changes made to the section on disorders related to use of psychoactive substances in India context has not been published so far. The current paper presents a critique of the changes made to the substance use disorder section in DSM-5. The rationale for these changes put forth by DSM-5 work group on substance related disorders have been discussed. Additionally, attempt has been made to highlight the possible future challenges consequent to the current nosological revision for substance use disorder category. Overall DSM-5 seems to be promising in fulfilling its goal of DSM-ICD harmonisation and movement towards an internationally compatible and practical diagnostic system for mental health disorders. It has increased the scope of addiction by inclusion of behavioural addiction. It has also tried to balance the categorical and dimensional approach to diagnosis. However, the real test of this newer edition of one of the most commonly used nosological systems will be during clinical care and research. This will help address the debatable issues regarding the changes that DSM-5 brings with it.

Clinical Validation Trial of a Diagnostic for Ebola Zaire Antigen Detection: Design Rationale and Challenges to Implementation

PubMed Central

Schieffelin, John; Moses, Lina M; Shaffer, Jeffrey; Goba, Augustine; Grant, Donald S

2015-01-01

The current Ebola outbreak in West Africa has affected more people than all previous outbreaks combined. The current diagnostic method of choice, quantitative polymerase chain reaction, requires specialized conditions as well as specially trained technicians. Insufficient testing capacity has extended the time from sample collection to results. These delays have led to further delays in the transfer and treatment to Ebola Treatment Units. A sensitive and specific point-of-care device that could be used reliably in low resource settings by healthcare workers with minimal training would increase the efficiency of triage and appropriate transfer of care. This article describes a study designed to validate the sensitivity and specificity of the ReEBOVTM RDT using venous whole blood and capillary blood obtained via fingerprick. We present the scientific and clinical rationale for the decisions made in the design of a diagnostic validation study to be conducted in an outbreak setting. The multi-site strategy greatly complicated implementation. In addition, a decrease in cases in one geographic area along with a concomitant increase in other areas made site selection challenging. Initiation of clinical trials during rapidly evolving outbreaks requires significant cooperation on a national level between research teams implementing studies and clinical care providers. Coordination and streamlining of approval process is essential if trials are to be implemented in a timely fashion. PMID:26768566

Get the Diagnosis: an evidence-based medicine collaborative Wiki for diagnostic test accuracy.

PubMed

Hammer, Mark M; Kohlberg, Gavriel D

2017-04-01

Despite widespread calls for its use, there are challenges to the implementation of evidence-based medicine (EBM) in clinical practice. In response to the challenges of finding timely, pertinent information on diagnostic test accuracy, we developed an online, crowd-sourced Wiki on diagnostic test accuracy called Get the Diagnosis (GTD, http://www.getthediagnosis.org). Since its launch in November 2008 till October 2015, GTD has accumulated information on 300 diagnoses, with 1617 total diagnostic entries. There are a total of 1097 unique diagnostic tests with a mean of 5.4 tests (range 0-38) per diagnosis. 73% of entries (1182 of 1617) have an associated sensitivity and specificity and 89% of entries (1432 of 1617) have associated peer-reviewed literature citations. Altogether, GTD contains 474 unique literature citations. For a sample of three diagnoses, the search precision (percentage of relevant results in the first 30 entries) in GTD was 100% as compared with a range of 13.3%-63.3% for PubMed and between 6.7% and 76.7% for Google Scholar. GTD offers a fast, precise and efficient way to look up diagnostic test accuracy. On three selected examples, GTD had a greater precision rate compared with PubMed and Google Scholar in identifying diagnostic test information. GTD is a free resource that complements other currently available resources. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Clinical applications of MS-based protein quantification.

PubMed

Sabbagh, Bassel; Mindt, Sonani; Neumaier, Michael; Findeisen, Peter

2016-04-01

Mass spectrometry-based assays are increasingly important in clinical laboratory medicine and nowadays are already commonly used in several areas of routine diagnostics. These include therapeutic drug monitoring, toxicology, endocrinology, pediatrics, and microbiology. Accordingly, some of the most common analyses are therapeutic drug monitoring of immunosuppressants, vitamin D, steroids, newborn screening, and bacterial identification. However, MS-based quantification of peptides and proteins for routine diagnostic use is rather rare up to now despite excellent analytical specificity and good sensitivity. Here, we want to give an overview over current fit-for-purpose assays for MS-based protein quantification. Advantages as well as challenges of this approach will be discussed with focus on feasibility for routine diagnostic use. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Revising the personality disorder diagnostic criteria for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V): consider the later life context.

PubMed

Balsis, Steve; Segal, Daniel L; Donahue, Cailin

2009-10-01

The categorical measurement approach implemented by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) personality disorder (PD) diagnostic system is theoretically and pragmatically limited. As a result, many prominent psychologists now advocate for a shift away from this approach in favor of more conceptually sound dimensional measurement. This shift is expected to improve the psychometric properties of the personality disorder (PD) diagnostic system and make it more useful for clinicians and researchers. The current article suggests that despite the probable benefits of such a change, several limitations will remain if the new diagnostic system does not closely consider the context of later life. A failure to address the unique challenges associated with the assessment of personality in older adults likely will result in the continued limited validity, reliability, and utility of the Diagnostic and Statistical Manual of Mental Disorders (DSM) system for this growing population. This article discusses these limitations and their possible implications. (c) 2009 APA, all rights reserved.

Diagnostic Challenges in Prostate Cancer and 68Ga-PSMA PET Imaging: A Game Changer?

PubMed

Zaman, Maseeh uz; Fatima, Nosheen; Zaman, Areeba; Sajid, Mahwsih; Zaman, Unaiza; Zaman, Sidra

2017-10-26

Prostate cancer (PC) is the most frequent solid tumor in men and the third most common cause of cancer mortality among men in developed countries. Current imaging modalities like ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI) and choline based positron emission (PET) tracing have disappointing sensitivity for detection of nodal metastasis and small tumor recurrence. This poses a diagnostic challenge in staging of intermediate to high risk PC and restaging of patients with biochemical recurrence (PSA >0.2 ng/ml). Gallium-68 labeled prostate specific membrane antigen (68Ga-PSMA) PET imaging has now emerged with a higher diagnostic yield. 68Ga-PSMA PET/CT or PET/MRI can be expected to offer a one-stop-shop for staging and restaging of PC. PSMA ligands labeled with alpha and beta emitters have also shown promising therapeutic efficacy for nodal, bone and visceral metastasis. Therefore a PSMA based theranostics approach for detection, staging, treatment, and follow-up of PC would appear to be highly valuable to achieve personalized PC treatment. Creative Commons Attribution License

An Incidental Renal Oncocytoma: 18F-Choline PET/MRI

PubMed Central

Mallia, Andrew; Bashir, Usman; Stirling, James; Wolfe, Konrad; Goh, Vicky; Cook, Gary

2016-01-01

PET/MRI is a new hybrid imaging modality and has the potential to become a powerful imaging tool. It is currently one of the most active areas of research in diagnostic imaging. The characterisation of an incidental renal lesion can be difficult. In particular, the differentiation of an oncocytoma from other solid renal lesions such as renal cell carcinoma (RCC) represents a diagnostic challenge. We describe the detection of an incidental renal oncocytoma in a 79-year gentleman who underwent a re-staging 18F-Choline PET/MRI following a rise in PSA values (4.07, nadir 1.3).

Nanopore Sequencing as a Rapidly Deployable Ebola Outbreak Tool.

PubMed

Hoenen, Thomas; Groseth, Allison; Rosenke, Kyle; Fischer, Robert J; Hoenen, Andreas; Judson, Seth D; Martellaro, Cynthia; Falzarano, Darryl; Marzi, Andrea; Squires, R Burke; Wollenberg, Kurt R; de Wit, Emmie; Prescott, Joseph; Safronetz, David; van Doremalen, Neeltje; Bushmaker, Trenton; Feldmann, Friederike; McNally, Kristin; Bolay, Fatorma K; Fields, Barry; Sealy, Tara; Rayfield, Mark; Nichol, Stuart T; Zoon, Kathryn C; Massaquoi, Moses; Munster, Vincent J; Feldmann, Heinz

2016-02-01

Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting samples to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at a field diagnostic laboratory in Liberia during the current Ebola virus outbreak.

Advances in addressing technical challenges of point-of-care diagnostics in resource-limited settings

PubMed Central

Wang, ShuQi; Lifson, Mark A.; Inci, Fatih; Liang, Li-Guo; Sheng, Ye-Feng; Demirci, Utkan

2016-01-01

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. PMID:26777725

Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.

PubMed

Martino, David; Dang, Thanh; Sexton-Oates, Alexandra; Prescott, Susan; Tang, Mimi L K; Dharmage, Shyamali; Gurrin, Lyle; Koplin, Jennifer; Ponsonby, Anne-Louise; Allen, Katrina J; Saffery, Richard

2015-05-01

The diagnosis of food allergy (FA) can be challenging because approximately half of food-sensitized patients are asymptomatic. Current diagnostic tests are excellent makers of sensitization but poor predictors of clinical reactivity. Thus oral food challenges (OFCs) are required to determine a patient's risk of reactivity. We sought to discover genomic biomarkers of clinical FA with utility for predicting food challenge outcomes. Genome-wide DNA methylation (DNAm) profiling was performed on blood mononuclear cells from volunteers who had undergone objective OFCs, concurrent skin prick tests, and specific IgE tests. Fifty-eight food-sensitized patients (aged 11-15 months) were assessed, half of whom were clinically reactive. Thirteen nonallergic control subjects were also assessed. Reproducibility was assessed in an additional 48 samples by using methylation data from an independent population of patients with clinical FA. Using a supervised learning approach, we discovered a DNAm signature of 96 CpG sites that predict clinical outcomes. Diagnostic scores were derived from these 96 methylation sites, and cutoffs were determined in a sensitivity analysis. Methylation biomarkers outperformed allergen-specific IgE and skin prick tests for predicting OFC outcomes. FA status was correctly predicted in the replication cohort with an accuracy of 79.2%. DNAm biomarkers with clinical utility for predicting food challenge outcomes are readily detectable in blood. The development of this technology in detailed follow-up studies will yield highly innovative diagnostic assays. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

PubMed

Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E; Joshi, Lokesh; Kilcoyne, Michelle

2015-01-01

Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques.

Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics

PubMed Central

Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E.; Joshi, Lokesh

2015-01-01

Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques. PMID:26509158

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

PubMed Central

Arvanitis, Marios; Anagnostou, Theodora; Fuchs, Beth Burgwyn; Caliendo, Angela M.

2014-01-01

SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use. PMID:24982319

Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population.

PubMed

Trotz-Williams, L A; Mercer, N J; Paphitis, K; Walters, J M; Wallace, D; Kristjanson, E; Gubbay, J; Mazzulli, T

2017-02-01

In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals. Copyright © 2017 American Society for Microbiology.

Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population

PubMed Central

Mercer, N. J.; Paphitis, K.; Walters, J. M.; Wallace, D.; Kristjanson, E.; Gubbay, J.; Mazzulli, T.

2016-01-01

ABSTRACT In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals. PMID:28003216

Important hemoprotozoan diseases of livestock: Challenges in current diagnostics and therapeutics: An update

PubMed Central

Maharana, Biswa Ranjan; Tewari, Anup Kumar; Saravanan, Buddhi Chandrasekaran; Sudhakar, Naduvanahalli Rajanna

2016-01-01

Hemoprotozoan parasites pose a serious threat to the livestock population in terms of mortality, reduced milk yield and lowered draft power. Diagnosis of these diseases often poses a challenging task. Needless to say that impact of disease in health and productivity is huge though a fair economic assessment on the quantum of economic loss associated is yet to be worked out from India. The diagnosis of hemoprotozoan infections largely depends on various laboratory-based diagnostic methods as the clinical manifestations are often inconspicuous and non-specific. Traditional diagnostic methods rely on microscopical demonstration of infective stages in blood or tissue fluids. However, it is laborious, lesser sensitive, and cannot differentiate between morphologically similar organisms. Recent development in the technologies has opened new avenues for improvement in the accurate diagnosis of parasitic infections. Serological tests are simple, fast but lack specificity. With advent of molecular techniques, as DNA hybridization assays, polymerase chain reaction and its modifications ensure the detection of infection in the latent phase of the disease. Nucleic acid-based assays are highly sensitive, free from immunocompetence and can differentiate between morphologically similar parasites. With the advent of newer diagnostics complemented with traditional ones will be of huge help for targeted selective treatment with better chemotherapeutic agents. PMID:27284225

The Challenges and Advances in Diagnosis of Vector-Borne Diseases: Where Do We Stand?

PubMed

Kuleš, Josipa; Potocnakova, Lenka; Bhide, Katarina; Tomassone, Laura; Fuehrer, Hans-Peter; Horvatić, Anita; Galan, Asier; Guillemin, Nicolas; Nižić, Petra; Mrljak, Vladimir; Bhide, Mangesh

2017-05-01

Vector-borne diseases (VBD) are of major importance to human and animal health. In recent years, VBD have been emerging or re-emerging in many geographical areas, alarming new disease threats and economic losses. The precise diagnosis of many of these diseases still remains a major challenge because of the lack of comprehensive data available on accurate and reliable diagnostic methods. Here, we conducted a systematic and in-depth review of the former, current, and upcoming techniques employed for the diagnosis of VBD.

Therapeutic challenges in renal cell carcinoma

PubMed Central

Penticuff, Justin C; Kyprianou, Natasha

2015-01-01

Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is highly resistant to systemic therapies. Elucidation of the angiogenesis pathways and their intrinsic signaling interactions with the genetic and metabolic disturbances within renal cell carcinoma variants has ushered in the era of “targeted therapies”. Advanced surgical interventions and novel drugs targeting VEGF and mTOR, have improved patient survival and prolonged clinically stable-disease states. This review discusses the current understanding of diagnostic challenges and the mechanism-based clinical evidence on therapeutic management of advanced RCC. PMID:26309897

Inherited and Acquired Muscle Weakness: A Moving Target for Diagnostic Muscle Biopsy.

PubMed

Stenzel, Werner; Schoser, Benedikt

2017-08-01

Inherited and acquired muscular weakness is caused by multiple conditions. While the inherited ones are mostly caused by mutations in genes coding for myopathic or neurogenic diseases, the acquired ones occur due to inflammatory, endocrine, or toxic etiologies. Precise diagnosis of a specific disease may be challenging and may require a multidisciplinary approach. What is the current place for a diagnostic biopsy of skeletal muscle? Diagnostic muscle biopsy lost in this context its first-tier place in the primary diagnostic workup for some diseases, but it is still mandatory for others. We here summarize conditions in which we believe a diagnostic sample is most relevant and mention those in which a biopsy may be secondary or can even be left out. We would like to stress that muscle biopsy nowadays has a new important place in description and definition of new diseases, for example, discovered by modern genetic approaches. Georg Thieme Verlag KG Stuttgart, New York.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

PubMed

Conwell, Darwin L; Lee, Linda S; Yadav, Dhiraj; Longnecker, Daniel S; Miller, Frank H; Mortele, Koenraad J; Levy, Michael J; Kwon, Richard; Lieb, John G; Stevens, Tyler; Toskes, Phillip P; Gardner, Timothy B; Gelrud, Andres; Wu, Bechien U; Forsmark, Christopher E; Vege, Santhi S

2014-11-01

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Mannitol challenge testing for asthma in a community cohort of young adults.

PubMed

White, Elisha C; de Klerk, Nicholas; Hantos, Zoltan; Priston, Monique; Hollams, Elysia M; James, Alan; Sly, Peter D; Holt, Patrick G; Hall, Graham L

2017-05-01

Mannitol challenge testing is an established tool for clinical asthma diagnosis, and can be performed outside of specialized respiratory laboratories. Despite applicability in both clinical and non-clinical populations, with different pre-test asthma probabilities, differences in diagnostic properties have not been well explored. This study aimed to quantify the diagnostic utility of mannitol challenge testing for asthma in a community cohort and a symptomatic wheezing subset of this cohort. During the 22-year follow-up of the Western Australian Pregnancy (Raine) Cohort, 772 participants (384 males) completed mannitol challenge and skin prick testing and respiratory health questionnaires, of whom 148 reporting wheeze in the past 12 months were included in a wheezing subset. Responsiveness to mannitol had low sensitivity (19%) and high specificity (97%) to identify current asthma in the complete cohort, with positive and negative predictive values (PPV and NPV) of 45% and 92%, respectively. Within the wheezing subset, sensitivity (19%) and specificity (94%) remained similar, but PPV increased to 79%, and NPV decreased to 52%. Our findings support previously reported high specificity and good PPV for mannitol challenge testing in symptomatic wheezing populations, and highlight the need for caution when interpreting mannitol test results in non-clinical populations. © 2016 Asian Pacific Society of Respirology.

Psychiatric comorbidities in asperger syndrome and high functioning autism: diagnostic challenges

PubMed Central

2012-01-01

Several psychiatric conditions, both internalizing and externalizing, have been documented in comorbidity with Asperger Syndrome (AS) and High Functioning Autism (HFA). In this review we examine the interplay between psychiatric comorbidities and AS/HFA. In particular, we will focus our attention on three main issues. First, we examine which psychiatric disorders are more frequently associated with AS/HFA. Second, we review which diagnostic tools are currently available for clinicians to investigate and diagnose the associated psychiatric disorders in individuals with AS/HFA. Third, we discuss the challenges that clinicians and researchers face in trying to determine whether the psychiatric symptoms are phenotypic manifestations of AS/HFA or rather they are the expression of a distinct, though comorbid, disorder. We will also consider the role played by the environment in the manifestation and interpretation of these symptoms. Finally, we will propose some strategies to try to address these issues, and we will discuss therapeutic implications. PMID:22731684

Microfluidics and Cancer: Are we there yet?

PubMed Central

Zhang, Jennifer Zhuo; Nagrath, Sunitha

2013-01-01

More than two decades ago, microfluidics began to show its impact in biological research. Since then, the field of microfluidics has evolving rapidly. Cancer is one of the leading causes of death worldwide. Microfluidics holds great promise in cancer diagnosis and also serves as an emerging tool for understanding cancer biology. Microfluidics can be valuable for cancer investigation due to its high sensitivity, high throughput, less material-consumption, low cost, and enhanced spatio-temporal control. The physical laws on microscale offer an advantage enabling the control of physics, biology, chemistry and physiology at cellular level. Furthermore, microfluidic based platforms are portable and can be easily designed for point-of-care diagnostics. Developing and applying the state of the art microfluidic technologies to address the unmet challenges in cancer can expand the horizons of not only fundamental biology but also the management of disease and patient care. Despite the various microfluidic technologies available in the field, few have been tested clinically, which can be attributed to the various challenges existing in bridging the gap between the emerging technology and real world applications. We present a review of role of microlfuidcs in cancer research, including the history, recent advances and future directions to explore where the field stand currently in addressing complex clinical challenges and future of it. This review identifies four critical areas in cancer research, in which microfluidics can change the current paradigm. These include cancer cell isolation, molecular diagnostics, tumor biology and high-throughput screening for therapeutics. In addition, some of our lab’s current research is presented in the corresponding sections. PMID:23358873

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

PubMed

Raizada, Neeraj; Khaparde, Sunil D; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M; Singh, Varinder; Umadevi, K R; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C H Surya; Mall, Shalini; Singh, Pooja; Saha, B K; Denkinger, Claudia M; Boehme, Catharina; Sarin, Sanjay

2018-01-01

Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population.

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India

PubMed Central

Raizada, Neeraj; Khaparde, Sunil D.; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M.; Singh, Varinder; Umadevi, K. R.; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C. H. Surya; Mall, Shalini; Singh, Pooja; Saha, B. K.; Denkinger, Claudia M.; Boehme, Catharina

2018-01-01

Background Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. Methods A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. Results The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65–8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9–9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. Conclusion The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population. PMID:29489887

Point-of-Care Diagnostics for Improving Maternal Health in South Africa

PubMed Central

Mashamba-Thompson, Tivani P.; Sartorius, Benn; Drain, Paul K.

2016-01-01

Improving maternal health is a global priority, particularly in high HIV-endemic, resource-limited settings. Failure to use health care facilities due to poor access is one of the main causes of maternal deaths in South Africa. “Point-of-care” (POC) diagnostics are an innovative healthcare approach to improve healthcare access and health outcomes in remote and resource-limited settings. In this review, POC testing is defined as a diagnostic test that is carried out near patients and leads to rapid clinical decisions. We review the current and emerging POC diagnostics for maternal health, with a specific focus on the World Health Organization (WHO) quality-ASSURED (Affordability, Sensitivity, Specificity, User friendly, Rapid and robust, Equipment free and Delivered) criteria for an ideal point-of-care test in resource-limited settings. The performance of POC diagnostics, barriers and challenges related to implementing POC diagnostics for maternal health in rural and resource-limited settings are reviewed. Innovative strategies for overcoming these barriers are recommended to achieve substantial progress on improving maternal health outcomes in these settings. PMID:27589808

Aircraft Turbine Engine Control Research at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Garg, Sanjay

2013-01-01

This paper provides an overview of the aircraft turbine engine control research at the NASA Glenn Research Center (GRC). A brief introduction to the engine control problem is first provided with a description of the state-of-the-art control law structure. A historical aspect of engine control development since the 1940s is then provided with a special emphasis on the contributions of GRC. With the increased emphasis on aircraft safety, enhanced performance, and affordability, as well as the need to reduce the environmental impact of aircraft, there are many new challenges being faced by the designers of aircraft propulsion systems. The Controls and Dynamics Branch (CDB) at GRC is leading and participating in various projects to develop advanced propulsion controls and diagnostics technologies that will help meet the challenging goals of NASA Aeronautics Research Mission programs. The rest of the paper provides an overview of the various CDB technology development activities in aircraft engine control and diagnostics, both current and some accomplished in the recent past. The motivation for each of the research efforts, the research approach, technical challenges, and the key progress to date are summarized.

Nanopore Sequencing as a Rapidly Deployable Ebola Outbreak Tool

PubMed Central

Groseth, Allison; Rosenke, Kyle; Fischer, Robert J.; Hoenen, Andreas; Judson, Seth D.; Martellaro, Cynthia; Falzarano, Darryl; Marzi, Andrea; Squires, R. Burke; Wollenberg, Kurt R.; de Wit, Emmie; Prescott, Joseph; Safronetz, David; van Doremalen, Neeltje; Bushmaker, Trenton; Feldmann, Friederike; McNally, Kristin; Bolay, Fatorma K.; Fields, Barry; Sealy, Tara; Rayfield, Mark; Nichol, Stuart T.; Zoon, Kathryn C.; Massaquoi, Moses; Munster, Vincent J.; Feldmann, Heinz

2016-01-01

Rapid sequencing of RNA/DNA from pathogen samples obtained during disease outbreaks provides critical scientific and public health information. However, challenges exist for exporting samples to laboratories or establishing conventional sequencers in remote outbreak regions. We successfully used a novel, pocket-sized nanopore sequencer at a field diagnostic laboratory in Liberia during the current Ebola virus outbreak. PMID:26812583

Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.

PubMed

Ravindra, Vijay M; Eli, Ilyas M; Schmidt, Meic H; Brockmeyer, Douglas L

2016-08-01

Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.

The use of biomarkers and molecular methods for the earlier diagnosis of invasive aspergillosis in immunocompromised patients.

PubMed

Ambasta, Anshula; Carson, Julie; Church, Deirdre L

2015-08-01

Invasive aspergillosis (IA) is an opportunistic infection that is often life threatening in the immunocompromised host. Early diagnosis is critical, especially given the efficacy and availability of several new anti-fungal therapies. Current (2008) diagnostic criteria have limited ability to detect early infection and are aimed at establishing disease. Although histopathology and culture techniques have traditionally been used to make a proven diagnosis of IA, their dependence on tissue samples and slow turnaround times hamper early confirmation of IA. Serologic detection of circulating galactomannan and 1,3-β-D-glucan fungal biomarkers show promise for improving the diagnosis of IA, and their use is included in the EORTC/MSG diagnostic criteria for IA. Numerous studies have evaluated the diagnostic performance of these two biomarkers and shown that they have suboptimal sensitivity when used alone for early diagnosis of proven IA. Currently available molecular assays also suffer from a lack of standardization. Evaluation of the use of different combinations of test methods to enhance diagnostic accuracy is also being done but prompt, accurate diagnosis of IA remains a clinical and diagnostic challenge. The clinical validity and limitations of biomarkers and current molecular methods for the early diagnosis of IA are summarized in this review with respect to the different patient populations at risk for this serious infection. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modern Pathologic Diagnosis of Renal Oncocytoma.

PubMed

Wobker, Sara E; Williamson, Sean R

2017-01-01

Oncocytoma is a well-defined benign renal tumor, with classic gross and histologic features, including a tan or mahogany-colored mass with central scar, microscopic nested architecture, bland cytology, and round, regular nuclei with prominent central nucleoli. As a result of variations in this classic appearance, difficulty in standardizing diagnostic criteria, and entities that mimic oncocytoma, such as eosinophilic variant chromophobe renal cell carcinoma and succinate dehydrogenase-deficient renal cell carcinoma, pathologic diagnosis remains a challenge. This review addresses the current state of pathologic diagnosis of oncocytoma, with emphasis on modern diagnostic markers, areas of controversy, and emerging techniques for less invasive diagnosis, including renal mass biopsy and advanced imaging.

GLUT1 deficiency syndrome in clinical practice.

PubMed

Klepper, Joerg

2012-07-01

GLUT1 deficiency syndrome (GLUT1DS) is caused by impaired glucose transport into brain and is effectively treated by means of a ketogenic diet. In clinical practice the diagnosis of GLUT1DS often is challenging due to the increasing complexity of symptoms, diagnostic cut-offs for hypoglycorrhachia and genetic heterogeneity. In terms of treatment alternative ketogenic diets and their long-term side effects as well as novel compounds such as alpha-lipoic acid and triheptanoin have raised a variety of issues. The current diagnostic and therapeutic approach to GLUT1DS is discussed in this review in view of these recent developments. Copyright © 2011. Published by Elsevier B.V.

Assembling Amperometric Biosensors for Clinical Diagnostics

PubMed Central

Belluzo, María Soledad; Ribone, María Élida; Lagier, Claudia Marina

2008-01-01

Clinical diagnosis and disease prevention routinely require the assessment of species determined by chemical analysis. Biosensor technology offers several benefits over conventional diagnostic analysis. They include simplicity of use, specificity for the target analyte, speed to arise to a result, capability for continuous monitoring and multiplexing, together with the potentiality of coupling to low-cost, portable instrumentation. This work focuses on the basic lines of decisions when designing electron-transfer-based biosensors for clinical analysis, with emphasis on the strategies currently used to improve the device performance, the present status of amperometric electrodes for biomedicine, and the trends and challenges envisaged for the near future. PMID:27879771

Pneumonia Updates on Legionella, Chlamydophila, and Mycoplasma Pneumonia

PubMed Central

Sharma, Lokesh; Losier, Ashley; Tolbert, Thomas; Dela Cruz, Charles S.; Marion, Chad R.

2017-01-01

SUMMARY CAP due to Legionella, Chlamydophyla, or Mycoplasma continues to be a diagnostic challenge due to the nonspecific clinical and radiographic presentations. The vague clinical presentations of atypical CAP contribute to its underdiagnosis and under-reporting. Advancements in diagnostic techniques bring hope to rapid and accurate diagnosis of atypical CAP. Macrolides and respiratory fluoroquinolones are currently the antibiotics of choice, but this may change in the near future as more antibiotics resistance patterns emerge for atypical CAP. Several controversies still exist in atypical CAP, underscoring the need for continued investigation of preventing atypical CAP and determine its association with chronic lung diseases. PMID:28159161

Ultrasound and MRI of nerves for monitoring disease activity and treatment effects in chronic dysimmune neuropathies - Current concepts and future directions.

PubMed

Décard, Bernhard F; Pham, Mirko; Grimm, Alexander

2018-01-01

New imaging modalities like high-resolution-ultrasound (HRUS) and MR-Neurography (MRN) are increasingly used for the evaluation of the peripheral nervous system. The increasing knowledge on morphological changes observed in different neuropathies has led to a better understanding of underlying pathophysiological processes. The diagnosis of acquired chronic dysimmune neuropathies (CDN) like chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis-Sumner Syndrome (LSS) or multifocal motor neuropathy (MMN) can be challenging. The current diagnostic criteria and outcome parameters are mainly based on clinical and electrophysiological parameters. Especially in CDN cases with atypical presentation or during early disease stages, the diagnostic accuracy is low and standardized protocols for the evaluation of disease activity and treatment response are lacking. The establishment of combined diagnostic criteria for CDN including imaging modalities could help to improve the diagnostic accuracy, allow a better differentiation of subtypes and facilitate the follow-up of disease course. The appropriate selection of eligible patients and sensitive monitoring of treatment response is mandatory future in treatment trials. In this article, we briefly summarize the clinical presentations and pathophysiological concepts of different CDN like CIDP, LSS and MMN. Furthermore, this review focuses on the diagnostic value of HRUS/MRN and its potential role for the monitoring of disease activity. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Clinical update for the diagnosis and treatment of Clostridium difficile infection

PubMed Central

IV, Edward C Oldfield; III, Edward C Oldfield; Johnson, David A

2014-01-01

Clostridium difficile infection (CDI) presents a rapidly evolving challenge in the battle against hospital-acquired infections. Recent advances in CDI diagnosis and management include rapid changes in diagnostic approach with the introduction of newer tests, such as detection of glutamate dehydrogenase in stool and polymerase chain reaction to detect the gene for toxin production, which will soon revolutionize the diagnostic approach to CDI. New medications and multiple medical society guidelines have introduced changing concepts in the definitions of severity of CDI and the choice of therapeutic agents, while rapid expansion of data on the efficacy of fecal microbiota transplantation heralds a revolutionary change in the management of patients suffering multiple relapses of CDI. Through a comprehensive review of current medical literature, this article aims to offer an intensive review of the current state of CDI diagnosis, discuss the strengths and limitations of available laboratory tests, compare both current and future treatments options and offer recommendations for best practice strategies. PMID:24729930

Circulating microparticles: square the circle

PubMed Central

2013-01-01

Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

Current methods of laboratory diagnosis of Chlamydia trachomatis infections.

PubMed Central

Black, C M

1997-01-01

Infections caused by Chlamydia trachomatis are probably the most common sexually transmitted diseases in the United States. Commonly unrecognized and often inadequately treated, chlamydial infections can ascend the reproductive tract and cause pelvic inflammatory disease, which often results in the devastating consequences of infertility, ectopic pregnancy, or chronic pelvic pain. C. trachomatis infections are also known to increase the risk for human immunodeficiency virus infection. The obligate intracellular life cycle of C. trachomatis has traditionally required laboratory diagnostic tests that are technically demanding, labor-intensive, expensive, and difficult to access. In spite of these historical challenges, however, laboratory diagnosis of C. trachomatis has been a rapidly advancing area in which there is presently a wide array of commercial diagnostic technologies, costs, manufacturers. This review describes and compares the diagnostic methods for C. trachomatis infection that are currently approved for use in the United States, including the newest DNA amplification technologies which are yet to be licensed for commercial use. Issues to consider in selecting a test for purposes of screening versus diagnosis based on prevalence, performance, legal, social, and cost issues are also discussed. PMID:8993862

Implementation of Cloud based next generation sequencing data analysis in a clinical laboratory.

PubMed

Onsongo, Getiria; Erdmann, Jesse; Spears, Michael D; Chilton, John; Beckman, Kenneth B; Hauge, Adam; Yohe, Sophia; Schomaker, Matthew; Bower, Matthew; Silverstein, Kevin A T; Thyagarajan, Bharat

2014-05-23

The introduction of next generation sequencing (NGS) has revolutionized molecular diagnostics, though several challenges remain limiting the widespread adoption of NGS testing into clinical practice. One such difficulty includes the development of a robust bioinformatics pipeline that can handle the volume of data generated by high-throughput sequencing in a cost-effective manner. Analysis of sequencing data typically requires a substantial level of computing power that is often cost-prohibitive to most clinical diagnostics laboratories. To address this challenge, our institution has developed a Galaxy-based data analysis pipeline which relies on a web-based, cloud-computing infrastructure to process NGS data and identify genetic variants. It provides additional flexibility, needed to control storage costs, resulting in a pipeline that is cost-effective on a per-sample basis. It does not require the usage of EBS disk to run a sample. We demonstrate the validation and feasibility of implementing this bioinformatics pipeline in a molecular diagnostics laboratory. Four samples were analyzed in duplicate pairs and showed 100% concordance in mutations identified. This pipeline is currently being used in the clinic and all identified pathogenic variants confirmed using Sanger sequencing further validating the software.

The relationship between challenging parenting behaviour and childhood anxiety disorders.

PubMed

Lazarus, Rebecca S; Dodd, Helen F; Majdandžić, Mirjana; de Vente, Wieke; Morris, Talia; Byrow, Yulisha; Bögels, Susan M; Hudson, Jennifer L

2016-01-15

This research investigates the relationship between challenging parenting behaviour and childhood anxiety disorders proposed by Bögels and Phares (2008). Challenging parenting behaviour involves the playful encouragement of children to go beyond their own limits, and may decrease children's risk for anxiety (Bögels and Phares, 2008). Parents (n=164 mothers and 144 fathers) of 164 children aged between 3.4 and 4.8 years participated in the current study. A multi-method, multi-informant assessment of anxiety was used, incorporating data from diagnostic interviews as well as questionnaire measures. Parents completed self-report measures of their parenting behaviour (n=147 mothers and 138 fathers) and anxiety (n=154 mothers and 143 fathers). Mothers reported on their child's anxiety via questionnaire as well as diagnostic interview (n=156 and 164 respectively). Of these children, 74 met criteria for an anxiety disorder and 90 did not. Fathers engaged in challenging parenting behaviour more often than mothers. Both mothers' and fathers' challenging parenting behaviour was associated with lower report of child anxiety symptoms. However, only mothers' challenging parenting behaviour was found to predict child clinical anxiety diagnosis. Shared method variance from mothers confined the interpretation of these results. Moreover, due to study design, it is not possible to delineate cause and effect. The finding with respect to maternal challenging parenting behaviour was not anticipated, prompting replication of these results. Future research should investigate the role of challenging parenting behaviour by both caregivers as this may have implications for parenting interventions for anxious children. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Aptamer-Functionalized Nanoparticles for Medical Applications: Challenges and Opportunities

PubMed Central

Xiao, Zeyu; Farokhzad, Omid C.

2012-01-01

With advances in aptamer selection technologies and nanomedicine, aptamer-functionalized nanoparticles are being explored as promising platforms for targeted therapeutic and diagnostic applications. In this Perspective, we outline recent progress in this field, as exemplified by Bamrungsap et al. in this issue of ACS Nano. Furthermore, we highlight the challenges and opportunities in translating current proof-of-concept designs into in vivo applications, with emphasis on the intrinsic properties of aptamers and their interplay with nanoparticles. With continuous efforts, we expect aptamer-functionalized nanoparticles to advance from preclinical into clinical development for further evaluation. PMID:22574989

Zika fever.

PubMed

Martínez de Salazar, Pablo; Suy, Anna; Sánchez-Montalvá, Adrián; Rodó, Carlota; Salvador, Fernando; Molina, Israel

2016-04-01

Zika fever is an arboviral systemic disease that has recently become a public health challenge of global concern after its spread through the Americas. This review highlights the current understanding on Zika virus epidemiology, its routes of transmission, clinical manifestations, diagnostic tests, and the current management, prevention and control strategies. It also delves the association between Zika infection and complications, such as microencephaly or Guillem-Barré syndrome. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Thomson scattering for core plasma on DEMO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mukhin, E. E.; Kurskiev, G. S.; Tolstyakov, S. Yu.

2014-08-21

This paper describes the challenges of Thomson scattering implementation for core plasma on DEMO and evaluates the capability to measure extremely high electron temperature range 0.5-40keV. A number of solutions to be developed for ITER diagnostics are suggested in consideration of their realization for DEMO. New approaches suggested for DEMO may also be of interest to ITER and currently operating magnetic confinement devices.

Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases

PubMed Central

Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe

2015-01-01

Study Objectives: The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Methods and Results: Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Conclusions: Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. Citation: Baiardi S, Vandi S, Pizza F, Alvisi L, Toscani L, Zambrelli E, Tinuper P, Mayer G, Plazzi G. Narcolepsy type 1 and idiopathic generalized epilepsy: diagnostic and therapeutic challenges in dual cases. J Clin Sleep Med 2015;11(11):1257–1262. PMID:26156948

Rapid diagnostic tests for malaria

PubMed Central

Daily, Jennifer; Hotte, Nora; Dolkart, Caitlin; Cunningham, Jane; Yadav, Prashant

2015-01-01

Abstract Maintaining quality, competitiveness and innovation in global health technology is a constant challenge for manufacturers, while affordability, access and equity are challenges for governments and international agencies. In this paper we discuss these issues with reference to rapid diagnostic tests for malaria. Strategies to control and eliminate malaria depend on early and accurate diagnosis. Rapid diagnostic tests for malaria require little training and equipment and can be performed by non-specialists in remote settings. Use of these tests has expanded significantly over the last few years, following recommendations to test all suspected malaria cases before treatment and the implementation of an evaluation programme to assess the performance of the malaria rapid diagnostic tests. Despite these gains, challenges exist that, if not addressed, could jeopardize the progress made to date. We discuss recent developments in rapid diagnostic tests for malaria, highlight some of the challenges and provide suggestions to address them. PMID:26668438

Current and Emerging Legionella Diagnostics for Laboratory and Outbreak Investigations

PubMed Central

Mercante, Jeffrey W.

2015-01-01

SUMMARY Legionnaires' disease (LD) is an often severe and potentially fatal form of bacterial pneumonia caused by an extensive list of Legionella species. These ubiquitous freshwater and soil inhabitants cause human respiratory disease when amplified in man-made water or cooling systems and their aerosols expose a susceptible population. Treatment of sporadic cases and rapid control of LD outbreaks benefit from swift diagnosis in concert with discriminatory bacterial typing for immediate epidemiological responses. Traditional culture and serology were instrumental in describing disease incidence early in its history; currently, diagnosis of LD relies almost solely on the urinary antigen test, which captures only the dominant species and serogroup, Legionella pneumophila serogroup 1 (Lp1). This has created a diagnostic “blind spot” for LD caused by non-Lp1 strains. This review focuses on historic, current, and emerging technologies that hold promise for increasing LD diagnostic efficiency and detection rates as part of a coherent testing regimen. The importance of cooperation between epidemiologists and laboratorians for a rapid outbreak response is also illustrated in field investigations conducted by the CDC with state and local authorities. Finally, challenges facing health care professionals, building managers, and the public health community in combating LD are highlighted, and potential solutions are discussed. PMID:25567224

Current knowledge and pending challenges in zoonosis caused by Mycobacterium bovis: a review.

PubMed

Pérez-Lago, Laura; Navarro, Yurena; García-de-Viedma, Darío

2014-10-01

Mycobacterium bovis is both the causative agent of bovine tuberculosis (TB) and a zoonotic pathogen. In humans, considerably fewer cases of TB are caused by M. bovis than M. tuberculosis; nevertheless, diagnostic limitations mean that currently available data on prevalence grossly underestimate the true dimension of the problem. The routes of transmission from animals to humans are well known and include direct exposure to infected animals or consumption of contaminated animal products. Application of fingerprinting tools facilitates analysis of the molecular epidemiology of M. bovis in animal-to-human and human-to-human transmission. Apart from cattle and M. bovis, other animal species and members within the M. tuberculosis complex can contribute to the zoonosis. Improvements in diagnostic techniques, application of more advanced discriminatory genotyping tools, and collaboration between veterinary and human health care researchers are key to our understanding of this zoonosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: Evidence-Based Report on Diagnostic Guidelines

PubMed Central

Conwell, Darwin L.; Lee, Linda S.; Yadav, Dhiraj; Longnecker, Daniel S.; Miller, Frank H.; Mortele, Koenraad J.; Levy, Michael J.; Kwon, Richard; Lieb, John G.; Stevens, Tyler; Toskes, Philip P.; Gardner, Timothy B.; Gelrud, Andres; Wu, Bechien U.; Forsmark, Christopher E.; Vege, Santhi S.

2016-01-01

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed and evidence based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable or insufficient evidence. A diagnostic (STEP-wise; S-survey, T-tomography, E-endoscopy and P-pancreas function testing) algorithm is proposed that proceeds from a non-invasive to a more invasive approach. This algorithm maximizes specificity (low false positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Futhermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (T-toxic, I-idiopathic, G-genetic, A- autoimmune, R-recurrent and O-obstructive) etiology, gland morphology (Cambridge criteria) and physiologic state (exocrine, endocrine function) for uniformity across future multi-center research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves. PMID:25333398

ICUS/CCUS/CHIP: basics & beyond.

PubMed

Jain, Mili; Tripathi, Anil

2017-10-01

Patients presenting with idiopathic cytopenia with non-diagnostic marrow morphology and a normal karyotype pose a diagnostic and therapeutic challenge. Additional diagnostic information from mutation analysis could provide important clinical insights. However, one has to be cautious during such diagnostic interpretations in view of the recent documentation of clonal somatic mutations in healthy elder individuals. Whether to regard clonality synonymous with malignant proliferation or a manifestation of ageing process is to be judged carefully. Areas covered: The review covers defining criteria and diagnostic work up for Idiopathic cytopenia of undetermined significance (ICUS), Clonal cytopenia of undetermined significance (CCUS), Clonal hematopoiesis of indeterminate potential (CHIP). It also presents the results from previous reports on this subject. In addition the evolution and potential impact of these entities is discussed. Expert commentary: Current evidence does not support the use of somatic mutations as presumptive evidence of myelodysplastic syndrome (MDS). Including CCUS under the category of MDS requires further insight on natural disease course. Longitudinal follow up study on ICUS, CCUS, CHIP may eventually identify the pathological significance of the clonal mutations. An absence of mutation however may still be useful as good predictor of not having MDS.

Efficient Probabilistic Diagnostics for Electrical Power Systems

NASA Technical Reports Server (NTRS)

Mengshoel, Ole J.; Chavira, Mark; Cascio, Keith; Poll, Scott; Darwiche, Adnan; Uckun, Serdar

2008-01-01

We consider in this work the probabilistic approach to model-based diagnosis when applied to electrical power systems (EPSs). Our probabilistic approach is formally well-founded, as it based on Bayesian networks and arithmetic circuits. We investigate the diagnostic task known as fault isolation, and pay special attention to meeting two of the main challenges . model development and real-time reasoning . often associated with real-world application of model-based diagnosis technologies. To address the challenge of model development, we develop a systematic approach to representing electrical power systems as Bayesian networks, supported by an easy-to-use speci.cation language. To address the real-time reasoning challenge, we compile Bayesian networks into arithmetic circuits. Arithmetic circuit evaluation supports real-time diagnosis by being predictable and fast. In essence, we introduce a high-level EPS speci.cation language from which Bayesian networks that can diagnose multiple simultaneous failures are auto-generated, and we illustrate the feasibility of using arithmetic circuits, compiled from Bayesian networks, for real-time diagnosis on real-world EPSs of interest to NASA. The experimental system is a real-world EPS, namely the Advanced Diagnostic and Prognostic Testbed (ADAPT) located at the NASA Ames Research Center. In experiments with the ADAPT Bayesian network, which currently contains 503 discrete nodes and 579 edges, we .nd high diagnostic accuracy in scenarios where one to three faults, both in components and sensors, were inserted. The time taken to compute the most probable explanation using arithmetic circuits has a small mean of 0.2625 milliseconds and standard deviation of 0.2028 milliseconds. In experiments with data from ADAPT we also show that arithmetic circuit evaluation substantially outperforms joint tree propagation and variable elimination, two alternative algorithms for diagnosis using Bayesian network inference.

Recurrent Pneumonia in Children: A Reasoned Diagnostic Approach and a Single Centre Experience.

PubMed

Montella, Silvia; Corcione, Adele; Santamaria, Francesca

2017-01-29

Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%-9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or minor problems, that do not require a diagnostic work-up, and those with an underlying disease. The aim of the current review is to discuss a reasoned diagnostic approach to RP in childhood. Particular emphasis has been placed on which children should undergo a diagnostic work-up and which tests should be performed. A pediatric case series is also presented, in order to document a single centre experience of RP. A management algorithm for the approach to children with RP, based on the evidence from a literature review, is proposed. Like all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach to pediatric RP and provide a useful guide to the clinician.

Bacillus "next generation" diagnostics: moving from detection toward subtyping and risk-related strain profiling.

PubMed

Ehling-Schulz, Monika; Messelhäusser, Ute

2013-01-01

The highly heterogeneous genus Bacillus comprises the largest species group of endospore forming bacteria. Because of their ubiquitous nature, Bacillus spores can enter food production at several stages resulting in significant economic losses and posing a potential risk to consumers due the capacity of certain Bacillus strains for toxin production. In the past, food microbiological diagnostics was focused on the determination of species using conventional culture-based methods, which are still widely used. However, due to the extreme intra-species diversity found in the genus Bacillus, DNA-based identification and typing methods are gaining increasing importance in routine diagnostics. Several studies showed that certain characteristics are rather strain-dependent than species-specific. Therefore, the challenge for current and future Bacillus diagnostics is not only the efficient and accurate identification on species level but also the development of rapid methods to identify strains with specific characteristics (such as stress resistance or spoilage potential), trace contamination sources, and last but not least discriminate potential hazardous strains from non-toxic strains.

[Molecular and immunohistochemical diagnostics in melanoma].

PubMed

Schilling, B; Griewank, K G

2016-07-01

To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

Non-contact high resolution Bessel beam probe for diagnostic imaging of cornea and trabecular meshwork region in eye

NASA Astrophysics Data System (ADS)

Murukeshan, V. M.; Jesmond, Hong Xun J.; Shinoj, V. K.; Baskaran, M.; Tin, Aung

2015-07-01

Primary angle closure glaucoma is a major form of disease that causes blindness in Asia and worldwide. In glaucoma, irregularities in the ocular aqueous outflow system cause an elevation in intraocular pressure (IOP) with subsequent death of retinal ganglion cells, resulting in loss of vision. High resolution visualization of the iridocorneal angle region has great diagnostic value in understanding the disease condition which enables monitoring of surgical interventions that decrease IOP. None of the current diagnostic techniques such as goniophotography, ultrasound biomicroscopy (UBM), anterior segment optical coherence tomography (AS-OCT) and RetCam™ can image with molecular specificity and required spatial resolution that can delineate the trabecular meshwork structures. This paper in this context proposes new concepts and methodology using Bessel beams based illumination and imaging for such diagnostic ocular imaging applications. The salient features using Bessel beams instead of the conventional Gaussian beam, and the optimization challenges in configuring the probe system will be illustrated with porcine eye samples.

The role of nurses/social workers in using a multidimensional guideline for diagnosis of anxiety and challenging behaviour in people with intellectual disabilities.

PubMed

Pruijssers, Addy; van Meijel, Berno; Maaskant, Marian; Keeman, Noortje; Teerenstra, Steven; van Achterberg, Theo

2015-07-01

This study seeks (1) to investigate the impact of the implementation of the 'Diagnostic Guideline for Anxiety and challenging behaviours in clients with intellectual disability' on nurses/social workers' knowledge and self-efficacy; and (2) to evaluate the role of nurses/social workers in the diagnostic process when applying the guideline. Nurses/social workers have extensive contact with clients with intellectual disabilities. Despite this key position, the contribution of nurses/social workers to the diagnosis of mental health problems and challenging behaviours is rather limited. The authors developed the multidimensional 'Diagnostic Guideline for Anxiety and challenging behaviours'. In this article, the implementation of this guideline is evaluated concerning knowledge and self-efficacy of nurses/social workers, as well the role of nurses/social workers in the diagnostic process. This study employed a comparative multiple case study design. Qualitative and quantitative research methods. Working with the 'Diagnostic Guideline for Anxiety and challenging behaviours' led to a statistically significant increase in knowledge and self-efficacy among the nurses/social workers in the experimental condition, compared with nurses/social workers in the control condition. Nurses/social workers and psychologists appreciated the more active contribution of the nurses/social workers in the diagnostic process. Working with the guideline increased the knowledge and self-efficacy of nurses/social workers, and led to more active participation of nurses/social workers in the diagnostic process. After following a training programme, nurses/social workers can effectively contribute to the diagnostic process in clients with anxiety and related challenging behaviours. © 2015 John Wiley & Sons Ltd.

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics

PubMed Central

2013-01-01

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing. MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT). Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology. PMID:24090398

A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics.

PubMed

Canonica, Giorgio Walter; Ansotegui, Ignacio J; Pawankar, Ruby; Schmid-Grendelmeier, Peter; van Hage, Marianne; Baena-Cagnani, Carlos E; Melioli, Giovanni; Nunes, Carlos; Passalacqua, Giovanni; Rosenwasser, Lanny; Sampson, Hugh; Sastre, Joaquin; Bousquet, Jean; Zuberbier, Torsten

2013-10-03

Molecular-based allergy (MA) diagnostics is an approach used to map the allergen sensitization of a patient at a molecular level, using purified natural or recombinant allergenic molecules (allergen components) instead of allergen extracts. Since its introduction, MA diagnostics has increasingly entered routine care, with currently more than 130 allergenic molecules commercially available for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased accuracy in allergy diagnosis and prognosis and plays an important role in three key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive sensitization in poly-sensitized patients, thereby improving the understanding of triggering allergens; (2) assessing, in selected cases, the risk of severe, systemic versus mild, local reactions in food allergy, thereby reducing unnecessary anxiety for the patient and the need for food challenge testing; and (3) identifying patients and triggering allergens for specific immunotherapy (SIT).Singleplex and multiplex measurement platforms are available for MA diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most comprehensive platform currently available, which involves a biochip technology to measure sIgE antibodies against more than one hundred allergenic molecules in a single assay. As the field of MA diagnostics advances, future work needs to focus on large-scale, population-based studies involving practical applications, elucidation and expansion of additional allergenic molecules, and support for appropriate test interpretation. With the rapidly expanding evidence-base for MA diagnosis, there is a need for allergists to keep abreast of the latest information. The aim of this consensus document is to provide a practical guide for the indications, determination, and interpretation of MA diagnostics for clinicians trained in allergology.

A proposal for the use of uniform diagnostic criteria for gestational diabetes in Europe: an opinion paper by the European Board & College of Obstetrics and Gynaecology (EBCOG).

PubMed

Benhalima, Katrien; Mathieu, Chantal; Damm, Peter; Van Assche, André; Devlieger, Roland; Desoye, Gernot; Corcoy, Rosa; Mahmood, Tahir; Nizard, Jacky; Savona-Ventura, Charles; Dunne, Fidelma

2015-07-01

Screening and diagnostic criteria for gestational diabetes (GDM) are inconsistent across Europe, and the development of a uniform GDM screening strategy is necessary. Such a strategy would create opportunities for more women to receive timely treatment for GDM. Developing a consensus on screening for GDM in Europe is challenging, as populations are diverse and healthcare delivery systems also differ. The European Board & College of Obstetrics and Gynaecology (EBCOG) has responded to this challenge by appointing a steering committee, including members of the EBCOG and the Diabetic Pregnancy Study Group (DPSG) associated with the EASD, to develop a proposal for the use of uniform diagnostic criteria for GDM in Europe. A proposal has been developed and has now been approved by the Council of the EBCOG. The current proposal is to screen for overt diabetes at the first prenatal contact using cut-off values for diabetes outside pregnancy, with particular efforts made to screen high-risk groups. When screening for GDM is performed at 24 weeks' gestation or later, the proposal is now to use the 75 g OGTT with the new WHO diagnostic criteria for GDM. However, more research is necessary to evaluate the best GDM screening strategy for different populations in Europe. Therefore, no clear recommendation has been made on whether a universal one-step, two-step or a risk-factor-based screening approach should be used. The use of the same WHO diagnostic GDM criteria across Europe will be an important step towards uniformity.

Single-particle imaging for biosensor applications

NASA Astrophysics Data System (ADS)

Yorulmaz, Mustafa; Isil, Cagatay; Seymour, Elif; Yurdakul, Celalettin; Solmaz, Berkan; Koc, Aykut; Ünlü, M. Selim

2017-10-01

Current state-of-the-art technology for in-vitro diagnostics employ laboratory tests such as ELISA that consists of a multi-step test procedure and give results in analog format. Results of these tests are interpreted by the color change in a set of diluted samples in a multi-well plate. However, detection of the minute changes in the color poses challenges and can lead to false interpretations. Instead, a technique that allows individual counting of specific binding events would be useful to overcome such challenges. Digital imaging has been applied recently for diagnostics applications. SPR is one of the techniques allowing quantitative measurements. However, the limit of detection in this technique is on the order of nM. The current required detection limit, which is already achieved with the analog techniques, is around pM. Optical techniques that are simple to implement and can offer better sensitivities have great potential to be used in medical diagnostics. Interference Microscopy is one of the tools that have been investigated over years in optics field. More of the studies have been performed in confocal geometry and each individual nanoparticle was observed separately. Here, we achieve wide-field imaging of individual nanoparticles in a large field-of-view ( 166 μm × 250 μm) on a micro-array based sensor chip in fraction of a second. We tested the sensitivity of our technique on dielectric nanoparticles because they exhibit optical properties similar to viruses and cells. We can detect non-resonant dielectric polystyrene nanoparticles of 100 nm. Moreover, we perform post-processing applications to further enhance visibility.

Squamous cell carcinoma of the breast as a clinical diagnostic challenge

PubMed Central

Jakubowska, Katarzyna; Kańczuga-Koda, Luiza; Kisielewski, Wojciech; Koda, Mariusz; Famulski, Waldemar

2018-01-01

Squamous cell carcinoma (SqCC) of the breast should be differentiated between the primary skin keratinizing squamous carcinoma and squamous metaplastic cancer. In the current study, the cases of two patients who were diagnosed with SqCC originated from skin and the breast were discussed. A fine-needle aspiration biopsy confirmed the presence of atypical squamous cells. In both cases, the microscopic examination of the surgical specimen revealed a malignant neoplasm differentiated into SqCC characterized by keratinizing cancer cells with abundant eosiphilic cytoplasm with large, hyperchromatic vesicular nuclei. Immunohistochemical studies showed negative for progesterone and estrogen receptors and human epidermal growth factor receptor 2. Moreover, negative expression of cytokeratin 7 and 20 was confirmed. The diagnosis of the both tumors was established based on the detailed analysis of clinical, macroscopical and microscopical information. SqCC localized in the breast is a great diagnostic challenge in pathomorphology and more attention should be paid for analysis of such lesions in daily practice. PMID:29556390

Factoring quality laboratory diagnosis into the malaria control agenda for sub-Saharan Africa.

PubMed

Aidoo, Michael

2013-09-01

Recent progress in malaria control in sub-Saharan Africa has been achieved primarily through provision of insecticide-treated nets, indoor residual spraying, and antimalarial drugs. Although these interventions are important, proper case identification and accurate measurement of their impact depend on quality diagnostic testing. Current availability of diagnostic testing for malaria in sub-Saharan Africa is inadequate to support disease management, prevention programs, and surveillance needs. Challenges faced include a dearth of skilled workforce, inadequate health systems infrastructure, and lack of political will. A coordinated approach to providing pre-service clinical and laboratory training together with systems that support a scale-up of laboratory services could provide means not only for effective malaria case management but also, management of non-malaria febrile illnesses, disease surveillance, and accurate control program evaluation. A synthesis of the challenges faced in ensuring quality malaria testing and how to include this information in the malaria control and elimination agenda are presented.

Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges

PubMed Central

Shirazian, Shayan; Aina, Olufemi; Park, Youngjun; Chowdhury, Nawsheen; Leger, Kathleen; Hou, Linle; Miyawaki, Nobuyuki; Mathur, Vandana S

2017-01-01

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing, often overlooked condition in patients with CKD and end-stage renal disease. It affects ~40% of patients with end-stage renal disease and has been associated with poor quality of life, poor sleep, depression, and mortality. Prevalence estimates vary based on the instruments used to diagnose CKD-aP, and standardized diagnostic instruments are sorely needed. Treatment studies have often yielded conflicting results. This is likely related to studies that are limited by small sample size, flawed designs, and nonstandardized diagnostic instruments. Several large well-designed treatment trials have recently been completed and may soon influence CKD-aP management. PMID:28176969

Propulsion Controls and Diagnostics Research at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Garg, Sanjay

2007-01-01

With the increased emphasis on aircraft safety, enhanced performance and affordability, and the need to reduce the environmental impact of aircraft, there are many new challenges being faced by the designers of aircraft propulsion systems. Also the propulsion systems required to enable the National Aeronautics and Space Administration (NASA) Vision for Space Exploration in an affordable manner will need to have high reliability, safety and autonomous operation capability. The Controls and Dynamics Branch (CDB) at NASA Glenn Research Center (GRC) in Cleveland, Ohio, is leading and participating in various projects in partnership with other organizations within GRC and across NASA, the U.S. aerospace industry, and academia to develop advanced controls and health management technologies that will help meet these challenges through the concept of Intelligent Propulsion Systems. This paper describes the current activities of the CDB under the NASA Aeronautics Research and Exploration Systems Missions. The programmatic structure of the CDB activities is described along with a brief overview of each of the CDB tasks including research objectives, technical challenges, and recent accomplishments. These tasks include active control of propulsion system components, intelligent propulsion diagnostics and control for reliable fault identification and accommodation, distributed engine control, and investigations into unsteady propulsion systems.

Gynecologic imaging: current and emerging applications.

PubMed

Iyer, V R; Lee, S I

2010-01-01

Common diagnostic challenges in gynecology and the role of imaging in their evaluation are reviewed. Etiologies of abnormal uterine bleeding identified on pelvic sonography and sonohysterography are presented. An algorithmic approach for characterizing an incidentally detected adnexal mass and use of magnetic resonance imaging for definitive diagnosis are discussed. Finally, the role of F18-fluorodeoxyglucose positron emission tomography in the management of gynecological malignancies, and pitfalls associated with their use are examined.

Innovation in nanomedicine through materials nanoarchitectonics.

PubMed

Kujawa, Piotr; Winnik, Françoise M

2013-06-18

Materials nanoarchitectonics has led to important innovations in the design and construction of systems in nanoelectronics, nanomachinery, and energy conversion. Recent publications point to the fact that the same approach may be applied successfully to other fields. In this Perspective, we define the key features of materials nanoarchitectonics and examine how they can be used to address current challenges in nanomedicine, placing emphasis on colloidal agents for therapeutic and diagnostic applications.

GENE-07. MOLECULAR NEUROPATHOLOGY 2.0 - INCREASING DIAGNOSTIC ACCURACY IN PEDIATRIC NEUROONCOLOGY

PubMed Central

Sturm, Dominik; Jones, David T.W.; Capper, David; Sahm, Felix; von Deimling, Andreas; Rutkoswki, Stefan; Warmuth-Metz, Monika; Bison, Brigitte; Gessi, Marco; Pietsch, Torsten; Pfister, Stefan M.

2017-01-01

Abstract The classification of central nervous system (CNS) tumors into clinically and biologically distinct entities and subgroups is challenging. Children and adolescents can be affected by >100 histological variants with very variable outcomes, some of which are exceedingly rare. The current WHO classification has introduced a number of novel molecular markers to aid routine neuropathological diagnostics, and DNA methylation profiling is emerging as a powerful tool to distinguish CNS tumor classes. The Molecular Neuropathology 2.0 study aims to integrate genome wide (epi-)genetic diagnostics with reference neuropathological assessment for all newly-diagnosed pediatric brain tumors in Germany. To date, >350 patients have been enrolled. A molecular diagnosis is established by epigenetic tumor classification through DNA methylation profiling and targeted panel sequencing of >130 genes to detect diagnostically and/or therapeutically useful DNA mutations, structural alterations, and fusion events. Results are aligned with the reference neuropathological diagnosis, and discrepant findings are discussed in a multi-disciplinary tumor board including reference neuroradiological evaluation. Ten FFPE sections as input material are sufficient to establish a molecular diagnosis in >95% of tumors. Alignment with reference pathology results in four broad categories: a) concordant classification (~77%), b) discrepant classification resolvable by tumor board discussion and/or additional data (~5%), c) discrepant classification without currently available options to resolve (~8%), and d) cases currently unclassifiable by molecular diagnostics (~10%). Discrepancies are enriched in certain histopathological entities, such as histological high grade gliomas with a molecularly low grade profile. Gene panel sequencing reveals predisposing germline events in ~10% of patients. Genome wide (epi-)genetic analyses add a valuable layer of information to routine neuropathological diagnostics. Our study provides insight into CNS tumors with divergent histopathological and molecular classification, opening new avenues for research discoveries and facilitating optimization of clinical management for affected patients in the future.

An appraisal of current dysphagia diagnosis and treatment strategies.

PubMed

Kaindlstorfer, Adolf; Pointner, Rudolph

2016-08-01

Dysphagia is a common, serious health problem with a wide variety of etiologies and manifestations. This review gives a general overview of diagnostic and therapeutic options for oropharyngeal as well as esophageal swallowing disorders respecting the considerable progress made over recent years. Diagnosis can be challenging and requires expertise in interpretation of symptoms and patient history. Endoscopy, barium radiography and manometry are still the diagnostic mainstays. Classification of esophageal motor-disorders has been revolutionized with the introduction of high-resolution esophageal pressure topography and a new standardized classification algorithm. Automated integrated impedance manometry is a promising upcoming tool for objective evaluation of oropharyngeal dysphagia, in non-obstructive esophageal dysphagia and prediction of post fundoplication dysphagia risk. Impedance planimetry provides new diagnostic information on esophageal and LES-distensibility and allows controlled therapeutic dilatation without the need for radiation. Peroral endoscopic myotomy is a promising therapeutic approach for achalasia and spastic motility disorders.

Molecular diagnostics for hereditary hearing loss in children.

PubMed

Sommen, Manou; Wuyts, Wim; Van Camp, Guy

2017-08-01

Hearing loss (HL) is the most common birth defect in industrialized countries with far-reaching social, psychological and cognitive implications. It is an extremely heterogeneous disease, complicating molecular testing. The introduction of next-generation sequencing (NGS) has resulted in great progress in diagnostics allowing to study all known HL genes in a single assay. The diagnostic yield is currently still limited, but has the potential to increase substantially. Areas covered: In this review the utility of NGS and the problems for comprehensive molecular testing for HL are evaluated and discussed. Expert commentary: Different publications have proven the appropriateness of NGS for molecular testing of heterogeneous diseases such as HL. However, several problems still exist, such as pseudogenic background of some genes and problematic copy number variant analysis on targeted NGS data. Another main challenge for the future will be the establishment of population specific mutation-spectra to achieve accurate personalized comprehensive molecular testing for HL.

The Use and Abuse of Diagnostic/Classification Criteria

PubMed Central

June, Rayford R.; Aggarwal, Rohit

2015-01-01

In rheumatic diseases, classification criteria have been developed to identify well-defined homogenous cohorts for clinical research. Although, they are commonly used in clinical practice, their use may not be appropriate for routine diagnostic clinical care. Classification criteria are being revised with improved methodology and further understanding of disease pathophysiology, but still may not encompass all unique clinical situations to be applied for diagnosis of heterogeneous, rare, evolving rheumatic diseases. Diagnostic criteria development is challenging primarily due to difficulty for universal application given significant differences in prevalence of rheumatic diseases based on geographical area and clinic settings. Despite these shortcomings, the clinician can still use classification criteria for understanding the disease as well as a guide for diagnosis with a few caveats. We present the limits of current classification criteria, describe their use and abuse in clinical practice, and how they should be used with caution when applied in clinics. PMID:26096094

High-frequency ultrasonography (HFUS) as a useful tool in differentiating between plaque morphea and extragenital lichen sclerosus lesions

PubMed Central

Reszke, Radomir; Szepietowski, Jacek C.

2017-01-01

Introduction Morphea and lichen sclerosus (LS) are chronic inflammatory diseases that may pose a diagnostic challenge for a physician. High-frequency ultrasonography (HFUS) is a versatile diagnostic method utilized in dermatologic practice, allowing monitoring the course of the disease, treatment response and differentiation between certain skin disorders. Aim To prove the usefulness of HFUS in differentiating between plaque morphea and extragenital LS lesions. Material and methods We examined 16 patients with plaque morphea and 4 patients with extragenital LS using 20 MHz taberna pro medicum TM (Germany) device. Results Investigations revealed hyperechogenic entrance echo in both morphea and LS lesions, whereas a distinct polycyclic surface of the entrance echo was detected exclusively in LS. Conclusions High-frequency ultrasonography is a current diagnostic modality that may prove useful in differentiating between morphea and LS lesions. PMID:29507565

Malignant pleural mesothelioma: an update on diagnosis and treatment options

PubMed Central

Kondola, Sanjana; Manners, David; Nowak, Anna K.

2016-01-01

Malignant pleural mesothelioma (MPM) represents a significant diagnostic and therapeutic challenge and is almost always a fatal disease. Imaging abnormalities are common, but have a limited role in distinguishing mesothelioma from metastatic pleural disease. Similarly, minimally invasive biomarkers have shown promise but also have limitations in the diagnosis of mesothelioma. In experienced centers, cytology and immunohistochemistry are now sufficient to diagnose the epithelioid subtype of mesothelioma, which can reduce the need for more invasive diagnostic investigations. Prognosis of MPM is modestly impacted by oncological treatments. Chemotherapy with cisplatin and pemetrexed is considered the standard of care, though the addition of bevacizumab to the platinum doublet may be the new standard of care. New targeted therapies have demonstrated some promise and are being addressed in clinical trials. This review focuses on the current data on the diagnostic and therapeutic issues of MPM. PMID:26873306

Pancreatic neuroendocrine neoplasms: a current summary of diagnostic, prognostic, and differential diagnostic information.

PubMed

Wick, M R; Graeme-Cook, F M

2001-06-01

Pancreatic endocrine tumors (PETs) continue to be challenging diagnostic and prognostic lesions in surgical pathology and clinical medicine. These neoplasms can be graded into 1 of 3 tiers, based on histologic characteristics in likeness to epithelial neuroendocrine tumors in other anatomic sites. However, grade 1 tumors are by far the most common and are the most difficult to prognosticate. The most helpful features by which to gauge the behavior of such lesions include size (3 cm or larger); mitotic activity (2 or more mitoses per 10 high-power [x400] microscopic fields); marked nuclear atypia, especially with atypical mitoticfigures; predominant tumor synthesis of gastrin, vasoactive intestinal polypeptide, somatostatin, glucagon, calcitonin, or adrenocorticotropic hormone; complete nonfunctionality of the tumor at an immunohistochemical level; or invasion of blood vessels, nerves, or adjacent organs by the neoplasm. Differential diagnosis of PETs includes lesions such as solid-pseudopapillary neoplasms, acinar carcinomas, metastatic neuroendocrine tumors, and plasmacytomas.

Sesame allergy: role of specific IgE and skin-prick testing in predicting food challenge results.

PubMed

Permaul, Perdita; Stutius, Lisa M; Sheehan, William J; Rangsithienchai, Pitud; Walter, Jolan E; Twarog, Frank J; Young, Michael C; Scott, Jordan E; Schneider, Lynda C; Phipatanakul, Wanda

2009-01-01

There are conflicting data regarding the diagnostic value of sesame-specific IgE and sesame skin test. Currently, there are no established thresholds that predict clinical reactivity. We examined the correlation of sesame ImmunoCAP and skin-prick test (SPT) results with oral challenge outcomes in children suspected of having a sesame food allergy. We conducted a retrospective chart review of children, aged 2-12 years, receiving a sesame ImmunoCAP level, SPT, and food challenge from January 2004 to August 2008 at Children's Hospital Boston and affiliated allergy clinics. Food challenges were conducted in cases of questionable clinical history or a negative ImmunoCAP and/or negative SPT despite a convincing history. Thirty-three oral sesame challenges were conducted. Of the 33 challenges performed, 21% (n = 7) failed and 79% (n = 26) passed. A sesame-specific IgE level of > or = 7 kU(A)/L showed specificity of >90%. An SPT wheal size of > or = 6 mm showed specificity of >90%. Receiver operator characteristic (ROC) curve analysis for sesame-specific IgE revealed an area under the curve (AUC) of 0.56. ROC curve analysis for SPT wheal size revealed an AUC of 0.67. To our knowledge, this study represents the largest number of sesame challenges performed to evaluate the diagnostic value of both sesame-specific IgE and SPT. Based on our sample, both tests are not good predictors of true sesame allergy as determined by an oral challenge. We were unable to establish a threshold with a 95% positive predictive value for both sesame-specific IgE and SPT.

The Mobility Assessment Course for the Diagnosis of Spatial Neglect: Taking a Step Forward?

PubMed Central

Grech, Megan; Stuart, Tracey; Williams, Lindy; Chen, Celia; Loetscher, Tobias

2017-01-01

Spatial neglect after stroke can be a challenging syndrome to diagnose under standard neuropsychological assessment. There is now sufficient evidence that those affected might demonstrate neglect behavior in everyday settings despite showing no signs of neglect during common neglect tasks. This discrepancy is attributed to the simplified and unrealistic nature of common pen and paper based tasks that do not match the demanding, novel, and complex environment of everyday life. As such, increasing task demands under more ecologically valid scenarios has become an important method of increasing test sensitivity. The main aim of the current study was to evaluate the diagnostic utility of the Mobility Assessment Course (MAC), an ecological task, for the assessment of neglect. If neglect becomes more apparent under more challenging task demands the MAC could prove to be more diagnostically accurate at detecting neglect than conventional methods, particularly as the time from initial brain damage increases. Data collected by Guide Dogs of SA/NT were retrospectively analyzed. The Receiver Operating Characteristic (ROC) curve, a measure of sensitivity and specificity, was used to investigate the diagnostic utility of the MAC and a series of paper and pencil tests in 67 right hemisphere stroke survivors. While the MAC proved to be a more sensitive neglect test (74.2%) when compared to the Star Cancellation (43.3%) and Line Bisection (35.7%) tests, this was at the expense of relatively low specificity. As a result, the ROC curve analysis showed no statistically discernable differences between tasks (p > 0.12), or between subacute and chronic groups for individual tasks (p > 0.45). It is concluded that, while the MAC is an ecologically valid alternative for assessing neglect, regarding its diagnostic accuracy, there is currently not enough evidence to suggest that it is a big step forward in comparison to the accuracy of conventional tests. PMID:29163331

Diagnosis of Growth Hormone Deficiency in Childhood

PubMed Central

Stanley, Takara

2012-01-01

Purpose of Review The diagnosis of growth hormone deficiency (GHD) in childhood is challenging, in large part due to the lack of a true gold standard and the relatively poor performance of available diagnostic testing. This review discusses recent literature on this topic. Recent Findings Auxology and clinical judgment remain the foundation for the diagnosis of GHD. Provocative GH testing is poorly reproducible, dependent on factors such as body composition and pubertal status, and further limited by significant variability among commercially available GH assays. Measurement of IGF-I and IGFBP-3 is not diagnostically useful in isolation but is helpful in combination with other diagnostic measures. Neuroimaging is also useful to inform diagnosis, as pituitary abnormalities suggest a higher likelihood of GHD persisting into adulthood. Although genetic testing is not routinely performed in the diagnosis of GHD at the present time, multiple recent reports raise the possibility that it may play a more important role in diagnosing GHD in the future. Summary Beyond physicians’ integrated assessment of auxology, clinical presentation, and bone age, current tools to diagnose GHD are sub-optimal. Recent literature emphasizes the need to reappraise our current practice and to consider new tools for diagnosis. PMID:22157400

Paper-based analytical devices for clinical diagnosis: recent advances in the fabrication techniques and sensing mechanisms

PubMed Central

Sher, Mazhar; Zhuang, Rachel; Demirci, Utkan; Asghar, Waseem

2017-01-01

Introduction There is a significant interest in developing inexpensive portable biosensing platforms for various applications including disease diagnostics, environmental monitoring, food safety, and water testing at the point-of-care (POC) settings. Current diagnostic assays available in the developed world require sophisticated laboratory infrastructure and expensive reagents. Hence, they are not suitable for resource-constrained settings with limited financial resources, basic health infrastructure, and few trained technicians. Cellulose and flexible transparency paper-based analytical devices have demonstrated enormous potential for developing robust, inexpensive and portable devices for disease diagnostics. These devices offer promising solutions to disease management in resource-constrained settings where the vast majority of the population cannot afford expensive and highly sophisticated treatment options. Areas covered In this review, the authors describe currently developed cellulose and flexible transparency paper-based microfluidic devices, device fabrication techniques, and sensing technologies that are integrated with these devices. The authors also discuss the limitations and challenges associated with these devices and their potential in clinical settings. Expert commentary In recent years, cellulose and flexible transparency paper-based microfluidic devices have demonstrated the potential to become future healthcare options despite a few limitations such as low sensitivity and reproducibility. PMID:28103450

Paper-based analytical devices for clinical diagnosis: recent advances in the fabrication techniques and sensing mechanisms.

PubMed

Sher, Mazhar; Zhuang, Rachel; Demirci, Utkan; Asghar, Waseem

2017-04-01

There is a significant interest in developing inexpensive portable biosensing platforms for various applications including disease diagnostics, environmental monitoring, food safety, and water testing at the point-of-care (POC) settings. Current diagnostic assays available in the developed world require sophisticated laboratory infrastructure and expensive reagents. Hence, they are not suitable for resource-constrained settings with limited financial resources, basic health infrastructure, and few trained technicians. Cellulose and flexible transparency paper-based analytical devices have demonstrated enormous potential for developing robust, inexpensive and portable devices for disease diagnostics. These devices offer promising solutions to disease management in resource-constrained settings where the vast majority of the population cannot afford expensive and highly sophisticated treatment options. Areas covered: In this review, the authors describe currently developed cellulose and flexible transparency paper-based microfluidic devices, device fabrication techniques, and sensing technologies that are integrated with these devices. The authors also discuss the limitations and challenges associated with these devices and their potential in clinical settings. Expert commentary: In recent years, cellulose and flexible transparency paper-based microfluidic devices have demonstrated the potential to become future healthcare options despite a few limitations such as low sensitivity and reproducibility.

Nanomedicines in gastroenterology and hepatology.

PubMed

Lamprecht, Alf

2015-04-01

Nanoscale systems are currently under investigation for multiple different diagnostic and therapeutic applications. These systems can be used to identify pathologically changed tissues or to selectively deliver drugs to these sites; both applications have an extremely high potential to ameliorate therapeutic outcomes for patients. Tissues as well as single cells can be targeted because of the small size of these systems, which enables enhanced diagnosis and increased specificity of therapy. Drug loads can be delivered directly to the site of action, which can result in a reduction in incidence and severity of adverse systemic effects. Several nano-based platform technologies are currently under investigation for use in therapeutic approaches, mainly for anti-inflammatory and anti-cancer therapies. Although many nanoscale systems show promising therapeutic outcomes in preclinical studies, only a limited number are ready for clinical use. This Review will discuss the diverse nanomaterials currently available and the first specific uses for select gastroenterological and hepatological pathologies. The discussion of diagnostic and therapeutic applications will consider realities of market introduction of these sometimes very complex systems in light of remaining regulatory challenges and hurdles for industrial production.

Challenges in reducing dengue burden; diagnostics, control measures and vaccines.

PubMed

Lam, Sai Kit

2013-09-01

Dengue is a major public health concern worldwide, with the number of infections increasing globally. The illness imposes the greatest economic and human burden on developing countries that have limited resources to deal with the scale of the problem. No cure for dengue exists; treatment is limited to rehydration therapy, and with vector control strategies proving to be relatively ineffective, a vaccine is an urgent priority. Despite the numerous challenges encountered in the development of a dengue vaccine, several vaccine candidates have shown promise in clinical development and it is believed that a vaccination program would be at least as cost-effective as current vector control programs. The lead candidate vaccine is a tetravalent, live attenuated, recombinant vaccine, which is currently in Phase III clinical trials. Vaccine introduction is a complex process that requires consideration and is discussed here. This review discusses the epidemiology, burden and pathogenesis of dengue, as well as the vaccine candidates currently in clinical development.

Dengue in the elderly: a review.

PubMed

Lin, Ray Junhao; Lee, Tau Hong; Leo, Yee Sin

2017-08-01

Changing dengue epidemiological trends have resulted in a shift in the disease burden to the adult population. Older adults suffer from poorer outcomes as compared to their younger counterparts, making clinical management of this sub-population particularly challenging. Areas covered: We present a review of the current literature on the changing epidemiology of dengue in the elderly, the atypical features of the clinical disease in this population with emphasis on severe disease presentations and challenges in the current management strategies. Expert commentary: Dengue in the elderly is an increasingly important yet greatly understudied area. There is an urgent need to refine the current diagnostic criteria to improve diagnosis, classification of disease severity and identify individuals in this population who are likely to progress to severe disease. Management strategies in this population would have to be adjusted to account for the increased number of co-morbidities. The role of the available dengue vaccines in this group is uncertain, and more studies into their safety and efficacy are critically needed.

An optimal transportation approach for nuclear structure-based pathology.

PubMed

Wang, Wei; Ozolek, John A; Slepčev, Dejan; Lee, Ann B; Chen, Cheng; Rohde, Gustavo K

2011-03-01

Nuclear morphology and structure as visualized from histopathology microscopy images can yield important diagnostic clues in some benign and malignant tissue lesions. Precise quantitative information about nuclear structure and morphology, however, is currently not available for many diagnostic challenges. This is due, in part, to the lack of methods to quantify these differences from image data. We describe a method to characterize and contrast the distribution of nuclear structure in different tissue classes (normal, benign, cancer, etc.). The approach is based on quantifying chromatin morphology in different groups of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the Fisher discriminant analysis and multidimensional scaling techniques. We show that the optimal transportation metric is able to measure relevant biological information as it enables automatic determination of the class (e.g., normal versus cancer) of a set of nuclei. We show that the classification accuracies obtained using this metric are, on average, as good or better than those obtained utilizing a set of previously described numerical features. We apply our methods to two diagnostic challenges for surgical pathology: one in the liver and one in the thyroid. Results automatically computed using this technique show potentially biologically relevant differences in nuclear structure in liver and thyroid cancers.

An optimal transportation approach for nuclear structure-based pathology

PubMed Central

Wang, Wei; Ozolek, John A.; Slepčev, Dejan; Lee, Ann B.; Chen, Cheng; Rohde, Gustavo K.

2012-01-01

Nuclear morphology and structure as visualized from histopathology microscopy images can yield important diagnostic clues in some benign and malignant tissue lesions. Precise quantitative information about nuclear structure and morphology, however, is currently not available for many diagnostic challenges. This is due, in part, to the lack of methods to quantify these differences from image data. We describe a method to characterize and contrast the distribution of nuclear structure in different tissue classes (normal, benign, cancer, etc.). The approach is based on quantifying chromatin morphology in different groups of cells using the optimal transportation (Kantorovich-Wasserstein) metric in combination with the Fisher discriminant analysis and multidimensional scaling techniques. We show that the optimal transportation metric is able to measure relevant biological information as it enables automatic determination of the class (e.g. normal vs. cancer) of a set of nuclei. We show that the classification accuracies obtained using this metric are, on average, as good or better than those obtained utilizing a set of previously described numerical features. We apply our methods to two diagnostic challenges for surgical pathology: one in the liver and one in the thyroid. Results automatically computed using this technique show potentially biologically relevant differences in nuclear structure in liver and thyroid cancers. PMID:20977984

Expanding Access to Malaria Diagnosis through Retail Shops in Western Kenya: What Do Shop Workers Think?

PubMed

Rusk, Andria; Goodman, Catherine; Naanyu, Violet; Koech, Beatrice; Obala, Andrew; O'Meara, Wendy Prudhomme

2013-01-01

Background. The common symptoms of malaria reduce the specificity of clinical diagnosis. Presumptive treatment is conventional but can lead to overdiagnosis of malaria, delay of appropriate treatment, overprescription of antimalarials, and drug resistance. Routine use of diagnostic tests can address many of these concerns. Though treatment is often procured from retailers, there is low availability of rapid diagnostic tests for malaria (MRDTs), a simple, inexpensive, and accurate diagnostic solution. We know little about the challenges to expanding access to diagnostics through these outlets. Methods. To understand the perceptions of the benefits and challenges to selling rapid diagnostic tests for malaria, we conducted focus group discussions with antimalarial retailers who serve the residents of the Webuye Health and Demographic Surveillance Site in western Kenya. Results. Medicine retailers perceived MRDTs to be beneficial to their customers and businesses but also included cost, fear of the tests, risks of self-treatment, and regulatory concerns among the challenges to using and selling MRDTs. Conclusion. MRDTs represent a viable approach to increase access to malaria diagnostic testing. Medicine retailers are eager for MRDTs to be made available to them. However, certain challenges remain to implementation in retail outlets and should be addressed in advance.

Atypical Pneumonia: Updates on Legionella, Chlamydophila, and Mycoplasma Pneumonia.

PubMed

Sharma, Lokesh; Losier, Ashley; Tolbert, Thomas; Dela Cruz, Charles S; Marion, Chad R

2017-03-01

Community-acquired pneumonia (CAP) has multiple causes and is associated with illness that requires admission to the hospital and mortality. The causes of atypical CAP include Legionella species, Chlamydophila, and Mycoplasma. Atypical CAP remains a diagnostic challenge and, therefore, likely is undertreated. This article reviews the advancements in the evaluation and treatment of patients and discusses current conflicts and controversies of atypical CAP. Copyright © 2016 Elsevier Inc. All rights reserved.

Improving early cycle economic evaluation of diagnostic technologies.

PubMed

Steuten, Lotte M G; Ramsey, Scott D

2014-08-01

The rapidly increasing range and expense of new diagnostics, compels consideration of a different, more proactive approach to health economic evaluation of diagnostic technologies. Early cycle economic evaluation is a decision analytic approach to evaluate technologies in development so as to increase the return on investment as well as patient and societal impact. This paper describes examples of 'early cycle economic evaluations' as applied to diagnostic technologies and highlights challenges in its real-time application. It shows that especially in the field of diagnostics, with rapid technological developments and a changing regulatory climate, early cycle economic evaluation can have a guiding role to improve the efficiency of the diagnostics innovation process. In the next five years the attention will move beyond the methodological and analytic challenges of early cycle economic evaluation towards the challenge of effectively applying it to improve diagnostic research and development and patient value. Future work in this area should therefore be 'strong on principles and soft on metrics', that is, the metrics that resonate most clearly with the various decision makers in this field.

Rolling Out Xpert® MTB/RIF for TB Detection in HIV-Infected Populations:An Opportunity for Systems Strengthening.

PubMed

Pathmanathan, Ishani; Date, Anand; Coggin, William L; Nkengasong, John; Piatek, Amy S; Alexander, Heather

2017-03-31

To eliminate preventable deaths, disease and suffering due to tuberculosis (TB), improved diagnostic capacity is critical. The Cepheid Xpert ® MTB/RIF assay is recommended by the World Health Organization as the initial diagnostic test for people with suspected HIV-associated TB. However, despite high expectations, its scale-up in real-world settings has faced challenges, often due to the systems that support it. In this commentary we discuss needs and opportunities for systems strengthening to support widespread scale-up of Xpert ® MTB/RIF as they relate to each step within the TB diagnostic cascade, from finding presumptive patients, to collecting, transporting and testing sputum specimens, to reporting and receiving results, to initiating and monitoring treatment and, ultimately, to ensuring successful and timely treatment and cure. Investments in evidence-based interventions at each step along the cascade and within the system as a whole will augment not only the utility of Xpert ® MTB/RIF, but also the successful implementation of future diagnostic tests. Xpert ® MTB/RIF will only improve patient outcomes if optimally implemented within the context of strong TB programs and systems. Roll-out of this technology to people living with HIV and others in resource-limited settings offers the opportunity to leverage current TB and HIV laboratory, diagnostic and programmatic investments, while also addressing challenges and strengthening coordination between laboratory systems, laboratory-program interfaces, and TB-HIV program interfaces. If successful, the benefits of this tool could extend beyond progress towards global End TB Strategy goals, to improve system-wide capacity for global disease detection and control.

Cystic Fibrosis Diagnostic Challenges over 4 Decades: Historical Perspectives and Lessons Learned.

PubMed

Farrell, Philip M; White, Terry B; Derichs, Nico; Castellani, Carlo; Rosenstein, Beryl J

2017-02-01

Because cystic fibrosis (CF) can be difficult to diagnose, and because information about the genetic complexities and pathologic basis of the disease has grown so rapidly over the decades, several consensus conferences have been held by the US CF Foundation, and a variety of other efforts to improve diagnostic practices have been organized by the European CF Society. Despite these efforts, the application of diagnostic criteria has been variable and caused confusion. To improve diagnosis and achieve standardization in terms and definitions worldwide, the CF Foundation in 2015 convened a committee of 32 experts in the diagnosis of CF from 9 countries. As part of the process, all previous consensus-seeking exercises sponsored by the CF Foundation, along with the important efforts of the European CF Society, were comprehensively and critically reviewed. The goal was to better understand why consensus conferences and their publications have not led to the desired results. Lessons learned from previous diagnosis consensus processes and products were identified. It was decided that participation in developing a consensus was generally not inclusive enough for global impact. It was also found that many efforts to address sweat test issues were valuable but did not always improve clinical practices as CF diagnostic testing evolved. It also became clear from this review that premature applications of potential diagnostic tests such as nasal potential difference and intestinal current measurement should be avoided until validation and standardization occur. Finally, we have learned that due to the significant and growing number of cases that are challenging to diagnose, an associated continuing medical education program is both desirable and necessary. It is necessary but not sufficient to organize and publish CF diagnosis consensus processes. Follow-up implementation efforts and monitoring practices seem essential. Copyright © 2016. Published by Elsevier Inc.

The future of novel diagnostics in medical mycology.

PubMed

Teles, Fernando; Seixas, Jorge

2015-04-01

Several fungal diseases have become serious threats to human health and life, especially upon the advent of human immunodeficiency virus/AIDS epidemics and of other typical immunosuppressive conditions of modern life. Accordingly, the burden posed by these diseases and, concurrently, by intensive therapeutic regimens against these diseases has increased worldwide. Existing and available rapid tests for point-of-care diagnosis of important fungal diseases could enable the limitations of current laboratory methods for detection and identification of medically important fungi to be surpassed, both in low-income countries and for first-line diagnosis (screening) in richer countries. As with conventional diagnostic methods and devices, former immunodiagnostics have been challenged by molecular biology-based platforms, as a way to enhance the sensitivity and shorten the assay time, thus enabling early and more accurate diagnosis. Most of these tests have been developed in-house, without adequate validation and standardization. Another challenge has been the DNA extraction step, which is especially critical when dealing with fungi. In this paper, we have identified three major research trends in this field: (1) the application of newer biorecognition techniques, often applied in analytical chemistry; (2) the development of new materials with improved physico-chemical properties; and (3) novel bioanalytical platforms, allowing fully automated testing. Keeping up to date with the fast technological advances registered in this field, primarily at the proof-of-concept level, is essential for wise assessment of those that are likely to be more cost effective and, as already observed for bacterial and viral pathogens, may provide leverage to the current tepid developmental status of novel and improved diagnostics for medical mycology. © 2015 The Authors.

Understanding Psychopathology

PubMed Central

Krueger, Robert F.; Markon, Kristian E.

2008-01-01

Research on psychopathology is at a historical crossroads. New technologies offer the promise of lasting advances in our understanding of the causes of human psychological suffering. Making the best use of these technologies, however, requires an empirically accurate model of psychopathology. Much current research is framed by the model of psychopathology portrayed in current versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM; American Psychiatric Association, 2000). Although the modern DSMs have been fundamental in advancing psychopathology research, recent research also challenges some assumptions made in the DSM—for example, the assumption that all forms of psychopathology are well conceived of as discrete categories. Psychological science has a critical role to play in working through the implications of this research and the challenges it presents. In particular, behavior-genetic, personality, and quantitative-psychological research perspectives can be melded to inform the development of an empirically based model of psychopathology that would constitute an evolution of the DSM. PMID:18392116

Feedback on the Surveillance 8 challenge: Vibration-based diagnosis of a Safran aircraft engine

NASA Astrophysics Data System (ADS)

Antoni, Jérôme; Griffaton, Julien; André, Hugo; Avendaño-Valencia, Luis David; Bonnardot, Frédéric; Cardona-Morales, Oscar; Castellanos-Dominguez, German; Daga, Alessandro Paolo; Leclère, Quentin; Vicuña, Cristián Molina; Acuña, David Quezada; Ompusunggu, Agusmian Partogi; Sierra-Alonso, Edgar F.

2017-12-01

This paper presents the content and outcomes of the Safran contest organized during the International Conference Surveillance 8, October 20-21, 2015, at the Roanne Institute of Technology, France. The contest dealt with the diagnosis of a civil aircraft engine based on vibration data measured in a transient operating mode and provided by Safran. Based on two independent exercises, the contest offered the possibility to benchmark current diagnostic methods on real data supplemented with several challenges. Outcomes of seven competing teams are reported and discussed. The object of the paper is twofold. It first aims at giving a picture of the current state-of-the-art in vibration-based diagnosis of rolling-element bearings in nonstationary operating conditions. Second, it aims at providing the scientific community with a benchmark and some baseline solutions. In this respect, the data used in the contest are made available as supplementary material.

[Clinical and health economic challenges of personalized medicine].

PubMed

Brüggenjürgen, B; Kornbluth, L; Ferrara, J V; Willich, S N

2012-05-01

Healthcare systems across the globe are currently challenged by aging populations, increases in chronic diseases and the difficult task of managing a healthcare budget. In this health economic climate, personalized medicine promises not only an improvement in healthcare delivery but also the possibility of more cost-effective therapies. It is important to remember, however, that personalized medicine has the potential to both increase and decrease costs. Each targeted therapy must be evaluated individually. However, standard clinical trial design is not suitable for personalized therapies. Therefore, both scientists and regulatory authorities will need to accept innovative study designs in order to validate personalized therapies. Hence correct economic evaluations are difficult to carry out due to lack of clear clinical evidence, longitudinal accounting and experience with patient/clinician behavior in the context of personalized medicine. In terms of reimbursement, payers, pharmaceutical companies and companion diagnostic manufacturers will also need to explore creative risk-sharing concepts. Germany is no exception to the challenges that face personalized medicine and for personalized medicine to really become the future of medicine many health economic challenges first need to be overcome. The health economic implications of personalized medicine remain unclear but it is certain that the expansion of targeted therapies in current healthcare systems will create a host of challenges.

Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases.

PubMed

Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe

2015-11-15

The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. © 2015 American Academy of Sleep Medicine.

New diagnostic methods for pneumonia in the ICU.

PubMed

Douglas, Ivor S

2016-04-01

Pneumonia leading to severe sepsis and critical illness including respiratory failure remains a common and therapeutically challenging diagnosis. Current clinical approaches to surveillance, early detection, and conventional culture-based microbiology are inadequate for optimal targeted antibiotic treatment and stewardship. Efforts to enhance diagnosis of community-acquired and health care-acquired pneumonia, including ventilator-associated pneumonia (VAP), are the focus of recent studies reviewed here. Newer surveillance definitions are sensitive for pneumonia in the ICU including VAP but consistently underdetect patients that are clinically shown to have bacterial VAP based on clinical diagnostic criteria and response to antibiotic treatment. Routinely measured plasma biomarkers, including procalcitonin and C-reactive protein, lack sufficient precision and predictive accuracy to inform diagnosis. Novel rapid microbiological diagnostics, including nucleic-acid amplification, mass spectrometry, and fluorescence microscopy-based technologies are promising approaches for the future. Exhaled breath biomarkers, including measurement of volatile organic compounds, represent a future approach. The integration of novel diagnostics for rapid microbial identification, resistance phenotyping, and antibiotic sensitivity testing into usual care practice could significantly transform the care of patients and potentially inform significantly improved targeted antimicrobial selection, de-escalation, and stewardship.

18F-FDG-PET/CT Angiography for the Diagnosis of Infective Endocarditis.

PubMed

Roque, A; Pizzi, M N; Cuéllar-Calàbria, H; Aguadé-Bruix, S

2017-02-01

This article reviews the current imaging role of 18 F-fluordeoxyglucose positron emission computed tomography ( 18 F-FDG-PET/CT) combined with cardiac CT angiography (CTA) in infective endocarditis and discusses the strengths and limitations of this technique. The diagnosis of infective endocarditis affecting prosthetic valves and intracardiac devices is challenging because echocardiography and, therefore, the modified Duke criteria have well-recognized limitations in this clinical scenario. The high sensitivity of 18 F-FDG-PET/CT for the detection of infection associated with the accurate definition of structural damage by gated cardiac CTA in a combined technique (PET/CTA) has provided a significant increase in diagnostic sensitivity for the detection of IE. PET/CTA has proven to be a useful diagnostic tool in patients with suspected infective endocarditis. The additional information provided by this technique improves diagnostic performance in prosthetic valve endocarditis when it is used in combination with the Duke criteria. The findings obtained in PET/CTA studies have been included as a major criterion in the recently updated diagnostic algorithm in infective endocarditis guidelines.

Adulticidal Susceptibility Evaluation of Aedes albopictus Using New Diagnostic Doses in Penang Island, Malaysia.

PubMed

Rahim, Junaid; Ahmad, Abu H; Ahmad, Hamdan; Ishak, Intan H; Rus, Adanan Che; Maimusa, Hamisu A

2017-09-01

Insecticide-based vector control approaches are facing challenges due to the development of resistance in vector mosquitoes. Therefore, a proper resistance surveillance program using baseline lethal concentrations is crucial for resistance management strategies. Currently, the World Health Organization's (WHO) diagnostic doses established for Aedes aegypti and Anopheles species are being used to study the resistance status of Aedes albopictus. In this study, we established the diagnostic doses for permethrin, deltamethrin, and malathion using a known susceptible reference strain. Five field-collected populations were screened against these doses, following the WHO protocol. This study established the diagnostic dose of malathion at 2.4%, permethrin at 0.95%, and deltamethrin at 0.28%, which differ from the WHO doses for Aedes aegypti and Anopheles spp. Among the insecticides tested on the 5 wild populations, only deltamethrin showed high effectiveness. Different susceptibility and resistance patterns were observed with permethrin, malathion, and dichloro-diphenyl-trichloroethane (DDT) at 4%. This study may assist the health authorities to improve future chemical-based vector control operations in dengue-endemic areas.

Bacillus “next generation” diagnostics: moving from detection toward subtyping and risk-related strain profiling

PubMed Central

Ehling-Schulz, Monika; Messelhäusser, Ute

2013-01-01

The highly heterogeneous genus Bacillus comprises the largest species group of endospore forming bacteria. Because of their ubiquitous nature, Bacillus spores can enter food production at several stages resulting in significant economic losses and posing a potential risk to consumers due the capacity of certain Bacillus strains for toxin production. In the past, food microbiological diagnostics was focused on the determination of species using conventional culture-based methods, which are still widely used. However, due to the extreme intra-species diversity found in the genus Bacillus, DNA-based identification and typing methods are gaining increasing importance in routine diagnostics. Several studies showed that certain characteristics are rather strain-dependent than species-specific. Therefore, the challenge for current and future Bacillus diagnostics is not only the efficient and accurate identification on species level but also the development of rapid methods to identify strains with specific characteristics (such as stress resistance or spoilage potential), trace contamination sources, and last but not least discriminate potential hazardous strains from non-toxic strains. PMID:23440299

Recent Advances in Targeted, Self-Assembling Nanoparticles to Address Vascular Damage Due to Atherosclerosis

PubMed Central

Chung, Eun Ji; Tirrell, Matthew

2016-01-01

Self-assembling nanoparticles functionalized with targeting moieties have significant potential for atherosclerosis nanomedicine. While self-assembly allows for easy construction (and degradation) of nanoparticles with therapeutic or diagnostic functionality, or both, the targeting agent can direct them to a specific molecular marker within a given stage of the disease. Therefore, supramolecular nanoparticles have been investigated in the last decade as molecular imaging agents or explored as nanocarriers that can decrease the systemic toxicity of drugs by producing accumulation predominantly in specific tissues of interest. In this review, we first describe the pathogenesis of atherosclerosis and the damage caused to vascular tissue, as well as the current diagnostic and treatment options. Then we provide an overview of targeted strategies using self-assembling nanoparticles and include liposomes, high density lipoproteins, protein cages, micelles, proticles, and perfluorocarbon nanoparticles. Finally, we elaborate on and provide an overview of current challenges, limitations, and future applications for personalized medicine in the context of atherosclerosis of self-assembling nanoparticles. PMID:26085109

Soft matter assemblies as nanomedicine platforms for cancer chemotherapy: a journey from market products towards novel approaches.

PubMed

Jäger, Eliézer; Giacomelli, Fernando C

2015-01-01

The current review aims to outline the likely medical applications of nanotechnology and the potential of the emerging field of nanomedicine. Nanomedicine can be defined as the investigation area encompassing the design of diagnostics and therapeutics at the nanoscale, including nanobots, nanobiosensors, nanoparticles and other nanodevices, for the remediation, prevention and diagnosis of a variety of illnesses. The ultimate goal of nanomedicine is to improve patient quality-of-life. Because nanomedicine includes the rational design of an enormous number of nanotechnology-based products focused on miscellaneous diseases, a variety of nanomaterials can be employed. Therefore, this review will focus on recent advances in the manufacture of soft matterbased nanomedicines specifically designed to improve diagnostics and cancer chemotherapy efficacy. It will be particularly highlighted liposomes, polymer-drug conjugates, drug-loaded block copolymer micelles and biodegradable polymeric nanoparticles, emphasizing the current investigations and potential novel approaches towards overcoming the remaining challenges in the field as well as formulations that are in clinical trials and marketed products.

Combining in Vitro Diagnostics with in Vivo Imaging for Earlier Detection of Pancreatic Ductal Adenocarcinoma: Challenges and Solutions

PubMed Central

Laeseke, Paul F.; Chen, Ru; Jeffrey, R. Brooke; Brentnall, Teresa A.

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is the fourth-leading cause of cancer-related death in the United States and is associated with a dismal prognosis, particularly when diagnosed at an advanced stage. Overall survival is significantly improved if PDAC is detected at an early stage prior to the onset of symptoms. At present, there is no suitable screening strategy for the general population. Available diagnostic serum markers are not sensitive or specific enough, and clinically available imaging modalities are inadequate for visualizing early-stage lesions. In this article, the role of currently available blood biomarkers and imaging tests for the early detection of PDAC will be reviewed. Also, the emerging biomarkers and molecularly targeted imaging agents being developed to improve the specificity of current imaging modalities for PDAC will be discussed. A strategy incorporating blood biomarkers and molecularly targeted imaging agents could lead to improved screening and earlier detection of PDAC in the future. © RSNA, 2015 PMID:26599925

Diagnostics for invasive Salmonella infections: current challenges and future directions

PubMed Central

Andrews, Jason R.; Ryan, Edward T.

2015-01-01

Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results in frequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics. PMID:25937611

Diagnostics for invasive Salmonella infections: Current challenges and future directions.

PubMed

Andrews, Jason R; Ryan, Edward T

2015-06-19

Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results in frequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics. Copyright © 2015. Published by Elsevier Ltd.

Zika vaccines and therapeutics: landscape analysis and challenges ahead.

PubMed

Wilder-Smith, Annelies; Vannice, Kirsten; Durbin, Anna; Hombach, Joachim; Thomas, Stephen J; Thevarjan, Irani; Simmons, Cameron P

2018-06-06

Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines. Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome. Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.

Evaluation of nanoparticle immunotoxicity

NASA Astrophysics Data System (ADS)

Dobrovolskaia, Marina A.; Germolec, Dori R.; Weaver, James L.

2009-07-01

The pharmaceutical industry is developing increasing numbers of drugs and diagnostics based on nanoparticles, and evaluating the immune response to these diverse formulations has become a challenge for scientists and regulatory agencies alike. An international panel of scientists and representatives from various agencies and companies reviewed the imitations of current tests at a workshop held at the National Cancer Institute in Frederick, Maryland. This article outlines practical strategies for identifying and controlling interferences in common evaluation methods and the implications for regulation.

Primary small bowel adenocarcinoma: current view on clinical features, risk and prognostic factors, treatment and outcome.

PubMed

Lech, Gustaw; Korcz, Wojciech; Kowalczyk, Emilia; Słotwiński, Robert; Słodkowski, Maciej

2017-11-01

Small bowel adenocarcinoma (SBA) is a rare but increasing cause of gastrointestinal malignancy, being both a diagnostic and therapeutic challenge. The goal of treatment is margin negative resection of a lesion and local lymphadenectomy, followed by modern adjuvant chemotherapy combinations in selected cases. Improved outcomes in patients with SBA are encouraging, but elucidation of mechanisms of carcinogenesis and risk factors as well as improved treatment for this malignancy is very needed.

Laboratory medicine: challenges and opportunities.

PubMed

Bossuyt, Xavier; Verweire, Kurt; Blanckaert, Norbert

2007-10-01

Technologic innovations have substantially improved the productivity of clinical laboratories, but the services provided by clinical laboratories are increasingly becoming commoditized. We reflect on how current developments may affect the future of laboratory medicine and how to deal with these changes. We argue that to be prepared for the future, clinical laboratories should enhance efficiency and reduce costs by forming alliances and networks; consolidating, integrating, or outsourcing; and more importantly, create additional value by providing knowledge services related to in vitro diagnostics.

New Challenges in the Treatment of Patients With Left Ventricular Support: LVAD Thrombosis.

PubMed

Nguyen, Ann B; Uriel, Nir; Adatya, Sirtaz

2016-12-01

Mechanical circulatory support has revolutionized the treatment of heart failure, affording patients significantly improved survival and quality of life. However, further advancements in this technology have been hindered by adverse events, particularly gastrointestinal bleeding, driveline infection, stroke, and device thrombosis. Recently, there has been a renewed focus on device thrombosis as the reported incidence has increased. This review focuses on an update on the diagnostic modalities and current treatment algorithms of this serious complication.

Expanding Access to Malaria Diagnosis through Retail Shops in Western Kenya: What Do Shop Workers Think?

PubMed Central

Koech, Beatrice; Obala, Andrew; O'Meara, Wendy Prudhomme

2013-01-01

Background. The common symptoms of malaria reduce the specificity of clinical diagnosis. Presumptive treatment is conventional but can lead to overdiagnosis of malaria, delay of appropriate treatment, overprescription of antimalarials, and drug resistance. Routine use of diagnostic tests can address many of these concerns. Though treatment is often procured from retailers, there is low availability of rapid diagnostic tests for malaria (MRDTs), a simple, inexpensive, and accurate diagnostic solution. We know little about the challenges to expanding access to diagnostics through these outlets. Methods. To understand the perceptions of the benefits and challenges to selling rapid diagnostic tests for malaria, we conducted focus group discussions with antimalarial retailers who serve the residents of the Webuye Health and Demographic Surveillance Site in western Kenya. Results. Medicine retailers perceived MRDTs to be beneficial to their customers and businesses but also included cost, fear of the tests, risks of self-treatment, and regulatory concerns among the challenges to using and selling MRDTs. Conclusion. MRDTs represent a viable approach to increase access to malaria diagnostic testing. Medicine retailers are eager for MRDTs to be made available to them. However, certain challenges remain to implementation in retail outlets and should be addressed in advance. PMID:23766923

The current and future state of companion diagnostics

PubMed Central

Agarwal, Amit; Ressler, Dan; Snyder, Glenn

2015-01-01

Companion diagnostics are an indispensable part of personalized medicine and will likely continue to rapidly increase in number and application to disease areas. The first companion diagnostics were launched in the 1980s and in the face of significant initial skepticism from drug developers as to whether segmenting a drug’s market through a diagnostic was advisable. The commercial success of drugs such as Herceptin® (trastuzumab) and Gleevec® (imatinib), which both require testing with companion diagnostics before they can be prescribed, has moved the entire companion diagnostic field forward. From an initial start of a handful of oncology drugs with corresponding diagnostics, the field has expanded to include multiple therapeutic areas, and the number of combinations has grown by 12-fold. Based on drugs in clinical trials, the rapid growth will likely continue for the foreseeable future. This expansion of companion diagnostics will also have a global component as markets in Europe will evolve in a similar but not identical pattern as the US. One of the greatest challenges to future growth in companion diagnostics is aligning the incentives of all stakeholders. A major driver of growth will continue to be the economic incentives for drug developers to pair their products with diagnostics. However, diagnostic companies are caught between the conflicting demands of two major stakeholders, pharmaceutical companies on one hand and payers/providers on the other. Regulators are also becoming more demanding in aligning development time lines between drugs and diagnostics. In order to survive and prosper, diagnostic companies will need to think more broadly about companion diagnostics than the historical match between a specific drug and a single diagnostic. They will also have to continue the process of consolidation and global expansion that the industry has already begun. Despite these potential obstacles, companion diagnostics have become one of the hottest areas of deal making in the diagnostic space in recent years, and the future trends continue to look bright. PMID:25897259

Women's infertility: challenges for practice.

PubMed

Carryer, J; Maclean, S

1998-03-01

Infertility is an issue for men and women but it is women who experience the majority of the diagnostic and treatment procedures. Nurses and midwives care for women in a variety of settings in which infertility is managed. This management is currently characterised by an escalation in related technologies and there is the potential for prolonged and complex endeavours to achieve a pregnancy. This paper reviews some pertinent literature from nursing, medicine, feminist scholars and the popular press to consider the ways in which infertility is understood and experienced. The challenge for nurses and midwives is in negotiating the differing perspectives in order to provide appropriate care to each individual woman as she experiences infertility and its management.

The future of clinical cancer genomics.

PubMed

Offit, Kenneth

2016-10-01

The current and future applications of genomics to the practice of preventive oncology are being impacted by a number of challenges. These include rapid advances in genomic science and technology that allow massively parallel sequencing of both tumors and the germline, a diminishing of intellectual property restrictions on diagnostic genetic applications, rapid expansion of access to the internet which includes mobile access to both genomic data and tools to communicate and interpret genetic data in a medical context, the expansion of for-profit diagnostic companies seeking to monetize genetic information, and a simultaneous effort to depict medical professionals as barriers to rather than facilitators of understanding one's genome. Addressing each of these issues will be required to bring "personalized" germline genomics to cancer prevention and care. A profound future challenge will be whether clinical cancer genomics will be "de-medicalized" by commercial interests and their advocates, or whether the future course of this field can be modulated in a responsible way that protects the public health while implementing powerful new medical tools for cancer prevention and early detection. Copyright © 2016. Published by Elsevier Inc.

Full-course drug challenge test in the diagnosis of delayed allergic reactions to penicillin.

PubMed

Borch, Jakob E; Bindslev-Jensen, Carsten

2011-01-01

Drug challenge test (DCT) has long been the most sensitive test in the allergological work-up when investigating for penicillin allergy. To improve sensitivity of the diagnostic work-up in diagnosing penicillin allergics with histories of allergic reactions on day 2 or later in the course of penicillin treatment. A full-course DCT was added to the current protocol if specific IgE, skin tests and DCT were all negative in patients who had a nonimmediate reaction to penicillin treatment. Sixteen patients with a history of an immediate reaction to penicillin treatment underwent testing with negative outcomes. Fifty percent of patients undergoing full-course DCT experienced a cutaneous adverse drug reaction. None of the controls reacted (p = 0.001). The mean time of reaction was 6 days. Penicillin V accounted for most reactions. Urticaria was the most frequent clinical reaction observed. Full-course DCT offers an improvement of sensitivity and predictive values of the diagnostic work-up of allergic reactions to penicillin occurring on day 2 of penicillin treatment or later. Copyright © 2011 S. Karger AG, Basel.

[Molecular Genetics as Best Evidence in Glioma Diagnostics].

PubMed

Masui, Kenta; Komori, Takashi

2016-03-01

The development of a genomic landscape of gliomas has led to the internally consistent, molecularly-based classifiers. However, development of a biologically insightful classification to guide therapy is still ongoing. Further, tumors are heterogeneous, and they change and adapt in response to drugs. The challenge of developing molecular classifiers that provide meaningful ways to stratify patients for therapy remains a major challenge for the field. Therefore, by incorporating molecular markers into the new World Health Organization (WHO) classification of tumors of the central nervous system, the traditional principle of diagnosis based on histologic criteria will be replaced by a multilayered approach combining histologic features and molecular information in an "integrated diagnosis", to define tumor entities as narrowly as possible. We herein review the current status of diagnostic molecular markers for gliomas, focusing on IDH mutation, ATRX mutation, 1p/19q co-deletion, and TERT promoter mutation in adult tumors, as well as BRAF and H3F3A aberrations in pediatric gliomas, the combination of which will be a promising endeavor to render molecular genetics as a best evidence in the glioma diagnositics.

Reflections on market access for personalized medicine: recommendations for Europe.

PubMed

Payne, Katherine; Annemans, Lieven

2013-01-01

This article aims to provide an overview of the current literature focusing on the reimbursement of personalized medicine across the European Union. The article starts by describing types of perspectives that are possible (general public, patient, payer, provider, service commissioner, and policymaker). The description of perspectives also explains the importance of understanding the different possible decision criteria and processes from the various perspectives by taking into account budget constraints. The article then focuses on an example of personalized medicine, namely, the use of companion diagnostic-medicine combinations, to describe the role of reimbursement/payer agencies across the European Union to control the introduction and coverage of such companion diagnostic-medicine technologies. The article touches on the strategic challenges and the use of economic evidence to introduce personalized medicine from a health policy perspective. The article also draws on empirical studies that have explored patients' and clinicians' views of examples of personalized medicine to illustrate the challenges for developing patient-centered and timely health care services. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

Recent Trends in the Serologic Diagnosis of Syphilis

PubMed Central

Singh, Ameeta E.

2014-01-01

Complexities in the diagnosis of syphilis continue to challenge clinicians. While direct tests (e.g., microscopy or PCR) are helpful in early syphilis, the mainstay of diagnosis remains serologic tests. The traditional algorithm using a nontreponemal test (NTT) followed by a treponemal test (TT) remains the standard in many parts of the world. More recently, the ability to automate the TT has led to the increasingly widespread use of reverse algorithms using treponemal enzyme immunoassays (EIAs). Rapid, point-of-care TTs are in widespread use in developing countries because of low cost, ease of use, and reasonable performance. However, none of the current diagnostic algorithms are able to distinguish current from previously treated infections. In addition, the reversal of traditional syphilis algorithms has led to uncertainty in the clinical management of patients. The interpretation of syphilis tests is further complicated by the lack of a reliable gold standard for syphilis diagnostics, and the newer tests can result in false-positive reactions similar to those seen with older tests. Little progress has been made in the area of serologic diagnostics for congenital syphilis, which requires assessment of maternal treatment and serologic response as well as clinical and laboratory investigation of the neonate for appropriate management. The diagnosis of neurosyphilis continues to require the collection of cerebrospinal fluid for a combination of NTT and TT, and, while newer treponemal EIAs look promising, more studies are needed to confirm their utility. This article reviews current tests and discusses current controversies in syphilis diagnosis, with a focus on serologic tests. PMID:25428245

Impact of the diagnostic changes to post-traumatic stress disorder for DSM-5 and the proposed changes to ICD-11.

PubMed

O'Donnell, Meaghan L; Alkemade, Nathan; Nickerson, Angela; Creamer, Mark; McFarlane, Alexander C; Silove, Derrick; Bryant, Richard A; Forbes, David

2014-09-01

There have been changes to the criteria for diagnosing post-traumatic stress disorder (PTSD) in DSM-5 and changes are proposed for ICD-11. To investigate the impact of the changes to diagnostic criteria for PTSD in DSM-5 and the proposed changes in ICD-11 using a large multisite trauma-exposed sample and structured clinical interviews. Randomly selected injury patients admitted to four hospitals were assessed 72 months post trauma (n = 510). Structured clinical interviews for PTSD and major depressive episode, as well as self-report measures of disability and quality of life were administered. Current prevalence of PTSD under DSM-5 scoring was not significantly different from DSM-IV (6.7% v. 5.9%, z = 0.53, P = 0.59). However, the ICD-11 prevalence was significantly lower than ICD-10 (3.3% v. 9.0%, z = -3.8, P<0.001). The PTSD current prevalence was significantly higher for DSM-5 than ICD-11 (6.7% v. 3.3%, z = 2.5, P = 0.01). Using ICD-11 tended to show lower rates of comorbidity with depression and a slightly lower association with disability. The diagnostic systems performed in different ways in terms of current prevalence rates and levels of comorbidity with depression, but on other broad key indicators they were relatively similar. There was overlap between those with PTSD diagnosed by ICD-11 and DSM-5 but a substantial portion met one but not the other set of criteria. This represents a challenge for research because the phenotype that is studied may be markedly different according to the diagnostic system used. Royal College of Psychiatrists.

Disorders of Excessive Daytime Sleepiness Including Narcolepsy and Idiopathic Hypersomnia.

PubMed

Berkowski, Joseph Andrew; Shelgikar, Anita Valanju

2016-09-01

Central disorders of hypersomnolence are rare conditions with a poorly understood pathophysiology, making the identification and management challenging for sleep clinicians. Clinical history is essential for ruling out secondary causes of hypersomnolence and distinguishing among diagnoses. Current diagnostic criteria rely heavily on the polysomnogram and multiple sleep latency test. The current focus of treatment of hypersomnolence is on drugs that promote alertness. Additionally, in the case of narcolepsy type 1, medication management addresses control of cataplexy, the hallmark symptom of this disorder. Elucidation of pathophysiology of these disorders in the future will be essential to better categorization and management. Published by Elsevier Inc.

Biomimetic Cross-Reactive Sensor Arrays: Prospects in Biodiagnostics

PubMed Central

Fitzgerald, J. E.

2016-01-01

Biomimetic cross-reactive sensor arrays have been used to detect and analyze a wide variety of vapour and liquid components in applications such as food science, public health and safety, and diagnostics. As technology has advanced over the past three decades, these systems have become selective, sensitive, and affordable. Currently, the need for non-invasive and accurate devices for early disease diagnosis remains a challenge. This review provides an overview of the various types of Biomimetic cross-reactive sensor arrays (also referred to as electronic noses and tongues in the literature), their current use and future directions, and an outlook for future technological development. PMID:28217300

Applications of antibodies in microfluidics-based analytical systems: challenges and strategies for success

NASA Astrophysics Data System (ADS)

O’Kennedy, Richard; Fitzgerald, Jenny; Cassedy, Arabelle; Crawley, Aoife; Zhang, Xin; Carrera, Sandro

2018-06-01

This review is designed to focus on antibodies and the attributes that make them ideal for applications in microfluidics-based diagnostic/separation platforms. The structures of different antibody formats and how they can be engineered to be highly effective in microfluidics-based environments will be highlighted. Suggested novel stratagems on the ideal way in which they can be employed in microfluidics systems, based on an informed knowledge of their structures and properties rather than random choice selection, as is often currently employed, will be provided. Finally, a critical assessment of current shortcomings in the approaches used along with possible ways for their resolution will be given.

Diagnosis of Ebola Virus Disease: Past, Present, and Future

PubMed Central

Brooks, Tim J. G.

2016-01-01

SUMMARY Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward. PMID:27413095

The Roles and Developments needed for Diagnostics in the ITER Fusion Device

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walsh, Michael

2015-07-01

Harnessing the power from Fusion on earth is an important and challenging task. Excellent work has been carried out in this area over the years with several demonstrations of the ability to produce power. Now, a new large device is being constructed in the south of France. This is called ITER. ITER is a large-scale scientific experiment that aims to demonstrate a possibility to produce commercial energy from fusion. This project is now well underway with the many teams working on the construction and completing various aspects of the design. This device will carry up to 15 MA of plasmamore » current and produce about 500 MW of power, 400 MW approximately in high energy neutrons. The typical temperatures of the electrons inside this device are in the region of a few hundred million Kelvin. It is maintained using a magnetic field. This device is pushing several boundaries from those currently existing. As a result of this, several technologies need to be developed or extended. This is especially true for the systems or diagnostics that measure the performance and provide the control signals for this device. A diagnostic set will be installed on the ITER machine to provide the measurements necessary to control, evaluate and optimize plasma performance in ITER and to further the understanding of plasma physics. These include amongst others, measurements of the plasma shape, temperature, density, impurity concentration, and particle and energy confinement times. The system will comprise about 45 individual measuring systems drawn from the full range of modern plasma diagnostic techniques, including magnetics, lasers, X-rays, neutron cameras, impurity monitors, particle spectrometers, radiation bolometers, pressure and gas analysis, and optical fibres. These devices will have to be made to work in the new and challenging environment inside the vacuum vessel. These systems will have to cope with a range of phenomena that extend the current knowledge in the Fusion field. One amongst them is the parasitic effect of the neutrons on the while all the performing with great accuracy and precision. The levels of neutral particle flux, neutron flux and neutron fluence will be respectively about 5, 10 and 10,000 times higher than the harshest experienced in today's machines. The pulse length of the fusion reaction-or the amount of time the reaction is sustained-will be about 100 times longer. (authors)« less

Improving the Accessibility and Efficiency of Point-of-Care Diagnostics Services in Low- and Middle-Income Countries: Lean and Agile Supply Chain Management.

PubMed

Kuupiel, Desmond; Bawontuo, Vitalis; Mashamba-Thompson, Tivani P

2017-11-29

Access to point-of-care (POC) diagnostics services is essential for ensuring rapid disease diagnosis, management, control, and surveillance. POC testing services can improve access to healthcare especially where healthcare infrastructure is weak and access to quality and timely medical care is a challenge. Improving the accessibility and efficiency of POC diagnostics services, particularly in resource-limited settings, may be a promising route to improving healthcare outcomes. In this review, the accessibility of POC testing is defined as the distance/proximity to the nearest healthcare facility for POC diagnostics service. This review provides an overview of the impact of POC diagnostics on healthcare outcomes in low- and middle-income countries (LMICs) and factors contributing to the accessibility of POC testing services in LMICs, focusing on characteristics of the supply chain management and quality systems management, characteristics of the geographical location, health infrastructure, and an enabling policy framework for POC diagnostics services. Barriers and challenges related to the accessibility of POC diagnostics in LMICs were also discussed. Bearing in mind the reported barriers and challenges as well as the disease epidemiology in LMICs, we propose a lean and agile supply chain management framework for improving the accessibility and efficiency of POC diagnostics services in these settings.

Accelerating the Development and Validation of New Value-Based Diagnostics by Leveraging Biobanks.

PubMed

Schneider, Daniel; Riegman, Peter H J; Cronin, Maureen; Negrouk, Anastassia; Moch, Holger; Balling, Rudi; Penault-Llorca, Frederiques; Zatloukal, Kurt; Horgan, Denis

The challenges faced in developing value-based diagnostics has resulted in few of these tests reaching the clinic, leaving many treatment modalities without matching diagnostics to select patients for particular therapies. Many patients receive therapies from which they are unlikely to benefit, resulting in worse outcomes and wasted health care resources. The paucity of value-based diagnostics is a result of the scientific challenges in developing predictive markers, specifically: (1) complex biology, (2) a limited research infrastructure supporting diagnostic development, and (3) the lack of incentives for diagnostic developers to invest the necessary resources. Better access to biospecimens can address some of these challenges. Methodologies developed to evaluate biomarkers from biospecimens archived from patients enrolled in randomized clinical trials offer the greatest opportunity to develop and validate high-value molecular diagnostics. An alternative opportunity is to access high-quality biospecimens collected from large public and private longitudinal observational cohorts such as the UK Biobank, the US Million Veteran Program, the UK 100,000 Genomes Project, or the French E3N cohort. Value-based diagnostics can be developed to work in a range of samples including blood, serum, plasma, urine, and tumour tissue, and better access to these high-quality biospecimens with clinical data can facilitate biomarker research. © 2016 S. Karger AG, Basel.

Improving the Accessibility and Efficiency of Point-of-Care Diagnostics Services in Low- and Middle-Income Countries: Lean and Agile Supply Chain Management

PubMed Central

Kuupiel, Desmond; Bawontuo, Vitalis

2017-01-01

Access to point-of-care (POC) diagnostics services is essential for ensuring rapid disease diagnosis, management, control, and surveillance. POC testing services can improve access to healthcare especially where healthcare infrastructure is weak and access to quality and timely medical care is a challenge. Improving the accessibility and efficiency of POC diagnostics services, particularly in resource-limited settings, may be a promising route to improving healthcare outcomes. In this review, the accessibility of POC testing is defined as the distance/proximity to the nearest healthcare facility for POC diagnostics service. This review provides an overview of the impact of POC diagnostics on healthcare outcomes in low- and middle-income countries (LMICs) and factors contributing to the accessibility of POC testing services in LMICs, focusing on characteristics of the supply chain management and quality systems management, characteristics of the geographical location, health infrastructure, and an enabling policy framework for POC diagnostics services. Barriers and challenges related to the accessibility of POC diagnostics in LMICs were also discussed. Bearing in mind the reported barriers and challenges as well as the disease epidemiology in LMICs, we propose a lean and agile supply chain management framework for improving the accessibility and efficiency of POC diagnostics services in these settings. PMID:29186013

Diagnostic challenges of childhood asthma.

PubMed

Bakirtas, Arzu

2017-01-01

Diagnosis of asthma in childhood is challenging. Both underdiagnosis and overdiagnosis of asthma are important issues. The present review gives information about challenging factors for an accurate diagnosis of childhood asthma. Although underdiagnosis of asthma in childhood has always been the most important diagnostic problem, overdiagnosis of asthma has also been increasingly recognized. This is probably due to diagnosis of asthma based on symptoms and signs alone. Demonstration of variable airflow obstruction by lung function tests is the most common asthma diagnostic tests used in practice and is therefore strongly recommended in children who can cooperate. Recently, an asthma guideline combining the clinical and economic evidences with sensitivity and specificity of diagnostic procedures was developed to improve accuracy of diagnosis and to avoid overdiagnosis. This guideline provided an algorithmic clinical and cost-effective approach and included fractional exhaled nitric oxide measurement as one of the diagnostic tests in addition to lung function. Diagnosis of asthma in children should be made by combining relevant history with at least two confirmatory diagnostic tests whenever possible. Diagnosis based on short-period treatment trials should be limited to young children who are unable to cooperate with these tests.

Challenges of implementing fibromyalgia treatment guidelines in current clinical practice.

PubMed

Arnold, Lesley M; Clauw, Daniel J

2017-09-01

The current diagnostic and treatment pathway for patients with fibromyalgia (FM) is lengthy, complex, and characterized by multiple physician visits with an average 2-year wait until diagnosis. It is clear that effective identification and appropriate treatment of FM remain a challenge in current clinical practice. Ideally, FM management involves a multidisciplinary approach with the preferable patient pathway originating in primary care but supported by a range of health care providers, including referral to specialist care when necessary. After the publication of individual clinical studies, high-quality reviews, and meta-analyses, recently published FM treatment guidelines have transitioned from an expert consensus to an evidence-based approach. Evidence-based guidelines provide a framework for ensuring early diagnosis and timely adoption of appropriate treatment. However, for successful outcomes, FM treatments must adopt a more holistic approach, which addresses more than just pain. Impact on the associated symptoms of fatigue and cognitive problems, sleep and mood disturbances, and lowered functional status are also important in judging the success of FM therapy. Recently published guidelines recommend the adoption of a symptom-based approach to guide pharmacologic treatment. Emerging treatment options for FM may be best differentiated on the basis of their effect on comorbid symptoms that are often associated with pain (e.g. sleep disturbance, mood, fatigue). The current review discusses the most recently published Canadian guidelines and the implications of the recent European League Against Rheumatism (EULAR) recommendations, with a focus on the challenges of implementing these guidelines in current clinical practice.

Microfluidic technology for molecular diagnostics.

PubMed

Robinson, Tom; Dittrich, Petra S

2013-01-01

Molecular diagnostics have helped to improve the lives of millions of patients worldwide by allowing clinicians to diagnose patients earlier as well as providing better ongoing therapies. Point-of-care (POC) testing can bring these laboratory-based techniques to the patient in a home setting or to remote settings in the developing world. However, despite substantial progress in the field, there still remain many challenges. Progress in molecular diagnostics has benefitted greatly from microfluidic technology. This chapter aims to summarise the more recent advances in microfluidic-based molecular diagnostics. Sections include an introduction to microfluidic technology, the challenges of molecular diagnostics, how microfluidic advances are working to solve these issues, some alternative design approaches, and detection within these systems.

Genetic tests in major psychiatric disorders-integrating molecular medicine with clinical psychiatry-why is it so difficult?

PubMed

Demkow, U; Wolańczyk, T

2017-06-13

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays' medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease.

Genetic tests in major psychiatric disorders—integrating molecular medicine with clinical psychiatry—why is it so difficult?

PubMed Central

Demkow, U; Wolańczyk, T

2017-01-01

With the advent of post-genomic era, new technologies create extraordinary possibilities for diagnostics and personalized therapy, transforming todays’ medicine. Rooted in both medical genetics and clinical psychiatry, the paper is designed as an integrated source of information of the current and potential future application of emerging genomic technologies as diagnostic tools in psychiatry, moving beyond the classical concept of patient approach. Selected approaches are presented, starting from currently used technologies (next-generation sequencing (NGS) and microarrays), followed by newer options (reverse phenotyping). Next, we describe an old concept in a new light (endophenotypes), subsequently coming up with a sophisticated and complex approach (gene networks) ending by a nascent field (computational psychiatry). The challenges and barriers that exist to translate genomic research to real-world patient assessment are further discussed. We emphasize the view that only a paradigm shift can bring a fundamental change in psychiatric practice, allowing to disentangle the intricacies of mental diseases. All the diagnostic methods, as described, are directed at uncovering the integrity of the system including many types of relations within a complex structure. The integrative system approach offers new opportunity to connect genetic background with specific diseases entities, or concurrently, with symptoms regardless of a diagnosis. To advance the field, we propose concerted cross-disciplinary effort to provide a diagnostic platform operating at the general level of genetic pathogenesis of complex-trait psychiatric disorders rather than at the individual level of a specific disease. PMID:28608853

Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Tulla, Kiara A; Maker, Ajay V

2018-03-01

Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia. A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines. Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia. Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.

Clinical Diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the Literature and Suggested Diagnostic Criteria

PubMed Central

Valtonen, Ville

2017-01-01

A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient’s history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS. PMID:28848553

Clinical Diagnosis of the Dampness and Mold Hypersensitivity Syndrome: Review of the Literature and Suggested Diagnostic Criteria.

PubMed

Valtonen, Ville

2017-01-01

A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient's history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS.

Peptidomics of urine and other biofluids for cancer diagnostics.

PubMed

Bauça, Josep Miquel; Martínez-Morillo, Eduardo; Diamandis, Eleftherios P

2014-08-01

Cancer is a leading cause of death worldwide. The low diagnostic sensitivity and specificity of most current cancer biomarkers make early cancer diagnosis a challenging task. The comprehensive study of peptides and small proteins in a living system, known as "peptidomics," represents an alternative technological approach to the discovery of potential biomarkers for the assessment of a wide variety of pathologies. This review examines the current status of peptidomics for several body fluids, with a focus on urine, for cancer diagnostics applications. Several studies have used high-throughput technologies to characterize the peptide content of different body fluids. Because of its noninvasive collection and high stability, urine is a valuable source of candidate cancer biomarkers. A wide variety of preanalytical issues concerning patient selection and sample handling need to be considered, because not doing so can affect the quality of the results by introducing bias and artifacts. Optimization of both the analytical strategies and the processing of bioinformatics data is also essential to minimize the false-discovery rate. Peptidomics-based studies of urine and other body fluids have yielded a number of biomolecules and peptide panels with potential for diagnosing different types of cancer, especially of the ovary, prostate, and bladder. Large-scale studies are needed to validate these molecules as cancer biomarkers. © 2013 American Association for Clinical Chemistry.

Tuberculosis of hip: A current concept review

PubMed Central

Saraf, Shyam Kumar; Tuli, Surendra Mohan

2015-01-01

Tuberculosis (TB) of the hip is second to spine only hence a good number of cases are visiting the medical facilities every year. Many present in the advanced stage of the disease due to delayed diagnosis. In early stages of TB of hip, there is a diagnostic dilemma when plain X-rays are negative. In the present time, diagnostic modalities have improved from the days when diagnosis was based essentially on clinicoradiological presentation alone. By the time definite radiological changes appear on plain X-ray, the disease has moderately advanced. The modern diagnostic facilities like ultrasonography (USG) or magnetic resonance imaging of the hip joint, USG guided aspiration of synovial fluid and obtaining the material for polymerase chain reaction and tissue diagnosis must be utilized. In the treatment, current emphasis is more on mobility with stability at hip. Joint debridement, skeletal traction, and mobilization exercises may give more satisfying results as compared to the immobilization by hip spica. Adults with advanced arthritis and healed infection should be informed and discussed the various treatment modalities including the joint replacement. More and more surgeons are taking up the challenge of putting the total hip replacement in the active stage of the disease. Until the long term results in active disease are well established, we recommend it for the healed disease only in selected cases. PMID:25593352

Tuberculosis of hip: A current concept review.

PubMed

Saraf, Shyam Kumar; Tuli, Surendra Mohan

2015-01-01

Tuberculosis (TB) of the hip is second to spine only hence a good number of cases are visiting the medical facilities every year. Many present in the advanced stage of the disease due to delayed diagnosis. In early stages of TB of hip, there is a diagnostic dilemma when plain X-rays are negative. In the present time, diagnostic modalities have improved from the days when diagnosis was based essentially on clinicoradiological presentation alone. By the time definite radiological changes appear on plain X-ray, the disease has moderately advanced. The modern diagnostic facilities like ultrasonography (USG) or magnetic resonance imaging of the hip joint, USG guided aspiration of synovial fluid and obtaining the material for polymerase chain reaction and tissue diagnosis must be utilized. In the treatment, current emphasis is more on mobility with stability at hip. Joint debridement, skeletal traction, and mobilization exercises may give more satisfying results as compared to the immobilization by hip spica. Adults with advanced arthritis and healed infection should be informed and discussed the various treatment modalities including the joint replacement. More and more surgeons are taking up the challenge of putting the total hip replacement in the active stage of the disease. Until the long term results in active disease are well established, we recommend it for the healed disease only in selected cases.

MO-E-12A-01: Quantitative Imaging: Techniques, Applications, and Challenges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, E; Jeraj, R; McNitt-Gray, M

The first symposium in the Quantitative Imaging Track focused on the introduction of quantitative imaging (QI) by illustrating the potential of QI in diagnostic and therapeutic applications in research and patient care, highlighting key challenges in implementation of such QI applications, and reviewing QI efforts of selected national and international agencies and organizations, including the FDA, NCI, NIST, and RSNA. This second QI symposium will focus more specifically on the techniques, applications, and challenges of QI. The first talk of the session will focus on modalityagnostic challenges of QI, beginning with challenges of the development and implementation of QI applicationsmore » in single-center, single-vendor settings and progressing to the challenges encountered in the most general setting of multi-center, multi-vendor settings. The subsequent three talks will focus on specific QI challenges and opportunities in the modalityspecific settings of CT, PET/CT, and MR. Each talk will provide information on modality-specific QI techniques, applications, and challenges, including current efforts focused on solutions to such challenges. Learning Objectives: Understand key general challenges of QI application development and implementation, regardless of modality. Understand selected QI techniques and applications in CT, PET/CT, and MR. Understand challenges, and potential solutions for such challenges, for the applications presented for each modality.« less

Laboratory Diagnosis of Tuberculosis in Resource-Poor Countries: Challenges and Opportunities

PubMed Central

Parsons, Linda M.; Somoskövi, Ákos; Gutierrez, Cristina; Lee, Evan; Paramasivan, C. N.; Abimiku, Alash'le; Spector, Steven; Roscigno, Giorgio; Nkengasong, John

2011-01-01

Summary: With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a country's national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each country's laboratory network. PMID:21482728

Active spectroscopic measurements using the ITER diagnostic system.

PubMed

Thomas, D M; Counsell, G; Johnson, D; Vasu, P; Zvonkov, A

2010-10-01

Active (beam-based) spectroscopic measurements are intended to provide a number of crucial parameters for the ITER device being built in Cadarache, France. These measurements include the determination of impurity ion temperatures, absolute densities, and velocity profiles, as well as the determination of the plasma current density profile. Because ITER will be the first experiment to study long timescale (∼1 h) fusion burn plasmas, of particular interest is the ability to study the profile of the thermalized helium ash resulting from the slowing down and confinement of the fusion alphas. These measurements will utilize both the 1 MeV heating neutral beams and a dedicated 100 keV hydrogen diagnostic neutral beam. A number of separate instruments are being designed and built by several of the ITER partners to meet the different spectroscopic measurement needs and to provide the maximum physics information. In this paper, we describe the planned measurements, the intended diagnostic ensemble, and we will discuss specific physics and engineering challenges for these measurements in ITER.

Right ventricular sarcoidosis: is it time for updated diagnostic criteria?

PubMed

Vakil, Kairav; Minami, Elina; Fishbein, Daniel P

2014-04-01

A 55-year-old woman with a history of complete heart block, atrial flutter, and progressive right ventricular failure was referred to our tertiary care center to be evaluated for cardiac transplantation. The patient's clinical course included worsening right ventricular dysfunction for 3 years before the current evaluation. Our clinical findings raised concerns about arrhythmogenic right ventricular cardiomyopathy. Noninvasive imaging, including a positron emission tomographic scan, did not reveal obvious myocardial pathologic conditions. Given the end-stage nature of the patient's right ventricular failure and her dependence on inotropic agents, she underwent urgent listing and subsequent heart transplantation. Pathologic examination of the explanted heart revealed isolated right ventricular sarcoidosis with replacement fibrosis. Biopsy samples of the cardiac allograft 6 months after transplantation showed no recurrence of sarcoidosis. This atypical presentation of isolated cardiac sarcoidosis posed a considerable diagnostic challenge. In addition to discussing the patient's case, we review the relevant medical literature and discuss the need for updated differential diagnostic criteria for end-stage right ventricular failure that mimics arrhythmogenic right ventricular cardiomyopathy.

Ion Traps at the Sun: Implications for Elemental Fractionation

NASA Astrophysics Data System (ADS)

Fleishman, Gregory D.; Musset, Sophie; Bommier, Véronique; Glesener, Lindsay

2018-04-01

Why the tenuous solar outer atmosphere, or corona, is much hotter than the underlying layers remains one of the greatest challenges for solar modeling. Detailed diagnostics of the coronal thermal structure come from extreme ultraviolet (EUV) emission. The EUV emission is produced by heavy ions in various ionization states and depends on the amount of these ions and on plasma temperature and density. Any nonuniformity of the elemental distribution in space or variability in time affects thermal diagnostics of the corona. Here we theoretically predict ionized chemical element concentrations in some areas of the solar atmosphere, where the electric current is directed upward. We then detect these areas observationally, by comparing the electric current density with the EUV brightness in an active region. We found a significant excess in EUV brightness in the areas with positive current density rather than negative. Therefore, we report the observational discovery of substantial concentrations of heavy ions in current-carrying magnetic flux tubes, which might have important implications for the elemental fractionation in the solar corona known as the first ionization potential effect. We call such areas of heavy ion concentration the “ion traps.” These traps hold enhanced ion levels until they are disrupted by a flare, whether large or small.

Counting individual ions in the air by tagging them with particles

NASA Astrophysics Data System (ADS)

Gorbunov, B.

2017-07-01

The quantification of ultra-low concentrations of molecules and ions in gases is of fundamental and practical importance for science and technology, for example, the detection of explosives in airports or biomarkers in medical diagnostics. Often the Faraday cup is employed to transfer ion concentrations in an electric current that is then amplified and measured. One of the main challenges is to increase the sensitivity of detection. A novel concept has been developed that enables detection of individual ions in gases by tagging them with neutral nano-objects. The concentration of ionized molecules was measured and a detection limit of 5 cm-3 was observed. It is anticipated that this concept opens doors for advances in detection sensitivity for many applications including security, medical diagnostic, trace chemical analysis.

[Thromboembolism prophylaxis in old age].

PubMed

Röhrig, Gabriele; Kolb, Gerald

2018-04-01

Anticoagulation in geriatric patients is challenging regarding the risk of bleeding complications and thromboembolic problems. Age, comorbidities, such as renal insufficiency and polymedication have a vital impact on bleeding and thromboembolic risks; however, age is not an exclusion criterion for withholding anticoagulation. Age is the main risk factor for deep vein thrombosis and atrial fibrillation becomes more relevant with aging. Older patients with atrial fibrillation have a particularly high risk of having a stroke. Therefore, very old patients benefit particularly from oral anticoagulation because the risk of bleeding is outweighed by the clinical benefit of stroke prevention. Risk of bleeding and thromboembolic problems can be easily assessed by established diagnostic tools. This article reviews the epidemiology of thromboembolic problems in the aged as well as current diagnostic and therapeutic steps for primary and secondary prevention.

Blood-based diagnostics of traumatic brain injuries

PubMed Central

Mondello, Stefania; Muller, Uwe; Jeromin, Andreas; Streeter, Jackson; Hayes, Ronald L; Wang, Kevin KW

2011-01-01

Traumatic brain injury is a major health and socioeconomic problem that affects all societies. However, traditional approaches to the classification of clinical severity are the subject of debate and are being supplemented with structural and functional neuroimaging, as the need for biomarkers that reflect elements of the pathogenetic process is widely recognized. Basic science research and developments in the field of proteomics have greatly advanced our knowledge of the mechanisms involved in damage and have led to the discovery and rapid detection of new biomarkers that were not available previously. However, translating this research for patients' benefits remains a challenge. In this article, we summarize new developments, current knowledge and controversies, focusing on the potential role of these biomarkers as diagnostic, prognostic and monitoring tools of brain-injured patients. PMID:21171922

Ductal carcinoma in situ of the breast: can biomarkers improve current management?

PubMed

Bartlett, John M S; Nofech-Moses, Sharon; Rakovitch, Eileen

2014-01-01

Screening for invasive cancer has led to a marked increase in the detection of ductal carcinoma in situ (DCIS). DCIS is, if appropriately managed, a low-risk disease which has a small chance of impacting on patient life expectancy. However, despite significant advances in prognostic marker development in invasive breast cancer, there are no validated diagnostic assays to inform treatment choice for women with DCIS. Therefore we are unable to target effective treatment strategies to women at high risk and avoid over-treatment of women at low risk of progression to invasive breast cancer. Paradoxically, one effect of this uncertainty is undertreatment of some women. We review current practice and research in the field to identify key challenges in the management of DCIS. The impact of clinical research, particularly on the over and undertreatment of women with DCIS is assessed. We note slow progress toward development of diagnostic biomarkers and highlight key opportunities to accelerate advances in this area. DCIS is a low-risk disease, its incidence is increasing, and current treatment is effective. However, many women are either over- or undertreated. Despite repeated calls for development of diagnostic biomarkers, progress in this area has been slow, reflecting a relative lack of investment of research effort and funding. Given the low event rate in treated patients and the lateness of recurrences, many previous studies have only limited power to identify independent prognostic and predictive biomarkers. However, the potential for such biomarkers to personalize treatment for DCIS is extremely high.

The radio-frequency fluctuation effect on the floating harmonic method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jaewon; Kim, Kyung-Hyun; Kim, Dong-Hwan

2016-08-15

The radio-frequency (RF) plasma diagnostics with an electrical probe facing a challenge, because the RF fluctuation oscillates the plasma potential and distorts the current-voltage (I-V) curve. As Langmuir probe is widely used in plasma diagnostics, many researchers have been studying the effect of RF fluctuation on probe and compensation methods. On the other hand, there have not been enough studies on the fluctuation effect on the floating harmonic method. Therefore, we investigated the impact of RF fluctuation on the floating harmonic method theoretically and experimentally. When the electrons are in ideal Maxwellian distribution, the floating potential is negatively shifted bymore » the RF fluctuation, but the fluctuation does not distort I-V curve around the floating potential. However, in practical plasmas, the I-V curve and their harmonic components are distorted. This RF fluctuation effect becomes more significant in a low density plasma with a high impedance sheath. The second harmonic current decreases with the RF fluctuation while the first harmonic current is merely affected. Therefore, the electron temperatures measured with the floating harmonic method under low density plasma with uncompensated probe are overestimated than the results obtained with the compensated probe.« less

Automated Quantitative Nuclear Cardiology Methods

PubMed Central

Motwani, Manish; Berman, Daniel S.; Germano, Guido; Slomka, Piotr J.

2016-01-01

Quantitative analysis of SPECT and PET has become a major part of nuclear cardiology practice. Current software tools can automatically segment the left ventricle, quantify function, establish myocardial perfusion maps and estimate global and local measures of stress/rest perfusion – all with minimal user input. State-of-the-art automated techniques have been shown to offer high diagnostic accuracy for detecting coronary artery disease, as well as predict prognostic outcomes. This chapter briefly reviews these techniques, highlights several challenges and discusses the latest developments. PMID:26590779

Managing the genomic revolution in cancer diagnostics.

PubMed

Nguyen, Doreen; Gocke, Christopher D

2017-08-01

Molecular tumor profiling is now a routine part of patient care, revealing targetable genomic alterations and molecularly distinct tumor subtypes with therapeutic and prognostic implications. The widespread adoption of next-generation sequencing technologies has greatly facilitated clinical implementation of genomic data and opened the door for high-throughput multigene-targeted sequencing. Herein, we discuss the variability of cancer genetic profiling currently offered by clinical laboratories, the challenges of applying rapidly evolving medical knowledge to individual patients, and the need for more standardized population-based molecular profiling.

Gastrointestinal Bleeding.

PubMed

Nable, Jose V; Graham, Autumn C

2016-05-01

Acute gastrointestinal bleeding is a commonly encountered chief complaint with a high morbidity and mortality. The emergency physician is challenged with prompt diagnosis, accurate risk assessment, and appropriate resuscitation of patients with gastrointestinal bleeding. Goals of care aim to prevent end-organ injury, manage comorbid illnesses, identify the source of bleeding, stop continued bleeding, support oxygen carrying capacity, and prevent rebleeding. This article reviews current strategies for risk stratification, diagnostic modalities, localization of bleeding, transfusion strategies, adjunct therapies, and reversal of anticoagulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Current Challenges in the First Principle Quantitative Modelling of the Lower Hybrid Current Drive in Tokamaks

NASA Astrophysics Data System (ADS)

Peysson, Y.; Bonoli, P. T.; Chen, J.; Garofalo, A.; Hillairet, J.; Li, M.; Qian, J.; Shiraiwa, S.; Decker, J.; Ding, B. J.; Ekedahl, A.; Goniche, M.; Zhai, X.

2017-10-01

The Lower Hybrid (LH) wave is widely used in existing tokamaks for tailoring current density profile or extending pulse duration to steady-state regimes. Its high efficiency makes it particularly attractive for a fusion reactor, leading to consider it for this purpose in ITER tokamak. Nevertheless, if basics of the LH wave in tokamak plasma are well known, quantitative modeling of experimental observations based on first principles remains a highly challenging exercise, despite considerable numerical efforts achieved so far. In this context, a rigorous methodology must be carried out in the simulations to identify the minimum number of physical mechanisms that must be considered to reproduce experimental shot to shot observations and also scalings (density, power spectrum). Based on recent simulations carried out for EAST, Alcator C-Mod and Tore Supra tokamaks, the state of the art in LH modeling is reviewed. The capability of fast electron bremsstrahlung, internal inductance li and LH driven current at zero loop voltage to constrain all together LH simulations is discussed, as well as the needs of further improvements (diagnostics, codes, LH model), for robust interpretative and predictive simulations.

View of the Challenger's payload bay and the Plasma Diagnostic package

NASA Image and Video Library

1985-08-01

51F-33-024 (29 July-6 Aug 1985) --- The Challenger's remote manipulator system (RMS) arm grasps the plasma diagnostics package (PDP) over the experiment-laden cargo bay of the earth orbiting spacecraft. The instrument pointing system, in a resting mode here, is prominent in the bay.

Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach.

PubMed

Mitsakakis, Konstantinos; Hin, Sebastian; Müller, Pie; Wipf, Nadja; Thomsen, Edward; Coleman, Michael; Zengerle, Roland; Vontas, John; Mavridis, Konstantinos

2018-02-03

Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium , is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools. In the field of vectors, an essential component of control programs is the detection of Plasmodium species within its mosquito vectors, particularly in the salivary glands, where the infective sporozoites reside. In addition, the identification of species composition and insecticide resistance alleles within vector populations is a primary task in routine monitoring activities, aiming to support control efforts. In this context, the use of converging diagnostics is highly desirable for providing comprehensive information, including differential fever diagnosis in humans, and mosquito species composition, infection status, and resistance to insecticides of vectors. Nevertheless, the two fields of human diagnostics and vector control are rarely combined, both at the diagnostic and at the data management end, resulting in fragmented data and mis- or non-communication between various stakeholders. To this direction, molecular technologies, their integration in automated platforms, and the co-assessment of data from multiple diagnostic sources through information and communication technologies are possible pathways towards a unified human vector approach.

Converging Human and Malaria Vector Diagnostics with Data Management towards an Integrated Holistic One Health Approach

PubMed Central

Mitsakakis, Konstantinos; Hin, Sebastian; Wipf, Nadja; Coleman, Michael; Zengerle, Roland; Vontas, John; Mavridis, Konstantinos

2018-01-01

Monitoring malaria prevalence in humans, as well as vector populations, for the presence of Plasmodium, is an integral component of effective malaria control, and eventually, elimination. In the field of human diagnostics, a major challenge is the ability to define, precisely, the causative agent of fever, thereby differentiating among several candidate (also non-malaria) febrile diseases. This requires genetic-based pathogen identification and multiplexed analysis, which, in combination, are hardly provided by the current gold standard diagnostic tools. In the field of vectors, an essential component of control programs is the detection of Plasmodium species within its mosquito vectors, particularly in the salivary glands, where the infective sporozoites reside. In addition, the identification of species composition and insecticide resistance alleles within vector populations is a primary task in routine monitoring activities, aiming to support control efforts. In this context, the use of converging diagnostics is highly desirable for providing comprehensive information, including differential fever diagnosis in humans, and mosquito species composition, infection status, and resistance to insecticides of vectors. Nevertheless, the two fields of human diagnostics and vector control are rarely combined, both at the diagnostic and at the data management end, resulting in fragmented data and mis- or non-communication between various stakeholders. To this direction, molecular technologies, their integration in automated platforms, and the co-assessment of data from multiple diagnostic sources through information and communication technologies are possible pathways towards a unified human vector approach. PMID:29401670

Role of nasal challenge and local eosinophilia in indirect exposure to cat in allergic rhinitis patients.

PubMed

Al Ahmad, M; Arifhodzic, N; Nurkic, J; Jusufovic, E; Hanoun, A L; Rodriguez, T

2018-01-17

Introduction. Sensitization to cat allergens is common worldwide. Currently, there is a trend towards costly and often unavailable diagnostic analysis. Objectives. The aim is to assess the reliability of skin prick test (SPT) and serum specific IgE (ssIgE) to cat sensitization, by performing nasal challenge test (NCT) in a community with low cat ownership but common presence of stray cats. Patients and methods. Forty-one pa-tients with perennial allergic rhinitis (AR) who were mono or polysensitized (including cat) were included. We had 31 cat non-owners and 10 present cat owners. SPT (> 5 mm / diameter), ssIgE (≥ 0.70 IU/ml), nasal smear for eosinophil (Eo) and NCT were compared between groups. Outcomes included nasal challenge score, nasal Eo positivity, peak inspiratory and expiratory flow (PIF and PEF) 2 and 8 hours after the NCT, and were compared to baseline. Results. Baseline SPT wheal size and ssIgE level were similar in both groups. NCT positivity was more frequent in cat owners. The strongest nasal reaction was on the top concentration in both groups. Nasal Eo positivity in cat owners was higher before and 2 hours after NCT, but similar to non-owners at last measurement. NCT positive cat non-owners had bigger SPT wheal size than NCT negative non-owners, but smaller than NCT positive cat owners. In contrast to PEF, a significant fall in PIF was noticed in both groups. Mono and polysensitised patients showed similar NCT positivity. Conclusion. Stray cats may pose a relevant risk of developing perennial AR. Regardless of cat ownership status, SPT and ssIgE should be the first diagnostic tool. Nasal Eo and NCT seem to be good diagnostic tools in cat non-owners if diagnosis is elusive.

Tuberculosis control in prisons: current situation and research gaps.

PubMed

Dara, Masoud; Acosta, Colleen D; Melchers, Natalie V S Vinkeles; Al-Darraji, Haider A A; Chorgoliani, Dato; Reyes, Hernan; Centis, Rosella; Sotgiu, Giovanni; D'Ambrosio, Lia; Chadha, Sarabjit S; Migliori, Giovanni Battista

2015-03-01

Tuberculosis (TB) in penitentiary services (prisons) is a major challenge to TB control. This review article describes the challenges that prison systems encounter in TB control and provides solutions for the more efficient use of limited resources based on the three pillars of the post-2015 End TB Strategy. This paper also proposes research priorities for TB control in prisons based on current challenges. Articles (published up to 2011) included in a recent systematic review on TB control in prisons were further reviewed. In addition, relevant articles in English (published 1990 to May 2014) were identified by searching keywords in PubMed and Google Scholar. Article bibliographies and conference abstracts were also hand-searched. Despite being a serious cause of morbidity and mortality among incarcerated populations, many prison systems encounter a variety of challenges that hinder TB control. These include, but are not limited to, insufficient laboratory capacity and diagnostic tools, interrupted supply of medicines, weak integration between civilian and prison TB services, inadequate infection control measures, and low policy priority for prison healthcare. Governmental commitment, partnerships, and sustained financing are needed in order to facilitate improvements in TB control in prisons, which will translate to the wider community. Copyright © 2015 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Leveling the Playing Field: Bringing Development of Biomarkers and Molecular Diagnostics up to the Standards for Drug Development

PubMed Central

Poste, George; Carbone, David P.; Parkinson, David R.; Verweij, Jaap; Hewitt, Stephen; Jessup, J. Milburn

2012-01-01

Molecular diagnostics are increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, or to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify pharmocogenetic risk of adverse drug reactions. The articles of this CCR Focus section on Molecular Diagnosis describe the development and use of markers for medical decision-making in the cancer patient. They define the sources of preanalytic variability to minimize as well as the regulatory and financial challenges in diagnostic development and integration into clinical practice. They also outline an NCI program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation with sufficient sensitivity, specificity and validity that is comparable to that used for development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval. A way to accomplish this is to emphasize Phase IV post-marketing hypothesis driven clinical trials with biological characterization that permits accurate definition of the association of low prevalence gene alterations with toxicity or response in large cohorts. PMID:22422403

Leveling the playing field: bringing development of biomarkers and molecular diagnostics up to the standards for drug development.

PubMed

Poste, George; Carbone, David P; Parkinson, David R; Verweij, Jaap; Hewitt, Stephen M; Jessup, J Milburn

2012-03-15

Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts.

Challenges in pediatric chronic inflammatory demyelinating polyneuropathy.

PubMed

Haliloğlu, Göknur; Yüksel, Deniz; Temoçin, Cağri Mesut; Topaloğlu, Haluk

2016-12-01

Chronic inflammatory demyelinating neuropathy, a treatable immune-mediated disease of the peripheral nervous system is less common in childhood compared to adults. Despite different sets of diagnostic criteria, lack of a reliable biologic marker leads to challenges in diagnosis, follow-up and treatment. Our first aim was to review clinical presentation, course, response to treatment, and prognosis in our childhood patients. We also aimed to document diagnostic and therapeutic pitfalls and challenges at the bedside. Our original cohort consisted of 23 pediatric patients who were referred to us with a clinical diagnosis of chronic inflammatory demyelinating neuropathy. Seven patients reaching to an alternative diagnosis were excluded. In the remaining patients, diagnostic, treatment and follow-up data were compared in typical patients who satisfied both clinical and electrodiagnostic criteria and atypical patients who failed to meet minimal research chronic inflammatory demyelinating neuropathy electrodiagnostic requirements. Eight of 16 patients (50%) met the minimal chronic inflammatory demyelinating neuropathy research diagnostic requirements. There was only a statistically significant difference (p = 0.010) in terms of European Neuromuscular Centre childhood chronic inflammatory diagnostic mandatory clinical criteria between the two groups. Misdiagnosis due to errors in electrophysiological interpretation (100%, n = 8), cerebrospinal fluid cytoalbuminologic dissociation (100%, n = 4 and/or subjective improvement on any immunotherapy modality (80 ± 19.27%)) was frequent. Pediatric CIDP is challenging in terms of diagnostic and therapeutic pitfalls at the bedside. Diagnostic errors due to electrophysiological interpretation, cerebrospinal fluid cytoalbuminologic dissociation, and/or subjective improvement on immunotherapy should be considered. Copyright © 2016 Elsevier B.V. All rights reserved.

Addressing the challenges of diagnostics demand and supply: insights from an online global health discussion platform.

PubMed

Engel, Nora; Wachter, Keri; Pai, Madhukar; Gallarda, Jim; Boehme, Catharina; Celentano, Isabelle; Weintraub, Rebecca

2016-01-01

Several barriers challenge development, adoption and scale-up of diagnostics in low and middle income countries. An innovative global health discussion platform allows capturing insights from the global health community on factors driving demand and supply for diagnostics. We conducted a qualitative content analysis of the online discussion 'Advancing Care Delivery: Driving Demand and Supply of Diagnostics' organised by the Global Health Delivery Project (GHD) (http://www.ghdonline.org/) at Harvard University. The discussion, driven by 12 expert panellists, explored what must be done to develop delivery systems, business models, new technologies, interoperability standards, and governance mechanisms to ensure that patients receive the right diagnostic at the right time. The GHD Online (GHDonline) platform reaches over 19 000 members from 185 countries. Participants (N=99) in the diagnostics discussion included academics, non-governmental organisations, manufacturers, policymakers, and physicians. Data was coded and overarching categories analysed using qualitative data analysis software. Participants considered technical characteristics of diagnostics as smaller barriers to effective use of diagnostics compared with operational and health system challenges, such as logistics, poor fit with user needs, cost, workforce, infrastructure, access, weak regulation and political commitment. Suggested solutions included: health system strengthening with patient-centred delivery; strengthened innovation processes; improved knowledge base; harmonised guidelines and evaluation; supply chain innovations; and mechanisms for ensuring quality and capacity. Engaging and connecting different actors involved with diagnostic development and use is paramount for improving diagnostics. While the discussion participants were not representative of all actors involved, the platform enabled a discussion between globally acknowledged experts and physicians working in different countries.

Celiac Disease: Diagnostic Standards and Dilemmas

PubMed Central

Kaswala, Dharmesh H.; Veeraraghavan, Gopal; Kelly, Ciaran P.; Leffler, Daniel A.

2015-01-01

Celiac Disease (CD) affects at least 1% of the population and evidence suggests that prevalence is increasing. The diagnosis of CD depends on providers being alert to both typical and atypical presentations and those situations in which patients are at high risk for the disease. Because of variable presentation, physicians need to have a low threshold for celiac testing. Robust knowledge of the pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools. Highly sensitive and specific serological assays including Endomysial Antibody (EMA), tissue transglutaminase (tTG), and Deamidated Gliadin Peptide (DGP) have greatly simplified testing for CD and serve as the foundation for celiac diagnosis. In addition, genetic testing for HLA DQ2 and DQ8 has become more widely available and there has been refinement of the gluten challenge for use in diagnostic algorithms. While diagnosis is usually straightforward, in special conditions including IgA deficiency, very young children, discrepant histology and serology, and adoption of a gluten free diet prior to testing, CD can be difficult to diagnose. In this review, we provide an overview of the history and current state of celiac disease diagnosis and provide guidance for evaluation of CD in difficult diagnostic circumstances. PMID:28943611

Intelligent model-based diagnostics for vehicle health management

NASA Astrophysics Data System (ADS)

Luo, Jianhui; Tu, Fang; Azam, Mohammad S.; Pattipati, Krishna R.; Willett, Peter K.; Qiao, Liu; Kawamoto, Masayuki

2003-08-01

The recent advances in sensor technology, remote communication and computational capabilities, and standardized hardware/software interfaces are creating a dramatic shift in the way the health of vehicles is monitored and managed. These advances facilitate remote monitoring, diagnosis and condition-based maintenance of automotive systems. With the increased sophistication of electronic control systems in vehicles, there is a concomitant increased difficulty in the identification of the malfunction phenomena. Consequently, the current rule-based diagnostic systems are difficult to develop, validate and maintain. New intelligent model-based diagnostic methodologies that exploit the advances in sensor, telecommunications, computing and software technologies are needed. In this paper, we will investigate hybrid model-based techniques that seamlessly employ quantitative (analytical) models and graph-based dependency models for intelligent diagnosis. Automotive engineers have found quantitative simulation (e.g. MATLAB/SIMULINK) to be a vital tool in the development of advanced control systems. The hybrid method exploits this capability to improve the diagnostic system's accuracy and consistency, utilizes existing validated knowledge on rule-based methods, enables remote diagnosis, and responds to the challenges of increased system complexity. The solution is generic and has the potential for application in a wide range of systems.

Navigating highly homologous genes in a molecular diagnostic setting: a resource for clinical next-generation sequencing.

PubMed

Mandelker, Diana; Schmidt, Ryan J; Ankala, Arunkanth; McDonald Gibson, Kristin; Bowser, Mark; Sharma, Himanshu; Duffy, Elizabeth; Hegde, Madhuri; Santani, Avni; Lebo, Matthew; Funke, Birgit

2016-12-01

Next-generation sequencing (NGS) is now routinely used to interrogate large sets of genes in a diagnostic setting. Regions of high sequence homology continue to be a major challenge for short-read technologies and can lead to false-positive and false-negative diagnostic errors. At the scale of whole-exome sequencing (WES), laboratories may be limited in their knowledge of genes and regions that pose technical hurdles due to high homology. We have created an exome-wide resource that catalogs highly homologous regions that is tailored toward diagnostic applications. This resource was developed using a mappability-based approach tailored to current Sanger and NGS protocols. Gene-level and exon-level lists delineate regions that are difficult or impossible to analyze via standard NGS. These regions are ranked by degree of affectedness, annotated for medical relevance, and classified by the type of homology (within-gene, different functional gene, known pseudogene, uncharacterized noncoding region). Additionally, we provide a list of exons that cannot be analyzed by short-amplicon Sanger sequencing. This resource can help guide clinical test design, supplemental assay implementation, and results interpretation in the context of high homology.Genet Med 18 12, 1282-1289.

3D Printing Provides a Precise Approach in the Treatment of Tetralogy of Fallot, Pulmonary Atresia with Major Aortopulmonary Collateral Arteries.

PubMed

Anwar, Shafkat; Rockefeller, Toby; Raptis, Demetrios A; Woodard, Pamela K; Eghtesady, Pirooz

2018-02-03

Patients with tetralogy of Fallot, pulmonary atresia, and multiple aortopulmonary collateral arteries (Tet PA MAPCAs) have a wide spectrum of anatomy and disease severity. Management of these patients can be challenging and often require multiple high-risk surgical and interventional catheterization procedures. These interventions are made challenging by complex anatomy that require the proceduralist to mentally reconstruct three-dimensional anatomic relationships from two-dimensional images. Three-dimensional (3D) printing is an emerging medical technology that provides added benefits in the management of patients with Tet PA MAPCAs. When used in combination with current diagnostic modalities and procedures, 3D printing provides a precise approach to the management of these challenging, high-risk patients. Specifically, 3D printing enables detailed surgical and interventional planning prior to the procedure, which may improve procedural outcomes, decrease complications, and reduce procedure-related radiation dose and contrast load.

Diagnostic Challenges of Central Nervous System Tuberculosis

PubMed Central

Loeffler, Ann M.; Honarmand, Somayeh; Flood, Jennifer M.; Baxter, Roger; Jacobson, Susan; Alexander, Rick; Glaser, Carol A.

2008-01-01

Central nervous system tuberculosis (TB) was identified in 20 cases of unexplained encephalitis referred to the California Encephalitis Project. Atypical features (encephalitic symptoms, rapid onset, age) and diagnostic challenges (insensitive cerebrospinal fluid [CSF] TB PCR result, elevated CSF glucose levels in patients with diabetes, negative result for tuberculin skin test) complicated diagnosis. PMID:18760024

Computer-Assisted Diagnostic Decision Support: History, Challenges, and Possible Paths Forward

ERIC Educational Resources Information Center

Miller, Randolph A.

2009-01-01

This paper presents a brief history of computer-assisted diagnosis, including challenges and future directions. Some ideas presented in this article on computer-assisted diagnostic decision support systems (CDDSS) derive from prior work by the author and his colleagues (see list in Acknowledgments) on the INTERNIST-1 and QMR projects. References…

[Current Status of Translational Research on Gastroesophageal Reflux Disease].

PubMed

Jeong, In Du; Park, Moo In

2016-09-25

The prevalence of gastroesophageal reflux disease (GERD) and the incidence of some of its complications have risen strikingly over the last few decades. With the increase in our understanding of the pathophysiology of GERD along with the development of proton pump inhibitors, the diagnostic and therapeutic approaches to GERD have changed dramatically over the past decade. However, GERD still poses a problem to many clinicians since the spectrum of the disease has evolved to encompass more challenging presentations such as refractory GERD and extra-esophageal manifestations. The aim of this article is to provide a review of available current translational research on GERD. This review includes acid pocket, ambulatory pH monitoring, impedance pH monitoring, mucosa impedance, and high resolution manometry. This article discusses current translational research on GERD.

Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective.

PubMed

Lee, Anne W M; Ma, Brigette B Y; Ng, Wai Tong; Chan, Anthony T C

2015-10-10

Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research. © 2015 by American Society of Clinical Oncology.

Windows on the human body--in vivo high-field magnetic resonance research and applications in medicine and psychology.

PubMed

Moser, Ewald; Meyerspeer, Martin; Fischmeister, Florian Ph S; Grabner, Günther; Bauer, Herbert; Trattnig, Siegfried

2010-01-01

Analogous to the evolution of biological sensor-systems, the progress in "medical sensor-systems", i.e., diagnostic procedures, is paradigmatically described. Outstanding highlights of this progress are magnetic resonance imaging (MRI) and spectroscopy (MRS), which enable non-invasive, in vivo acquisition of morphological, functional, and metabolic information from the human body with unsurpassed quality. Recent achievements in high and ultra-high field MR (at 3 and 7 Tesla) are described, and representative research applications in Medicine and Psychology in Austria are discussed. Finally, an overview of current and prospective research in multi-modal imaging, potential clinical applications, as well as current limitations and challenges is given.

Maternal Plasma DNA and RNA Sequencing for Prenatal Testing.

PubMed

Tamminga, Saskia; van Maarle, Merel; Henneman, Lidewij; Oudejans, Cees B M; Cornel, Martina C; Sistermans, Erik A

2016-01-01

Cell-free DNA (cfDNA) testing has recently become indispensable in diagnostic testing and screening. In the prenatal setting, this type of testing is often called noninvasive prenatal testing (NIPT). With a number of techniques, using either next-generation sequencing or single nucleotide polymorphism-based approaches, fetal cfDNA in maternal plasma can be analyzed to screen for rhesus D genotype, common chromosomal aneuploidies, and increasingly for testing other conditions, including monogenic disorders. With regard to screening for common aneuploidies, challenges arise when implementing NIPT in current prenatal settings. Depending on the method used (targeted or nontargeted), chromosomal anomalies other than trisomy 21, 18, or 13 can be detected, either of fetal or maternal origin, also referred to as unsolicited or incidental findings. For various biological reasons, there is a small chance of having either a false-positive or false-negative NIPT result, or no result, also referred to as a "no-call." Both pre- and posttest counseling for NIPT should include discussing potential discrepancies. Since NIPT remains a screening test, a positive NIPT result should be confirmed by invasive diagnostic testing (either by chorionic villus biopsy or by amniocentesis). As the scope of NIPT is widening, professional guidelines need to discuss the ethics of what to offer and how to offer. In this review, we discuss the current biochemical, clinical, and ethical challenges of cfDNA testing in the prenatal setting and its future perspectives including novel applications that target RNA instead of DNA. © 2016 Elsevier Inc. All rights reserved.

Biomarkers and personalized medicine: current status and further perspectives with special focus on dermatology.

PubMed

Landeck, Lilla; Kneip, Christoph; Reischl, Joachim; Asadullah, Khusru

2016-05-01

Biomarkers are of increasingly high importance in medicine, particularly in the realm of 'personalized medicine'. They are valuable for predicting prognosis and dose selection. Moreover, they may be helpful in detecting therapeutic and adverse responses and in patient stratification based on efficacy or safety prediction. Thus, biomarkers are essential tools for the selection of appropriate patients for treatment with certain drugs to and enable personalized medicine, that is 'providing the right treatment to the right patient, at the right dose at the right time'. Currently, there are six drugs approved for dermatological indications with recommended or mandatory biomarker testing. Most of them are used to treat melanoma and human immunodeficiency virus infection. In contrast to the few fully validated biomarkers, many exploratory biomarkers and biomarker candidates have potential applications. Prognostic biomarkers are of particular significance for malignant conditions. Similarly, diagnostic biomarkers are important in autoimmune diseases. Disease severity biomarkers are helpful tools in the treatment for inflammatory skin diseases. Identification, qualification and implementation of the different kinds of biomarkers are challenging and frequently necessitate collaborative efforts. This is particularly true for stratification biomarkers that require a companion diagnostic marker that is co-developed with a certain drug. In this article general definitions and requirements for biomarkers as well as for the impact of biomarkers in dermatology are reviewed and opportunities and challenges are discussed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Experimental Validation of a Resilient Monitoring and Control System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wen-Chiao Lin; Kris R. E. Villez; Humberto E. Garcia

2014-05-01

Complex, high performance, engineering systems have to be closely monitored and controlled to ensure safe operation and protect public from potential hazards. One of the main challenges in designing monitoring and control algorithms for these systems is that sensors and actuators may be malfunctioning due to malicious or natural causes. To address this challenge, this paper addresses a resilient monitoring and control (ReMAC) system by expanding previously developed resilient condition assessment monitoring systems and Kalman filter-based diagnostic methods and integrating them with a supervisory controller developed here. While the monitoring and diagnostic algorithms assess plant cyber and physical health conditions,more » the supervisory controller selects, from a set of candidates, the best controller based on the current plant health assessments. To experimentally demonstrate its enhanced performance, the developed ReMAC system is then used for monitoring and control of a chemical reactor with a water cooling system in a hardware-in-the-loop setting, where the reactor is computer simulated and the water cooling system is implemented by a machine condition monitoring testbed at Idaho National Laboratory. Results show that the ReMAC system is able to make correct plant health assessments despite sensor malfunctioning due to cyber attacks and make decisions that achieve best control actions despite possible actuator malfunctioning. Monitoring challenges caused by mismatches between assumed system component models and actual measurements are also identified for future work.« less

Localized Surface Plasmon Resonance Biosensing: Current Challenges and Approaches

PubMed Central

Unser, Sarah; Bruzas, Ian; He, Jie; Sagle, Laura

2015-01-01

Localized surface plasmon resonance (LSPR) has emerged as a leader among label-free biosensing techniques in that it offers sensitive, robust, and facile detection. Traditional LSPR-based biosensing utilizes the sensitivity of the plasmon frequency to changes in local index of refraction at the nanoparticle surface. Although surface plasmon resonance technologies are now widely used to measure biomolecular interactions, several challenges remain. In this article, we have categorized these challenges into four categories: improving sensitivity and limit of detection, selectivity in complex biological solutions, sensitive detection of membrane-associated species, and the adaptation of sensing elements for point-of-care diagnostic devices. The first section of this article will involve a conceptual discussion of surface plasmon resonance and the factors affecting changes in optical signal detected. The following sections will discuss applications of LSPR biosensing with an emphasis on recent advances and approaches to overcome the four limitations mentioned above. First, improvements in limit of detection through various amplification strategies will be highlighted. The second section will involve advances to improve selectivity in complex media through self-assembled monolayers, “plasmon ruler” devices involving plasmonic coupling, and shape complementarity on the nanoparticle surface. The following section will describe various LSPR platforms designed for the sensitive detection of membrane-associated species. Finally, recent advances towards multiplexed and microfluidic LSPR-based devices for inexpensive, rapid, point-of-care diagnostics will be discussed. PMID:26147727

Diagnosis and Treatment of the Cardiovascular Consequences of Fabry Disease.

PubMed

Baig, S; Vijapurapu, R; Alharbi, F; Nordin, S; Kozor, R; Moon, J; Bembi, B; Geberhiwot, T; Steeds, R P

2018-06-06

Fabry Disease (FD) has been a diagnostic challenge since it was first recognised in 1898, with patients traditionally suffering from considerable delay before a diagnosis is made. Cardiac involvement is the current leading cause of death in FD. A combination of improved enzyme assays, availability of genetic profiling, together with more organised clinical services for rare diseases, has led to a rapid growth in the prevalence of FD. The earlier and more frequent diagnosis of asymptomatic individuals before development of the phenotype has focussed attention on early detection of organ involvement and closer monitoring of disease progression. The high cost of enzyme replacement therapy at a time of constraint within many health economies moreover, has challenged clinicians to target treatment effectively. This article provides an outline of FD for the general physician and summarises the aetiology and pathology of FD, the cardiovascular (CV) consequences thereof, modalities used in diagnosis, and then discusses current indications for treatment, including pharmacotherapy and device implantation.

Implantable and ingestible medical devices with wireless telemetry functionalities: a review of current status and challenges.

PubMed

Kiourti, Asimina; Psathas, Konstantinos A; Nikita, Konstantina S

2014-01-01

Wireless medical telemetry permits the measurement of physiological signals at a distance through wireless technologies. One of the latest applications is in the field of implantable and ingestible medical devices (IIMDs) with integrated antennas for wireless radiofrequency (RF) communication (telemetry) with exterior monitoring/control equipment. Implantable medical devices (MDs) perform an expanding variety of diagnostic and therapeutic functions, while ingestible MDs receive significant attention in gastrointestinal endoscopy. Design of such wireless IIMD telemetry systems is highly intriguing and deals with issues related to: operation frequency selection, electronics and powering, antenna design and performance, and modeling of the wireless channel. In this paper, we attempt to comparatively review the current status and challenges of IIMDs with wireless telemetry functionalities. Full solutions of commercial IIMDs are also recorded. The objective is to provide a comprehensive reference for scientists and developers in the field, while indicating directions for future research. © 2013 Wiley Periodicals, Inc.

Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

PubMed

Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

2016-08-15

A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and Kopetz, p. 3989. ©2016 American Association for Cancer Research.

The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic.

PubMed

van Veen, Leonieke N; Heron, Michiel; Batstra, Manou; van Haard, Paul M M; de Groot, Hans

2016-06-02

To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value. Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose. The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge. This study shows that component-resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group.

Developmental dyscalculia.

PubMed

Kucian, Karin; von Aster, Michael

2015-01-01

Numerical skills are essential in our everyday life, and impairments in the development of number processing and calculation have a negative impact on schooling and professional careers. Approximately 3 to 6 % of children are affected from specific disorders of numerical understanding (developmental dyscalculia (DD)). Impaired development of number processing skills in these children is characterized by problems in various aspects of numeracy as well as alterations of brain activation and brain structure. Moreover, DD is assumed to be a very heterogeneous disorder putting special challenges to define homogeneous diagnostic criteria. Finally, interdisciplinary perspectives from psychology, neuroscience and education can contribute to the design for interventions, and although results are still sparse, they are promising and have shown positive effects on behaviour as well as brain function. In the current review, we are going to give an overview about typical and atypical development of numerical abilities at the behavioural and neuronal level. Furthermore, current status and obstacles in the definition and diagnostics of DD are discussed, and finally, relevant points that should be considered to make an intervention as successful as possible are summarized.

Should the diagnostic and therapeutic protocols for adrenal incidentalomas be changed?

PubMed

Mateo-Gavira, Isabel; Vilchez-López, Francisco Javier; Larrán-Escandón, Laura; Ojeda-Schuldt, María Belén; Tinoco, Cristina López; Aguilar-Diosdado, Manuel

2015-01-01

The prevalence of adrenal incidentalomas is increasing with the aging of the population and the use of high resolution imaging technics. Current protocols propose a comprehensive monitoring of their functional and morphological state, but with no conclusive clinical evidence that endorses it. Retrospective study of 96 patients diagnosed with adrenal incidentaloma between 2008 and 2012. We evaluated clinical, functional and imaging at baseline and during follow-up. Initially, 9 cases were surgically removed: 4 due to hyperfunction (2 Cushing syndromes and 2 pheochromocytomas) and 5 due to size larger than 4cm. During follow-up one case of pheochromocytoma was diagnosed and another grew more than 1cm, needing surgery. In 98.86% of nonfunctional and benign lesions, there was no functional and/or morphological changes in the final evaluation. The results of our study challenge the validity of current diagnostic-therapeutic protocols of incidentalomas, which should be reassessed in prospective studies taking into account efficiency characteristics. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Temporal evolution of acute respiratory distress syndrome definitions.

PubMed

Fioretto, José R; Carvalho, Werther B

2013-01-01

to review the evolution of acute respiratory distress syndrome (ARDS) definitions and present the current definition for the syndrome. a literature review and selection of the most relevant articles on ARDS definitions was performed using the MEDLINE®/PubMed® Resource Guide database (last ten years), in addition to including the most important articles (classic articles) that described the disease evolution. the review included the following subjects: introduction; importance of definition; description of the first diagnostic criterion and subsequently used definitions, such as acute lung injury score; definition by the American-European Consensus Conference, and its limitations; description of the definition by Delphi, and its problems; accuracy of the aforementioned definitions; description of most recent definition (the Berlin definition), and its limitations; and practical importance of the new definition. ARDS is a serious disease that remains an ongoing diagnostic and therapeutic challenge. The evolution of definitions used to describe the disease shows that studies are needed to validate the current definition, especially in pediatrics, where the data are very scarce. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

X-ray Diffraction and Multi-Frame Phase Contrast Imaging Diagnostics for IMPULSE at the Advanced Photon Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iverson, Adam; Carlson, Carl; Young, Jason

2013-07-08

The diagnostic needs of any dynamic loading platform present unique technical challenges that must be addressed in order to accurately measure in situ material properties in an extreme environment. The IMPULSE platform (IMPact system for Ultrafast Synchrotron Experiments) at the Advanced Photon Source (APS) is no exception and, in fact, may be more challenging, as the imaging diagnostics must be synchronized to both the experiment and the 60 ps wide x-ray bunches produced at APS. The technical challenges of time-resolved x-ray diffraction imaging and high-resolution multi-frame phase contrast imaging (PCI) are described in this paper. Example data from recent IMPULSEmore » experiments are shown to illustrate the advances and evolution of these diagnostics with a focus on comparing the performance of two intensified CCD cameras and their suitability for multi-frame PCI. The continued development of these diagnostics is fundamentally important to IMPULSE and many other loading platforms and will benefit future facilities such as the Dynamic Compression Sector at APS and MaRIE at Los Alamos National Laboratory.« less

Chronic orchialgia: Review of treatments old and new

PubMed Central

Tojuola, Bayo; Layman, Jeffrey; Kartal, Ibrahim; Gudelogul, Ahmet; Brahmbhatt, Jamin; Parekattil, Sijo

2016-01-01

Introduction: Chronic orchialgia is historically and currently a challenging disease to treat. It is a diagnostic and therapeutic challenge for physicians. Conservative therapy has served as the first line of treatment. For those who fail conservative therapy, surgical intervention may be required. We aim to provide a review of currently available surgical options and novel surgical treatment options. Methods: A review of current literature was performed using PubMed. Literature discussing treatment options for chronic orchialgia were identified. The following search terms were used to identify literature that was relevant to this review: Chronic orchialgia, testicular pain, scrotal content pain, and microsurgical denervation of the spermatic cord (MDSC). Results: The incidence of chronic orchialgia has been increasing over time. In the USA, it affects up to 100,000 men per year due to varying etiologies. The etiology of chronic orchialgia can be a confounding problem. Conservative therapy should be viewed as the first line therapy. Studies have reported poor success rates. Current surgical options for those who fail conservative options include varicocelectomy, MDSC, epididymectomy, and orchiectomy. Novel treatment options include microcryoablation of the peri-spermatic cord, botox injection, and amniofix injection. Conclusion: Chronic orchialgia has been and will continue to be a challenging disease to treat due to its multiple etiologies and variable treatment outcomes. Further studies are needed to better understand the problem. Treatment options for patients with chronic orchialgia are improving. Additional studies are warranted to better understand the long-term durability of this treatment options. PMID:26941490

Knitting the Threads of Silk through Time: Behçet's Disease—Past, Present, and Future

PubMed Central

Stack, Austin G.; Fraser, Alexander D.

2017-01-01

Behçet's disease (BD) is a chronic relapsing vasculitis that affects vessels of all types and sizes with a broad spectrum of phenotypic heterogeneity and complex immunopathogenesis. Efforts by the scientific community to resolve the unmet needs of BD and gaps in our knowledge have been hampered by considerable challenges that primarily relate to the rare nature of the disease in many parts of the world and its heterogeneity. Controversies remain in many aspects of the disease including the diagnostic criteria, immunopathogenesis and biomarker discovery, geographical variation, and therapeutic considerations. In this review, we highlight recent advances in our scientific understanding of BD, shed new insights into diagnostic and treatment strategies, and discuss residual gaps in our knowledge that will serve as the basis for current and future research. PMID:29081805

Sudden unexpected death in epilepsy genetics: Molecular diagnostics and prevention.

PubMed

Goldman, Alica M; Behr, Elijah R; Semsarian, Christopher; Bagnall, Richard D; Sisodiya, Sanjay; Cooper, Paul N

2016-01-01

Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Dielectrophoresis for Biomedical Sciences Applications: A Review

PubMed Central

Abd Rahman, Nurhaslina; Ibrahim, Fatimah; Yafouz, Bashar

2017-01-01

Dielectrophoresis (DEP) is a label-free, accurate, fast, low-cost diagnostic technique that uses the principles of polarization and the motion of bioparticles in applied electric fields. This technique has been proven to be beneficial in various fields, including environmental research, polymer research, biosensors, microfluidics, medicine and diagnostics. Biomedical science research is one of the major research areas that could potentially benefit from DEP technology for diverse applications. Nevertheless, many medical science research investigations have yet to benefit from the possibilities offered by DEP. This paper critically reviews the fundamentals, recent progress, current challenges, future directions and potential applications of research investigations in the medical sciences utilizing DEP technique. This review will also act as a guide and reference for medical researchers and scientists to explore and utilize the DEP technique in their research fields. PMID:28245552

Functional protease profiling for diagnosis of malignant disease.

PubMed

Findeisen, Peter; Neumaier, Michael

2012-01-01

Clinical proteomic profiling by mass spectrometry (MS) aims at uncovering specific alterations within mass profiles of clinical specimens that are of diagnostic value for the detection and classification of various diseases including cancer. However, despite substantial progress in the field, the clinical proteomic profiling approaches have not matured into routine diagnostic applications so far. Their limitations are mainly related to high-abundance proteins and their complex processing by a multitude of endogenous proteases thus making rigorous standardization difficult. MS is biased towards the detection of low-molecular-weight peptides. Specifically, in serum specimens, the particular fragments of proteolytically degraded proteins are amenable to MS analysis. Proteases are known to be involved in tumour progression and tumour-specific proteases are released into the blood stream presumably as a result of invasive progression and metastasis. Thus, the determination of protease activity in clinical specimens from patients with malignant disease can offer diagnostic and also therapeutic options. The identification of specific substrates for tumour proteases in complex biological samples is challenging, but proteomic screens for proteases/substrate interactions are currently experiencing impressive progress. Such proteomic screens include peptide-based libraries, differential isotope labelling in combination with MS, quantitative degradomic analysis of proteolytically generated neo-N-termini, monitoring the degradation of exogenous reporter peptides with MS, and activity-based protein profiling. In the present article, we summarize and discuss the current status of proteomic techniques to identify tumour-specific protease-substrate interactions for functional protease profiling. Thereby, we focus on the potential diagnostic use of the respective approaches. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Practitioner review: Social (pragmatic) communication disorder conceptualization, evidence and clinical implications.

PubMed

Norbury, Courtenay F

2014-03-01

DSM-5 sees the introduction of Social (Pragmatic) Communication Disorder (SPCD), characterized by persistent difficulties using verbal and nonverbal communication for social purposes, in the absence of restricted and repetitive interests and behaviours. There is currently much confusion about the precise diagnostic criteria for SPCD and how this disorder relates to autism spectrum disorders (ASD), previous descriptions of pragmatic language impairment (PLI) and more specific language disorders (LD). Proposed criteria for SPCD are outlined. A selective review of the evidence considers whether these criteria form a cohesive and distinct diagnostic entity. Approaches to assessment and intervention are discussed. Implementing the new diagnosis is currently challenged by a lack of well-validated and reliable assessment measures, and observed continuities between SPCD and other neurodevelopmental disorders. High rates of comorbidity between SPCD and other seemingly disparate disorders (including conduct disorder, ADHD and disorders of known genetic origin) raise questions about the utility of this diagnostic category. SPCD is probably best conceptualized as a dimensional symptom profile that may be present across a range of neurodevelopmental disorders, although there is an urgent need to investigate the latent structure of SPCD using consistent diagnostic criteria. In addition, social communication and aspects of pragmatic language may be dissociated, with the latter heavily influenced by structural language attainments. Finally, there is a dearth of reliable and culturally valid assessment measures with which to make a differential diagnosis, and few rigorously tested intervention programmes. The implications for research and clinical practice are outlined. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Recent Advances in Exosomal Protein Detection Via Liquid Biopsy Biosensors for Cancer Screening, Diagnosis, and Prognosis.

PubMed

Liu, Chang; Yang, Yunchen; Wu, Yun

2018-03-08

Current cancer diagnostic methods are challenged by low sensitivity, high false positive rate, limited tumor information, uncomfortable or invasive procedures, and high cost. Liquid biopsy that analyzes circulating biomarkers in body fluids represents a promising solution to these challenges. Exosomes are one of the promising cancer biomarkers for liquid biopsy because they are cell-secreted, nano-sized, extracellular vesicles that stably exist in all types of body fluids. Exosomes transfer DNAs, RNAs, proteins, and lipids from parent cells to recipient cells for intercellular communication and play important roles in cancer initiation, progression, and metastasis. Many liquid biopsy biosensors have been developed to offer non- or minimally-invasive, highly sensitive, simple, rapid, and cost-effective cancer diagnostics. This review summarized recent advances of liquid biopsy biosensors with a focus on the detection of exosomal proteins as biomarkers for cancer screening, diagnosis, and prognosis. We reviewed six major types of liquid biopsy biosensors including immunofluorescence biosensor, colorimetric biosensor, surface plasmon resonance (SPR) biosensor, surface-enhanced Raman scattering (SERS) biosensor, electrochemical biosensor, and nuclear magnetic resonance (NMR) biosensor. We shared our perspectives on future improvement of exosome-based liquid biopsy biosensors to accelerate their clinical translation.

Critical components required to improve deployable laboratory biological hazards identification

NASA Astrophysics Data System (ADS)

Niemeyer, Debra M.

2004-08-01

An ever-expanding global military mission necessitates quick and accurate identification of biological hazards, whether naturally occurring or man-made. Coupled with an ever-present threat of biological attack, an expanded U.S. presence in worn-torn locations like Southwest Asia presents unique public health challenges. We must heed modern day "lessons learned" from Operation Desert Shield and the Soviet Afghanistan Campaign and guard against rapid incapacitation of troop strength from endemic disease and biological attack. To minimize readiness impacts, field hygiene is enforced, and research on better medical countermeasures such as antibiotics and vaccines continues. However, there are no preventions or remedies for all military-relevant infectious diseases or biological agents. A deployable, streamlined, self-contained diagnostic and public health surveillance laboratory capability with a reach-back communication is critical to meeting global readiness challenges. Current deployable laboratory packages comprise primarily diagnostic or environmental sample testing capabilities. Discussion will focus on critical components needed to improve existing laboratory assets, and to facilitate deployment of small, specialized packages far forward. The ideal laboratory model described will become an essential tool for the Combatant or Incident Commander to maintain force projection in the expeditionary environment.

Accounting for isotopic clustering in Fourier transform mass spectrometry data analysis for clinical diagnostic studies.

PubMed

Kakourou, Alexia; Vach, Werner; Nicolardi, Simone; van der Burgt, Yuri; Mertens, Bart

2016-10-01

Mass spectrometry based clinical proteomics has emerged as a powerful tool for high-throughput protein profiling and biomarker discovery. Recent improvements in mass spectrometry technology have boosted the potential of proteomic studies in biomedical research. However, the complexity of the proteomic expression introduces new statistical challenges in summarizing and analyzing the acquired data. Statistical methods for optimally processing proteomic data are currently a growing field of research. In this paper we present simple, yet appropriate methods to preprocess, summarize and analyze high-throughput MALDI-FTICR mass spectrometry data, collected in a case-control fashion, while dealing with the statistical challenges that accompany such data. The known statistical properties of the isotopic distribution of the peptide molecules are used to preprocess the spectra and translate the proteomic expression into a condensed data set. Information on either the intensity level or the shape of the identified isotopic clusters is used to derive summary measures on which diagnostic rules for disease status allocation will be based. Results indicate that both the shape of the identified isotopic clusters and the overall intensity level carry information on the class outcome and can be used to predict the presence or absence of the disease.

Diaphorina citri (Hemiptera: Liviidae) Vector Competence for the Citrus Greening Pathogen 'Candidatus Liberibacter Asiaticus'.

PubMed

Tabachnick, Walter J

2015-06-01

Characterizing the vector competence of Diaphorina citri Kuwayama for 'Candidatus Liberibacter asiaticus,' the pathogen causing citrus greening, is essential for understanding the epidemiology of this disease that is threatening the U.S. citrus industry. Vector competence studies have been difficult because of the biology of D. citri, the inability to culture the pathogen, and the available diagnostic methods used to detect the bacteria in plant and insect tissues. The methods employed in many studies of D. citri vector competence may have overestimated amounts of live 'Ca. L. asiaticus' in both plant and insect tissues, and it is possible that the amounts of phloem ingested by psyllids may not contain sufficient detectable pathogen using current diagnostic methods. As a result of the difficulty in characterizing D. citri vector competence, the several daunting challenges for providing D. citri that are unable to inoculate 'Ca. L. asiaticus', as a novel method to control greening are discussed. Suggestions to overcome some of these challenges are provided. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Clinical microbiology laboratory and imported parasitic diseases].

PubMed

Martín-Rabadán, Pablo; Martínez-Ruiz, Rocío; Cuadros, Juan; Cañavate, Carmen

2010-12-01

Imported parasitosis represents an increasingly frequent diagnostic challenge for microbiology laboratories. A surge in immigration and international travel has led to a rise in the number of imported cases of parasitosis, and this trend is expected to continue in the future. The present article addresses this challenge by reviewing recommended diagnostic approaches and tests. Currently, microscopy is always recommended when analysing blood samples for parasites. If malaria is suspected, rapid antigen testing (including at least HRP2 antigen) should also be performed. The work-up for suspected leishmaniasis should include serology, culture, and in selected cases detection of antigen in urine. In suspected Chagas disease, two different serological tests should be performed. PCR for blood protozoa is highly sensitive, although it cannot be used to rule out Chagas disease, since this condition may be present without parasitemia. Accurate diagnosis of intestinal amebiasis usually requires PCR or antigen detection tests. In helminthiasis, traditional microscopy may need to be complemented with other tests, such as agar plate culture for strongyloidiasis, Og4C3 antigen detection for bancroftian filariasis, and antibody detection test for filariasis and schistosomiasis. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Primary care and cancer: Facing the challenge of early diagnosis and survivorship.

PubMed

Round, Thomas

2017-05-01

With ageing populations and an increasing lifetime risk of cancer, primary care will continue to play an increasingly important role in early diagnosis and cancer survivorship, especially with the lowering of risk thresholds for referral and diagnostic investigations. However, primary care in many countries is in crisis with increasing workloads for primary care physicians. Potential solutions to these challenges will be outlined including development of multidisciplinary teams, diagnostic decision support, increasing access to diagnostics and cost-effective referral pathways. © 2017 John Wiley & Sons Ltd.

Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn’s Colitides

PubMed Central

Korolkova, Olga Y; Myers, Jeremy N; Pellom, Samuel T; Wang, Li; M’Koma, Amosy E

2015-01-01

BACKGROUND As accessible diagnostic approaches fail to differentiate between ulcerative colitis (UC) and Crohn’s colitis (CC) in one-third of patients with predominantly colonic inflammatory bowel disease (IBD), leading to inappropriate therapy, we aim to investigate the serum cytokine levels in these patients in search of molecular biometric markers delineating UC from CC. METHODS We measured 38 cytokines, chemokines, and growth factors using magnetic-bead-based multiplex immunoassay in 25 UC patients, 28 CC patients, and 30 controls. Our results are compared with those from a review of current literature regarding advances in serum cytokine profiles and associated challenges preventing their use for diagnostic/prognostic purposes. RESULTS Univariate analysis showed statistically significant increases of eotaxin, GRO, and TNF-α in UC patients compared to controls (Ctrl); interferon γ, interleukin (IL)-6, and IL-7 in CC group compared to Ctrl; and IL-8 in both UC and CC versus Ctrl. No cytokines were found to be different between UC and CC. A generalized linear model identified combinations of cytokines, allowing the identification of UC and CC patients, with area under the curve (AUC) = 0.936, as determined with receiver operating characteristic (ROC) analysis. CONCLUSIONS The current knowledge available about circulating cytokines in IBD is often contradictory. The development of an evidence-based tool using cytokines for diagnostic accuracy is still preliminary. PMID:26078592

Measures to Improve Diagnostic Safety in Clinical Practice

PubMed Central

Singh, Hardeep; Graber, Mark L; Hofer, Timothy P

2016-01-01

Timely and accurate diagnosis is foundational to good clinical practice and an essential first step to achieving optimal patient outcomes. However, a recent Institute of Medicine report concluded that most of us will experience at least one diagnostic error in our lifetime. The report argues for efforts to improve the reliability of the diagnostic process through better measurement of diagnostic performance. The diagnostic process is a dynamic team-based activity that involves uncertainty, plays out over time, and requires effective communication and collaboration among multiple clinicians, diagnostic services, and the patient. Thus, it poses special challenges for measurement. In this paper, we discuss how the need to develop measures to improve diagnostic performance could move forward at a time when the scientific foundation needed to inform measurement is still evolving. We highlight challenges and opportunities for developing potential measures of “diagnostic safety” related to clinical diagnostic errors and associated preventable diagnostic harm. In doing so, we propose a starter set of measurement concepts for initial consideration that seem reasonably related to diagnostic safety, and call for these to be studied and further refined. This would enable safe diagnosis to become an organizational priority and facilitate quality improvement. Health care systems should consider measurement and evaluation of diagnostic performance as essential to timely and accurate diagnosis and to the reduction of preventable diagnostic harm. PMID:27768655

Towards a Tool for Malaria Supply Chain Management Improvement in Rural Ghana.

PubMed

Carlo, Lorena; Bakken, Suzanne; Mamykina, Lena; Kodie, Richmond; Kanter, Andrew S

2015-01-01

The maintenance of adequate quantities of antimalarial medicines and rapid diagnostic tests (RDTs) at health facilities in rural areas of sub-Saharan Africa is a challenging task because of poor supply chain management. Antimalarial stock-outs in the communities could lead patients (that need to travel long distances to get medications) to remain untreated, develop severe malaria and die. A prototype to improve the management of health commodities in rural Ghana through the visualization of current stock levels and the forecasting of commodities is proposed.

Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes

PubMed Central

2016-01-01

Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities. PMID:27909577

[Future challenges in multiple sclerosis].

PubMed

Fernández, Óscar

2014-12-01

Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes.

PubMed

González-de-Olano, David; Matito, Almudena; Orfao, Alberto; Escribano, Luis

2016-01-01

Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities.

Accelerating the Translation of Nanomaterials in Biomedicine

PubMed Central

Mitragotri, Samir; Anderson, Daniel G.; Chen, Xiaoyuan; Chow, Edward K.; Ho, Dean; Kabanov, Alexander V.; Karp, Jeffrey M.; Kataoka, Kazunori; Mirkin, Chad A.; Petrosko, Sarah Hurst; Shi, Jinjun; Stevens, Molly M.; Sun, Shouheng; Teoh, Sweehin; Venkatraman, Subbu S.; Xia, Younan; Wang, Shutao; Gu, Zhen; Xu, Chenjie

2017-01-01

Due to their size and tailorable physicochemical properties, nanomaterials are an emerging class of structures utilized in biomedical applications. There are now many prominent examples of nanomaterials being used to improve human health, in areas ranging from imaging and diagnostics to therapeutics and regenerative medicine. An overview of these examples reveals several common areas of synergy and future challenges. This Nano Focus discusses the current status and future potential of promising nanomaterials and their translation from the laboratory to the clinic, by highlighting a handful of successful examples. PMID:26115196

Impetigo and scabies - Disease burden and modern treatment strategies.

PubMed

Yeoh, Daniel K; Bowen, Asha C; Carapetis, Jonathan R

2016-07-05

Impetigo and scabies both present different challenges in resource-limited compared with industrialised settings. Severe complications of these skin infections are common in resource-limited settings, where the burden of disease is highest. The microbiology, risk factors for disease, diagnostic approaches and availability and suitability of therapies also vary according to setting. Taking this into account we aim to summarise recent data on the epidemiology of impetigo and scabies and describe the current evidence around approaches to individual and community based treatment. Copyright © 2016. Published by Elsevier Ltd.

A cDNA microarray gene expression data classifier for clinical diagnostics based on graph theory.

PubMed

Benso, Alfredo; Di Carlo, Stefano; Politano, Gianfranco

2011-01-01

Despite great advances in discovering cancer molecular profiles, the proper application of microarray technology to routine clinical diagnostics is still a challenge. Current practices in the classification of microarrays' data show two main limitations: the reliability of the training data sets used to build the classifiers, and the classifiers' performances, especially when the sample to be classified does not belong to any of the available classes. In this case, state-of-the-art algorithms usually produce a high rate of false positives that, in real diagnostic applications, are unacceptable. To address this problem, this paper presents a new cDNA microarray data classification algorithm based on graph theory and is able to overcome most of the limitations of known classification methodologies. The classifier works by analyzing gene expression data organized in an innovative data structure based on graphs, where vertices correspond to genes and edges to gene expression relationships. To demonstrate the novelty of the proposed approach, the authors present an experimental performance comparison between the proposed classifier and several state-of-the-art classification algorithms.

Design calculations for a xenon plasma x-ray shield to protect the NIF optical Thomson scattering diagnostic

NASA Astrophysics Data System (ADS)

Swadling, G. F.; Ross, J. S.; Datte, P.; Moody, J.; Divol, L.; Jones, O.; Landen, O.

2016-11-01

An Optical Thomson Scattering (OTS) diagnostic is currently being developed for the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. This diagnostic is designed to make measurements of the hohlraum plasma parameters, such as the electron temperature and the density, during inertial confinement fusion (ICF) experiments. NIF ICF experiments present a very challenging environment for optical measurements; by their very nature, hohlraums produce intense soft x-ray emission, which can cause "blanking" (radiation induced opacity) of the radiation facing optical components. The soft x-ray fluence at the surface of the OTS blast shield, 60 cm from the hohlraum, is estimated to be ˜8 J cm-2. This is significantly above the expected threshold for the onset of "blanking" effects. A novel xenon plasma x-ray shield is proposed to protect the blast shield from x-rays and mitigate "blanking." Estimates suggest that an areal density of 1019 cm-2 Xe atoms will be sufficient to absorb 99.5% of the soft x-ray flux. Two potential designs for this shield are presented.

Malaria Diagnosis across the International Centers of Excellence for Malaria Research: Platforms, Performance, and Standardization

PubMed Central

Kobayashi, Tamaki; Gamboa, Dionicia; Ndiaye, Daouda; Cui, Liwang; Sutton, Patrick L.; Vinetz, Joseph M.

2015-01-01

Diagnosis is “the act of identifying a disease, illness, or problem by examining someone or something.” When an individual with acute fever presents for clinical attention, accurate diagnosis leading to specific, prompt treatment often saves lives. As applied to malaria, not only individual patient diagnosis is important but also assessing population-level malaria prevalence using appropriate diagnostic methods is essential for public health purposes. Similarly, identifying (diagnosing) fake antimalarial medications prevents the use of counterfeit drugs that can have disastrous effects. Therefore, accurate diagnosis in broad areas related to malaria is fundamental to improving health-care delivery, informing funding agencies of current malaria situations, and aiding in the prioritization of regional and national control efforts. The International Centers of Excellence for Malaria Research (ICEMR), supported by the U.S. National Institute of Allergy and Infectious Diseases, has collaborated on global efforts to improve malaria diagnostics by working to harmonize and systematize procedures across different regions where endemicity and financial resources vary. In this article, the different diagnostic methods used across each ICEMR are reviewed and challenges are discussed. PMID:26259937

Current and future molecular diagnostics for ocular infectious diseases.

PubMed

Doan, Thuy; Pinsky, Benjamin A

2016-11-01

Confirmation of ocular infections can pose great challenges to the clinician. A fundamental limitation is the small amounts of specimen that can be obtained from the eye. Molecular diagnostics can circumvent this limitation and have been shown to be more sensitive than conventional culture. The purpose of this review is to describe new molecular methods and to discuss the applications of next-generation sequencing-based approaches in the diagnosis of ocular infections. Efforts have focused on improving the sensitivity of pathogen detection using molecular methods. This review describes a new molecular target for Toxoplasma gondii-directed polymerase chain reaction assays. Molecular diagnostics for Chlamydia trachomatis and Acanthamoeba species are also discussed. Finally, we describe a hypothesis-free approach, metagenomic deep sequencing, which can detect DNA and RNA pathogens from a single specimen in one test. In some cases, this method can provide the geographic location and timing of the infection. Pathogen-directed PCRs have been powerful tools in the diagnosis of ocular infections for over 20 years. The use of next-generation sequencing-based approaches, when available, will further improve sensitivity of detection with the potential to improve patient care.

Design calculations for a xenon plasma x-ray shield to protect the NIF optical Thomson scattering diagnostic.

PubMed

Swadling, G F; Ross, J S; Datte, P; Moody, J; Divol, L; Jones, O; Landen, O

2016-11-01

An Optical Thomson Scattering (OTS) diagnostic is currently being developed for the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. This diagnostic is designed to make measurements of the hohlraum plasma parameters, such as the electron temperature and the density, during inertial confinement fusion (ICF) experiments. NIF ICF experiments present a very challenging environment for optical measurements; by their very nature, hohlraums produce intense soft x-ray emission, which can cause "blanking" (radiation induced opacity) of the radiation facing optical components. The soft x-ray fluence at the surface of the OTS blast shield, 60 cm from the hohlraum, is estimated to be ∼8 J cm -2 . This is significantly above the expected threshold for the onset of "blanking" effects. A novel xenon plasma x-ray shield is proposed to protect the blast shield from x-rays and mitigate "blanking." Estimates suggest that an areal density of 10 19 cm -2 Xe atoms will be sufficient to absorb 99.5% of the soft x-ray flux. Two potential designs for this shield are presented.

View of the Challenger's payload bay and the Plasma Diagnostic package

NASA Technical Reports Server (NTRS)

1985-01-01

The solar optical universal polarimeter (SOUP) experiment is visible among the cluster of Spacelab 2 hardware in the cargo bay of the Shuttle Challenger. Various components of the instrument positioning system (IPS) are conspicuous at the center of the frame. The Plasma Diagnostic package (PDP) is seen attached to the remote manipulator system (RMS) above the open payload bay.

The Effect of Diagnostic Label on Care Staff's Perceptions of Cause of Challenging Behaviour in Individuals with Learning Disabilities

ERIC Educational Resources Information Center

Gifford, Clive; Knott, Fiona

2016-01-01

Background: This study investigated whether care staff's causal attributions and emotional reactions to the challenging behaviour displayed by service users were influenced by the service user's diagnostic label. Materials and Method: One hundred and twenty care staff were randomly allocated to one of three conditions. Participants viewed a video…

Computer-assisted diagnostic decision support: history, challenges, and possible paths forward.

PubMed

Miller, Randolph A

2009-09-01

This paper presents a brief history of computer-assisted diagnosis, including challenges and future directions. Some ideas presented in this article on computer-assisted diagnostic decision support systems (CDDSS) derive from prior work by the author and his colleagues (see list in Acknowledgments) on the INTERNIST-1 and QMR projects. References indicate the original sources of many of these ideas.

Management of pain in patients with temporomandibular disorder (TMD): challenges and solutions

PubMed Central

Gil-Martínez, Alfonso; Paris-Alemany, Alba; López-de-Uralde-Villanueva, Ibai; La Touche, Roy

2018-01-01

Thanks to advances in neuroscience, biopsychosocial models for diagnostics and treatment (including physical, psychological, and pharmacological therapies) currently have more clinical support and scientific growth. At present, a conservative treatment approach prevails over surgery, given it is less aggressive and usually results in satisfactory clinical outcomes in mild–moderate temporomandibular disorder (TMD). The aim of this review is to evaluate the recent evidence, identify challenges, and propose solutions from a clinical point of view for patients with craniofacial pain and TMD. The treatment we propose is structured in a multi-modal approach based on a biobehavioral approach that includes medical, physiotherapeutic, psychological, and dental treatments. We also propose a new biobehavioral model regarding pain perception and motor behavior for the diagnosis and treatment of patients with painful TMD. PMID:29588615

Model-based reasoning in SSF ECLSS

NASA Technical Reports Server (NTRS)

Miller, J. K.; Williams, George P. W., Jr.

1992-01-01

The interacting processes and reconfigurable subsystems of the Space Station Freedom Environmental Control and Life Support System (ECLSS) present a tremendous technical challenge to Freedom's crew and ground support. ECLSS operation and problem analysis is time-consuming for crew members and difficult for current computerized control, monitoring, and diagnostic software. These challenges can be at least partially mitigated by the use of advanced techniques such as Model-Based Reasoning (MBR). This paper will provide an overview of MBR as it is being applied to Space Station Freedom ECLSS. It will report on work being done to produce intelligent systems to help design, control, monitor, and diagnose Freedom's ECLSS. Specifically, work on predictive monitoring, diagnosability, and diagnosis, with emphasis on the automated diagnosis of the regenerative water recovery and air revitalization processes will be discussed.

Challenges in surgical pathology of adrenocortical tumours.

PubMed

Erickson, Lori A

2018-01-01

Adrenocortical carcinomas are rare tumours that can be diagnostically challenging. Numerous multiparametric scoring systems and diagnostic algorithms have been proposed to differentiate adrenocortical adenoma from adrenocortical carcinoma. Adrenocortical neoplasms must also be differentiated from other primary adrenal tumours, such as phaeochromocytoma and unusual primary adrenal tumours, as well as metastases to the adrenal gland. Myxoid, oncocytic and sarcomatoid variants of adrenocortical tumours must be recognized so that they are not confused with other tumours. The diagnostic criteria for oncocytic adrenocortical carcinoma are different from those for conventional adrenocortical carcinomas. Adrenocortical neoplasms in children are particularly challenging to diagnose, as histological features of malignancy in adrenocortical neoplasms in adults may not be associated with aggressive disease in the tumours of children. Recent histological and immunohistochemical studies and more comprehensive and integrated genomic characterizations continue to advance our understanding of the tumorigenesis of these aggressive neoplasms, and may provide additional diagnostic and prognostic utility and guide the development of therapeutic targets. © 2017 John Wiley & Sons Ltd.

Advances and challenges in biosensor-based diagnosis of infectious diseases

PubMed Central

Sin, Mandy LY; Mach, Kathleen E; Wong, Pak Kin; Liao, Joseph C

2014-01-01

Rapid diagnosis of infectious diseases and timely initiation of appropriate treatment are critical determinants that promote optimal clinical outcomes and general public health. Conventional in vitro diagnostics for infectious diseases are time-consuming and require centralized laboratories, experienced personnel and bulky equipment. Recent advances in biosensor technologies have potential to deliver point-of-care diagnostics that match or surpass conventional standards in regards to time, accuracy and cost. Broadly classified as either label-free or labeled, modern biosensors exploit micro- and nanofabrication technologies and diverse sensing strategies including optical, electrical and mechanical transducers. Despite clinical need, translation of biosensors from research laboratories to clinical applications has remained limited to a few notable examples, such as the glucose sensor. Challenges to be overcome include sample preparation, matrix effects and system integration. We review the advances of biosensors for infectious disease diagnostics and discuss the critical challenges that need to be overcome in order to implement integrated diagnostic biosensors in real world settings. PMID:24524681

Current limitations and recommendations to improve testing ...

EPA Pesticide Factsheets

In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across organizations, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or the environment. Current test systems include in silico, in vitro and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormonal pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1)adequately sensitive species and life-stages, 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern, and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive in regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to, and guidance for existing test methods, and to reduce uncertainty. For example, in vitro high throughput

Active and Passive Diagnostic Signatures of Special Nuclear Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myers, William L.; Karpius, Peter Joseph; Myers, Steven Charles

2017-05-26

An overview will be given discussing signatures associated with special nuclear materials acquired using both active and passive diagnostic techniques. Examples of how technology advancements have helped improve diagnostic capabilities to meet the challenges of today’s applications will be discussed.

Antibiotic-Resistant Acinetobacter baumannii Increasing Success Remains a Challenge as a Nosocomial Pathogen

PubMed Central

Gonzalez-Villoria, Ana Maria; Valverde-Garduno, Veronica

2016-01-01

Antibiotic-resistant infectious bacteria currently imply a high risk and therefore constitute a strong challenge when treating patients in hospital settings. Characterization of these species and of particular strains is a priority for the establishment of diagnostic tests and preventive procedures. The relevance of Acinetobacter baumannii as a problematic microorganism in inpatient facilities, particularly intensive care units, has increased over time. This review aims to draw attention to (i) the historical emergence of carbapenem-resistant Acinetobacter baumannii, (ii) the current status of surveillance needs in Latin America, and (iii) recent data suggesting that A. baumannii continues to spread and evolve in hospital settings. First, we present synopsis of the series of events leading to the discovery and precise identification of this microorganism in hospital settings. Then key events in the acquisition of antibiotic-resistant genes by this microorganism are summarized, highlighting the race between new antibiotic generation and emergence of A. baumannii resistant strains. Here we review the historical development of this species as an infectious threat, the current state of its distribution, and antibiotic resistance characteristics, and we discuss future prospects for its control. PMID:26966582

Interpretation and expectation in childhood anxiety disorders: age effects and social specificity.

PubMed

Creswell, Cathy; Murray, Lynne; Cooper, Peter

2014-01-01

Theory and treatment for childhood anxiety disorders typically implicates children's negative cognitions, yet little is known about the characteristics of thinking styles of clinically anxious children. In particular, it is unclear whether differences in thinking styles between children with anxiety disorders and non-anxious children vary as a function of child age, whether particular cognitive distortions are associated with childhood anxiety disorders at different child ages, and whether cognitive content is disorder-specific. The current study addressed these questions among 120 7-12 year old children (53% female) who met diagnostic criteria for social anxiety disorder, other anxiety disorder, or who were not currently anxious. Contrary to expectations, threat interpretation was not inflated amongst anxious compared to non-anxious children at any age, although older (10-12 year old) anxious children did differ from non-anxious children on measures of perceived coping. The notion of cognitive-content specificity was not supported across the age-range. The findings challenge current treatment models of childhood anxiety, and suggest that a focus on changing anxious children's cognitions is not warranted in mid-childhood, and in late childhood cognitive approaches may be better focussed on promoting children's perceptions of control rather than challenging threat interpretations.

The diagnostic value of skin prick testing in children with food allergy.

PubMed

Hill, David J; Heine, Ralf G; Hosking, Clifford S

2004-10-01

The diagnostic accuracy of the skin prick test (SPT) in food allergy is controversial. We have developed diagnostic cut-off levels for SPT in children with allergy to cow milk, egg and peanut. Based on 555 open food challenges in 467 children (median age 3.0 yr) we defined food-specific SPT weal diameters that were '100% diagnostic' for allergy to cow milk (>or=8 mm), egg (>or=7 mm) and peanut (>or=8 mm). In children < 2 yr of age, the corresponding weal diameters were >or=6 mm, >or=5 mm and >or=4 mm, respectively. These SPT cut-off levels were prospectively validated in 90 consecutive children

Windows on the Human Body – in Vivo High-Field Magnetic Resonance Research and Applications in Medicine and Psychology

PubMed Central

Moser, Ewald; Meyerspeer, Martin; Fischmeister, Florian Ph. S.; Grabner, Günther; Bauer, Herbert; Trattnig, Siegfried

2010-01-01

Analogous to the evolution of biological sensor-systems, the progress in “medical sensor-systems”, i.e., diagnostic procedures, is paradigmatically described. Outstanding highlights of this progress are magnetic resonance imaging (MRI) and spectroscopy (MRS), which enable non-invasive, in vivo acquisition of morphological, functional, and metabolic information from the human body with unsurpassed quality. Recent achievements in high and ultra-high field MR (at 3 and 7 Tesla) are described, and representative research applications in Medicine and Psychology in Austria are discussed. Finally, an overview of current and prospective research in multi-modal imaging, potential clinical applications, as well as current limitations and challenges is given. PMID:22219684

Application of iron oxide nanoparticles in glioma imaging and therapy: from bench to bedside

NASA Astrophysics Data System (ADS)

Liu, Heng; Zhang, Jun; Chen, Xiao; Du, Xue-Song; Zhang, Jin-Long; Liu, Gang; Zhang, Wei-Guo

2016-04-01

Gliomas are the most common primary brain tumors and have a very dismal prognosis. However, recent advancements in nanomedicine and nanotechnology provide opportunities for personalized treatment regimens to improve the poor prognosis of patients suffering from glioma. This comprehensive review starts with an outline of the current status facing glioma. It then provides an overview of the state-of-the-art applications of iron oxide nanoparticles (IONPs) to glioma diagnostics and therapeutics, including MR contrast enhancement, drug delivery, cell labeling and tracking, magnetic hyperthermia treatment and magnetic particle imaging. It also addresses current challenges associated with the biological barriers and IONP design with an emphasis on recent advances and innovative approaches for glioma targeting strategies. Opportunities for future development are highlighted.

[Pathophysiology of hypertension : What are our current concepts?].

PubMed

Jordan, J

2015-03-01

In the year 2015, many questions regarding the pathophysiology of essential arterial hypertension remain unresolved. Substantial scientific progress has been made in various medical areas aided by novel molecular"omics" techniques. The findings could then be implemented in diagnostic and therapeutic procedures. In the field of hypertension research such methods have been applied in very large cohorts but have contributed less to pathophysiological understanding and clinical management than expected. The findings on the pathophysiological importance of baroreflex mechanisms, natriuretic peptides and osmotically inactive sodium storage discussed in this article all have something in common: all are based on small, carefully conducted human physiological investigations and often challenge current textbook knowledge. Nevertheless, these findings have opened up new research fields and are likely to affect clinical care.

Biomarkers for CNS involvement in pediatric lupus

PubMed Central

Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

2015-01-01

CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

Advances in the Care of Transgender Children and Adolescents

PubMed Central

Shumer, Daniel E; Nokoff, Natalie J; Spack, Norman P

2016-01-01

Children and adolescents with gender dysphoria are presenting for medical attention at increasing rates. Standards of Care have been developed which outline appropriate mental health support and hormonal interventions for transgender youth. This article defines terminology related to gender identity, reviews the history of medical interventions for transgender persons, outlines what is known about gender identity development, and reviews mental health disparities faced by this patient population. We provide an overview of medical management options for transgender adolescents meeting diagnostic criteria for gender dysphoria including pubertal suppression, cross-sex hormones, longitudinal screening and anticipatory guidance. We describe current challenges in the field and provide information about how care is currently being provided in the US and Canada. We conclude with 5 brief case examples. PMID:27426896

Application of iron oxide nanoparticles in glioma imaging and therapy: from bench to bedside.

PubMed

Liu, Heng; Zhang, Jun; Chen, Xiao; Du, Xue-Song; Zhang, Jin-Long; Liu, Gang; Zhang, Wei-Guo

2016-04-21

Gliomas are the most common primary brain tumors and have a very dismal prognosis. However, recent advancements in nanomedicine and nanotechnology provide opportunities for personalized treatment regimens to improve the poor prognosis of patients suffering from glioma. This comprehensive review starts with an outline of the current status facing glioma. It then provides an overview of the state-of-the-art applications of iron oxide nanoparticles (IONPs) to glioma diagnostics and therapeutics, including MR contrast enhancement, drug delivery, cell labeling and tracking, magnetic hyperthermia treatment and magnetic particle imaging. It also addresses current challenges associated with the biological barriers and IONP design with an emphasis on recent advances and innovative approaches for glioma targeting strategies. Opportunities for future development are highlighted.

Exploring the Case for a Global Alliance for Medical Diagnostics Initiative

PubMed Central

Mugambi, Melissa L.; Palamountain, Kara M.; Gallarda, Jim; Drain, Paul K.

2017-01-01

In recent years, the private and public sectors have increased investments in medical diagnostics for low- and middle-income countries (LMICs). Despite these investments, numerous barriers prevent the adoption of existing diagnostics and discourage the development and introduction of new diagnostics in LMICs. In the late 1990s, the global vaccine community had similar challenges, as vaccine coverage rates stagnated and the introduction of new vaccines was viewed as a distraction to delivering existing vaccines. To address these challenges, the international community came together and formed the Global Alliance for Vaccines Initiative (GAVI). Sixteen years after the formation of GAVI, we see evidence of a healthier global vaccine landscape. We discuss how GAVI’s four guiding principles (product, health systems strengthening, financing and market shaping) might apply to the advancement of medical diagnostics in LMICs. We present arguments for the international community and existing organizations to establish a Global Alliance for Medical Diagnostics Initiative (GAMDI). PMID:28134750

HIV testing updates and challenges: when regulatory caution and public health imperatives collide.

PubMed

Branson, Bernard M

2015-03-01

Numerous improvements in HIV testing technology led recently to the first revision of recommendations for diagnostic laboratory testing in the USA in 25 years. Developments in HIV testing continue to produce tests that identify HIV infection earlier with faster turnaround times for test results. These play an important role in identifying HIV infection during the highly infectious acute phase, which has implication for both patient management and public health interventions to control the spread of HIV. Access to these developments, however, is often delayed by the regulatory apparatus for approval and oversight of HIV testing in the USA. This article summarizes recent developments in HIV diagnostic testing technology, outlines their implications for clinical management and public health, describes current systems of regulatory oversight for HIV testing in the USA, and proposes alternatives that could expedite access to improved tests as they become available.

Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer

PubMed Central

Takai, Erina; Yachida, Shinichi

2016-01-01

Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The “liquid biopsy” addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer. PMID:27784960

Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer.

PubMed

Takai, Erina; Yachida, Shinichi

2016-10-14

Most pancreatic cancer patients present with advanced metastatic disease, resulting in extremely poor 5-year survival, mainly because of the lack of a reliable modality for early detection and limited therapeutic options for advanced disease. Therefore, there is a need for minimally-invasive diagnostic tools for detecting pancreatic cancer at an early stage, when curative surgery and also novel therapeutic approaches including precision medicine may be feasible. The "liquid biopsy" addresses these unmet clinical needs based on the concept that simple peripheral blood sampling and detection of circulating tumor DNA (ctDNA) could provide diagnostic information. In this review, we provide an overview of the current status of blood-based tests for diagnosis of pancreatic cancer and the potential utility of ctDNA for precision medicine. We also discuss challenges that remain to be addressed in developing practical ctDNA-based liquid biopsy approaches for early diagnosis of pancreatic cancer.

Operationalizing diagnostic criteria for Alzheimer’s disease and other age-related cognitive impairment—Part 1*

PubMed Central

Mayeux, Richard; Reitz, Christiane; Brickman, Adam M.; Haan, Mary N.; Manly, Jennifer J.; Glymour, M. Maria; Weiss, Christopher C.; Yaffe, Kristine; Middleton, Laura; Hendrie, Hugh C.; Warren, Lauren H.; Hayden, Kathleen M.; Welsh-Bohmer, Kathleen A.; Breitner, John C. S.; Morris, John C.

2011-01-01

Population studies strive to determine the prevalence of Alzheimer dementia but prevalence estimates vary widely. The challenges faced by several noted population studies for Alzheimer dementia in operationalizing current clinical diagnostic criteria for Alzheimer’s disease (AD) are reviewed. Differences in case ascertainment, methodological biases, cultural and educational influences on test performance, inclusion of special populations such as underrepresented minorities and the oldest old, and detection of the earliest symptomatic stages of underlying AD are considered. Classification of Alzheimer dementia may be improved by the incorporation of biomarkers for AD if the sensitivity, specificity, and predictive value of the biomarkers are established and if they are appropriate for epidemiological studies as may occur should a plasma biomarker be developed. Biomarkers for AD also could facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in “mixed dementia”. PMID:21255741

Prosthetic Device Infections.

PubMed

Martinez, Raquel M; Bowen, Thomas R; Foltzer, Michael A

2016-08-01

The immunocompromised host is a particularly vulnerable population in whom routine and unusual infections can easily and frequently occur. Prosthetic devices are commonly used in these patients and the infections associated with those devices present a number of challenges for both the microbiologist and the clinician. Biofilms play a major role in device-related infections, which may contribute to failed attempts to recover organisms from routine culture methods. Moreover, device-related microorganisms can be difficult to eradicate by antibiotic therapy alone. Changes in clinical practice and advances in laboratory diagnostics have provided significant improvements in the detection and accurate diagnosis of device-related infections. Disruption of the bacterial biofilm plays an essential role in recovering the causative agent in culture. Various culture and nucleic acid amplification techniques are more accurate to guide directed treatment regimens. This chapter reviews the performance characteristics of currently available diagnostic assays and summarizes published guidelines, where available, for addressing suspected infected prosthetic devices.

Improvements in diagnostic tools for early detection of psoriatic arthritis.

PubMed

D'Angelo, Salvatore; Palazzi, Carlo; Gilio, Michele; Leccese, Pietro; Padula, Angela; Olivieri, Ignazio

2016-11-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized by a wide clinical spectrum. The early diagnosis of PsA is currently a challenging topic. Areas covered: The literature was extensively reviewed for studies addressing the topic area "diagnosis of psoriatic arthritis". This review will summarize improvements in diagnostic tools, especially referral to the rheumatologist, the role of patient history and clinical examination, laboratory tests, and imaging techniques in getting an early and correct diagnosis of PsA. Expert commentary: Due to the heterogeneity of its expression, PsA may be easily either overdiagnosed or underdiagnosed. A diagnosis of PsA should be taken into account every time a patient with psoriasis or a family history of psoriasis shows peripheral arthritis, especially if oligoarticular or involving the distal interphalangeal joints, enthesitis or dactylitis. Magnetic resonance imaging and ultrasonography are useful for diagnosing PsA early, particularly when isolated enthesitis or inflammatory spinal pain occur.

Management of Respiratory Infections with Use of Procalcitonin: Moving toward More Personalized Antibiotic Treatment Decisions.

PubMed

Wirz, Yannick; Branche, Angela; Wolff, Michel; Welte, Tobias; Nobre, Vandack; Reinhart, Konrad; Falsey, Ann R; Damas, Pierre; Beishuizen, Albertus; Deliberato, Rodrigo O; Shehabi, Yahya; Jensen, Jens-Ulrik S; Mueller, Beat; Schuetz, Philipp

2017-12-08

Due to overlap of clinical findings and low sensitivity of bacterial diagnostic tests, differentiation between bacterial and viral respiratory tract infections remains challenging, ultimately leading to antibiotic overuse in this population of patients. Addition of procalcitonin, a blood biomarker expressed by epithelial cells in response to bacterial infections, to the clinical assessment leads to a reduction in inappropriate antibiotic initiation. Procalcitonin also provides prognostic information about the resolution of illness, and significant decreases over time are a strong signal for the discontinuation of antibiotics. Current evidence from randomized trials indicates that procalcitonin-guided antibiotic stewardship results in a reduction in antibiotic use and antibiotic side effects, which importantly translates into improved survival of patients with respiratory infections. Inclusion of procalcitonin into antibiotic stewardship algorithms thus improves the diagnostic and therapeutic management of patients presenting with respiratory illnesses and holds great promise to mitigate the global bacterial resistance crisis.

Update on eating disorders: current perspectives on avoidant/restrictive food intake disorder in children and youth

PubMed Central

Norris, Mark L; Spettigue, Wendy J; Katzman, Debra K

2016-01-01

Avoidant/restrictive food intake disorder (ARFID) is a new eating disorder diagnosis that was introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM) fifth edition. The fourth edition of the DSM had failed to adequately capture a cohort of children, adolescents, and adults who are unable to meet appropriate nutritional and/or energy needs, for reasons other than drive for thinness, leading to significant medical and/or psychological sequelae. With the introduction of ARFID, researchers are now starting to better understand the presentation, clinical characteristics, and complexities of this disorder. This article outlines the diagnostic criteria for ARFID with specific focus on children and youth. A case example of a patient with ARFID, factors that differentiate ARFID from picky eating, and the estimated prevalence in pediatric populations are discussed, as well as clinical and treatment challenges that impact health care providers providing treatment for patients. PMID:26855577

Update on eating disorders: current perspectives on avoidant/restrictive food intake disorder in children and youth.

PubMed

Norris, Mark L; Spettigue, Wendy J; Katzman, Debra K

2016-01-01

Avoidant/restrictive food intake disorder (ARFID) is a new eating disorder diagnosis that was introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM) fifth edition. The fourth edition of the DSM had failed to adequately capture a cohort of children, adolescents, and adults who are unable to meet appropriate nutritional and/or energy needs, for reasons other than drive for thinness, leading to significant medical and/or psychological sequelae. With the introduction of ARFID, researchers are now starting to better understand the presentation, clinical characteristics, and complexities of this disorder. This article outlines the diagnostic criteria for ARFID with specific focus on children and youth. A case example of a patient with ARFID, factors that differentiate ARFID from picky eating, and the estimated prevalence in pediatric populations are discussed, as well as clinical and treatment challenges that impact health care providers providing treatment for patients.

Orphan diseases of the nose and paranasal sinuses: Pathogenesis – clinic – therapy

PubMed Central

Laudien, Martin

2015-01-01

Rare rhinological diseases are a diagnostic challenge. Sometimes it takes months or even years from the primary manifestation of the disease until the definitive diagnosis is establibshed. During these times the disease proceeds in an uncontrolled or insufficiently treated way. (Irreversible) damage results and sometimes life-threatening situations occur. The unexpected course of a (misdiagnosed) disease should lead to further diagnostic reflections and steps in order to detect also rare diseases as early as possible. The present paper discusses granulomatous diseases of the nose and paranasal sinuses caused by mycobacteria, treponema, Klebsiella, fungi, and protozoa as well as vasculitis, sarcoidosis, rosacea, cocaine-induced midline destruction, nasal extranodal NK/T cell lymphoma, and cholesterol granuloma. Furthermore, diseases with disorders of the mucociliary clearance such as primary ciliary dyskinesia and cystic fibrosis are presented, taking into consideration the current literature. PMID:26770278

Tourette's: syndrome, disorder or spectrum? Classificatory challenges and an appraisal of the DSM criteria.

PubMed

Robertson, Mary May; Eapen, Valsamma

2014-10-01

The fifth version of the Diagnostic and statistical manual of mental disorders (DSM-5) was released in May 2013 after 14 years of development and almost two decades after the last edition DSM-IV was published in 1994. We review the DSM journey with regards to Tourette Syndrome from the original publication of DSM 1 in 1952 till date. In terms of changes in DSM 5, the major shift has come in the placement of Tourette Syndrome under the 'Neurodevelopmental Disorders' alongside other disorders with a developmental origin. This review provides an overview of the changes in DSM-5 highlighting key points for clinical practice and research along with a snap shot of the current use of DSM as a classificatory system in different parts of the world and suggestions for improving the subtyping and the diagnostic confidence. Copyright © 2014 Elsevier B.V. All rights reserved.

A Practical Approach to the Diagnosis of Pelvic Inflammatory Disease

PubMed Central

Jaiyeoba, Oluwatosin; Soper, David E.

2011-01-01

The diagnosis of acute pelvic inflammatory disease (PID) is usually based on clinical criteria and can be challenging for even the most astute clinicians. Although diagnostic accuracy is advocated, antibiotic treatment should be instituted if there is a diagnosis of cervicitis or suspicion of acute PID. Currently, no single test or combination of diagnostic indicators have been found to reliably predict PID, and laparoscopy cannot be recommended as a first line tool for PID diagnosis. For this reason, the clinician is left with maintaining a high index of suspicion for the diagnosis as he/she evaluates the lower genital tract for inflammation and the pelvic organs for tenderness in women with genital tract symptoms and a risk for sexually transmitted infection. This approach should minimize treating women without PID with antibiotics and optimize the diagnosis in a practical and cost-effective way. PMID:21822367

A review of cellphone microscopy for disease detection.

PubMed

Dendere, R; Myburg, N; Douglas, T S

2015-12-01

The expansion in global cellphone network coverage coupled with advances in cellphone imaging capabilities present an opportunity for the advancement of cellphone microscopy as a low-cost alternative to conventional microscopy for disease detection in resource-limited regions. The development of cellphone microscopy has also benefitted from the availability of low-cost miniature microscope components such as low-power light-emitting diodes and ball lenses. As a result, researchers are developing hardware and software techniques that would enable such microscopes to produce high-resolution, diagnostic-quality images. This approach may lead to more widespread delivery of diagnostic services in resource-limited areas where there is a shortage of the skilled labour required for conventional microscopy and where prevalence of infectious and other diseases is still high. In this paper, we review current techniques, clinical applications and challenges faced in the field of cellphone microscopy. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

A ferrofluidic deformable mirror for ophthalmology

NASA Astrophysics Data System (ADS)

Macpherson, J. B.; Thibault, S.; Borra, E. F.; Ritcey, A. M.; Carufel, N.; Asselin, D.; Jerominek, H.; Campbell, M. C. W.

2005-09-01

Optical aberrations reduce the imaging quality of the human eye. In addition to degrading vision, this limits our ability to illuminate small points of the retina for therapeutic, surgical or diagnostic purposes. When viewing the rear of the eye, aberrations cause structures in the fundus to appear blurred, limiting the resolution of ophthalmoscopes (diagnostic instruments used to image the eye). Adaptive optics, such as deformable mirrors may be used to compensate for aberrations, allowing the eye to work as a diffraction-limited optical element. Unfortunately, this type of correction has not been widely available for ophthalmic applications because of the expense and technical limitations of current deformable mirrors. We present preliminary design and characterisation of a deformable mirror suitable for ophthalmology. In this ferrofluidic mirror, wavefronts are reflected from a fluid whose surface shape is controlled by a magnetic field. Challenges in design are outlined, as are advantages over traditional deformable mirrors.

Associations between diagnostic patterns and stages in ovarian cancer

DOE PAGES

Bogie, Kath; Xu, Yifan; Ma, Junheng; ...

2017-08-30

Ovarian cancer (OvCa) is the fifth leading cause of cancer deaths in women and remains the most deadly gynecological cancer. The disease places a debilitating burden on the US population, in terms of mortality, morbidity, individual suffering and loss of productivity for all women with OvCa. National expenditures for OvCa care were estimated at $5.12B in 2010. The high fatality of OvCa is attributed to the fact that most patients are diagnosed at a late stage, with 63% diagnosed at Stage III or later. Effective early-stage diagnosis is challenging because there are no approved screening procedures for the general population,more » which has led to OvCa being termed1 the “silent killer”. We have previously shown that public awareness and knowledge about OvCa is poor among the general population. It has also been reported that ovarian masses have often been misdiagnosed, although there was some association of pre-diagnostic symptoms with OvCa and with OvCa diagnostic stages. The motivation for the current study was to examine the association of diagnostic patterns (determined by the responses from ‘frontline’ clinicians, specifically primary care physicians (PCPs) and emergency room (ER) doctors, together with follow-up by specialists), with OvCa stages.« less

Associations between diagnostic patterns and stages in ovarian cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogie, Kath; Xu, Yifan; Ma, Junheng

Ovarian cancer (OvCa) is the fifth leading cause of cancer deaths in women and remains the most deadly gynecological cancer. The disease places a debilitating burden on the US population, in terms of mortality, morbidity, individual suffering and loss of productivity for all women with OvCa. National expenditures for OvCa care were estimated at $5.12B in 2010. The high fatality of OvCa is attributed to the fact that most patients are diagnosed at a late stage, with 63% diagnosed at Stage III or later. Effective early-stage diagnosis is challenging because there are no approved screening procedures for the general population,more » which has led to OvCa being termed1 the “silent killer”. We have previously shown that public awareness and knowledge about OvCa is poor among the general population. It has also been reported that ovarian masses have often been misdiagnosed, although there was some association of pre-diagnostic symptoms with OvCa and with OvCa diagnostic stages. The motivation for the current study was to examine the association of diagnostic patterns (determined by the responses from ‘frontline’ clinicians, specifically primary care physicians (PCPs) and emergency room (ER) doctors, together with follow-up by specialists), with OvCa stages.« less

Diagnostic and Prognostic Value of CMR T1-Mapping in Patients With Heart Failure and Preserved Ejection Fraction.

PubMed

Rommel, Karl-Philipp; Lücke, Christian; Lurz, Philipp

2017-10-01

Heart failure with preserved ejection fraction (HFpEF) presents a major challenge in modern cardiology. Although this syndrome is of increasing prevalence and is associated with unfavorable outcomes, treatment trials have failed to establish effective therapies. Currently, solutions to this dilemma are being investigated, including categorizing and characterizing patients more diversely to individualize treatment. In this regard, new imaging techniques might provide important information. Diastolic dysfunction is a diagnostic and pathophysiological cornerstone in HFpEF and is believed to be caused by systemic inflammation with the development of interstitial myocardial fibrosis and myocardial stiffening. Cardiac magnetic resonance (CMR) T 1 -mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. This review provides an overview of the potential of myocardial tissue characterization with CMR T 1 mapping in HFpEF patients, outlining its diagnostic and prognostic implications and discussing future directions. We conclude that CMR T 1 mapping is potentially an effective tool for patient characterization in large-scale epidemiological, diagnostic, and therapeutic HFpEF trials beyond traditional imaging parameters. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

T1 and T2 mapping in myocarditis: seeing beyond the horizon of Lake Louise criteria and histopathology.

PubMed

Puntmann, Valentina O; Zeiher, Andreas M; Nagel, Eike

2018-05-01

Myocarditis and its sequelae remain an unconquered clinical problem, disproportionately affecting the young. Several hurdles beset myocarditis, including non-specific symptoms, heterogeneous clinical presentation, dynamic disease stages, underscored by an absence of an easy diagnostic test or a specific treatment. Areas covered: The current diagnostic means are poorly equipped to counter the challenge; the gold standard by invasive endomyocardial biopsy relies on availability of expert procedural and reading skill. The tissue diagnostic criteria were developed to improve readers agreement with clinical diagnosis, and not based on evidence for differential treatment or improved prognosis. The Lake-Louise Criteria represented a first step towards a non-invasive diagnosis. They require extensive imaging, which is insufficiently robust with poor diagnostic confidence and tissue pathophysiological validation; they similarly lack evidence of improved outcome by guiding clinical management. T1 and T2 mapping are a step-change, providing robust, short and quantifiable imaging application, which can veritably reflect the dynamic and heterogeneous underlying disease. Expert commentary: T1 and T2 mapping harbours a unique potential for an objective non-invasive disease recognition and treatment discovery in myocarditis. These measures should enter independently into clinical experimentation, with a high priority for outcome and therapeutic studies.

The diagnosis of idiopathic pulmonary fibrosis: current and future approaches

PubMed Central

Martinez, Fernando J; Chisholm, Alison; Collard, Harold R; Flaherty, Kevin R; Myers, Jeffrey; Raghu, Ganesh; Walsh, Simon LF; White, Eric S; Richeldi, Luca

2017-01-01

With the recent development of two effective treatments for patients with idiopathic pulmonary fibrosis, an accurate diagnosis is crucial. The traditional approach to diagnosis emphasises the importance of thorough clinical and laboratory evaluations to exclude secondary causes of disease. High-resolution CT is a critical initial diagnostic test and acts as a tool to identify patients who should undergo surgical lung biopsy to secure a definitive histological diagnosis of usual interstitial pneumonia pattern. This diagnostic approach faces several challenges. Many patients with suspected idiopathic pulmonary fibrosis present with atypical high-resolution CT characteristics but are unfit for surgical lung biopsy, therefore preventing a confident diagnosis. The state of the art suggests an iterative, multidisciplinary process that incorporates available clinical, laboratory, imaging, and histological features. Recent research has explored genomic techniques to molecularly phenotype patients with interstitial lung disease. In the future, clinicians will probably use blood-specific or lung-specific molecular markers in combination with other clinical, physiological, and imaging features to enhance diagnostic efforts, refine prognostic recommendations, and influence the initial or subsequent treatment options. There is an urgent and increasing need for well designed, large, prospective studies measuring the effect of different diagnostic approaches. Ultimately, this will help to inform the development of guidelines and tailor clinical practice for the benefit of patients. PMID:27932290

Advances in the diagnosis of premenstrual syndrome and premenstrual dysphoric disorder.

PubMed

Futterman, Lori A

2010-01-01

Premenstrual disorders negatively impact the quality of life and functional ability of millions of women. The two generally recognized premenstrual disorders are premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). These disorders are characterized by a wide variety of nonspecific mood, somatic and behavioral symptoms that occur only during the late luteal phase of a woman's cycle and disappear soon after the onset of menstruation. This paper reviews the diagnostic criteria for PMS and PMDD, describes some of the more common symptom diaries and other tools used to diagnose premenstrual disorders, and discusses the challenges inherent in diagnosing PMS and PMDD. A survey of peer-reviewed articles and relevant texts provided diagnostic criteria, descriptions of diagnostic tools and information about diagnostic challenges. The many nonspecific symptoms associated with premenstrual disorders complicate the diagnostic process. The use of proven symptom diaries and other diagnostic tools should aid in the differential diagnosis of premenstrual disorders. Patients need to report bothersome premenstrual symptoms, and clinicians should become more proficient in the diagnostic process in order to prevent underdiagnosis of these disorders.

Central nervous system Aspergillus infection after epidural analgesia: diagnosis, therapeutic challenges, and literature review

PubMed Central

Genzen, Jonathan R.; Kenney, Barton

2009-01-01

Aspergillus terreus was identified in an intra-dural spinal biopsy specimen from an African female with recurrent headache and hydrocephalus. Prior laboratory testing of cerebrospinal fluid (CSF) was non-diagnostic, despite extensive central nervous system (CNS) involvement. CNS Aspergillus infection presents a diagnostic and therapeutic challenge and is reviewed in the context of this particularly instructive and difficult case. PMID:19717262

Ethical aspects of personality disorders.

PubMed

Bendelow, Gillian

2010-11-01

To review recent literature around the controversial diagnosis of personality disorder, and to assess the ethical aspects of its status as a medical disorder. The diagnostic currency of personality disorder as a psychiatric/medical disorder has a longstanding history of ethical and social challenges through critiques of the medicalization of deviance. More recently controversies by reflexive physicians around the inclusion of the category in the forthcoming revisions of International Classification of Diseases and Diagnostic and Statistical Manual of Mental Disorders classifications reflect the problems of value-laden criteria, with the diagnostic category being severely challenged from within psychiatry as well as from without. The clinical diagnostic criteria for extremely value-laden psychiatric conditions such as personality disorder need to be analyzed through the lens of values-based medicine, as well as through clinical evidence, as the propensity for political and sociolegal appropriation of the categories can render their clinical and diagnostic value meaningless.

Magnetic bead-quantum dot assay for detection of a biomarker for traumatic brain injury

NASA Astrophysics Data System (ADS)

Kim, Chloe; Searson, Peter C.

2015-10-01

Current diagnostic methods for traumatic brain injury (TBI), which accounts for 15% of all emergency room visits, are limited to neuroimaging modalities. The challenges of accurate diagnosis and monitoring of TBI have created the need for a simple and sensitive blood test to detect brain-specific biomarkers. Here we report on an assay for detection of S100B, a putative biomarker for TBI, using antibody-conjugated magnetic beads for capture of the protein, and antibody-conjugated quantum dots for optical detection. From Western Blot, we show efficient antigen capture and concentration by the magnetic beads. Using magnetic bead capture and quantum dot detection in serum samples, we show a wide detection range and detection limit below the clinical cut-off level.Current diagnostic methods for traumatic brain injury (TBI), which accounts for 15% of all emergency room visits, are limited to neuroimaging modalities. The challenges of accurate diagnosis and monitoring of TBI have created the need for a simple and sensitive blood test to detect brain-specific biomarkers. Here we report on an assay for detection of S100B, a putative biomarker for TBI, using antibody-conjugated magnetic beads for capture of the protein, and antibody-conjugated quantum dots for optical detection. From Western Blot, we show efficient antigen capture and concentration by the magnetic beads. Using magnetic bead capture and quantum dot detection in serum samples, we show a wide detection range and detection limit below the clinical cut-off level. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05608j

Army requirements for micro and nanotechnology-based sensors in weapons health and battlefield environmental monitoring applications

NASA Astrophysics Data System (ADS)

Ruffin, Paul; Brantley, Christina; Edwards, Eugene; Hutcheson, Guilford

2006-03-01

The Army Aviation and Missile Research, Development, and Engineering Center (AMRDEC) and the Army Research Laboratory (ARL) have initiated a joint advanced technology demonstration program entitled "Prognostics/Diagnostics for the Future Force (PDFF)" with a key objective of developing low or no power embedded sensor suites for harsh environmental monitoring. The most critical challenge of the program is to specify requirements for the embedded sensor suites which will perform on-board diagnostics, maintain a history of sensor data, and forecast weapon health. The authors are currently collaborating with the PDFF program managers and potential customers to quantify the requirements for remotely operated, micro/nano-technology-based sensors for a host of candidate weapon systems. After requirements are finalized, current micro/nanotechnology-based temperature, humidity, g-shock, vibration and chemical sensors for monitoring the out-gassing of weapons propellant, as well as hazardous gaseous species on the battlefield and in urban environments will be improved to meet the full requirements of the PDFF program. In this paper, performance requirements such as power consumption, reliability, maintainability, survivability, size, and cost, along with the associated technical challenges for micro/nanotechnology-based sensor systems operating in military environments, are discussed. In addition, laboratory results from the design and testing of a wireless sensor array, which was developed using a thin film of functionalized carbon nanotube materials, are presented. Conclusions from the research indicate that the detection of bio-hazardous materials is possible using passive and active wireless sensors based on monitoring the reflected phase from the sensor.

Microfluidic point-of-care diagnostics for resource-poor environments

NASA Astrophysics Data System (ADS)

Laksanasopin, Tassaneewan; Chin, Curtis D.; Moore, Hannah; Wang, Jennifer; Cheung, Yuk Kee; Sia, Samuel K.

2009-05-01

Point-of-care (POC) diagnostics have tremendous potential to improve human health in remote and resource-poor settings. However, the design criteria for diagnostic tests appropriate in settings with limited infrastructure are unique and challenging. Here we present a custom optical reader which quantifies silver absorbance from heterogeneous immunoassays. The reader is simple and low-cost and suited for POC diagnostics.

The Evolution of Teleophthalmology Programs in the United Kingdom: Beyond Diabetic Retinopathy Screening.

PubMed

Sim, Dawn A; Mitry, Danny; Alexander, Philip; Mapani, Adam; Goverdhan, Srini; Aslam, Tariq; Tufail, Adnan; Egan, Catherine A; Keane, Pearse A

2016-02-01

Modern ophthalmic practice in the United Kingdom is faced by the challenges of an aging population, increasing prevalence of systemic pathologies with ophthalmic manifestations, and emergent treatments that are revolutionary but dependent on timely monitoring and diagnosis. This represents a huge strain not only on diagnostic services but also outpatient management and surveillance capacity. There is an urgent need for newer means of managing this surge in demand and the socioeconomic burden it places on the health care system. Concurrently, there have been exponential increases in computing power, expansions in the strength and ubiquity of communications technologies, and developments in imaging capabilities. Advances in imaging have been not only in terms of resolution, but also in terms of anatomical coverage, allowing new inferences to be made. In spite of this, image analysis techniques are still currently superseded by expert ophthalmologist interpretation. Teleophthalmology is therefore currently perfectly placed to face this urgent and immediate challenge of provision of optimal and expert care to remote and multiple patients over widespread geographical areas. This article reviews teleophthalmology programs currently deployed in the United Kingdom, focusing on diabetic eye care but also discussing glaucoma, emergency eye care, and other retinal diseases. We examined current programs and levels of evidence for their utility, and explored the relationships between screening, teleophthalmology, disease detection, and monitoring before discussing aspects of health economics pertinent to diabetic eye care. The use of teleophthalmology presents an immense opportunity to manage the steadily increasing demand for eye care, but challenges remain in the delivery of practical, viable, and clinically proven solutions. © 2016 Diabetes Technology Society.

The Evolution of Teleophthalmology Programs in the United Kingdom

PubMed Central

Sim, Dawn A.; Mitry, Danny; Alexander, Philip; Mapani, Adam; Goverdhan, Srini; Aslam, Tariq; Tufail, Adnan; Egan, Catherine A.; Keane, Pearse A.

2016-01-01

Modern ophthalmic practice in the United Kingdom is faced by the challenges of an aging population, increasing prevalence of systemic pathologies with ophthalmic manifestations, and emergent treatments that are revolutionary but dependent on timely monitoring and diagnosis. This represents a huge strain not only on diagnostic services but also outpatient management and surveillance capacity. There is an urgent need for newer means of managing this surge in demand and the socioeconomic burden it places on the health care system. Concurrently, there have been exponential increases in computing power, expansions in the strength and ubiquity of communications technologies, and developments in imaging capabilities. Advances in imaging have been not only in terms of resolution, but also in terms of anatomical coverage, allowing new inferences to be made. In spite of this, image analysis techniques are still currently superseded by expert ophthalmologist interpretation. Teleophthalmology is therefore currently perfectly placed to face this urgent and immediate challenge of provision of optimal and expert care to remote and multiple patients over widespread geographical areas. This article reviews teleophthalmology programs currently deployed in the United Kingdom, focusing on diabetic eye care but also discussing glaucoma, emergency eye care, and other retinal diseases. We examined current programs and levels of evidence for their utility, and explored the relationships between screening, teleophthalmology, disease detection, and monitoring before discussing aspects of health economics pertinent to diabetic eye care. The use of teleophthalmology presents an immense opportunity to manage the steadily increasing demand for eye care, but challenges remain in the delivery of practical, viable, and clinically proven solutions. PMID:26830492

The after breakfast 50-g, 1-hour glucose challenge test in urban Mexican pregnant women: its sensitivity and specificity evaluated by three diagnostic criteria for gestational diabetes mellitus.

PubMed

Espinosa de los Monteros, A; Parra, A; Hidalgo, R; Zambrana, M

1999-04-01

To study the sensitivity and specificity of the 50-g, 1-hour gestational glucose challenge test performed 1 to 2 hours after a non-standardized home breakfast in urban Mexican women by using three different gestational diabetes mellitus diagnostic criteria. Four hundred and forty-five consecutive women of 24-28 weeks gestation were studied. The glucose challenge test was performed in the fed state and a week later a fasting 100-g, 3-hours oral glucose tolerance test was carried out in all of them. Duplicate serum glucose concentrations were determined by a glucose-oxidase method. Sensitivity and specificity were calculated using three different diagnostic criteria for gestational diabetes mellitus. The glucose challenge test performed as indicated, with a cutoff of 7.8 mmol/L, had 88-89% sensitivity and 85-87% specificity when using as diagnostic criteria those proposed by the National Diabetes Data Group and by Carpenter & Coustan; by using Sacks et al. criteria, the values were 82% and 88%, respectively. Considering only pregnant women > or = 25 years of age, the sensitivity increased to 92% with the National Diabetes Data Group criteria. Pregnant women < 25 years of age had significantly lower blood glucose values than those with age > or = 25 years during the glucose tolerance test. For the general group the sensitivity of the glucose challenge test performed 1 to 2 hours after breakfast was similar, based on the National Diabetes Data Group and the Carpenter & Coustan's diagnostic criteria for gestational diabetes mellitus. However, when pregnant women > or = 25 years of age were considered, the use of the former criteria yielded a slightly better sensitivity.

Diagnostic properties of the methacholine and mannitol bronchial challenge tests: a comparison study.

PubMed

Kim, Min-Hye; Song, Woo-Jung; Kim, Tae-Wan; Jin, Hyun-Jung; Sin, You-Seob; Ye, Young-Min; Kim, Sang-Heon; Park, Heung-Woo; Lee, Byung-Jae; Park, Hae-Sim; Yoon, Ho-Joo; Choi, Dong-Chull; Min, Kyung-Up; Cho, Sang-Heon

2014-08-01

Airway hyperresponsiveness is a common feature of asthma. Methacholine and mannitol are two representative agonists for bronchial challenge. They have theoretically different mechanisms of action, and may have different diagnostic properties. However, their difference has not been directly evaluated among Korean adults. In this study, we compare the diagnostic properties of methacholine and mannitol bronchial provocation tests. Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral hospitals in Korea. Participants were challenged with each of methacholine and mannitol inhalation on different days. Their diagnostic utility was evaluated by calculating their sensitivity and specificity for asthma diagnosis. Response-dose ratio was also compared. A total of 50 asthmatic adults and 54 controls were enrolled (mean age 43.8 years). The sensitivity and specificity of mannitol challenge (defined by a PD15 of <635 mg) were 48.0% and 92.6%, respectively, whereas those of methacholine (defined by a PC20 of <16 mg/mL) were 42.0% and 98.1%, respectively. Twenty asthmatic participants (24%) showed positive response to a single agonist only. In the receiver operating curve analyses using response-dose ratio values, area under the curve was 0.77 (95% confidence interval (CI): 0.68-0.86) for mannitol, and 0.89 (95% CI: 0.83-0.95) for methacholine. The correlations between log- transformed mannitol and methacholine response-dose ratios were significant but moderate (r = 0.683, P < 0.001). The present study demonstrated overall similar diagnostic properties of two diagnostic tests, but also suggested their intercomplementary roles for asthma. The clinical trial registration number at ClinicalTrial.gov is NCT02104284. © 2014 Asian Pacific Society of Respirology.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Climate Model Diagnostic Analyzer Web Service System

NASA Astrophysics Data System (ADS)

Lee, S.; Pan, L.; Zhai, C.; Tang, B.; Kubar, T. L.; Li, J.; Zhang, J.; Wang, W.

2015-12-01

Both the National Research Council Decadal Survey and the latest Intergovernmental Panel on Climate Change Assessment Report stressed the need for the comprehensive and innovative evaluation of climate models with the synergistic use of global satellite observations in order to improve our weather and climate simulation and prediction capabilities. The abundance of satellite observations for fundamental climate parameters and the availability of coordinated model outputs from CMIP5 for the same parameters offer a great opportunity to understand and diagnose model biases in climate models. In addition, the Obs4MIPs efforts have created several key global observational datasets that are readily usable for model evaluations. However, a model diagnostic evaluation process requires physics-based multi-variable comparisons that typically involve large-volume and heterogeneous datasets, making them both computationally- and data-intensive. In response, we have developed a novel methodology to diagnose model biases in contemporary climate models and implementing the methodology as a web-service based, cloud-enabled, provenance-supported climate-model evaluation system. The evaluation system is named Climate Model Diagnostic Analyzer (CMDA), which is the product of the research and technology development investments of several current and past NASA ROSES programs. The current technologies and infrastructure of CMDA are designed and selected to address several technical challenges that the Earth science modeling and model analysis community faces in evaluating and diagnosing climate models. In particular, we have three key technology components: (1) diagnostic analysis methodology; (2) web-service based, cloud-enabled technology; (3) provenance-supported technology. The diagnostic analysis methodology includes random forest feature importance ranking, conditional probability distribution function, conditional sampling, and time-lagged correlation map. We have implemented the new methodology as web services and incorporated the system into the Cloud. We have also developed a provenance management system for CMDA where CMDA service semantics modeling, service search and recommendation, and service execution history management are designed and implemented.

Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: a double-blind placebo-controlled study.

PubMed

Kukkonen, A K; Pelkonen, A S; Mäkinen-Kiljunen, S; Voutilainen, H; Mäkelä, M J

2015-10-01

Component-resolved diagnostics offers a modern tool in peanut allergy, but studies applying consistently double-blind placebo-controlled challenges are lacking. We aimed to optimize diagnostics for moderate-to-severe peanut allergy in a birch-endemic region and to create an oral-peanut challenge with its allergen activity characterized. We performed double-blind placebo-controlled peanut challenges for a referred sample of 6- to 18-year-olds with peanut sensitization or a high suspicion of peanut allergy, including anaphylaxis. We measured specific IgE (sIgE) to Ara h 1, 2, 3, 6, 8, and 9. Testing of allergen activity of the challenge products was by IgE microarray inhibition. Of the 102 patients, 69 were challenge positive: 25 (36%) had severe, 36 (52%) moderate, and 8 (12%) mild symptoms; 38 (37%) received adrenalin. SIgE to Ara h 6 AUC 0.98 (95%CI, 0.96-1.00) was the best marker of moderate-to-severe allergy. When sIgE to Ara h 2 and Ara h 6 was measured together, all (100%) severe reactions at low doses were successfully diagnosable. SIgE to Ara h 8 had no diagnostic value, AUC 0.42 (95%CI, 0.30-0.52). Both nonroasted and roasted peanut inhibited 100% of IgE binding to Ara h 1, 2, 3, and 6. Nonroasted peanut inhibited 87% of IgE binding to Ara h 8, roasted inhibited 30%. The products lacked Ara h 9 activity. Co-sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. SIgE to Ara h 8 added no diagnostic value. Component-resolved diagnostics reduce the need for oral challenges in peanut allergy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Emerging Resistance, New Antimicrobial Agents  …  but No Tests! The Challenge of Antimicrobial Susceptibility Testing in the Current US Regulatory Landscape.

PubMed

Humphries, R M; Hindler, J A

2016-07-01

Accurate and timely performance of antimicrobial susceptibility testing (AST) by the clinical laboratory is paramount to combating antimicrobial resistance. The ability of laboratories in the United States to effectively perform ASTs is challenged by several factors. Some, such as new resistance mechanisms and the associated evolution of testing recommendations and breakpoints, are inevitable. Others are entirely man-made. These include unnecessarily strict US Food and Drug Administration (FDA) limitations on how commercial AST systems can be used for diagnostic testing, the absence of up-to-date performance data on these systems, and the lack of commercially available FDA-cleared tests for newer antimicrobial agents or for older agents with updated breakpoints. This viewpoint will highlight contemporary AST challenges faced by the clinical laboratory, and propose some solutions. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Pollution exposure on marine protected areas: A global assessment.

PubMed

Partelow, Stefan; von Wehrden, Henrik; Horn, Olga

2015-11-15

Marine protected areas (MPAs) face many challenges in their aim to effectively conserve marine ecosystems. In this study we analyze the extent of pollution exposure on the global fleet of MPAs. This includes indicators for current and future pollution and the implications for regionally clustered groups of MPAs with similar biophysical characteristics. To cluster MPAs into characteristic signature groups, their bathymetry, baseline biodiversity, distance from shore, mean sea surface temperature and mean sea surface salinity were used. We assess the extent at which each signature group is facing exposure from multiple pollution types. MPA groups experience similar pollution exposure on a regional level. We highlight how the challenges that MPAs face can be addressed through governance at the appropriate scale and design considerations for integrated terrestrial and marine management approaches within regional level networks. Furthermore, we present diagnostic social-ecological indicators for addressing the challenges facing unsuccessful MPAs with practical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sinus venosus atrial septal defect as a cause of palpitations and dyspnea in an adult: a diagnostic imaging challenge.

PubMed

Donovan, Michael S; Kassop, David; Liotta, Robert A; Hulten, Edward A

2015-01-01

Sinus venosus atrial septal defects (SV-ASD) have nonspecific clinical presentations and represent a diagnostic imaging challenge. Transthoracic echocardiography (TTE) remains the initial diagnostic imaging modality. However, detection rates have been as low as 12%. Transesophageal echocardiography (TEE) improves diagnostic accuracy though it may not detect commonly associated partial anomalous pulmonary venous return (PAPVR). Cardiac magnetic resonance (CMR) imaging provides a noninvasive, highly sensitive and specific imaging modality of SV-ASD. We describe a case of an adult male with exercise-induced, paroxysmal supraventricular tachycardia who presented with palpitations and dyspnea. Despite nondiagnostic imaging results on TTE, CMR proved to be instrumental in visualizing a hemodynamically significant SV-ASD with PAPVR that ultimately led to surgical correction.

Sinus Venosus Atrial Septal Defect as a Cause of Palpitations and Dyspnea in an Adult: A Diagnostic Imaging Challenge

PubMed Central

Donovan, Michael S.; Kassop, David; Liotta, Robert A.; Hulten, Edward A.

2015-01-01

Sinus venosus atrial septal defects (SV-ASD) have nonspecific clinical presentations and represent a diagnostic imaging challenge. Transthoracic echocardiography (TTE) remains the initial diagnostic imaging modality. However, detection rates have been as low as 12%. Transesophageal echocardiography (TEE) improves diagnostic accuracy though it may not detect commonly associated partial anomalous pulmonary venous return (PAPVR). Cardiac magnetic resonance (CMR) imaging provides a noninvasive, highly sensitive and specific imaging modality of SV-ASD. We describe a case of an adult male with exercise-induced, paroxysmal supraventricular tachycardia who presented with palpitations and dyspnea. Despite nondiagnostic imaging results on TTE, CMR proved to be instrumental in visualizing a hemodynamically significant SV-ASD with PAPVR that ultimately led to surgical correction. PMID:25705227

Atherosclerotic renovascular disease – epidemiology, treatment and current challenges

PubMed Central

Vassallo, Diana

2017-01-01

The neutral results of recent large randomized controlled trials comparing renal revascularization with optimal medical therapy in patients with atherosclerotic renovascular disease (ARVD) have cast doubt on the role of revascularization in the management of unselected patients with this condition. However, these studies have strengthened the evidence base for the role of contemporary intensive medical vascular protection therapy and aggressive risk factor control in improving clinical outcomes in ARVD. Patients presenting with ‘high-risk’ clinical features such as uncontrolled hypertension, rapidly declining renal function or flash pulmonary oedema are underrepresented in these studies; hence these results may not be applicable to all patients with ARVD. In this ‘high-risk’ subgroup, conservative management may not be sufficient in preventing adverse events, and indeed, observational evidence suggests that this specific patient subgroup may gain benefit from timely renal revascularization. Current challenges include the development of novel diagnostic techniques to establish haemodynamic significance of a stenosis, patient risk stratification and prediction of post-revascularization outcomes to ultimately facilitate patient selection for revascularization. In this paper we describe the epidemiology of this condition and discuss treatment recommendations for this condition in light of the results of recent randomized controlled trials while highlighting important clinical unmet needs and challenges faced by clinicians managing this condition. PMID:29056991

Current Issues in Randomized Clinical Trials of Neurodegenerative Disorders at Enrolment and Reporting: Diagnosis, Recruitment, Representativeness of Patients, Ethnicity, and Quality of Reporting.

PubMed

Logroscino, Giancarlo; Capozzo, Rosa; Tortelli, Rosanna; Marin, Benoît

2016-01-01

The investigator is faced with several challenges when planning a randomized clinical trial (RCT). In the early phase, issues are particularly challenging for RCTs in neurodegenerative disorders (NDD). At the time of inclusion in the study, an early and accurate diagnosis is mandatory. Variability of diagnostic criteria, mostly based on clinical grounds, lag time between onset and enrolment, and phenotypic heterogeneity are the main drivers of diagnostic complexity. High-quality data in terms of diagnostic reliability, phenotypic description, follow-up, and evaluation of outcomes are key determinants and are highly conditioned by the expertise of the investigators and center recruitment rate. Representativeness of NDD patients is mandatory to postulate the generalizability of the results of RCTs. There is, however, a systematic selection bias in terms of age (more likely to be younger), sex (more likely to be male), ethnicity (more likely to be of European/Caucasian origin), and other prognostic factors (more likely to be favorable). In the publication phase, researchers need to report properly all of the main features of the RCT. Consolidated Standards of Reporting Trials (CONSORT) facilitates the report and interpretation of RCTs, but adherence to these guidelines needs to be improved. Several issues discussed in this review may alter the internal and external validity of an RCT. To date, the impact on phenotype at study entry has often been overlooked. A differential effect of the selection of subjects and of specific clinical and nonclinical features needs to be systematically explored in the RCT planning phase. © 2016 S. Karger AG, Basel.

Common genetic risk factors for coronary artery disease: new opportunities for prevention?

PubMed

Hamrefors, Viktor

2017-05-01

Atherosclerotic cardiovascular disease (CVD) is a leading cause of mortality and morbidity worldwide, with coronary artery disease (CAD) being the single leading cause of death. Better control of risk factors, enhanced diagnostic techniques and improved medical therapies have all substantially decreased the mortality of CAD in developed countries. However, CAD and other forms of atherosclerotic CVD are projected to remain the leading cause of death by 2030 and we face a number of challenges if the outcomes of CAD are to be further improved. The fact that a substantial fraction of high-risk subjects do not reach treatment goals for important risk factors is one of these challenges. At the same time, there is also a non-negotiable fraction of 'concealed' high-risk subjects who are not detected by current risk algorithms and diagnostic modalities. In recent years, we have started to rapidly increase our knowledge of the framework of common genetics underlying CAD and atherosclerotic CVD in the population. In conjunction with modern diagnostic and therapeutic options, this new genetic knowledge may provide a valuable tool for further improvements in prevention. This review summarizes the recent findings from the search for common genetic risk factors for CAD. Furthermore, the author discusses how such recent findings could potentially be used in a number of clinical applications within CAD prevention, including in clinical risk stratification, in prediction of drug treatment response and in the search for targets for novel preventive therapies. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

FISH analysis for diagnostic evaluation of challenging melanocytic lesions.

PubMed

Zimmermann, A K; Hirschmann, A; Pfeiffer, D; Paredes, B E; Diebold, J

2010-09-01

The differential diagnosis of malignant melanomas and atypical melanocytic nevi is still a diagnostic challenge. The currently accepted morphologic criteria show substantial interobserver variability, likewise immunohistochemical studies are often not able to discriminate these lesions reliably. Techniques that support diagnostic accuracy are of the greatest importance considering the growing incidence of malignant melanomas and their increase in younger patients. In this study we analyzed the feasibility of fluorescence in situ hybridization (FISH) analysis for the discrimination of malignant and benign melanocytic tumors. A panel of DNA probes was used to detect chromosomal aberrations of chromosomes 6 and 11. On a series of 5 clearly malignant and benign melanocytic tumors we confirmed the applicability of the test. Then we focused on examination of ambiguous melanocytic lesions, where atypical cells are often difficult to relocalize in the 4',6-Diamidino-2-phenylindol (DAPI)-fluorescence stain. FISH analyses were conducted on destained H&E-stained slides. By comparison of the DAPI-image with photos taken from the H&E stain, unambiguous assignment of the FISH results to the conspicuous groups of cells was possible. The results of FISH analysis were consistent with the conventional diagnosis in 11 of 14 small ambiguous lesions. Of the remaining 3 cases, 2 showed FISH-results close to the cut-off level. Comparison of FISH results on thin and thick sections revealed that the cut-off values have to be adapted for 2 microm destained sections. In conclusion, FISH analysis is a useful and applicable tool for assessment of even smallest melanocytic neoplasms, although there will remain unclear cases that cannot be solved even after additional FISH evaluation.

Stakeholder perspectives on the use of pig meat inspection as a health and welfare diagnostic tool in the Republic of Ireland and Northern Ireland; a SWOT analysis.

PubMed

Devitt, C; Boyle, L; Teixeira, D L; O'Connell, N E; Hawe, M; Hanlon, A

2016-01-01

A SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis is a strategic management tool applied to policy planning and decision-making. This short report presents the results of a SWOT analysis, carried out with n  = 16 stakeholders i) involved in the pig industry in the Republic of Ireland and Northern Ireland, and ii) in general animal welfare and food safety policy areas. As part of a larger study called PIGWELFIND, the analysis sought to explore the potential development of pig meat inspection as an animal welfare and diagnostic tool. The final SWOT framework comprised two strengths, three opportunities, six weaknesses, and five threats. Issues around relationships and communication between producers and their veterinary practitioner, processors and producers were common to both the strengths and weakness clusters. Practical challenges within the processing plant were also named. Overall, the SWOT framework complements results reported in Devitt et al. (Ir Vet J 69:2, 2016) regarding problematic issues within the current system of information feedback on meat inspection especially within the Republic of Ireland, and the wider challenges of communication and problems of distrust. The results of the SWOT analysis support the conclusions from Devitt et al. (Ir Vet J 69:2, 2016), that trust between all stakeholders across the supply chain will be essential for the development of an effective environment in which to realise the full diagnostic potential of MI data. Further stakeholder engagement could seek to apply the findings of the SWOT analysis to a policy Delphi methodology, as used elsewhere.

The evolving threat of influenza viruses of animal origin and the challenges in developing appropriate diagnostics.

PubMed

Mak, Polly W Y; Jayawardena, Shanthi; Poon, Leo L M

2012-11-01

An H1N1 subtype of swine origin caused the first influenza pandemic in this century. This pandemic strain was a reassortant of avian, swine, and human influenza viruses. Many diagnostic laboratories were overwhelmed by the testing demands related to this pandemic. Nevertheless, there remains the threat of other animal influenza viruses, such as highly pathogenic H5N1. As a part of pandemic preparedness, it is essential to identify the diagnostic challenges that will accompany the next pandemic. We discuss the natural reservoir of influenza viruses and the possible role of livestock in the emergence of pandemic strains. The current commonly used molecular tests for influenza diagnosis or surveillance are also briefly reviewed. Some of these approaches are also used to detect animal viruses. Unfortunately, owing to a lack of systematic surveillance of animal influenza viruses, established tests may not be able to detect pandemic strains that have yet to emerge from the animal reservoir. Thus, multiple strategies need to be developed for better identification of influenza viruses. In addition, molecular assays for detection of mutations associated with antiviral resistance and for viral segment reassortments should also be encouraged. Influenza viruses are highly dynamic viruses. Regular and systematic influenza surveillance in both humans and animals is essential to provide a more comprehensive picture of the prevalent influenza viruses. To better prepare for the next pandemic, we should develop some simple and easy-to-use tests for characterizing newly emerging influenza viruses. © 2012 American Association for Clinical Chemistry

Update on community-acquired bacterial meningitis: guidance and challenges.

PubMed

van Ettekoven, C N; van de Beek, D; Brouwer, M C

2017-09-01

The existing heterogeneity in diagnostic work-up and treatment strategies in bacterial meningitis was the incentive to develop a European evidence-based guideline, which was published in 2016 by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Infections of the Brain (ESGIB). To summarize salient features of the guideline, identify recent developments and challenges currently faced. The ESCMID guideline, ongoing trial registries. Epidemiology, clinical symptoms, diagnostic work-up and therapy strategies of acute bacterial meningitis. The incidence of bacterial meningitis has decreased following pneumococcal and meningococcal conjugate vaccine introduction. In the diagnosis of bacterial meningitis the clinical characteristics and laboratory parameters are of limited diagnostic accuracy and therefore cerebrospinal fluid analysis remains the principal contributor to the final diagnosis. The ESCMID guideline advises to start empiric treatment within one hour of arrival in all suspected meningitis cases, and choice of antibiotics needs to be differentiated according to the patient's age, risk factors, and local resistance rates of pneumococci. Dexamethasone is the only proven adjunctive treatment and should be started together with the antibiotics. The follow-up of surviving patients should include evaluation for hearing loss and pneumococcal vaccination to prevent recurrences. Future perspectives include further development and implementation of vaccines, and new treatments aimed at further reducing the inflammatory response. Studies on implementation of the new guideline should determine adherence and evaluate whether improved prognosis can be achieved by following protocolled management strategies. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Research highlights: increasing paper possibilities.

PubMed

Wu, Chueh-Yu; Adeyiga, Oladunni; Lin, Jonathan; Di Carlo, Dino

2014-09-07

In this issue we highlight three recent papers that demonstrate new strategies to extend the capabilities of paper microfluidics. Paper (a mesh of porous fibers) has a long history as a substrate to perform biomolecular assays. Traditional lateral flow immunoassays (LFAs) are widely used for rapid diagnostic tests, and perform well when a yes or no answer is required and the analyte of interest is at relatively high concentrations. High concentrations are required because usually only a small volume of analyte-containing fluid flows past the detection region, leading to a limited signal. Further, the small pores within paper matrices prevent the use of paper to control the flow of larger particles and cells, limiting the use of paper microfluidics for cell-based diagnostics. The work we highlight addresses these important unmet challenges in paper microfluidics: enriching low concentration analytes to a higher concentration in a smaller volume that can be processed effectively, and using paper to pump flows in larger channels amenable to cells. Applying these new approaches may allow diagnosis of disease states currently technically unachievable using current LFA systems, while maintaining many of the "un-instrumented" advantages of an assay on self-wicking paper.

On Informatics Diagnostics and Informatics Therapeutics - Good Medical Informatics Research Is Needed Here.

PubMed

Haux, Reinhold

2017-01-01

In the era of digitization some new procedures play an increasing role for diagnosis as well as for therapy: informatics diagnostics and informatics therapeutics. Challenges for such procedures are described. It is discussed, when research on such diagnostics and therapeutics can be regarded as good research. Examples are mentioned for informatics diagnostics and informatics therapeutics, which are based on health-enabling technologies.

Epidemiology of eating disorders, eating disordered behaviour, and body image disturbance in males: a narrative review.

PubMed

Mitchison, Deborah; Mond, Jonathan

2015-01-01

Challenges to epidemiological studies of eating and related body image disturbance disorders in males include, in addition to low base rates and the predominance of residual diagnostic categories, the female-centric nature of current classification schemes and the consequent lack of appropriate assessment instruments. In this narrative review, we summarise epidemiological data regarding the prevalence and correlates of eating disorders, related body image disturbance disorders, and eating disorder features in males. Attention is focused on disorders most likely to be observed among males, such as muscle dysmorphia and muscularity-oriented excessive exercise. It is argued that, given the multiple challenges involved in research of this kind, a focus on features is more likely to advance the field than a focus on diagnoses. In terms of correlates, we focus on impairment and help-seeking, since these issues are most relevant in informing public health burden, service provision, and related issues. We end with some thoughts about current gaps in the knowledge base and directions for future research that we consider to be most promising.

Photonic crystals: emerging biosensors and their promise for point-of-care applications.

PubMed

Inan, Hakan; Poyraz, Muhammet; Inci, Fatih; Lifson, Mark A; Baday, Murat; Cunningham, Brian T; Demirci, Utkan

2017-01-23

Biosensors are extensively employed for diagnosing a broad array of diseases and disorders in clinical settings worldwide. The implementation of biosensors at the point-of-care (POC), such as at primary clinics or the bedside, faces impediments because they may require highly trained personnel, have long assay times, large sizes, and high instrumental cost. Thus, there exists a need to develop inexpensive, reliable, user-friendly, and compact biosensing systems at the POC. Biosensors incorporated with photonic crystal (PC) structures hold promise to address many of the aforementioned challenges facing the development of new POC diagnostics. Currently, PC-based biosensors have been employed for detecting a variety of biotargets, such as cells, pathogens, proteins, antibodies, and nucleic acids, with high efficiency and selectivity. In this review, we provide a broad overview of PCs by explaining their structures, fabrication techniques, and sensing principles. Furthermore, we discuss recent applications of PC-based biosensors incorporated with emerging technologies, including telemedicine, flexible and wearable sensing, smart materials and metamaterials. Finally, we discuss current challenges associated with existing biosensors, and provide an outlook for PC-based biosensors and their promise at the POC.

Challenges of bacterial meningitis case management in low income settings: an experience from Ethiopia.

PubMed

Gudina, Esayas Kebede; Tesfaye, Markos; Adane, Aynishet; Lemma, Kinfe; Shibiru, Tamiru; Pfister, Hans-Walter; Klein, Matthias

2016-07-01

To investigate the current diagnostic and therapeutic strategies used in the care of patients with suspected bacterial meningitis at teaching hospitals in Ethiopia. This was a hospital-based retrospective study conducted at four teaching hospitals in different regions of Ethiopia. Participants were patients aged 14 years and older treated for suspected bacterial meningitis. Presenting complaints, diagnostic strategies used and treatments given were obtained from clinical records. A total of 425 patients were included in the study; 52.7% were men and 83.8% were younger than 50 years. Fever, headache, neck stiffness and impaired consciousness were the most common clinical presentations; 55.5% underwent lumbar puncture. Overall, only 96 (22.6%) patients had cerebrospinal fluid abnormalities compatible with bacterial meningitis. A causative bacterium was identified in only 14 cases. Ceftriaxone was used as the empiric treatment of choice, either alone or in combination with other antibiotics; 17.6% of patients were also given vancomycin. Adjunctive dexamethasone was given to 50.4%. Most patients treated as bacterial meningitis did not receive a proper diagnostic workup. The choice of antibiotic was not tailored to the specific clinical condition of the patient. Such an approach may result in poor treatment outcomes and lead to antibiotic resistance. Management of patients with suspected bacterial meningitis should be supported by analysis of cerebrospinal fluid, and treatment should be tailored to local evidence and current evidence-based recommendations. © 2016 John Wiley & Sons Ltd.

Infectious Diseases in Older Adults of Long-Term Care Facilities: Update on Approach to Diagnosis and Management.

PubMed

Jump, Robin L P; Crnich, Christopher J; Mody, Lona; Bradley, Suzanne F; Nicolle, Lindsay E; Yoshikawa, Thomas T

2018-04-01

The diagnosis, treatment, and prevention of infectious diseases in older adults in long-term care facilities (LTCFs), particularly nursing facilities, remains a challenge for all health providers who care for this population. This review provides updated information on the currently most important challenges of infectious diseases in LTCFs. With the increasing prescribing of antibiotics in older adults, particularly in LTCFs, the topic of antibiotic stewardship is presented in this review. Following this discussion, salient points on clinical relevance, clinical presentation, diagnostic approach, therapy, and prevention are discussed for skin and soft tissue infections, infectious diarrhea (Clostridium difficile and norovirus infections), bacterial pneumonia, and urinary tract infection, as well as some of the newer approaches to preventive interventions in the LTCF setting. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Economic evaluations of point of care testing strategies for active tuberculosis.

PubMed

Zwerling, Alice; Dowdy, David

2013-06-01

Point of care (POC) diagnostics are often hailed as having the potential to transform tuberculosis (TB) control efforts. However, POC testing is better conceptualized as a system of diagnosis and treatment, not simply a test that can provide rapid, deployable results. Economic evaluations may help decision makers allocate scarce resources for TB control, but evaluations of POC testing face unique challenges that include evaluating the full diagnostic system, incorporating implementation costs, translating diagnostic results into health and accounting for downstream treatment costs. For economic evaluations to reach their full potential as decision-making tools for POC testing in TB, these challenges must be understood and addressed.

Practical Challenges of Current Video Rate OCT Elastography: Accounting for Dynamic and Static Tissue Properties

PubMed Central

Brezinski, Mark E

2017-01-01

Optical coherence tomography (OCT) elastography (OCTE) has the potential to be an important diagnostic tool for pathologies including coronary artery disease, osteoarthritis, malignancies, and even dental caries. Many groups have performed OCTE, including our own, using a wide range of approaches. However, we will demonstrate current OCTE approaches are not scalable to real-time, in vivo imaging. As will be discussed, among the most important reasons is current designs focus on the system and not the target. Specifically, tissue dynamic responses are not accounted, with examples being the tissue strain response time, preload variability, and conditioning variability. Tissue dynamic responses, and to a lesser degree static tissue properties, prevent accurate video rate modulus assessments for current embodiments. Accounting for them is the focus of this paper. A top-down approach will be presented to overcome these challenges to real time in vivo tissue characterization. Discussed first is an example clinical scenario where OTCE would be of substantial relevance, the prevention of acute myocardial infarction or heart attacks. Then the principles behind OCTE are examined. Next, constrains on in vivo application of current OCTE are evaluated, focusing on dynamic tissue responses. An example is the tissue strain response, where it takes about 20 msec after a stress is applied to reach plateau. This response delay is not an issue at slow acquisition rates, as most current OCTE approaches are preformed, but it is for video rate OCTE. Since at video rate each frame is only 30 msec, for essentially all current approaches this means the strain for a given stress is changing constantly during the B-scan. Therefore the modulus can’t be accurately assessed. This serious issue is an even greater problem for pulsed techniques as it means the strain/modulus for a given stress (at a location) is unpredictably changing over a B-scan. The paper concludes by introducing a novel video rate approach to overcome these challenges. PMID:29286052

Practical Challenges of Current Video Rate OCT Elastography: Accounting for Dynamic and Static Tissue Properties.

PubMed

Brezinski, Mark E

2014-12-01

Optical coherence tomography (OCT) elastography (OCTE) has the potential to be an important diagnostic tool for pathologies including coronary artery disease, osteoarthritis, malignancies, and even dental caries. Many groups have performed OCTE, including our own, using a wide range of approaches. However, we will demonstrate current OCTE approaches are not scalable to real-time, in vivo imaging. As will be discussed, among the most important reasons is current designs focus on the system and not the target. Specifically, tissue dynamic responses are not accounted, with examples being the tissue strain response time, preload variability, and conditioning variability. Tissue dynamic responses, and to a lesser degree static tissue properties, prevent accurate video rate modulus assessments for current embodiments. Accounting for them is the focus of this paper. A top-down approach will be presented to overcome these challenges to real time in vivo tissue characterization. Discussed first is an example clinical scenario where OTCE would be of substantial relevance, the prevention of acute myocardial infarction or heart attacks. Then the principles behind OCTE are examined. Next, constrains on in vivo application of current OCTE are evaluated, focusing on dynamic tissue responses. An example is the tissue strain response, where it takes about 20 msec after a stress is applied to reach plateau. This response delay is not an issue at slow acquisition rates, as most current OCTE approaches are preformed, but it is for video rate OCTE. Since at video rate each frame is only 30 msec, for essentially all current approaches this means the strain for a given stress is changing constantly during the B-scan. Therefore the modulus can't be accurately assessed. This serious issue is an even greater problem for pulsed techniques as it means the strain/modulus for a given stress (at a location) is unpredictably changing over a B-scan. The paper concludes by introducing a novel video rate approach to overcome these challenges.

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

PubMed Central

Jayol, Aurélie; Nordmann, Patrice

2017-01-01

SUMMARY Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented. PMID:28275006

Transforming the diagnosis of tuberculosis: an editorial board member's opinion at the 15th year of Expert Review of Molecular Diagnostics.

PubMed

Pai, Madhukar; Raison, Claire

2015-03-01

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.

Current Nucleic Acid Extraction Methods and Their Implications to Point-of-Care Diagnostics.

PubMed

Ali, Nasir; Rampazzo, Rita de Cássia Pontello; Costa, Alexandre Dias Tavares; Krieger, Marco Aurelio

2017-01-01

Nucleic acid extraction (NAE) plays a vital role in molecular biology as the primary step for many downstream applications. Many modifications have been introduced to the original 1869 method. Modern processes are categorized into chemical or mechanical, each with peculiarities that influence their use, especially in point-of-care diagnostics (POC-Dx). POC-Dx is a new approach aiming to replace sophisticated analytical machinery with microanalytical systems, able to be used near the patient, at the point of care or point of need . Although notable efforts have been made, a simple and effective extraction method is still a major challenge for widespread use of POC-Dx. In this review, we dissected the working principle of each of the most common NAE methods, overviewing their advantages and disadvantages, as well their potential for integration in POC-Dx systems. At present, it seems difficult, if not impossible, to establish a procedure which can be universally applied to POC-Dx. We also discuss the effects of the NAE chemicals upon the main plastic polymers used to mass produce POC-Dx systems. We end our review discussing the limitations and challenges that should guide the quest for an efficient extraction method that can be integrated in a POC-Dx system.

Mutation status of the mediator complex subunit 12 (MED12) in uterine leiomyomas and concurrent/metachronous multifocal peritoneal smooth muscle nodules (leiomyomatosis peritonealis disseminata).

PubMed

Rieker, Ralf J; Agaimy, Abbas; Moskalev, Evgeny A; Hebele, Simone; Hein, Alexander; Mehlhorn, Grit; Beckmann, Matthias W; Hartmann, Arndt; Haller, Florian

2013-06-01

The pathogenesis and classification of multicentric smooth muscle tumours with benign appearance and concurrent/metachronous uterine and peritoneal involvement is controversial and may on occasion be diagnostically challenging. Leiomyomatosis peritonealis disseminata (LPD) is a rare condition affecting women of reproductive age, characterised by the occurrence of multiple small peritoneal smooth muscle nodules with bland histology. We investigated a total of 12 uterine and seven concurrent/metachronous peritoneal smooth muscle nodules with benign appearance from two females for mutations in the mediator complex subunit 12 (MED12), which has recently been identified as the most frequent genetic aberration in uterine leiomyomas. The first case harboured different MED12 mutations in the peritoneal nodules. Mutational status of peritoneal nodules was discordant with that of the uterine leiomyomas. The second case displayed the same MED12 mutation in all five peritoneal nodules, but this mutation was not detected in her current uterine leiomyomas. Our results suggest that smooth muscle neoplasms with benign appearance of the primary and secondary müllerian system share a similar genetic background of MED12 mutation in combination with oestrogen dependency. Analysis of MED12 mutation status might be a valuable adjunct tool for the future classification of these sometimes diagnostically challenging multicentric tumours.

Current Nucleic Acid Extraction Methods and Their Implications to Point-of-Care Diagnostics

PubMed Central

Ali, Nasir; Rampazzo, Rita de Cássia Pontello; Krieger, Marco Aurelio

2017-01-01

Nucleic acid extraction (NAE) plays a vital role in molecular biology as the primary step for many downstream applications. Many modifications have been introduced to the original 1869 method. Modern processes are categorized into chemical or mechanical, each with peculiarities that influence their use, especially in point-of-care diagnostics (POC-Dx). POC-Dx is a new approach aiming to replace sophisticated analytical machinery with microanalytical systems, able to be used near the patient, at the point of care or point of need. Although notable efforts have been made, a simple and effective extraction method is still a major challenge for widespread use of POC-Dx. In this review, we dissected the working principle of each of the most common NAE methods, overviewing their advantages and disadvantages, as well their potential for integration in POC-Dx systems. At present, it seems difficult, if not impossible, to establish a procedure which can be universally applied to POC-Dx. We also discuss the effects of the NAE chemicals upon the main plastic polymers used to mass produce POC-Dx systems. We end our review discussing the limitations and challenges that should guide the quest for an efficient extraction method that can be integrated in a POC-Dx system. PMID:28785592

NASA Glenn Research in Controls and Diagnostics for Intelligent Aerospace Propulsion Systems

NASA Technical Reports Server (NTRS)

2005-01-01

With the increased emphasis on aircraft safety, enhanced performance and affordability, and the need to reduce the environmental impact of aircraft, there are many new challenges being faced by the designers of aircraft propulsion systems. Also the propulsion systems required to enable the NASA (National Aeronautics and Space Administration) Vision for Space Exploration in an affordable manner will need to have high reliability, safety and autonomous operation capability. The Controls and Dynamics Branch at NASA Glenn Research Center (GRC) in Cleveland, Ohio, is leading and participating in various projects in partnership with other organizations within GRC and across NASA, the U.S. aerospace industry, and academia to develop advanced controls and health management technologies that will help meet these challenges through the concept of Intelligent Propulsion Systems. The key enabling technologies for an Intelligent Propulsion System are the increased efficiencies of components through active control, advanced diagnostics and prognostics integrated with intelligent engine control to enhance operational reliability and component life, and distributed control with smart sensors and actuators in an adaptive fault tolerant architecture. This paper describes the current activities of the Controls and Dynamics Branch in the areas of active component control and propulsion system intelligent control, and presents some recent analytical and experimental results in these areas.

NanoString, a novel digital color-coded barcode technology: current and future applications in molecular diagnostics.

PubMed

Tsang, Hin-Fung; Xue, Vivian Weiwen; Koh, Su-Pin; Chiu, Ya-Ming; Ng, Lawrence Po-Wah; Wong, Sze-Chuen Cesar

2017-01-01

Formalin-fixed, paraffin-embedded (FFPE) tissue sample is a gold mine of resources for molecular diagnosis and retrospective clinical studies. Although molecular technologies have expanded the range of mutations identified in FFPE samples, the applications of existing technologies are limited by the low nucleic acids yield and poor extraction quality. As a result, the routine clinical applications of molecular diagnosis using FFPE samples has been associated with many practical challenges. NanoString technologies utilize a novel digital color-coded barcode technology based on direct multiplexed measurement of gene expression and offer high levels of precision and sensitivity. Each color-coded barcode is attached to a single target-specific probe corresponding to a single gene which can be individually counted without amplification. Therefore, NanoString is especially useful for measuring gene expression in degraded clinical specimens. Areas covered: This article describes the applications of NanoString technologies in molecular diagnostics and challenges associated with its applications and the future development. Expert commentary: Although NanoString technology is still in the early stages of clinical use, it is expected that NanoString-based cancer expression panels would play more important roles in the future in classifying cancer patients and in predicting the response to therapy for better personal therapeutic care.

Diagnosis of asthma: diagnostic testing.

PubMed

Brigham, Emily P; West, Natalie E

2015-09-01

Asthma is a heterogeneous disease, encompassing both atopic and non-atopic phenotypes. Diagnosis of asthma is based on the combined presence of typical symptoms and objective tests of lung function. Objective diagnostic testing consists of 2 components: (1) demonstration of airway obstruction, and (2) documentation of variability in degree of obstruction. A review of current guidelines and literature was performed regarding diagnostic testing for asthma. Spirometry with bronchodilator reversibility testing remains the mainstay of asthma diagnostic testing for children and adults. Repetition of the test over several time points may be necessary to confirm airway obstruction and variability thereof. Repeated peak flow measurement is relatively simple to implement in a clinical and home setting. Bronchial challenge testing is reserved for patients in whom the aforementioned testing has been unrevealing but clinical suspicion remains, though is associated with low specificity. Demonstration of eosinophilic inflammation, via fractional exhaled nitric oxide measurement, or atopy, may be supportive of atopic asthma, though diagnostic utility is limited particularly in nonatopic asthma. All efforts should be made to confirm the diagnosis of asthma in those who are being presumptively treated but have not had objective measurements of variability in the degree of obstruction. Multiple testing modalities are available for objective confirmation of airway obstruction and variability thereof, consistent with a diagnosis of asthma in the appropriate clinical context. Providers should be aware that both these characteristics may be present in other disease states, and may not be specific to a diagnosis of asthma. © 2015 ARS-AAOA, LLC.

Gastrointestinal perforations in children: a continuing challenge to nonoperative treatment of blunt abdominal trauma.

PubMed

Ulman, I; Avanoğlu, A; Ozcan, C; Demircan, M; Ozok, G; Erdener, A

1996-07-01

The present trend towards conservative management of hemodynamically stable pediatric trauma patients may be increasing the risk of delay in the diagnosis of traumatic hollow viscus perforations (HVP). The purpose of this study is to determine whether there is a delay in the diagnosis of HVP because of expectant management. A survey of factors leading to diagnostic delay was also made and the value of current diagnostic tools were reevaluated. In 1,283 trauma admissions between 1980-1994, 34 patients were operated for HVP caused by blunt abdominal trauma. Sites of perforation were; stomach (four), duodenum (five), jejunum (12), ileum (nine), and jejunum/ileum (four). Signs of peritoneal irritation were positive in 32 of 34 patients. There was free air in only six of 24 abdominal roentgenograms. Free peritoneal fluid without solid organ injury was detected in only four out of 13 patients with ultrasound. Peritoneal lavage was diagnostic in eight of nine patients. Time from admission to operating room averaged 24 +/- 4.1 (mean +/- standard deviation) hours. Eleven patients died after the operation mostly because of accompanying head injury. Only two of the deaths were the result of sepsis originating from the perforated bowel. There is an apparent delay in the diagnosis of traumatic HVP in this series. Signs of peritoneal irritation are the most consistent findings of HVP after blunt abdominal trauma in children. Persistence of abdominal signs indicates peritoneal lavage, which has a high diagnostic sensitivity for HVP compared to other diagnostic modalities.

New concepts for an old problem: the diagnosis of endometrial hyperplasia

PubMed Central

Sanderson, Peter A.; Critchley, Hilary O.D.; Williams, Alistair R.W.; Arends, Mark J.; Saunders, Philippa T.K.

2017-01-01

Abstract BACKGROUND Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and ‘atypical’ forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging. OBJECTIVE AND RATIONALE EC is the most common gynaecological malignancy in developed countries. The incidence of EC is rising, with alarming increases described in the 40–44-year-old age group. This review appraises the current EH classification systems used to stratify women at risk of malignant progression to EC. In addition, we summarize the evidence base regarding the use of immunohistochemical biomarkers for EH and discuss an emerging role for genomic analysis. SEARCH METHODS PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2000 to January 2016. The following search terms were used: ‘endometrial hyperplasia’, ‘endometrial intraepithelial neoplasia’, ‘atypical hyperplasia’, ‘complex atypical hyperplasia’, ‘biomarker’, ‘immunohistochemistry’, ‘progression’, ‘genomic’, ‘classification’ and ‘stratification’. OUTCOMES Recent changes to EH classification reflect our current understanding of the genesis of endometrioid ECs. The concept of endometrial intraepithelial neoplasia (EIN) as a mutationally activated, monoclonal pre-malignancy represents a fundamental shift from the previously held notion that unopposed oestrogenic stimulation causes ever-increasing hyperplastic proliferation, with accumulating cytological atypia that imperceptibly leads to the development of endometrioid EC. Our review highlights several key biomarker candidates that have been described as both diagnostic tools for EH and markers of progression to EC. We propose that, moving forwards, a ‘panel’ approach of combinations of the immunohistochemical biomarkers described in this review may be more informative since no single candidate can currently fill the entire role. WIDER IMPLICATIONS EC has historically been considered a predominantly postmenopausal disease. Owing in part to the current unprecedented rates of obesity, we are starting to see signs of a shift towards a rising incidence of EC amongst pre- and peri-menopausal woman. This creates unique challenges both diagnostically and therapeutically. Furthering our understanding of the premalignant stages of EC development will allow us to pursue earlier diagnosis and facilitate appropriate stratification of women at risk of developing EC, permitting timely and appropriate therapeutic interventions. PMID:27920066

New concepts for an old problem: the diagnosis of endometrial hyperplasia.

PubMed

Sanderson, Peter A; Critchley, Hilary O D; Williams, Alistair R W; Arends, Mark J; Saunders, Philippa T K

2017-03-01

Endometrial hyperplasia (EH) is a uterine pathology representing a spectrum of morphological endometrial alterations. It is predominantly characterized by an increase in the endometrial gland-to-stroma ratio when compared to normal proliferative endometrium. The clinical significance of EH lies in the associated risk of progression to endometrioid endometrial cancer (EC) and 'atypical' forms of EH are regarded as premalignant lesions. Traditional histopathological classification systems for EH exhibit wide and varying degrees of diagnostic reproducibility and, as a consequence, standardized patient management can be challenging. EC is the most common gynaecological malignancy in developed countries. The incidence of EC is rising, with alarming increases described in the 40-44-year-old age group. This review appraises the current EH classification systems used to stratify women at risk of malignant progression to EC. In addition, we summarize the evidence base regarding the use of immunohistochemical biomarkers for EH and discuss an emerging role for genomic analysis. PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2000 to January 2016. The following search terms were used: 'endometrial hyperplasia', 'endometrial intraepithelial neoplasia', 'atypical hyperplasia', 'complex atypical hyperplasia', 'biomarker', 'immunohistochemistry', 'progression', 'genomic', 'classification' and 'stratification'. Recent changes to EH classification reflect our current understanding of the genesis of endometrioid ECs. The concept of endometrial intraepithelial neoplasia (EIN) as a mutationally activated, monoclonal pre-malignancy represents a fundamental shift from the previously held notion that unopposed oestrogenic stimulation causes ever-increasing hyperplastic proliferation, with accumulating cytological atypia that imperceptibly leads to the development of endometrioid EC. Our review highlights several key biomarker candidates that have been described as both diagnostic tools for EH and markers of progression to EC. We propose that, moving forwards, a 'panel' approach of combinations of the immunohistochemical biomarkers described in this review may be more informative since no single candidate can currently fill the entire role. EC has historically been considered a predominantly postmenopausal disease. Owing in part to the current unprecedented rates of obesity, we are starting to see signs of a shift towards a rising incidence of EC amongst pre- and peri-menopausal woman. This creates unique challenges both diagnostically and therapeutically. Furthering our understanding of the premalignant stages of EC development will allow us to pursue earlier diagnosis and facilitate appropriate stratification of women at risk of developing EC, permitting timely and appropriate therapeutic interventions. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

What do providers, payers and patients need from comparative effectiveness research on diagnostics? The case of HER2/Neu testing in breast cancer.

PubMed

Trosman, Julia R; Weldon, Christine B; Schink, Julian C; Gradishar, William J; Benson, Al B

2013-07-01

Comparing effectiveness of diagnostic tests is one of the highest priorities for comparative effectiveness research (CER) set by the Institute of Medicine. Our study aims to identify what information providers, payers and patients need from CER on diagnostics, and what challenges they encounter implementing comparative information on diagnostic alternatives in practice and policy. Using qualitative research methods and the example of two alternative protocols for HER2 testing in breast cancer, we conducted interviews with 45 stakeholders: providers (n = 25) from four academic and eight nonacademic institutions, executives (n = 13) from five major US private payers and representatives (n = 7) from two breast cancer patient advocacies. The need for additional scientific evidence to determine the preferred HER2 protocol was more common for advocates than payers (100 vs 54%; p = 0.0515) and significantly more common for advocates than providers (100 vs 40%; p = 0.0077). The availability of information allowing assessment of the implementation impact from alternative diagnostic protocols on provider institutions may mitigate the need for additional scientific evidence for some providers and payers (24 and 46%, respectively). The cost-effectiveness of alternative protocols from the societal perspective is important to payers and advocates (69 and 71%, respectively) but not to providers (0%; p = 0.0001 and p = 0.0001). The lack of reporting laboratory practices is a more common implementation challenge for payers and advocates (77 and 86%, respectively) than for providers (32%). The absence of any mechanism for patient involvement was recognized as a challenge by payers and advocates (69 and 100%, respectively) but not by providers (0%; p = 0.0001 and p = 0.0001). Comparative implementation research is needed to inform the stakeholders considering diagnostic alternatives. Transparency of laboratory practices is an important factor in enabling implementation of CER on diagnostics in practice and policy. The incongruent views of providers versus patient advocates and payers on involving patients in diagnostic decisions is a concerning challenge to utilizing the results of CER.

Psychiatric Disorders: Diagnosis to Therapy

PubMed Central

Krystal, John H.; State, Matthew W.

2014-01-01

Recent findings in a range of scientific disciplines are challenging the conventional wisdom regarding the etiology, classification and treatment of psychiatric disorders. This review focuses on the current state of the psychiatric diagnostic nosology and recent progress in three areas: genomics, neuroimaging, and therapeutics development. The accelerating pace of novel and unexpected findings is transforming the understanding of mental illness and represents a hopeful sign that the approaches and models that have sustained the field for the past 40 years are yielding to a flood of new data and presaging the emergence of a new and more powerful scientific paradigm. PMID:24679536

THz based electron bunch length monitoring at the quasi-cw SRF accelerator ELBE

NASA Astrophysics Data System (ADS)

Green, Bertram; Kovalev, Sergey; Fisher, Alan; Bauer, Christian; Kuntzsch, Michael; Lehnert, Ulf; Schurig, Rico; Goltz, Torsten; Michel, Peter; Stojanovic, Nikola; Gensch, Michael

2014-03-01

In the past few years the quasi-cw SRF electron accelerator ELBE has been upgraded so that it now allows to compress electron bunches to the sub-picosecond regime. The actual optimization and control of the electron bunch form represents one of the largest challenges of the coming years. In particular with respect to the midterm goal to utilize the ultra-short electron bunches for Laser-Thomson scattering experiments or high field THz experiments. Current developments of THz based electron bunch diagnostic are discussed and an outlook into future developments is given.

Chronic pancreatitis: A diagnostic dilemma

PubMed Central

Duggan, Sinead N; Ní Chonchubhair, Hazel M; Lawal, Oladapo; O’Connor, Donal B; Conlon, Kevin C

2016-01-01

Typical clinical symptoms of chronic pancreatitis are vague and non-specific and therefore diagnostic tests are required, none of which provide absolute diagnostic certainly, especially in the early stages of disease. Recently-published guidelines bring much needed structure to the diagnostic work-up of patients with suspected chronic pancreatitis. In addition, novel diagnostic modalities bring promise for the future. The assessment and diagnosis of pancreatic exocrine insufficiency remains challenging and this review contests the accepted perspective that steatorrhea only occurs with > 90% destruction of the gland. PMID:26900292

Prevention of preterm birth: harnessing science to address the global epidemic.

PubMed

Rubens, Craig E; Sadovsky, Yoel; Muglia, Louis; Gravett, Michael G; Lackritz, Eve; Gravett, Courtney

2014-11-12

Preterm birth is a leading cause of infant morbidity and mortality worldwide, but current interventions to prevent prematurity are largely ineffective. Preterm birth is increasingly recognized as an outcome that can result from a variety of pathological processes. Despite current research efforts, the mechanisms underlying these processes remain poorly understood and are influenced by a range of biological and environmental factors. Research with modern techniques is needed to understand the mechanisms responsible for preterm labor and birth and identify targets for diagnostic and therapeutic solutions. This review evaluates the state of reproductive science relevant to understanding the causes of preterm birth, identifies potential targets for prevention, and outlines challenges and opportunities for translating research findings into effective interventions. Copyright © 2014, American Association for the Advancement of Science.

[Gender theory and politics: historical fragments and current challenges].

PubMed

Meyer, Dagmar Estermann

2004-01-01

This text approaches contemporary gender theories and politics focusing on the tensions permeating these theories. It briefly revisits historical aspects to introduce an understanding of the to the concept of gender in the field of Feminist Studies, and discusses the theoretical and political developments associated with its use. It presents some results from investigations that make the positions of the subject of woman, and particularly the subject of mother, problematic in discourses running through current health and education policies and programs. It concludes by suggesting that studies relating gender, health and education from this perspective contribute to understanding and outlining power structures that come into play with certain educational emphases, knowledge, diagnostic instruments, and ways of assisting and educating women, men and children in these areas today.

A tiered approach to distinguish sources of gasoline and diesel spills.

PubMed

Xiong, Wenhui; Bernesky, Ryan; Bechard, Robert; Michaud, Guy; Lang, Jeremy

2014-07-15

Approximately 11% and 25% of annual Canadian oil spill accidents are gasoline and diesel spills, respectively. Gasoline and diesel spills are a challenge to conventional environmental forensic techniques because refinery processes remove most of the higher molecular weight biomarkers. This study presents a tiered environmental forensics strategy that includes such information as site operational history, geology/hydrogeology, GC/FID pre-screening, volatile GC/MS, semi-volatile GC/MS, and GC/MS selected ion monitoring (SIM) chromatograms for fingerprinting of gasoline and diesel spills. GC/FID pre-screening analysis identified the presence of two individual gasoline and diesel plumes at a fuel service station (study site). The gasoline plume is present between the upgradient fuel underground storage tanks (USTs) and the downgradient diesel plume, suggesting that the diesel impacts to groundwater may not be originated from the current UST leakage. Similar distribution of C3-alkylbenzenes (the most stable chemicals in gasoline) and the consistent diagnostic ratios of the analyte pairs with similar solubility indicate that the source for the dissolved gasoline constituents in the gasoline impacted zone likely originated from a gasoline leakage from the current USTs on the study site. In the diesel impacted zone, the distinct distribution and diagnostic ratios of sesquiterpanes (biomarkers for diesel) and alkylated PAHs confirm that the diesel plume originate from different crude oil sources than the current USTs. Copyright © 2014 Elsevier B.V. All rights reserved.

Between-Visit Variability in FEV1 as a Diagnostic Test for Asthma in Adults.

PubMed

Dean, Benjamin W; Birnie, Erin E; Whitmore, G A; Vandemheen, Katherine L; Boulet, Louis-Philippe; FitzGerald, J Mark; Ainslie, Martha; Gupta, Samir; Lemiere, Catherine; Field, Stephen K; McIvor, R Andrew; Hernandez, Paul; Mayers, Irvin; Aaron, Shawn D

2018-06-07

The reliability of using between-visit variation in FEV1 to diagnose asthma is understudied, and hence uncertain. To determine if FEV1 variability measured over recurrent visits is significantly associated with a diagnosis of current asthma. Randomly-selected adults (N=964) with a history of physician-diagnosed asthma were studied from 2005-2007 and from 2012-2016. A diagnosis of current asthma was confirmed in those participants who exhibited bronchial hyper-responsiveness to methacholine and/or acute worsening of asthma symptoms while being weaned off asthma medications. Regression analyses and receiver operating curves were used to evaluate the ability of between-visit FEV1 variability to diagnose asthma. A current diagnosis of asthma was confirmed in 584 of 964 participants (60%). Between-visit absolute variability in FEV1 was significantly greater in those in whom current asthma was confirmed, compared to those in whom current asthma was ruled out (7.3% vs 4.8%, mean difference between the 2 groups = 2.5%; 95% CI: 1.7-3.3%). However, a 12 percent and 200 mL between-visit variation in FEV1, which is the diagnostic threshold recommended by GINA, exhibited a sensitivity of only 0.17 and a specificity of 0.94 for confirming current asthma. A between-visit absolute variability in FEV1 ≥ 12% and 200 ml increased the pre-test probability of asthma from 60% to a post-test probability of 81%. A 12% and 200 mL between-visit variation in FEV1, if present, has reasonably good specificity for diagnosing asthma, but has poor sensitivity compared to bronchial challenge testing. Between-visit variability in FEV1 is a relatively unhelpful test to establish a diagnosis of asthma.

The Health Technology Assessment of companion diagnostics: experience of NICE.

PubMed

Byron, Sarah K; Crabb, Nick; George, Elisabeth; Marlow, Mirella; Newland, Adrian

2014-03-15

Companion diagnostics are used to aid clinical decision making to identify patients who are most likely to respond to treatment. They are becoming increasingly important as more new pharmaceuticals receive licensed indications that require the use of a companion diagnostic to identify the appropriate patient subgroup for treatment. These pharmaceuticals have proven benefit in the treatment of some cancers and other diseases, and also have potential to precisely tailor treatments to the individual in the future. However, the increasing use of companion diagnostics could place a substantial burden on health system resources to provide potentially high volumes of testing. This situation, in part, has led policy makers and Health Technology Assessment (HTA) bodies to review the policies and methods used to make reimbursement decisions for pharmaceuticals requiring companion diagnostics. The assessment of a pharmaceutical alongside the companion diagnostic used in the clinical trials may be relatively straightforward, although there are a number of challenges associated with assessing pharmaceuticals where a range of alternative companion diagnostics are available for use in routine clinical practice. The UK HTA body, the National Institute for Health and Care Excellence (NICE), has developed policy for considering companion diagnostics using its Technology Appraisal and Diagnostics Assessment Programs. Some HTA bodies in other countries have also adapted their policies and methods to accommodate the assessment of companion diagnostics. Here, we provide insight into the HTA of companion diagnostics for reimbursement decisions and how the associated challenges are being addressed, in particular by NICE. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

Diagnosis of viral hepatitis

PubMed Central

Easterbrook, Philippa J.; Roberts, Teri; Sands, Anita; Peeling, Rosanna

2017-01-01

Purpose of review Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and HIV–HBV and HCV coinfection are major causes of chronic liver disease worldwide. Testing and diagnosis is the gateway for access to both treatment and prevention services, but there remains a large burden of undiagnosed infection globally. We review the global epidemiology, key challenges in the current hepatitis testing response, new tools to support the hepatitis global response (2016–2020 Global Hepatitis Health Sector strategy, and 2017 WHO guidelines on hepatitis testing) and future directions and innovations in hepatitis diagnostics. Recent findings Key challenges in the current hepatitis testing response include lack of quality-assured serological and low-cost virological in-vitro diagnostics, limited facilities for testing, inadequate data to guide country-specific hepatitis testing approaches, stigmatization of those with or at risk of viral hepatitis and lack of guidelines on hepatitis testing for resource-limited settings. The new Global Hepatitis Health Sector strategy sets out goals for elimination of viral hepatitis as a public health threat by 2030 and gives outcome targets for reductions in new infections and mortality, as well as service delivery targets that include testing, diagnosis and treatment. The 2017 WHO hepatitis testing guidelines for adults, adolescents and children in low-income and middle-income countries outline the public health approach to strengthen and expand current testing practices for viral hepatitis and addresses who to test (testing approaches), which serological and virological assays to use (testing strategies) as well as interventions to promote linkage to prevention and care. Summary Future directions and innovations in hepatitis testing include strategies to improve access such as through use of existing facility and community-based testing opportunities for hepatitis testing, near-patient or point-of-care assays for virological markers (nucleic acid testing and HCV core antigen), dried blood spot specimens used with different serological and nucleic acid test assays, multiplex and multi-disease platforms to enable testing for multiple analytes/pathogens and potential self-testing for viral hepatitis. PMID:28306597

Characterization and identification of proteases secreted by Aspergillus fumigatus using free flow electrophoresis and MS.

PubMed

Neustadt, Madlen; Costina, Victor; Kupfahl, Claudio; Buchheidt, Dieter; Eckerskorn, Christoph; Neumaier, Michael; Findeisen, Peter

2009-06-01

Early diagnosis of life-threatening invasive aspergillosis in neutropenic patients remains challenging because current laboratory methods have limited diagnostic sensitivity and/or specificity. Aspergillus species are known to secrete various pathogenetically relevant proteases and the monitoring of their protease activity in serum specimens might serve as a new diagnostic approach.For the characterization and identification of secreted proteases, the culture supernatant of Aspergillus fumigatus was fractionated using free flow electrophoresis (Becton Dickinson). Protease activity of separated fractions was measured using fluorescently labeled reporter peptides. Fractions were also co-incubated in parallel with various protease inhibitors that specifically inhibit a distinct class of proteases e.g. metallo- or cysteine-proteases. Those fractions with high protease activity were further subjected to LC-MS/MS analysis for protease identification. The highest protease activity was measured in fractions with an acidic pH range. The results of the 'inhibitor-panel' gave a clear indication that it is mainly metallo- and serine-proteases that are involved in the degradation of reporter peptides. Furthermore, several proteases were identified that facilitate the optimization of reporter peptides for functional protease profiling as a diagnostic tool for invasive aspergillosis.

Design calculations for a xenon plasma x-ray shield to protect the NIF optical Thomson scattering diagnostic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swadling, G. F.; Ross, J. S.; Datte, P.

An Optical Thomson Scattering (OTS) diagnostic is currently being developed for the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. This diagnostic is designed to make measurements of the hohlraum plasma parameters, such as the electron temperature and the density, during inertial confinement fusion (ICF) experiments. NIF ICF experiments present a very challenging environment for optical measurements; by their very nature, hohlraums produce intense soft x-ray emission, which can cause “blanking” (radiation induced opacity) of the radiation facing optical components. The soft x-ray fluence at the surface of the OTS blast shield, 60 cm from the hohlraum, is estimatedmore » to be ∼8 J cm{sup −2}. This is significantly above the expected threshold for the onset of “blanking” effects. A novel xenon plasma x-ray shield is proposed to protect the blast shield from x-rays and mitigate “blanking.” Estimates suggest that an areal density of 10{sup 19} cm{sup −2} Xe atoms will be sufficient to absorb 99.5% of the soft x-ray flux. Two potential designs for this shield are presented.« less

Design calculations for a xenon plasma x-ray shield to protect the NIF optical Thomson scattering diagnostic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swadling, G. F.; Ross, J. S.; Datte, P.

An Optical Thomson Scattering (OTS) diagnostic is currently being developed for the National Ignition Facility (NIF) at Lawrence Livermore National Labs (LLNL). This diagnostic is designed to make measurements of hohlraum plasma parameters, such as the electron temperature and density, during inertial confinement fusion (ICF) experiments. NIF ICF experiments present a very challenging environment for optical measurements; by their very nature hohlraums produce intense soft x-ray emission, which can cause “blanking” (radiation induced opacity) of the radiation facing optical components. The soft x-ray fluence at the surface of the OTS blast shield, 60 cm from the hohlraum, is estimated tomore » be ~ 8 J cm -2. This is then significantly above the expected threshold for the onset of “blanking” effects. A novel Xenon Plasma X-ray Shield (XPXS) has been proposed to protect the blast shield from x-rays and mitigate “blanking”. Finally, these estimates suggest that an areal density of 10 19 cm -2 Xe atoms will be sufficient to absorb 99.5% the soft x-ray flux. Two potential designs for this shield are presented.« less

Proceedings of the 2011 National Toxicology Program Satellite Symposium

PubMed Central

Boorman, Gary; Crabbs, Torrie A.; Kolenda-Roberts, Holly; Latimer, Ken; Miller, Andrew D.; Muravnick, Kathleen B.; Nyska, Abraham; Ochoa, Ricardo; Pardo, Ingrid D.; Ramot, Yuval; Rao, Deepa B.; Schuh, JoAnn; Suttie, Andrew; Travlos, Greg S.; Ward, Jerrold M.; Wolf, Jeffrey C.; Elmore, Susan A.

2012-01-01

The 2011 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held in Denver, Colorado in advance of the Society of Toxicologic Pathology’s 30th Annual Meeting. The goal of the NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting or discussion. Some lesions and topics covered during the symposium include: proliferative lesions from various fish species including ameloblastoma, gas gland hyperplasia, nodular regenerative hepatocellular hyperplasia, and malignant granulosa cell tumor; spontaneous cystic hyperplasia in the stomach of CD1 mice and histiocytic aggregates in the duodenal villous tips of treated mice; an olfactory neuroblastoma in a cynomolgus monkey; various rodent skin lesions, including follicular parakeratotic hyperkeratosis, adnexal degeneration, and epithelial intracytoplasmic accumulations; oligodendroglioma and microgliomas in rats; a diagnostically challenging microcytic, hypochromic, responsive anemia in rats; a review of microcytes and microcytosis; nasal lesions associated with green tea extract and Ginkgo biloba in rats; corneal dystrophy in Dutch belted rabbits; valvulopathy in rats; and lymphoproliferative disease in a cynomolgus monkey. PMID:22089839

TummyTrials: A Feasibility Study of Using Self-Experimentation to Detect Individualized Food Triggers.

PubMed

Karkar, Ravi; Schroeder, Jessica; Epstein, Daniel A; Pina, Laura R; Scofield, Jeffrey; Fogarty, James; Kientz, Julie A; Munson, Sean A; Vilardaga, Roger; Zia, Jasmine

2017-05-02

Diagnostic self-tracking, the recording of personal information to diagnose or manage a health condition, is a common practice, especially for people with chronic conditions. Unfortunately, many who attempt diagnostic self-tracking have trouble accomplishing their goals. People often lack knowledge and skills needed to design and conduct scientifically rigorous experiments, and current tools provide little support. To address these shortcomings and explore opportunities for diagnostic self-tracking, we designed, developed, and evaluated a mobile app that applies a self-experimentation framework to support patients suffering from irritable bowel syndrome (IBS) in identifying their personal food triggers. TummyTrials aids a person in designing, executing, and analyzing self-experiments to evaluate whether a specific food triggers their symptoms. We examined the feasibility of this approach in a field study with 15 IBS patients, finding that participants could use the tool to reliably undergo a self-experiment. However, we also discovered an underlying tension between scientific validity and the lived experience of self-experimentation. We discuss challenges of applying clinical research methods in everyday life, motivating a need for the design of self-experimentation systems to balance rigor with the uncertainties of everyday life.

Design calculations for a xenon plasma x-ray shield to protect the NIF optical Thomson scattering diagnostic

DOE PAGES

Swadling, G. F.; Ross, J. S.; Datte, P.; ...

2016-07-21

An Optical Thomson Scattering (OTS) diagnostic is currently being developed for the National Ignition Facility (NIF) at Lawrence Livermore National Labs (LLNL). This diagnostic is designed to make measurements of hohlraum plasma parameters, such as the electron temperature and density, during inertial confinement fusion (ICF) experiments. NIF ICF experiments present a very challenging environment for optical measurements; by their very nature hohlraums produce intense soft x-ray emission, which can cause “blanking” (radiation induced opacity) of the radiation facing optical components. The soft x-ray fluence at the surface of the OTS blast shield, 60 cm from the hohlraum, is estimated tomore » be ~ 8 J cm -2. This is then significantly above the expected threshold for the onset of “blanking” effects. A novel Xenon Plasma X-ray Shield (XPXS) has been proposed to protect the blast shield from x-rays and mitigate “blanking”. Finally, these estimates suggest that an areal density of 10 19 cm -2 Xe atoms will be sufficient to absorb 99.5% the soft x-ray flux. Two potential designs for this shield are presented.« less

The main challenges that remain in applying high-throughput sequencing to clinical diagnostics.

PubMed

Loeffelholz, Michael; Fofanov, Yuriy

2015-01-01

Over the last 10 years, the quality, price and availability of high-throughput sequencing instruments have improved to the point that this technology may be close to becoming a routine tool in the diagnostic microbiology laboratory. Two groups of challenges, however, have to be resolved in order to move this powerful research technology into routine use in the clinical microbiology laboratory. The computational/bioinformatics challenges include data storage cost and privacy concerns, requiring analysis to be performed without access to cloud storage or expensive computational infrastructure. The logistical challenges include interpretation of complex results and acceptance and understanding of the advantages and limitations of this technology by the medical community. This article focuses on the approaches to address these challenges, such as file formats, algorithms, data collection, reporting and good laboratory practices.

In Vitro Gluten Challenge Test for Celiac Disease Diagnosis.

PubMed

Khalesi, Maryam; Jafari, Seyed Ali; Kiani, Mohammadali; Picarelli, Antonio; Borghini, Raffaele; Sadeghi, Ramin; Eghtedar, Alireza; Ayatollahi, Hosein; Kianifar, Hamid R

2016-02-01

The in vitro gluten challenge test is an important diagnostic modality in celiac disease (CD), especially in patients who begin treatment with a gluten-free diet before adequate diagnostic workup or in cases with atypical CD. Available literature was reviewed regarding the accuracy of the in vitro gluten challenge test for CD diagnosis. MEDLINE, Scopus, and Google Scholar were searched, and studies that used serology and bowel biopsy as the criterion standard for diagnosis were included in our study. Data on authors, publication year, characteristics of the patient and control groups, patients' diet, duration of the gluten challenge test, histology findings, endomysial antibody (EMA) and anti-tissue transglutaminase (tTG) levels, CD markers, and intercellular cell adhesion molecule-1, and human leukocyte antigens before and after the gluten challenge test were extracted. Overall, 15 studies were included in this meta-analysis. Pooled sensitivity %/specificity % was 84/99 for EMA after the challenge, 52/96 for EMA without the challenge, 95.5/98.3 for anti-tTG after the challenge, and 95.1/98.3 for anti-tTG without the challenge test. Sensitivity/specificity for immunological markers were 89/97 for the percentage of CD25⁺-lamina propria lymphocytes, 96/91 for the percentage of CD3⁺-lamina propria lymphocytes, and 96.1/85.7 for the percentage of intercellular cell adhesion molecule-1-lamina propria lymphocytes. The factors that increased the sensitivity of EMA were longer test duration, and the evaluation of patients on a gluten-containing diet or short-term gluten-free diet. The in vitro gluten challenge test can be a useful part of the diagnostic workup of CD, rather than only a model to evaluate its mechanisms.

Drug hypersensitivity in children: report from the pediatric task force of the EAACI Drug Allergy Interest Group.

PubMed

Gomes, E R; Brockow, K; Kuyucu, S; Saretta, F; Mori, F; Blanca-Lopez, N; Ott, H; Atanaskovic-Markovic, M; Kidon, M; Caubet, J-C; Terreehorst, I

2016-02-01

When questioned, about 10% of the parents report suspected hypersensitivity to at least one drug in their children. However, only a few of these reactions can be confirmed as allergic after a diagnostic workup. There is still a lack of knowledge on drug hypersensitivity (DH) epidemiology, clinical spectrum, and appropriate diagnostic methods particularly in children. Meanwhile, the tools used for DH management in adults are applied also for children. Whereas this appears generally acceptable, some aspects of DH and management differ with age. Most reactions in children are still attributed to betalactams. Some manifestations, such as nonsteroidal anti-inflammatory drug-associated angioedema and serum sickness-like reactions, are more frequent among young patients as compared to adults. Risk factors such as viral infections are particularly frequent in children, making the diagnosis challenging. The practicability and validity of skin test and other diagnostic procedures need further assessment in children. This study presents an up-to-date review on epidemiology, clinical spectrum, diagnostic tools, and current management of DH in children. A new general algorithm for the study of these reactions in children is proposed. Data are presented focusing on reported differences between pediatric and adult patients, also identifying unmet needs to be addressed in further research. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of mimotopes of Mycobacterium leprae as potential diagnostic reagents.

PubMed

Alban, Silvana M; de Moura, Juliana Ferreira; Minozzo, João Carlos; Mira, Marcelo Távora; Soccol, Vanete Thomaz

2013-01-25

An early diagnostic test for detecting infection in leprosy is fundamental for reducing patients' sequelae. The currently used lepromin is not adequate for disease diagnosis and, so far, no antigen to be used in intradermoreaction has proved to be sensitive and specific for that purpose. Aiming at identifying new reagents to be used in skin tests, candidate antigens were investigated. Random peptide phage display libraries were screened by using antibodies from leprosy patients in order to identify peptides as diagnostic reagents. Seven different phage clones were identified using purified antibodies pooled from sera of leprosy patients. When the clones were tested with serum samples by ELISA, three of them, 5A, 6A and 1B, allowed detecting a larger number of leprosy patients when compared to controls. The corresponding peptides expressed by selected phage clones were chemically synthesized. A pilot study was undertaken to assess the use of peptides in skin tests. The intradermal challenge with peptides in animals previously sensitized with Mycobacterium leprae induced a delayed-type hypersensitivity with peptide 5A (2/5) and peptide 1B (1/5). In positive controls, there was a 3/5 reactivity for lepromin and a 4/5 reactivity of the sensitized animals with soluble extract of M. leprae. The preliminary data suggest that may be possible to develop reagents with diagnostic potential based on peptide mimotopes selected by phage display using polyclonal human antibodies.

Soft X-ray tomography in support of impurity control in tokamaks

NASA Astrophysics Data System (ADS)

Mlynar, J.; Mazon, D.; Imrisek, M.; Loffelmann, V.; Malard, P.; Odstrcil, T.; Tomes, M.; Vezinet, D.; Weinzettl, V.

2016-10-01

This contribution reviews an important example of current developments in diagnostic systems and data analysis tools aimed at improved understanding and control of transport processes in magnetically confined high temperature plasmas. The choice of tungsten for the plasma facing components of ITER and probably also DEMO means that impurity control in fusion plasmas is now a crucial challenge. Soft X-ray (SXR) diagnostic systems serve as a key sensor for experimental studies of plasma impurity transport with a clear prospective of its control via actuators based mainly on plasma heating systems. The SXR diagnostic systems typically feature high temporal resolution but limited spatial resolution due to access restrictions. In order to reconstruct the spatial distribution of the SXR radiation from line integrated measurements, appropriate tomographic methods have been developed and validated, while novel numerical methods relevant for real-time control have been proposed. Furthermore, in order to identify the main contributors to the SXR plasma radiation, at least partial control over the spectral sensitivity range of the detectors would be beneficial, which motivates for developments of novel SXR diagnostic methods. Last, but not least, semiconductor photosensitive elements cannot survive in harsh conditions of future fusion reactors due to radiation damage, which calls for development of radiation hard SXR detectors. Present research in this field is exemplified on recent results from tokamaks COMPASS, TORE SUPRA and the Joint European Torus JET. Further planning is outlined.

Hyperthermostable binding molecules on phage: Assay components for point-of-care diagnostics for active tuberculosis infection.

PubMed

Zhao, Ning; Spencer, John; Schmitt, Margaret A; Fisk, John D

2017-03-15

Tuberculosis is the leading cause of death from infectious disease worldwide. The low sensitivity, extended processing time, and high expense of current diagnostics are major challenges to the detection and treatment of tuberculosis. Mycobacterium tuberculosis ornithine transcarbamylase (Mtb OTC, Rv1656) has been identified in the urine of patients with active TB infection and is a promising target for point-of-care diagnostics. Specific binding proteins with low nanomolar affinities for Mtb OTC were selected from a phage display library built upon a hyperthermostable Sso7d scaffold. Phage particles displaying Sso7d variants were utilized to generate a sandwich ELISA-based assay for Mtb OTC. The assay response is linear between 2 ng/mL and 125 ng/mL recombinant Mtb OTC and has a limit of detection of 400 pg/mL recombinant Mtb OTC. The assay employing a phage-based detection reagent is comparable to commercially-available antibody-based biosensors. Importantly, the assay maintains functionality at both neutral and basic pH in presence of salt and urea over the range of concentrations typical for human urine. Phage-based diagnostic systems may feature improved physical stability and cost of production relative to traditional antibody-based reagents, without sacrificing specificity and sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals.

PubMed

Roscoe, Donna M; Hu, Yun-Fu; Philip, Reena

2015-01-01

Companion diagnostics are essential for the safe and effective use of the corresponding therapeutic products. The US FDA has approved a number of companion diagnostics used to select cancer patients for treatment with contemporaneously approved novel therapeutics. The processes of co-development and co-approval of a therapeutic product and its companion diagnostic have been a learning experience that continues to evolve. Using several companion diagnostics as examples, this article describes the challenges associated with the scientific, clinical and regulatory hurdles faced by FDA and industry alike. Taken together, this discussion is intended to assist manufacturers toward a successful companion diagnostics development plan.

Measures to Improve Diagnostic Safety in Clinical Practice.

PubMed

Singh, Hardeep; Graber, Mark L; Hofer, Timothy P

2016-10-20

Timely and accurate diagnosis is foundational to good clinical practice and an essential first step to achieving optimal patient outcomes. However, a recent Institute of Medicine report concluded that most of us will experience at least one diagnostic error in our lifetime. The report argues for efforts to improve the reliability of the diagnostic process through better measurement of diagnostic performance. The diagnostic process is a dynamic team-based activity that involves uncertainty, plays out over time, and requires effective communication and collaboration among multiple clinicians, diagnostic services, and the patient. Thus, it poses special challenges for measurement. In this paper, we discuss how the need to develop measures to improve diagnostic performance could move forward at a time when the scientific foundation needed to inform measurement is still evolving. We highlight challenges and opportunities for developing potential measures of "diagnostic safety" related to clinical diagnostic errors and associated preventable diagnostic harm. In doing so, we propose a starter set of measurement concepts for initial consideration that seem reasonably related to diagnostic safety and call for these to be studied and further refined. This would enable safe diagnosis to become an organizational priority and facilitate quality improvement. Health-care systems should consider measurement and evaluation of diagnostic performance as essential to timely and accurate diagnosis and to the reduction of preventable diagnostic harm.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Reproducibility of haemodynamical simulations in a subject-specific stented aneurysm model--a report on the Virtual Intracranial Stenting Challenge 2007.

PubMed

Radaelli, A G; Augsburger, L; Cebral, J R; Ohta, M; Rüfenacht, D A; Balossino, R; Benndorf, G; Hose, D R; Marzo, A; Metcalfe, R; Mortier, P; Mut, F; Reymond, P; Socci, L; Verhegghe, B; Frangi, A F

2008-07-19

This paper presents the results of the Virtual Intracranial Stenting Challenge (VISC) 2007, an international initiative whose aim was to establish the reproducibility of state-of-the-art haemodynamical simulation techniques in subject-specific stented models of intracranial aneurysms (IAs). IAs are pathological dilatations of the cerebral artery walls, which are associated with high mortality and morbidity rates due to subarachnoid haemorrhage following rupture. The deployment of a stent as flow diverter has recently been indicated as a promising treatment option, which has the potential to protect the aneurysm by reducing the action of haemodynamical forces and facilitating aneurysm thrombosis. The direct assessment of changes in aneurysm haemodynamics after stent deployment is hampered by limitations in existing imaging techniques and currently requires resorting to numerical simulations. Numerical simulations also have the potential to assist in the personalized selection of an optimal stent design prior to intervention. However, from the current literature it is difficult to assess the level of technological advancement and the reproducibility of haemodynamical predictions in stented patient-specific models. The VISC 2007 initiative engaged in the development of a multicentre-controlled benchmark to analyse differences induced by diverse grid generation and computational fluid dynamics (CFD) technologies. The challenge also represented an opportunity to provide a survey of available technologies currently adopted by international teams from both academic and industrial institutions for constructing computational models of stented aneurysms. The results demonstrate the ability of current strategies in consistently quantifying the performance of three commercial intracranial stents, and contribute to reinforce the confidence in haemodynamical simulation, thus taking a step forward towards the introduction of simulation tools to support diagnostics and interventional planning.

Lack of knowledge and availability of diagnostic equipment could hinder the diagnosis of sarcopenia and its management.

PubMed

Reijnierse, Esmee M; de van der Schueren, Marian A E; Trappenburg, Marijke C; Doves, Marjan; Meskers, Carel G M; Maier, Andrea B

2017-01-01

Sarcopenia is an emerging clinical challenge in an ageing population and is associated with serious negative health outcomes. This study aimed to assess the current state of the art regarding the knowledge about the concept of sarcopenia and practice of the diagnostic strategy and management of sarcopenia in a cohort of Dutch healthcare professionals (physicians, physiotherapists, dietitians and others) attending a lecture cycle on sarcopenia. This longitudinal study included Dutch healthcare professionals (n = 223) who were asked to complete a questionnaire before, directly after and five months after (n = 80) attending a lecture cycle on the pathophysiology of sarcopenia, diagnostic strategy and management of sarcopenia, i.e. interventions and collaboration. Before attendance, 69.7% of healthcare professionals stated to know the concept of sarcopenia, 21.4% indicated to know how to diagnose sarcopenia and 82.6% had treated patients with suspected sarcopenia. 47.5% used their clinical view as diagnostic strategy. Handgrip strength was the most frequently used objective diagnostic measure (33.9%). Five months after attendance, reported use of diagnostic tests was increased, i.e. handgrip strength up to 67.4%, gait speed up to 72.1% and muscle mass up to 20.9%. Bottlenecks during implementation of the diagnostic strategy were experienced by 67.1%; lack of awareness among other healthcare professionals, acquisition of equipment and time constraints to perform the diagnostic measures were reported most often. Before attendance, 36.4% stated not to consult a physiotherapists or exercise therapists (PT/ET) or dietitian for sarcopenia interventions, 10.5% consulted a PT/ET, 32.7% a dietitian and 20.5% both a PT/ET and dietitian. Five months after attendance, these percentages were 28.3%, 21.7%, 30.0% and 20.0% respectively. The concept of sarcopenia is familiar to most Dutch healthcare professionals but application in practice is hampered, mostly by lack of knowledge, availability of equipment, time constraints and lack of collaboration.

Lack of knowledge and availability of diagnostic equipment could hinder the diagnosis of sarcopenia and its management

PubMed Central

Reijnierse, Esmee M.; de van der Schueren, Marian A. E.; Trappenburg, Marijke C.; Doves, Marjan; Meskers, Carel G. M.

2017-01-01

Objectives Sarcopenia is an emerging clinical challenge in an ageing population and is associated with serious negative health outcomes. This study aimed to assess the current state of the art regarding the knowledge about the concept of sarcopenia and practice of the diagnostic strategy and management of sarcopenia in a cohort of Dutch healthcare professionals (physicians, physiotherapists, dietitians and others) attending a lecture cycle on sarcopenia. Material and methods This longitudinal study included Dutch healthcare professionals (n = 223) who were asked to complete a questionnaire before, directly after and five months after (n = 80) attending a lecture cycle on the pathophysiology of sarcopenia, diagnostic strategy and management of sarcopenia, i.e. interventions and collaboration. Results Before attendance, 69.7% of healthcare professionals stated to know the concept of sarcopenia, 21.4% indicated to know how to diagnose sarcopenia and 82.6% had treated patients with suspected sarcopenia. 47.5% used their clinical view as diagnostic strategy. Handgrip strength was the most frequently used objective diagnostic measure (33.9%). Five months after attendance, reported use of diagnostic tests was increased, i.e. handgrip strength up to 67.4%, gait speed up to 72.1% and muscle mass up to 20.9%. Bottlenecks during implementation of the diagnostic strategy were experienced by 67.1%; lack of awareness among other healthcare professionals, acquisition of equipment and time constraints to perform the diagnostic measures were reported most often. Before attendance, 36.4% stated not to consult a physiotherapists or exercise therapists (PT/ET) or dietitian for sarcopenia interventions, 10.5% consulted a PT/ET, 32.7% a dietitian and 20.5% both a PT/ET and dietitian. Five months after attendance, these percentages were 28.3%, 21.7%, 30.0% and 20.0% respectively. Conclusion The concept of sarcopenia is familiar to most Dutch healthcare professionals but application in practice is hampered, mostly by lack of knowledge, availability of equipment, time constraints and lack of collaboration. PMID:28968456

Recent lab-on-chip developments for novel drug discovery.

PubMed

Khalid, Nauman; Kobayashi, Isao; Nakajima, Mitsutoshi

2017-07-01

Microelectromechanical systems (MEMS) and micro total analysis systems (μTAS) revolutionized the biochemical and electronic industries, and this miniaturization process became a key driver for many markets. Now, it is a driving force for innovations in life sciences, diagnostics, analytical sciences, and chemistry, which are called 'lab-on-a-chip, (LOC)' devices. The use of these devices allows the development of fast, portable, and easy-to-use systems with a high level of functional integration for applications such as point-of-care diagnostics, forensics, the analysis of biomolecules, environmental or food analysis, and drug development. In this review, we report on the latest developments in fabrication methods and production methodologies to tailor LOC devices. A brief overview of scale-up strategies is also presented together with their potential applications in drug delivery and discovery. The impact of LOC devices on drug development and discovery has been extensively reviewed in the past. The current research focuses on fast and accurate detection of genomics, cell mutations and analysis, drug delivery, and discovery. The current research also differentiates the LOC devices into new terminology of microengineering, like organ-on-a-chip, stem cells-on-a-chip, human-on-a-chip, and body-on-a-chip. Key challenges will be the transfer of fabricated LOC devices from lab-scale to industrial large-scale production. Moreover, extensive toxicological studies are needed to justify the use of microfabricated drug delivery vehicles in biological systems. It will also be challenging to transfer the in vitro findings to suitable and promising in vivo models. WIREs Syst Biol Med 2017, 9:e1381. doi: 10.1002/wsbm.1381 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Updates in Mirizzi syndrome

PubMed Central

Valderrama-Treviño, Alan Isaac; Espejel-Deloiza, Mariana; Chernitzky-Camaño, Jonathan; Barrera Mera, Baltazar; Estrada-Mata, Aranza Guadalupe; Ceballos-Villalva, Jesús Carlos; Acuña Campos, Jonathan; Argüero-Sánchez, Rubén

2017-01-01

Mirizzi syndrome, known as extrinsic bile compression syndrome, is a rare complication of cholecystitis and chronic cholelithiasis, secondary to the obliteration of the infundibulum of the gallbladder or cystic duct caused by the impact of one or more calculations in these anatomical structures, which leads to compression of the adjacent bile duct, resulting in partial or complete obstruction of the common hepatic duct, triggering liver dysfunction. Our aim is to identify and describe the current epidemiology, diagnostic methods, and treatment of Mirizzi syndrome. A literature search was performed using different databases, including Medline, Cochrane, Embase, Medscape, PubMed, using keywords: Mirizzi syndrome, epidemiology, markers, pathophysiology, clinical presentation, diagnosis, and treatment. Selected original articles, review articles or case reports from 1997 to 2015 were collected, written in English or Spanish. The endoscopic retrograde cholangiopancreatography (ERCP) is the most accurate diagnostic method. The traditional treatment has been surgery and involves an incision at the bottom of the gallbladder and calculus removal. If fistulas are observed, it is performed a partial cholecystectomy; otherwise, a cholecystocholedochoduodenostomy is an alternative. Endoscopic treatment includes biliary drainage and stone extraction. Many surgeons claim that laparoscopic cholecystectomy is contraindicated in Mirizzi syndrome because of the presence of inflammatory tissue and adhesions in the Calot’s triangle. If dissection is attempt, it can cause unnecessary injury to the bile duct. However, other surgeons consider the laparoscopic approach is feasible, although technically challenging. Currently, laparoscopic cholecystectomy for this condition is considered controversial and technically challenging; however, it has shown that with the right skills and equipment, it is a safe and feasible way to treat some cases of Mirizzi syndrome type I and II. PMID:28653000

Development and evaluation of a Sarcocystis neurona-specific IgM capture enzyme-linked immunosorbent assay.

PubMed

Murphy, J E; Marsh, A E; Reed, S M; Meadows, C; Bolten, K; Saville, W J A

2006-01-01

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of horses caused primarily by the protozoal parasite Sarcocystis neurona. Currently available antemortem diagnostic testing has low specificity. The hypothesis of this study was that serum and cerebrospinal fluid (CSF) of horses experimentally challenged with S neurona would have an increased S neurona-specific IgM (Sn-IgM) concentration after infection, as determined by an IgM capture enzyme linked immunoassay (ELISA). The ELISA was based on the S neurona low molecular weight protein SNUCD-1 antigen and the monoclonal antibody 2G5 labeled with horseradish peroxidase. The test was evaluated using serum and CSF from 12 horses experimentally infected with 1.5 million S neurona sporocysts and 16 horses experimentally infected with varying doses (100 to 100,000) of S neurona sporocysts, for which results of histopathologic examination of the central nervous system were available. For horses challenged with 1.5 million sporocysts, there was a significant increase in serum Sn-IgM concentrations compared with values before infection at weeks 2-6 after inoculation (P < .0001). For horses inoculated with lower doses of S neurona, there were significant increases in serum Sn-IgM concentration at various points in time after inoculation, depending on the challenge dose (P < .01). In addition, there was a significant increase between the CSF Sn-IgM concentrations before and after inoculation (P < .0001). These results support further evaluation of the assay as a diagnostic test during the acute phase of EPM.

Diagnosis - the limiting focus of taxonomy.

PubMed

Sturmberg, Joachim P; Martin, Carmel M

2016-02-01

The focus on the diagnosis is a pivotal aspect of medical practice since antiquity. Diagnostic taxonomy helped to categorize ailments to improve medical care, and in its social sense resulted in validation of the sick role for some, but marginalization or stigmatization for others. In the medical industrial complex, diagnostic taxonomy structured health care financing, management and practitioner remuneration. However, with increasing demands from multiple agencies, there are increasing unintended and unwarranted consequences of our current taxonomies and diagnostic processes resulting from the conglomeration of underpinning concepts, theories, information and motivations. We argue that the increasing focus on the diagnosis resulted in excessive compartmentalization - 'partialism' - of medical practice, diminishing medical care and being naively simplistic in light of the emerging understanding of the interconnected nature of the diseasome. The human is a complex organic system of interconnecting dynamics and feedback loops responding to internal and external forces including genetic, epigenetic and environmental attractors, rather than the sum of multiple discrete organs which can develop isolated diseases or multiple morbidities. Solutions to these unintended consequences of many contemporary health system processes involve revisiting the nature of diagnostic taxonomies and the processes of their construction. A dynamic taxonomic framework would shift to more relevant attractors at personal, clinical and health system levels recognizing the non-linear nature of health and disease. Human health at an individual, group and population level is the ability to adapt to internal and external stressors with resilience throughout the life course, yet diagnostic taxonomies are increasingly constructed around fixed anchors. Understanding diagnosis as dissecting, pigeonholing or bean counting (learning by dividing) is no longer useful, the challenge for the future is to understand the big picture (learning by connecting). Diagnostic categorization needs to embrace a meta-learning approach open to human variability. © 2014 John Wiley & Sons, Ltd.

Painful Shoulder in Swimmers: A Diagnostic Challenge.

ERIC Educational Resources Information Center

McMaster, William C.

1986-01-01

This article discusses the incidence, diagnosis, and treatment of painful shoulder in swimmers, including: regional problems that can cause shoulder pain; physical, clinical, and laboratory tests for diagnostic use; and approaches to management of the problem. (Author/CB)

Proceedings of the 2015 National Toxicology Program Satellite Symposium

PubMed Central

Elmore, Susan A.; Farman, Cindy A.; Hailey, James R.; Kovi, Ramesh C.; Malarkey, David E.; Morrison, James P.; Neel, Jennifer; Pesavento, Patricia A.; Porter, Brian F.; Szabo, Kathleen A.; Teixeira, Leandro B. C.; Quist, Erin M.

2016-01-01

The 2015 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Minneapolis, Minnesota at the ACVP/ASVCP/STP combined meeting. The goal of this symposium is to present and discuss diagnostic pathology challenges or nomenclature issues. Because of the combined meeting, both laboratory and domestic animal cases were presented. This article presents summaries of the speakers’ talks, including challenging diagnostic cases or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included hepatocellular lesions; a proposed harmonized diagnostic approach to rat cardiomyopathy; crop milk in a bird; avian feeding accoutrement; heat exchanger in a tuna; metastasis of a tobacco carcinogen-induced pulmonary carcinoma; neurocytoma in a rat; pituicytoma in a rat; rodent mammary gland whole mounts; dog and rat alveolar macrophage ultrastructure; dog and rat pulmonary phospholipidosis; alveolar macrophage aggregation in a dog; degenerating yeast in a cat liver aspirate; myeloid leukemia in lymph node aspirates from a dog; Trypanosoma cruzi in a dog; solanum toxicity in a cow; bovine astrovirus; malignant microglial tumor; and nomenclature challenges from the Special Senses International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) organ working group (OWG). PMID:27075180

Current challenges and pitfalls in the pharmacological treatment of depression

PubMed Central

Popa-Velea, O; Gheorghe, IR; Truţescu, CI; Purcărea, VL

2015-01-01

The multifactorial etiology of depression obliges needs an individual assessment, the psychopharmacological approach involving a biopsychosocial analysis for each individual case. The rebalancing of the depressive patient, seen as a return to a normal level of psychosocial functioning and reduced risk of relapse is achieved with a prompt and constant support of specialized teams. Treatment should include psychopharmacological and psychosocial approaches, the results being interrelated and contributing to the prognosis of the disorder. Progress in clinical and pharmacological research, vivid dynamics of socio-economic environment, the complexity of diagnostic evaluation and the need for an interdisciplinary approach may cause difficulties in addressing the depressive patient and the ethical controversies. The aim of this paper is to present a brief analysis of challenges encountered in the present psychiatric practice, starting from the heterogeneity of depressive manifestations and finishing with the prioritization of interventional forms. PMID:25866576

Composites of Polymer Hydrogels and Nanoparticulate Systems for Biomedical and Pharmaceutical Applications

PubMed Central

Zhao, Fuli; Yao, Dan; Guo, Ruiwei; Deng, Liandong; Dong, Anjie; Zhang, Jianhua

2015-01-01

Due to their unique structures and properties, three-dimensional hydrogels and nanostructured particles have been widely studied and shown a very high potential for medical, therapeutic and diagnostic applications. However, hydrogels and nanoparticulate systems have respective disadvantages that limit their widespread applications. Recently, the incorporation of nanostructured fillers into hydrogels has been developed as an innovative means for the creation of novel materials with diverse functionality in order to meet new challenges. In this review, the fundamentals of hydrogels and nanoparticles (NPs) were briefly discussed, and then we comprehensively summarized recent advances in the design, synthesis, functionalization and application of nanocomposite hydrogels with enhanced mechanical, biological and physicochemical properties. Moreover, the current challenges and future opportunities for the use of these promising materials in the biomedical sector, especially the nanocomposite hydrogels produced from hydrogels and polymeric NPs, are discussed. PMID:28347111

Perspectives on Creating Clinically Relevant Blast Models for Mild Traumatic Brain Injury and Post Traumatic Stress Disorder Symptoms

PubMed Central

Brenner, Lisa A.; Bahraini, Nazanin; Hernández, Theresa D.

2012-01-01

Military personnel are returning from Iraq and Afghanistan and reporting non-specific physical (somatic), behavioral, psychological, and cognitive symptoms. Many of these symptoms are frequently associated with mild traumatic brain injury (mTBI) and/or post traumatic stress disorder (PTSD). Despite significant attention and advances in assessment and intervention for these two conditions, challenges persist. To address this, clinically relevant blast models are essential in the full characterization of this type of injury, as well as in the testing and identification of potential treatment strategies. In this publication, existing diagnostic challenges and current treatment practices for mTBI and/or PTSD will be summarized, along with suggestions regarding how what has been learned from existing models of PTSD and traditional mechanism (e.g., non-blast) traumatic brain injury can be used to facilitate the development of clinically relevant blast models. PMID:22408635

Evidentiary Reasoning in Diagnostic Classification Models

ERIC Educational Resources Information Center

Levy, Roy

2009-01-01

In "Unique Characteristics of Diagnostic Classification Models: A Comprehensive Review of the Current State-of-the-Art," Rupp and Templin (2008) undertake the ambitious task of providing a thorough portrait of the current state of diagnostic classification models (DCM). In this commentary, the author applauds Rupp and Templin for their…

The bedside diagnostic accuracy of a novice reflectance confocal microscopy reader for skin cancer detection in vivo in real-time: understanding challenges and potential pitfalls

NASA Astrophysics Data System (ADS)

Jain, Manu; Pulijal, Sri Varsha; Rajadhyaksha, Milind

2017-02-01

Reflectance confocal microscopy (RCM) is a non-invasive device that images skin lesions in vivo at a cellular resolution to guide management of patient care. While previous studies have demonstrated high accuracy of RCM in diagnosing skin cancers, most of these studies were performed by experts as a blinded analysis off-site and does not reflect true clinical scenario. We assessed the diagnostic potential of a novice RCM reader, in clinical settings, at the bedside. Over a period of 15 months (August 2015- November 2016), 168 lesions (from 128 cases) were imaged with RCM to determine BCC and or melanoma in dermoscopically equivocal lesions. To evaluate the learning curve of the novice reader, diagnostic accuracy was evaluated at the end of 15 months, as well as during the first half (8 months) and latter half (seven months) of the study. Histopathological diagnosis was available in 95/168 lesions, including 38 melanocytic lesions (ML: 13 melanomas and 25 nevi) and 57 non-melanocytic lesions (NML: 26 BCCs, 4 SCCs and 27 benign). The remaining 73/168 lesions (43.45%) were not biopsied (received topical treatment, monitoring). On RCM, 22/26 (84.61%) BCCs and 11/13 (84.61%) melanomas were correctly diagnosed. BCC was missed in 3/26 (11.53%) lesions and melanoma in 2/13 (15.38%) lesions; these lesions were diagnosed mostly as superficial BCCs and focal epidermal changes overlying deeply situated melanoma nodule on histopathology, respectively. False positive diagnosis of BCC was obtained in 7/23 (30.4%) lesions and of melanoma in 2/22 (4.5%) lesions; these were diagnosed mostly as benign inflamed keratosis and moderately atypical dysplastic nevus on histopathology, respectively. In 7 lesions BCC or melanoma could not be ruled out. A marked increase in the sensitivity and specificity was noticed between the two halves of the study. An overall high diagnostic accuracy of 80.28% with high sensitivity and specificity of 80.68% and 80.8%, respectively in diagnosing skin cancers was obtained. Based on this study, we identified some current limitations and potential pitfalls of RCM. The fact that the diagnostic accuracy of the novice reader increased with time, indicates a learning curve reading RCM images. Additionally, current technical limitations of RCM such as inability to differentiate various cell types, sampling error, and, shallow depth of imaging also lead to false diagnosis. Efforts are ongoing to overcome these challenges by building US based teaching-training program and through a multimodal imaging approach for better diagnosis and patient care.

Current Advances on Virus Discovery and Diagnostic Role of Viral Metagenomics in Aquatic Organisms

PubMed Central

Munang'andu, Hetron M.; Mugimba, Kizito K.; Byarugaba, Denis K.; Mutoloki, Stephen; Evensen, Øystein

2017-01-01

The global expansion of the aquaculture industry has brought with it a corresponding increase of novel viruses infecting different aquatic organisms. These emerging viral pathogens have proved to be a challenge to the use of traditional cell-cultures and immunoassays for identification of new viruses especially in situations where the novel viruses are unculturable and no antibodies exist for their identification. Viral metagenomics has the potential to identify novel viruses without prior knowledge of their genomic sequence data and may provide a solution for the study of unculturable viruses. This review provides a synopsis on the contribution of viral metagenomics to the discovery of viruses infecting different aquatic organisms as well as its potential role in viral diagnostics. High throughput Next Generation sequencing (NGS) and library construction used in metagenomic projects have simplified the task of generating complete viral genomes unlike the challenge faced in traditional methods that use multiple primers targeted at different segments and VPs to generate the entire genome of a novel virus. In terms of diagnostics, studies carried out this far show that viral metagenomics has the potential to serve as a multifaceted tool able to study and identify etiological agents of single infections, co-infections, tissue tropism, profiling viral infections of different aquatic organisms, epidemiological monitoring of disease prevalence, evolutionary phylogenetic analyses, and the study of genomic diversity in quasispecies viruses. With sequencing technologies and bioinformatics analytical tools becoming cheaper and easier, we anticipate that metagenomics will soon become a routine tool for the discovery, study, and identification of novel pathogens including viruses to enable timely disease control for emerging diseases in aquaculture. PMID:28382024

Biosafety principles and practices for the veterinary diagnostic laboratory.

PubMed

Kozlovac, Joseph; Schmitt, Beverly

2015-01-01

Good biosafety and biocontainment programs and practices are critical components of the successful operation of any veterinary diagnostic laboratory. In this chapter we provide information and guidance on critical biosafety management program elements, facility requirements, protective equipment, and procedures necessary to ensure that the laboratory worker and the environment are adequately protected in the challenging work environment of the veterinary diagnostic laboratory in general and provide specific guidance for those laboratories employing molecular diagnostic techniques.

Regulatory challenges for in vitro diagnostics in a global environment.

PubMed

Longwell, A

1994-06-01

U.S. medical products are marketed globally and are designed to meet needs of medical practitioners and their patients throughout the world. However, differences in how these products are regulated in different countries can pose challenges for the global marketer. This paper explores some of the differences between proposed and extant U.S. and European regulations for in vitro diagnostic products in terms of documentation, records, and labelling. It will describe some of the practical implications of these differences.

Atypical sarcoidosis-associated uveitis: diagnostic challenges.

PubMed

Cehajic Kapetanovic, Jasmina; Jones, Nicholas P; Steeples, Laura R

2018-05-30

Sarcoidosis is a multisystem disease of unknown aetiology with pulmonary involvement in most patients. Uveitis is common and often characteristic. We report a case of ocular sarcoidosis with grossly atypical contiguous optic neuropathy and choroiditis and describe the diagnostic challenges in this highly unusual presentation. High-dose systemic corticosteroid and immunosuppressive treatment was required for sustained control of intraocular inflammation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Type 1 diabetes: Awareness, management and challenges: Current scenario in India

PubMed Central

Kumar, K.M. Prasanna; Saboo, Banshi; Rao, P.V.; Sarda, Archana; Viswanathan, Vijay; Kalra, Sanjay; Sethi, Bipin; Shah, Nalini; Srikanta, S.S.; Jain, Sunil M; Raghupathy, P.; Shukla, Rishi; Jhingan, Ashok; Chowdhury, Subhankar; Jabbar, P.K.; Kanungo, Alok; Joshi, Rajesh; Kumar, Surendra; Tandon, Nikhil; Khadilkar, Vaman; Chadha, Manoj

2015-01-01

Type 1 diabetes mellitus (T1DM) has a wide presence in children and has a high mortality rates. The disease, if left unmanaged, poses various challenges to the patient and healthcare providers, including development of diabetic complications and thus decreasing the life expectancy of the affected child. The challenges of T1DM include awareness of the disease that is very poor among the general public and also in parents of T1DM children along with the health care professionals. The challenge of lack of awareness of T1DM can be met by increasing public awareness programs, conducting workshops for diabetes educators regarding T1DM in children, newsletters, CMEs, online courses, and by structured teaching modules for diabetes educators. Diagnosis of T1DM was a challenge a few decades ago but the situation has improved today with diagnostic tests and facilities, made available even in villages. Investigation facilities and infrastructure, however, are very poor at the primary care level, especially in rural areas. Insulin availability, acceptability, and affordability are also major problems, compounded by the various types of insulin that are available in the market with a varied price range. But effective use of insulin remains a matter of utmost importance. PMID:25941655

Availability of Diagnostic and Treatment Services for Acute Stroke in Frontier Counties in Montana and Northern Wyoming

ERIC Educational Resources Information Center

Okon, Nicholas J.; Rodriguez, Daniel V.; Dietrich, Dennis W.; Oser, Carrie S.; Blades, Lynda L.; Burnett, Anne M.; Russell, Joseph A.; Allen, Martha J.; Chasson, Linda; Helgerson, Steven D.; Gohdes, Dorothy; Harwell, Todd S.

2006-01-01

Context: Rapid diagnosis and treatment of ischemic stroke can lead to improved patient outcomes. Hospitals in rural and frontier counties, however, face unique challenges in providing diagnostic and treatment services for acute stroke. Purpose: The aim of this study was to assess the availability of key diagnostic technology and programs for acute…

Multiomics tools for the diagnosis and treatment of rare neurological disease.

PubMed

Crowther, L M; Poms, M; Plecko, Barbara

2018-05-01

Conventional workup of rare neurological disease is frequently hampered by diagnostic delay or lack of diagnosis. While biomarkers have been established for many neurometabolic disorders, improved methods are required for diagnosis of previously unidentified or underreported causes of rare neurological disease. This would result in a higher diagnostic yield and increased patient numbers required for interventional studies. Recent studies using next-generation sequencing and metabolomics have led to identification of novel disease-causing genes and biomarkers. This combined approach can assist in overcoming challenges associated with analyzing and interpreting the large amount of data obtained from each technique. In particular, metabolomics can support the pathogenicity of sequence variants in genes encoding enzymes or transporters involved in metabolic pathways. Moreover, metabolomics can show the broader perturbation caused by inborn errors of metabolism and identify a metabolic fingerprint of metabolic disorders. As such, using "omics" has great potential to meet the current needs for improved diagnosis and elucidation of rare neurological disease.

[Early congenital syphilis: a case report].

PubMed

Cavagnaro S M, Felipe; Pereira R, Teresita; Pérez P, Carla; Vargas Del V, Fernanda; Sandoval C, Carmen

2014-02-01

Congenital syphilis (CS) is a multisystemic infection of the newborn (NB) which can produce severe symptoms, and in some cases, even be fatal. In recent years, the incidence of syphilis has increased worldwide and similarly, the cases of CS in neonates have increased. To report two cases of early and severe presentation of CS, focusing on the importance of prevention of vertical transmission and monitoring of treated mothers. The diagnostic difficulties are discussed. Two premature newborns that were diagnosed with probable CS present in the newborn period are presented. In the first case, due to a high index of suspicion, but without confirmatory testing, treatment was started with good clinical response. In the second case, CS was confirmed through positive serology and the specific treatment was given. CS has significant diagnostic challenges as there is no test for early confirmation, therefore, a high index of suspicion might be key in the treatment and consequent prognosis. Due to the current epidemiology of the condition, it is also important to focus on preventive measures.

Precision nutrition - review of methods for point-of-care assessment of nutritional status.

PubMed

Srinivasan, Balaji; Lee, Seoho; Erickson, David; Mehta, Saurabh

2017-04-01

Precision nutrition encompasses prevention and treatment strategies for optimizing health that consider individual variability in diet, lifestyle, environment and genes by accurately determining an individual's nutritional status. This is particularly important as malnutrition now affects a third of the global population, with most of those affected or their care providers having limited means of determining their nutritional status. Similarly, program implementers often have no way of determining the impact or success of their interventions, thus hindering their scale-up. Exciting new developments in the area of point-of-care diagnostics promise to provide improved access to nutritional status assessment, as a first step towards enabling precision nutrition and tailored interventions at both the individual and community levels. In this review, we focus on the current advances in developing portable diagnostics for assessment of nutritional status at point-of-care, along with the numerous design challenges in this process and potential solutions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Emerging Role of MicroRNAs as Liquid Biopsy Biomarkers in Gastrointestinal Cancers

PubMed Central

Shigeyasu, Kunitoshi; Toden, Shusuke; Zumwalt, Timothy J.; Okugawa, Yoshinaga; Goel, Ajay

2017-01-01

Cancer has emerged as a leading cause of mortality worldwide, claiming over 8 million lives annually. Gastrointestinal (GI) cancers account for ~35% of these mortalities. Recent advances in diagnostic and treatment strategies have reduced mortality among GI cancer patients, yet a significant number of patients still develop late-stage cancer, where treatment options are inadequate. Emerging interests in ‘liquid biopsies’ have encouraged investigators to identify and develop clinically-relevant noninvasive genomic and epigenomic signatures that can be exploited as biomarkers capable of detecting premalignant and early-stage cancers. In this context, microRNAs (miRNAs), which are small non-coding RNAs that are frequently dysregulated in cancers, have emerged as promising entities for such diagnostic purposes. Albeit the future looks promising, current approaches for detecting miRNAs in blood and other biofluids remain inadequate. This review summarizes existing efforts to exploit circulating miRNAs as cancer biomarkers, evaluates their potential and challenges as liquid biopsy-based biomarkers for GI cancers. PMID:28143873

Childhood functional abdominal pain: mechanisms and management.

PubMed

Korterink, Judith; Devanarayana, Niranga Manjuri; Rajindrajith, Shaman; Vlieger, Arine; Benninga, Marc A

2015-03-01

Chronic abdominal pain is one of the most common clinical syndromes encountered in day to day clinical paediatric practice. Although common, its definition is confusing, predisposing factors are poorly understood and the pathophysiological mechanisms are not clear. The prevailing viewpoint in the pathogenesis involves the inter-relationship between changes in hypersensitivity and altered motility, to which several risk factors have been linked. Making a diagnosis of functional abdominal pain can be a challenge, as it is unclear which further diagnostic tests are necessary to exclude an organic cause. Moreover, large, well-performed, high-quality clinical trials for effective agents are lacking, which undermines evidence-based treatment. This Review summarizes current knowledge regarding the epidemiology, pathophysiology, risk factors and diagnostic work-up of functional abdominal pain. Finally, management options for children with functional abdominal pain are discussed including medications, dietary interventions, probiotics and psychological and complementary therapies, to improve understanding and to maximize the quality of care for children with this condition.

Dynamic MRI-based computer aided diagnostic systems for early detection of kidney transplant rejection: A survey

NASA Astrophysics Data System (ADS)

Mostapha, Mahmoud; Khalifa, Fahmi; Alansary, Amir; Soliman, Ahmed; Gimel'farb, Georgy; El-Baz, Ayman

2013-10-01

Early detection of renal transplant rejection is important to implement appropriate medical and immune therapy in patients with transplanted kidneys. In literature, a large number of computer-aided diagnostic (CAD) systems using different image modalities, such as ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), and radionuclide imaging, have been proposed for early detection of kidney diseases. A typical CAD system for kidney diagnosis consists of a set of processing steps including: motion correction, segmentation of the kidney and/or its internal structures (e.g., cortex, medulla), construction of agent kinetic curves, functional parameter estimation, diagnosis, and assessment of the kidney status. In this paper, we survey the current state-of-the-art CAD systems that have been developed for kidney disease diagnosis using dynamic MRI. In addition, the paper addresses several challenges that researchers face in developing efficient, fast and reliable CAD systems for the early detection of kidney diseases.

Molecular diagnostics in gastric cancer.

PubMed

Bornschein, Jan; Leja, Marcis; Kupcinskas, Juozas; Link, Alexander; Weaver, Jamie; Rugge, Massimo; Malfertheiner, Peter

2014-01-01

Despite recent advances in individualised targeted therapy, gastric cancer remains one of the most challenging diseases in gastrointestinal oncology. Modern imaging techniques using endoscopic filter devices and in vivo molecular imaging are designed to enable early detection of the cancer and surveillance of patients at risk. Molecular characterisation of the tumour itself as well as of the surrounding inflammatory environment is more sophisticated in the view of tailored therapies and individual prognostic assessment. The broad application of high throughput techniques for the description of genome wide patterns of structural (copy number aberrations, single nucleotide polymorphisms, methylation pattern) and functional (gene expression profiling, proteomics, miRNA) alterations in the cancer tissue lead not only to a better understanding of the tumour biology but also to a description of gastric cancer subtypes independent from classical stratification systems. Biostatistical means are required for the interpretation of the massive amount of data generated by these approaches. In this review we give an overview on the current knowledge of diagnostic methods for detection, description and understanding of gastric cancer disease.

Music therapy with disorders of consciousness: current evidence and emergent evidence-based practice.

PubMed

Magee, Wendy L; O'Kelly, Julian

2015-03-01

Patients with prolonged disorders of consciousness (PDOC) stemming from acquired brain injury present one of the most challenging clinical populations in neurological rehabilitation. Because of the complex clinical presentation of PDOC patients, treatment teams are confronted with many medicolegal, ethical, philosophical, moral, and religious issues in day-to-day care. Accurate diagnosis is of central concern, relying on creative approaches from skilled clinical professionals using combined behavioral and neurophysiological measures. This paper presents the latest evidence for using music as a diagnostic tool with PDOC, including recent developments in music therapy interventions and measurement. We outline standardized clinical protocols and behavioral measures to produce diagnostic outcomes and examine recent research illustrating a range of benefits of music-based methods at behavioral, cardiorespiratory, and cortical levels using video, electrocardiography, and electroencephalography methods. These latest developments are discussed in the context of evidence-based practice in rehabilitation with clinical populations. © 2014 New York Academy of Sciences.

A Formidable Foe is Sabotaging Your Results: What You Should Know about Biofilms and Wound Healing

PubMed Central

Barker, Jenny C; Khansa, Ibrahim; Gordillo, Gayle M

2017-01-01

Learning Objectives After reading this article, the participant should be able to: 1. Describe biofilm pathogenesis as it relates to problem wounds, 2. Understand the pre-clinical and clinical evidence implicating biofilm in problem wounds, 3. Explain the diagnostic and treatment challenges that biofilms create for problem wounds, 4. Demonstrate a basic understanding of emerging strategies aimed at counteracting these processes. Summary Biofilm represents a protected mode of growth for bacteria, allowing them to evade standard diagnostic techniques and avoid eradication by standard therapies. Though only recently discovered, biofilm has existed for millennia and complicates nearly every aspect of medicine. Biofilm impacts wound healing by allowing bacteria to evade immune responses, prolonging inflammation and disabling skin barrier function. It is important to understand why problem wounds persist despite state-of-the-art treatment, why they are difficult to accurately diagnose, and why they recur. The aim of this article is to focus on current gaps in knowledge related to problem wounds, specifically, biofilm infection. PMID:28445380

Pharmaceuticals and Stem Cells in Autism Spectrum Disorders: Wishful Thinking?

PubMed

Sivanesan, Senthilkumar; Tan, Aaron; Jeyaraj, Rebecca; Lam, James; Gole, Monica; Hardan, Antonio; Ashkan, Keyoumars; Rajadas, Jayakumar

2017-02-01

We provide a contemporary account of the key pathologic events pertaining to autism: the theory of oxidative stress and inflammatory causes, ideas of immune dysfunction, the probable biomarkers that can be used for diagnostics, and the use of pharmaceuticals and stem cells as possible candidates for the treatment of autism spectrum disorders (ASDs). ASDs are a group of complex neurodevelopmental conditions characterized by abnormal patterns of attention and impaired social and communication skills. ASDs are also associated with numerous functional challenges and potentially harmful deficits, including restricted and repetitive behaviors, anxiety, irritability, seizures, and self-harm. Although the exact causes of ASDs are unknown, it is suggested that genetic, epigenetic, and environmental factors play critical roles. More recent findings support evidence for synaptic defects and impairments in brain information processing that are linked to social and perceptual skills. Owing to the clinical heterogeneity and lack of precise diagnostic tools, current therapeutic approaches aimed at managing ASD-associated conditions are not definitive. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests.

PubMed

Harrington, Jennifer; Palmert, Mark R

2012-09-01

Determining the etiology of delayed puberty during initial evaluation can be challenging. Specifically, clinicians often cannot distinguish constitutional delay of growth and puberty (CDGP) from isolated hypogonadotropic hypogonadism (IHH), with definitive diagnosis of IHH awaiting lack of spontaneous puberty by age 18 yr. However, the ability to make a timely, correct diagnosis has important clinical implications. The aim was to describe and evaluate the literature regarding the ability of diagnostic tests to distinguish CDGP from IHH. A PubMed search was performed using key words "puberty, delayed" and "hypogonadotropic hypogonadism," and citations within retrieved articles were reviewed to identify studies that assessed the utility of basal and stimulation tests in the diagnosis of delayed puberty. Emphasis was given to a test's ability to distinguish prepubertal adolescents with CDGP from those with IHH. Basal gonadotropin and GnRH stimulation tests have limited diagnostic specificity, with overlap in gonadotropin levels between adolescents with CDGP and IHH. Stimulation tests using more potent GnRH agonists and/or human chorionic gonadotropin may have better discriminatory value, but small study size, lack of replication of diagnostic thresholds, and prolonged protocols limit clinical application. A single inhibin B level in two recent studies demonstrated good differentiation between groups. Distinguishing IHH from CDGP is an important clinical issue. Basal inhibin B may offer a simple, discriminatory test if results from recent studies are replicated. However, current literature does not allow for recommendation of any diagnostic test for routine clinical use, making this an important area for future investigation.

Should cognitive impairment be included in the diagnostic criteria for schizophrenia?

PubMed

Keefe, Richard S E

2008-02-01

Neurocognitive impairment is considered a core component of schizophrenia, and is increasingly under investigation as a potential treatment target. On average, cognitive impairment is severe to moderately severe compared to healthy controls, and almost all patients with schizophrenia demonstrate cognitive decrements compared to their expected level if they had not developed the illness. Compared to patients with affective disorders, cognitive impairment in schizophrenia appears earlier, is more severe, and is more independent of clinical symptoms. Although the DSM-IV-TR and ICD-10 descriptions of schizophrenia include several references to cognitive impairment, neither the diagnostic criteria nor the subtypology of schizophrenia include a requirement of cognitive impairment. This paper forwards for consideration a proposal that the diagnostic criteria include a specific criterion of "a level of cognitive functioning suggesting a consistent severe impairment and/or a significant decline from premorbid levels considering the patient's educational, familial, and socioeconomic background". The inclusion of this criterion may increase the "point of rarity" with affective psychoses and may increase clinicians' awareness of cognitive impairment, potentially leading to more accurate prognosis, better treatment outcomes, and a clearer diagnostic signal for genetic and biological studies. Future research will need to address the validity of these possibilities. The reliable determination of cognitive impairment as part of a standard diagnostic evaluation will present challenges to diagnosticians with limited resources or insufficient expertise. Cognitive assessment methods for clinicians, including brief assessments and interview-based assessments, are discussed. Given the current emphasis on the development of cognitive treatments, the evaluation of cognition in schizophrenia is an essential component of mental health education.

Biomarkers for the differentiation of sepsis and SIRS: the need for the standardisation of diagnostic studies.

PubMed

Hall, T C; Bilku, D K; Al-Leswas, D; Horst, C; Dennison, A R

2011-12-01

Sepsis is a leading cause of death in the critically ill patient. It is a heterogeneous disease and it is frequently difficult to make an unequivocal and expeditious diagnosis. The current 'gold standard' in diagnosing sepsis is the blood culture but this is only available after a significant time delay. Mortality rates from sepsis remain high, however, the introduction of sepsis care bundles in its management has produced significant improvements in patient outcomes. Central to goal-directed resuscitation is the timely and accurate diagnosis of sepsis. The rapid diagnosis and commencement of the appropriate therapies has been shown to reduce the mortality. Biomarkers are already used in clinical practice to aid other more traditional diagnostic tests. In the absence of an adequate gold standard to diagnose sepsis, there has been considerable and growing interest in trying to identify suitable biomarkers. There is currently an unmet need in the medical literature to communicate the importance of the challenges relating to the rapid diagnosis and implementation of goal-directed therapy in sepsis and the underlying concepts that are directing these investigations. This article reviews the more novel biomarkers investigated to differentiate systemic inflammatory response syndrome from sepsis. The biomarkers described reflect the difficulties in making evidence-based recommendations particularly when interpreting studies where the methodology is of poor quality and the results are conflicting. We are reminded of our responsibilities to ensure high quality and standardised study design as articulated by the STAndards for the Reporting of Diagnostic accuracy studies (STARD) initiative.

Diagnostic Tools for Performance Evaluation of Innovative In-Situ Remediation Technologies at Chlorinated Solvent-Contaminated Sites

DTIC Science & Technology

2011-07-01

to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT...these innovative methods with conventional diagnostic tools that are currently used for assessing bioremediation performance. 132 Rula Deeb (510) 596...conventional diagnostic tools that are currently used for assessing bioremediation performance. DEMONSTRATION RESULTS 3-D multi-level systems

Irritable bowel syndrome: A clinical review

PubMed Central

Soares, Rosa LS

2014-01-01

Irritable bowel syndrome (IBS) remains a clinical challenge in the 21st century. It’s the most commonly diagnosed gastrointestinal condition and also the most common reason for referral to gastroenterology clinics. Its can affect up to one in five people at some point in their lives, and has a significantly impact of life quality and health care utilization. The prevalence varies according to country and criteria used to define IBS. Various mechanisms and theories have been proposed about its etiology, but the biopsychosocial model is the most currently accepted for IBS. The complex of symptoms would be the result of the interaction between psychological, behavioral, psychosocial and environmental factors. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria III is the current gold-standard for the diagnoses of IBS. Secure positive evidence of IBS by means of specific disease marker is currently not possible and cannot be currently recommended for routine diagnosis. There is still no clinical evidence to recommend the use of biomarkers in blood to diagnose IBS. However, a number of different changes in IBS patients were demonstrated in recent years, some of which can be used in the future as a diagnostic support. IBS has no definitive treatment but could be controlled by non-pharmacologic management eliminating of some exacerbating factors such certain drugs, stressor conditions and changes in dietary habits.The traditional pharmacologic management of IBS has been symptom based and several drugs have been used. However, the cornerstone of its therapy is a solid patient physician relationship. This review will provide a summary of pathophysiology, diagnostic criteria and current and emerging therapies for IBS. PMID:25232249

dropEst: pipeline for accurate estimation of molecular counts in droplet-based single-cell RNA-seq experiments.

PubMed

Petukhov, Viktor; Guo, Jimin; Baryawno, Ninib; Severe, Nicolas; Scadden, David T; Samsonova, Maria G; Kharchenko, Peter V

2018-06-19

Recent single-cell RNA-seq protocols based on droplet microfluidics use massively multiplexed barcoding to enable simultaneous measurements of transcriptomes for thousands of individual cells. The increasing complexity of such data creates challenges for subsequent computational processing and troubleshooting of these experiments, with few software options currently available. Here, we describe a flexible pipeline for processing droplet-based transcriptome data that implements barcode corrections, classification of cell quality, and diagnostic information about the droplet libraries. We introduce advanced methods for correcting composition bias and sequencing errors affecting cellular and molecular barcodes to provide more accurate estimates of molecular counts in individual cells.

ViDI: Virtual Diagnostics Interface. Volume 2; Unified File Format and Web Services as Applied to Seamless Data Transfer

NASA Technical Reports Server (NTRS)

Fleming, Gary A. (Technical Monitor); Schwartz, Richard J.

2004-01-01

The desire to revolutionize the aircraft design cycle from its currently lethargic pace to a fast turn-around operation enabling the optimization of non-traditional configurations is a critical challenge facing the aeronautics industry. In response, a large scale effort is underway to not only advance the state of the art in wind tunnel testing, computational modeling, and information technology, but to unify these often disparate elements into a cohesive design resource. This paper will address Seamless Data Transfer, the critical central nervous system that will enable a wide variety of varied components to work together.

Genetic Advances in Autism: Heterogeneity and Convergence on Shared Pathways

PubMed Central

Bill, Brent R.; Geschwind, Daniel H.

2009-01-01

The autism spectrum disorders (ASD) are a heterogeneous set of developmental disorders characterized at their core by deficits in social interaction and communication. Current psychiatric nosology groups this broad set of disorders with strong genetic liability and multiple etiologies into the same diagnostic category. This heterogeneity has challenged genetic analyses. But shared patient resources, genomic technologies, more refined phenotypes, and novel computational approaches have begun to yield dividends in defining the genetic mechanisms at work. Over the last five years, a large number of autism susceptibility loci have emerged, redefining our notion of autism’s etiologies, and reframing how we think about ASD. PMID:19477629

Cardiac magnetic resonance in hypertrophic cardiomyopathy: current state of the art.

PubMed

Kwon, Deborah H; Desai, Milind Y

2010-01-01

Hypertrophic cardiomyopathy is a complex disorder with significant heterogeneity in clinical characteristics and natural history. Traditionally, the diagnosis has been based on clinical assessment and echocardiography; however, persistent challenges in its noninvasive evaluation remain. Hence, improved diagnostic techniques could lead to better risk stratification of patients, which would potentially identify patients likely to benefit from effective therapies. Recent studies have demonstrated the increasing utility of cardiac magnetic resonance in the management of this disease. With the increasing utilization of genetics, cardiac magnetic resonance is likely to play an even more important role in discerning the subtle morphologic differences seen in such patients with similar genotypic profiles.

Current and future molecular diagnostics for prion diseases.

PubMed

Lehto, Marty T; Peery, Harry E; Cashman, Neil R

2006-07-01

It is now widely held that the infectious agents underlying the transmissible spongiform encephalopathies are prions, which are primarily composed of a misfolded, protease-resistant isoform of the host prion protein. Untreatable prion disorders include some human diseases, such as Creutzfeldt-Jakob disease, and diseases of economically important animals, such as bovine spongiform encephalopathy (cattle) and chronic wasting disease (deer and elk). Detection and diagnosis of prion disease (and presymptomatic incubation) is contingent upon developing novel assays, which exploit properties uniquely possessed by this misfolded protein complex, rather than targeting an agent-specific nucleic acid. This review highlights some of the conventional and disruptive technologies developed to respond to this challenge.

A narrow view: The conceptualization of sexual problems in human sexuality textbooks.

PubMed

Stelzl, Monika; Stairs, Brittany; Anstey, Hannah

2018-02-01

This study examined the ways in which the meaning of 'sexual problems' is constructed and defined in undergraduate human sexuality textbooks. Drawing on feminist and critical discourse frameworks, the dominant as well as the absent/marginalized discourses were identified using critical discourse analysis. Sexual difficulties were largely framed by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders. Thus, medical discourse was privileged. Alternative conceptualizations and frameworks, such as the New View of Women's Sexual Problems, were included marginally and peripherally. We argue that current constructions of sexuality knowledge reinforce, rather than challenge, existing hegemonic discourses of sexuality.

Enzyme-Activated Fluorogenic Probes for Live-Cell and in Vivo Imaging.

PubMed

Chyan, Wen; Raines, Ronald T

2018-06-20

Fluorogenic probes, small-molecule sensors that unmask brilliant fluorescence upon exposure to specific stimuli, are powerful tools for chemical biology. Those probes that respond to enzymatic activity illuminate the complex dynamics of biological processes at a level of spatiotemporal detail and sensitivity unmatched by other techniques. Here, we review recent advances in enzyme-activated fluorogenic probes for biological imaging. We organize our survey by enzyme classification, with emphasis on fluorophore masking strategies, modes of enzymatic activation, and the breadth of current and future applications. Key challenges such as probe selectivity and spectroscopic requirements are described alongside of therapeutic, diagnostic, and theranostic opportunities.

A global perspective on mechanical prosthetic heart valve thrombosis: Diagnostic and therapeutic challenges

PubMed Central

Gürsoy, Mustafa Ozan; Kalçık, Macit; Yesin, Mahmut; Karakoyun, Süleyman; Bayam, Emrah; Gündüz, Sabahattin; Özkan, Mehmet

2016-01-01

Prosthetic valve thrombosis is one of the major causes of primary valve failure, which can be life-threatening. Multimodality imaging is necessary for determination of leaflet immobilization, cause of underlying pathology (thrombus versus pannus or both), and whether thrombolytic therapy attempt in the patient would be successful or surgery is needed. Current guidelines for the management of prosthetic valve thrombosis lack definitive class I recommendations due to lack of randomized controlled trials, and usually leave the choice of treatment to the clinician’s experience. In this review, we aimed to summarize the pathogenesis, diagnosis, and management of mechanical prosthetic valve thrombosis. PMID:28005024

Managing and monitoring tuberculosis using web-based tools in combination with traditional approaches

PubMed Central

Chapman, Ann LN; Darton, Thomas C; Foster, Rachel A

2013-01-01

Tuberculosis (TB) remains a global health emergency. Ongoing challenges include the coordination of national and international control programs, high levels of drug resistance in many parts of the world, and availability of accurate and rapid diagnostic tests. The increasing availability and reliability of Internet access throughout both affluent and resource-limited countries brings new opportunities to improve TB management and control through the integration of web-based technologies with traditional approaches. In this review, we explore current and potential future use of web-based tools in the areas of TB diagnosis, treatment, epidemiology, service monitoring, and teaching and training. PMID:24294008

A "Trans-Dyadic" Perspective on the Goldwater Rule.

PubMed

Plakun, Eric M

2017-11-01

The Goldwater Rule has been debated, redefined, and debated further since the election of Donald Trump as President of the United States. This column offers a perspective on the Goldwater Rule that moves beyond psychiatry's current preoccupation with precision DSM-5 diagnosis of individuals, which ethically requires consent or other legal authorization for release of diagnostic information to others, and into the realm of leadership as seen through the "trans-dyadic" lens of psychoanalytic understanding of large group processes on a societal level. Concepts from large group psychology are introduced to illustrate "trans-dyadic" perspectives on leadership that do not challenge the Goldwater Rule.

Pernicious Anemia: Fundamental and Practical Aspects in Diagnosis.

PubMed

Tun, Aung Myint; Thein, Kyaw Zin; Myint, Zin War; Oo, Thein Hlaing

2017-11-08

Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity and diverse clinical presentations. Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for the evaluation of cobalamin deficiency and PA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

CHALLENGES IN SETTING UP QUALITY CONTROL IN DIAGNOSTIC RADIOLOGY FACILITIES IN NIGERIA.

PubMed

Inyang, S O; Egbe, N O; Ekpo, E

2015-01-01

The Nigerian Nuclear Regulatory Authority (NNRA) was established to regulate and control the use of radioactive and radiation emitting sources in Nigeria. Quality control (QC) on diagnostic radiology equipment form part of the fundamental requirements for the authorization of diagnostic radiology facilities in the Country. Some quality control tests (output, exposure linearity and reproducibility) were measured on the x-ray machines in the facilities that took part in the study. Questionnaire was developed to evaluate the frequencies at which QC tests were conducted in the facilities and the challenges in setting up QC. Results show great variation in the values of the QC parameters measured. Inadequate cooperation by facilities management, lack of QC equipment and insufficient staff form the major challenges in setting up QC in the facilities under study. The responses on the frequencies at which QC tests should be conducted did not correspond to the recommended standards; indicating that personnel were not familiar with QC implementation and may require further training on QC.

NAIMA as a solution for future GMO diagnostics challenges.

PubMed

Dobnik, David; Morisset, Dany; Gruden, Kristina

2010-03-01

In the field of genetically modified organism (GMO) diagnostics, real-time PCR has been the method of choice for target detection and quantification in most laboratories. Despite its numerous advantages, however, the lack of a true multiplexing option may render real-time PCR less practical in the face of future GMO detection challenges such as the multiplicity and increasing complexity of new transgenic events, as well as the repeated occurrence of unauthorized GMOs on the market. In this context, we recently reported the development of a novel multiplex quantitative DNA-based target amplification method, named NASBA implemented microarray analysis (NAIMA), which is suitable for sensitive, specific and quantitative detection of GMOs on a microarray. In this article, the performance of NAIMA is compared with that of real-time PCR, the focus being their performances in view of the upcoming challenge to detect/quantify an increasing number of possible GMOs at a sustainable cost and affordable staff effort. Finally, we present our conclusions concerning the applicability of NAIMA for future use in GMO diagnostics.

Diagnostic methods for platelet bacteria screening: current status and developments.

PubMed

Störmer, Melanie; Vollmer, Tanja

2014-02-01

Bacterial contamination of blood components and the prevention of transfusion-associated bacterial infection still remains a major challenge in transfusion medicine. Over the past few decades, a significant reduction in the transmission of viral infections has been achieved due to the introduction of mandatory virus screening. Platelet concentrates (PCs) represent one of the highest risks for bacterial infection. This is due to the required storage conditions for PCs in gas-permeable containers at room temperature with constant agitation, which support bacterial proliferation from low contamination levels to high titers. In contrast to virus screening, since 1997 in Germany bacterial testing of PCs is only performed as a routine quality control or, since 2008, to prolong the shelf life to 5 days. In general, bacterial screening of PCs by cultivation methods is implemented by the various blood services. Although these culturing systems will remain the gold standard, the significance of rapid methods for screening for bacterial contamination has increased over the last few years. These new methods provide powerful tools for increasing the bacterial safety of blood components. This article summarizes the course of policies and provisions introduced to increase bacterial safety of blood components in Germany. Furthermore, we give an overview of the different diagnostic methods for bacterial screening of PCs and their current applicability in routine screening processes.

Mixed states in bipolar disorder - changes in DSM-5 and current treatment recommendations.

PubMed

Betzler, Felix; Stöver, Laura Apollonia; Sterzer, Philipp; Köhler, Stephan

2017-11-01

Mixed states in affective disorders represent a particular challenge in clinical routine, characterized by a complicated course of treatment and a worse treatment response. Clinical features of mixed states and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria are presented and critical discussed. We then performed a systematic review using the terms 'bipolar', 'mixed' and 'randomized' to evaluate current treatment options. For pharmacological treatment of mixed states in total, there is still insufficient data from RCTs. However, there is some evidence for efficacy in mixed states from RCTs for atypical antipsychotics, especially olanzapine, aripiprazole and asenapine as well as mood stabilizers as valproate and carbamazepine. Mixed states are of a high clinical relevance and the DSM-5 criteria substantially reduced the diagnostic threshold. Besides advantages of a better characterization of patients with former DSM-IV-defined mixed episodes, disadvantages arise for example differential diagnoses with a substantial overlap in symptoms such as borderline personality disorders. Atypical antipsychotics, valproate and carbamazepine demonstrated efficacy in a limited sample of RCTs. The number of RCTs in the treatment of mixed states is highly limited. Furthermore, nearly all studies were funded by pharmaceutical companies which may lead to an underestimation of classical mood stabilizers such as lithium.

Clinical application of high throughput molecular screening techniques for pharmacogenomics

PubMed Central

Wiita, Arun P; Schrijver, Iris

2011-01-01

Genetic analysis is one of the fastest-growing areas of clinical diagnostics. Fortunately, as our knowledge of clinically relevant genetic variants rapidly expands, so does our ability to detect these variants in patient samples. Increasing demand for genetic information may necessitate the use of high throughput diagnostic methods as part of clinically validated testing. Here we provide a general overview of our current and near-future abilities to perform large-scale genetic testing in the clinical laboratory. First we review in detail molecular methods used for high throughput mutation detection, including techniques able to monitor thousands of genetic variants for a single patient or to genotype a single genetic variant for thousands of patients simultaneously. These methods are analyzed in the context of pharmacogenomic testing in the clinical laboratories, with a focus on tests that are currently validated as well as those that hold strong promise for widespread clinical application in the near future. We further discuss the unique economic and clinical challenges posed by pharmacogenomic markers. Our ability to detect genetic variants frequently outstrips our ability to accurately interpret them in a clinical context, carrying implications both for test development and introduction into patient management algorithms. These complexities must be taken into account prior to the introduction of any pharmacogenomic biomarker into routine clinical testing. PMID:23226057

Diagnostic performance of automated liquid culture and molecular line probe assay in smear-negative pulmonary tuberculosis.

PubMed

Kotwal, Aarti; Biswas, Debasis; Raghuvanshi, Shailendra; Sindhwani, Girish; Kakati, Barnali; Sharma, Shweta

2017-04-01

The diagnosis of smear-negative pulmonary tuberculosis (PTB) is particularly challenging, and automated liquid culture and molecular line probe assays (LPA) may prove particularly useful. The objective of our study was to evaluate the diagnostic potential of automated liquid culture (ALC) technology and commercial LPA in sputum smear-negative PTB suspects. Spot sputum samples were collected from 145 chest-symptomatic smear-negative patients and subjected to ALC, direct drug susceptibility test (DST) testing and LPA, as per manufacturers' instructions. A diagnostic yield of 26.2% was observed among sputum smear-negative TB suspects with 47.4% of the culture isolates being either INH- and/or rifampicin-resistant. Complete agreement was observed between the results of ALC assay and LPA except for two isolates which demonstrated sensitivity to INH and rifampicin at direct DST but were rifampicin-resistant in LPA. Two novel mutations were also detected among the multidrug isolates by LPA. In view of the diagnostic challenges associated with the diagnosis of TB in sputum smear-negative patients, our study demonstrates the applicability of ALC and LPA in establishing diagnostic evidence of TB.

The pursuit of better diagnostic performance: a human factors perspective.

PubMed

Henriksen, Kerm; Brady, Jeff

2013-10-01

Despite the relatively slow start in treating diagnostic error as an amenable research topic at the beginning of the patient safety movement, interest has steadily increased over the past few years in the form of solicitations for research, regularly scheduled conferences, an expanding literature and even a new professional society. Yet improving diagnostic performance increasingly is recognised as a multifaceted challenge. With the aid of a human factors perspective, this paper addresses a few of these challenges, including questions that focus on who owns the problem, treating cognitive and system shortcomings as separate issues, why knowledge in the head is not enough, and what we are learning from health information technology (IT) and the use of checklists. To encourage empirical testing of interventions that aim to improve diagnostic performance, a systems engineering approach making use of rapid-cycle prototyping and simulation is proposed. To gain a fuller understanding of the complexity of the sociotechnical space where diagnostic work is performed, a final note calls for the formation of substantive partnerships with those in disciplines beyond the clinical domain.

Hiro and Evans currents in Vertical Disruption Event

NASA Astrophysics Data System (ADS)

Zakharov, Leonid; Xujing Li Team; Sergei Galkin Team

2014-10-01

The notion of Tokamak Magneto-Hydrodynamics (TMHD), which explicitly reflects the anisotropy of a high temperature tokamak plasma is introduced. The set of TMHD equations is formulated for simulations of macroscopic plasma dynamics and disruptions in tokamaks. Free from the Courant restriction on the time step, this set of equations is appropriate for high performance plasmas and does not require any extension of the MHD plasma model. At the same time, TMHD requires the use of magnetic field aligned numerical grids. The TMHD model was used for creation of theory of the Wall Touching Kink and Vertical Modes (WTKM and WTVM), prediction of Hiro and Evans currents, design of an innovative diagnostics for Hiro current measurements, installed on EAST device. While Hiro currents have explained the toroidal asymmetry in the plasma current measurements in JET disruptions, the Evans currents explain the tile current measurements in tokamaks. The recently developed Vertical Disruption Code (VDE) have demonstrated 5 regimes of VDE and confirmed the generation of both Hiro and Evans currents. The results challenge the 24 years long misinterpretation of the tile currents in tokamaks as ``halo'' currents, which were a product of misuse of equilibrium reconstruction for VDE. This work is supported by US DoE Contract No. DE-AC02-09-CH1146.

The present and the future in the diagnosis and management of celiac disease

PubMed Central

Castillo, Natalia E.; Theethira, Thimmaiah G.; Leffler, Daniel A.

2015-01-01

Celiac disease is an autoimmune enteropathy caused by gluten in genetically predisposed individuals. In celiac disease, adaptive and innate immune activation results in intestinal damage and a wide range of clinical manifestations. In the past, celiac disease was thought to result in signs and symptoms solely related to the gastrointestinal tract. Now, more than half of the adult population presents with extra-intestinal manifestations that can also be expected to improve on a gluten-free diet. For this reason, it is recommended that physicians have a low threshold of suspicion for celiac disease. Current knowledge of the immune pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools and therapeutics. Over the years, highly sensitive and specific serological assays, in addition to genetic markers, have been found to target specific steps in the cascade pathway of celiac disease. Also the advent of the gluten challenge has enabled experts to design diagnostic algorithms and monitor clinical responses in clinical trials. The gluten challenge has provided substantial benefit in the advance of novel therapeutics as an adjuvant treatment to the gluten free diet. Generally, a strict gluten-free diet is highly burdensome to patients and can be limited in its efficacy. Alternative therapies—including gluten modification, modulation of intestinal permeability and immune response—could be central to the future treatment of celiac disease. PMID:25326000

The Challenges of Prevention, Diagnosis and Treatment of Ischemic Heart Disease in Women

PubMed Central

Brewer, LaPrincess C.; Svatikova, Anna

2017-01-01

Increasing evidence suggests that there are significant differences in the presentation, diagnosis and treatment of ischemic heart disease in women compared to men. Women often present with atypical symptoms, and this, in association with a consistent underestimation of their risk for ischemic heart disease, leads to underdiagnosis and undertreatment in women. Cardiovascular risk factors unique to women have only recently been recognized, and moreover, traditional risk factors have recently been shown to have greater impacts on women. Consequently, women suffer more disability and poorer clinical outcomes, with higher cardiovascular morbidity and mortality. These discrepancies may in part be secondary to the higher prevalence of nonobstructive coronary artery disease in women with persistent chest pain symptoms as compared to men when evaluated invasively. Focused diagnostic and therapeutic strategies unique to women are thus needed, but unfortunately, such sex-specific guidelines do not yet exist, largely due to lack of awareness, both on the part of providers and patients, as well as a paucity of evidence-based research specific to women. Although underutilized in women, diagnostic modalities, including functional and anatomic cardiac tests as well as physiologic assessments of endothelial and microvascular function, are useful for establishing the diagnosis and prognosis of suspected ischemic heart disease in women. This review discusses the current challenges of prevention, diagnosis and treatment of ischemic heart disease in women. PMID:26210899

International Issues: Teleneurology in humanitarian crises: Lessons from the Médecins Sans Frontières experience.

PubMed

Saadi, Altaf; Mateen, Farrah J

2017-07-18

Humanitarian emergencies defined by armed conflict, political strife, famine, or natural disaster can devastate populations rapidly. Neurologic disorders accompany these complex humanitarian emergencies but often go unheeded, exacerbated by a scarcity of neurologists. Teleneurology offers the promise of neurologic care remotely in the face of this inadequate local clinician supply. We describe our experiences as voluntary neurology teleconsultants with Médecins Sans Frontières in order to highlight both the promises and challenges of teleneurology in humanitarian contexts. We identified the major advantages of this service as (1) minimal resources and incurred costs while (2) changing a patient's clinical course favorably, and (3) creating a community for the field referrer and neurology specialist. Current challenges include (1) limited diagnostic resources and difficult diagnostic and therapeutic decision-making, (2) need for greater continuity and familiarity between the field site and neurologist, (3) gaps in the US neurology curriculum to provide expertise for all sites, (4) lack of follow-up and feedback from the field to advise future cases, and (5) low frequency of consultations. Growth opportunities include eventual expansion to the development of a community of neurologists who can provide context-specific care and maximize use of multimedia at low Internet bandwidth. Lessons from our experience may help optimize teleneurology's effect and reduce disparities in neurologic care, particularly in humanitarian crises. © 2017 American Academy of Neurology.

MERALGIA PARESTHETICA: A REVIEW OF THE LITERATURE

PubMed Central

Kolber, Morey J.; Salamh, Paul A.

2013-01-01

Background and Purpose: Meralgia Paresthetica (MP) is a nerve entrapment which may cause pain, paresthesias, and sensory loss within the distribution of the lateral cutaneous nerve of the thigh. When the differential diagnosis of lateral or anterolateral thigh pain is inconclusive, MP should be considered as a potential source. MP produces similar signs and symptoms as those associated with more common diagnoses such as lumbar spine pathology. This clinical commentary will review the most relevant literature on MP with an emphasis on recognition and management of this condition. Description of Topic with Related Evidence: The authors reviewed the most relevant published literature on MP from 1970 to 2013 located using the databases PubMed, CINAHL, and Proquest. Discussion/Relation to Clinical Practice: MP still remains a diagnostic challenge since it can mimic other common diagnoses. Understanding the current literature surrounding the diagnosis and treatment of MP is essential for clinicians practicing in the outpatient environment. The consensus on the most effective non‐surgical and surgical interventions is still limited, as is the research on physical therapy interventions for this condition. Perhaps the lack of research and global consensus represents a knowledge deficit that makes MP a challenge to diagnose and successfully treat. Future collaborative studies are needed to improve the clinical diagnostics and understanding of interventions for this pathology. Level of Evidence: 5 PMID:24377074

Diagnosis and management of testosterone deficiency.

PubMed

McBride, James A; Carson, Culley C; Coward, Robert M

2015-01-01

Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD.

Diagnosis and management of testosterone deficiency

PubMed Central

McBride, James A; Carson, Culley C; Coward, Robert M

2015-01-01

Testosterone supplementation therapy (TST) use has dramatically increased over the past decade, due to the availability of newer agents, aggressive marketing, and an increasing incidence of testosterone deficiency (TD). Despite the increase in TST, a degree of ambiguity remains as to the exact diagnostic criteria of TD, and administration and monitoring of TST. One explanation for this phenomenon is the complex role testosterone plays in multiple physiologic pathways. Numerous medical co-morbidities and medications can alter testosterone levels resulting in a wide range of nonspecific clinical signs and symptoms of TD. The diagnosis is also challenging due to the lack of a definitive serum total testosterone level that reliably correlates with symptoms. This observation is particularly true in the aging male and is exacerbated by inconsistencies between different laboratory assays. Several prominent medical societies have developed guideline statements to clarify the diagnosis, but they differ from each other and with expert opinion in several ways. Aside from diagnostic dilemmas, there are numerous subtle advantages and disadvantages of the various testosterone agents to appreciate. The available TST agents have changed significantly over the past decade similar to the trends in the diagnosis of TD. Therefore, as the usage of TST increases, clinicians will be challenged to maintain an up-to-date understanding of TD and TST. The purpose of this review is to provide a clear description of the current strategies for diagnosis and management of TD. PMID:25532575

[Current macro-diagnostic trends of forensic medicine in the Czech Republic].

PubMed

Frišhons, Jan; Kučerová, Štěpánka; Jurda, Mikoláš; Sokol, Miloš; Vojtíšek, Tomáš; Hejna, Petr

2017-01-01

Over the last few years, advanced diagnostic methods have penetrated in the realm of forensic medicine in addition to standard autopsy techniques supported by traditional X-ray examination and macro-diagnostic laboratory tests. Despite the progress of imaging methods, the conventional autopsy has remained basic and essential diagnostic tool in forensic medicine. Postmortem computed tomography and magnetic resonance imaging are far the most progressive modern radio diagnostic methods setting the current trend of virtual autopsies all over the world. Up to now, only two institutes of forensic medicine have available postmortem computed tomography for routine diagnostic purposes in the Czech Republic. Postmortem magnetic resonance is currently unattainable for routine diagnostic use and was employed only for experimental purposes. Photogrammetry is digital method focused primarily on body surface imaging. Recently, the most fruitful results have been yielded from the interdisciplinary cooperation between forensic medicine and forensic anthropology with the implementation of body scanning techniques and 3D printing. Non-invasive and mini-invasive investigative methods such as postmortem sonography and postmortem endoscopy was unsystematically tested for diagnostic performance with good outcomes despite of limitations of these methods in postmortem application. Other futuristic methods, such as the use of a drone to inspect the crime scene are still experimental tools. The authors of the article present a basic overview of the both routinely and experimentally used investigative methods and current macro-diagnostic trends of the forensic medicine in the Czech Republic.

Preoperative Molecular Markers in Thyroid Nodules.

PubMed

Sahli, Zeyad T; Smith, Philip W; Umbricht, Christopher B; Zeiger, Martha A

2018-01-01

The need for distinguishing benign from malignant thyroid nodules has led to the pursuit of differentiating molecular markers. The most common molecular tests in clinical use are Afirma ® Gene Expression Classifier (GEC) and Thyroseq ® V2. Despite the rapidly developing field of molecular markers, several limitations exist. These challenges include the recent introduction of the histopathological diagnosis "Non-Invasive Follicular Thyroid neoplasm with Papillary-like nuclear features", the correlation of genetic mutations within both benign and malignant pathologic diagnoses, the lack of follow-up of molecular marker negative nodules, and the cost-effectiveness of molecular markers. In this manuscript, we review the current published literature surrounding the diagnostic value of Afirma ® GEC and Thyroseq ® V2. Among Afirma ® GEC studies, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) ranged from 75 to 100%, 5 to 53%, 13 to 100%, and 20 to 100%, respectively. Among Thyroseq ® V2 studies, Se, Sp, PPV, and NPV ranged from 40 to 100%, 56 to 93%, 13 to 90%, and 48 to 97%, respectively. We also discuss current challenges to Afirma ® GEC and Thyroseq ® V2 utility and clinical application, and preview the future directions of these rapidly developing technologies.

Transforming Pain Medicine: Adapting to Science and Society

PubMed Central

Borsook, David; Kalso, Eija

2013-01-01

The field of chronic pain medicine is currently facing enormous challenges. The incidence of chronic pain is increasing worldwide, particularly in the developed world. As a result, chronic pain is imposing a growing burden on Western societies in terms of cost of medical care and lost productivity. This burden is exacerbated by the fact that despite research efforts and a huge expenditure on treatment for chronic pain, clinicians have no highly effective treatments or definitive diagnostic measures for patients. The lack of an objective measure for pain impedes basic research into the biological and psychological mechanisms of chronic pain and clinical research into treatment efficacy. The development of objective measurements of pain and ability to predict treatment responses in the individual patient is critical to improving pain management. Finally, pain medicine must embrace the development of a new evidence-based therapeutic model that recognizes the highly individual nature of responsiveness to pain treatments, integrates bio-psycho-behavioral approaches, and requires proof of clinical effectiveness for the various treatments we offer our patients. In the long-term these approaches will contribute to providing better diagnoses and more effective treatments to lessen the current challenges in pain medicine. PMID:23468059

Assessment of anorexia nervosa: an overview of universal issues and contextual challenges

PubMed Central

2013-01-01

Aim Anorexia Nervosa (AN) is a complex and clinically challenging syndrome. Intended for specialist audiences, this narrative review aims to summarise the available literature related to assessment in the adult patient context, synthesising both research evidence and clinical consensus guidelines. Method We provide a review of the available literature on specialist assessment of AN focusing on common trajectories into assessment, obstacles accessing assessment, common presenting issues and barriers to the assessment process, the necessary scope of assessment, and tools and techniques. It describes the further step of synthesising assessment information in ways that can inform resultant care plans. Results In addition to assessment of core behaviours and diagnostic skills, considerations for the expert assessor include the functions of primary care, systemic and personal barriers, knowledge of current assessment tools and research pertaining to comorbid pathology in AN, assessing severity of illness, role of family at assessment, as well as medical, nutritional and compulsory elements of assessment. Conclusion Comprehensive assessment of AN in the current healthcare context still remains largely the remit of the specialist ED clinician. Assessment should remain an on-going process, paying particular attention to available empirical evidence, thereby reducing the gap between research and practice. PMID:24999408

Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer's disease.

PubMed

Janel, N; Alexopoulos, P; Badel, A; Lamari, F; Camproux, A C; Lagarde, J; Simon, S; Feraudet-Tarisse, C; Lamourette, P; Arbones, M; Paul, J L; Dubois, B; Potier, M C; Sarazin, M; Delabar, J M

2017-06-20

Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.

When Less Is More: How Fewer Diagnostic Criteria Can Indicate Greater Severity

ERIC Educational Resources Information Center

Cooper, Luke D.; Balsis, Steve

2009-01-01

For diagnosing many mental disorders, the current "Diagnostic and Statistical Manual of Mental Disorders" ("DSM") system weights each diagnostic criterion equally--each criterion counts the same toward meeting the diagnostic threshold. Research on the diagnostic efficiency of criteria, however, reveals that some diagnostic criteria are more useful…

Quantitative Value of Aldosterone-Renin Ratio for Detection of Aldosterone-Producing Adenoma: The Aldosterone-Renin Ratio for Primary Aldosteronism (AQUARR) Study.

PubMed

Maiolino, Giuseppe; Rossitto, Giacomo; Bisogni, Valeria; Cesari, Maurizio; Seccia, Teresa Maria; Plebani, Mario; Rossi, Gian Paolo

2017-05-21

Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false-positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone-producing adenoma as reference index. We also assessed whether the post-captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false-positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post-captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between-area under the curve difference, 0.005; 95% CI, -0.031 to 0.040; P =0.7 for comparison, and 0.05; 95% CI, -0.061 to 0.064; P =0.051 for comparison, respectively). These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Diagnostic overshadowing and other challenges involved in the diagnostic process of patients with mental illness who present in emergency departments with physical symptoms--a qualitative study.

PubMed

Shefer, Guy; Henderson, Claire; Howard, Louise M; Murray, Joanna; Thornicroft, Graham

2014-01-01

We conducted a qualitative study in the Emergency Departments (EDs) of four hospitals in order to investigate the perceived scope and causes of 'diagnostic overshadowing'--the misattribution of physical symptoms to mental illness--and other challenges involved in the diagnostic process of people with mental illness who present in EDs with physical symptoms. Eighteen doctors and twenty-one nurses working in EDs and psychiatric liaisons teams in four general hospitals in the UK were interviewed. Interviewees were asked about cases in which mental illness interfered with diagnosis of physical problems and about other aspects of the diagnostic process. Interviews were transcribed and analysed thematically. Interviewees reported various scenarios in which mental illness or factors related to it led to misdiagnosis or delayed treatment with various degrees of seriousness. Direct factors which may lead to misattribution in this regard are complex presentations or aspects related to poor communication or challenging behaviour of the patient. Background factors are the crowded nature of the ED environment, time pressures and targets and stigmatising attitudes held by a minority of staff. The existence of psychiatric liaison team covering the ED twenty-four hours a day, seven days a week, can help reduce the risk of misdiagnosis of people with mental illness who present with physical symptoms. However, procedures used by emergency and psychiatric liaison staff require fuller operationalization to reduce disagreement over where responsibilities lie.

Tularemia without lesions in grey tree squirrels: A diagnostic challenge

USDA-ARS?s Scientific Manuscript database

Fifteen cases of Francisella tularenesis infection (tularemia) were identified in western grey (Sciurus griseus) and eastern grey (Sciurus carolinesis) squirrels submitted to the Washington Animal Disease Diagnostic Laboratory between 2008 and 2011. All of the squirrels originated in Washington stat...

Current Realities of Delivering Mammography Services in the Community: Do Challenges with Staffing and Scheduling Exist?

PubMed Central

D'Orsi, Carl; Tu, Shin-Ping; Nakano, Connie; Carney, Patricia A.; Abraham, Linn A.; Taplin, Stephen H.; Hendrick, R. Edward; Cutter, Gary R.; Berns, Eric; Barlow, William E.; Elmore, Joann G.

2011-01-01

PURPOSE To evaluate the current (2001–2002) capacity of community-based mammography facilities to deliver screening and diagnostic services in the United States. MATERIALS AND METHODS Institutional review board approvals and patient consent were obtained. A mailed survey was sent to 53 eligible mammography facilities in three states (Washington, New Hampshire, and Colorado). Survey questions assessed equipment and staffing availability, as well as appointment waiting times for screening and diagnostic mammography services. Criterion-related content and construct validity were obtained first by means of a national advisory committee of academic, scientific, and clinical colleagues in mammography that reviewed literature on existing surveys and second by pilot testing a series of draft surveys among community mammography facilities not inclusive of the study facilities. The final survey results were independently double entered into a relational database with programmed data checks. The data were sent encrypted by means of file transfer protocol to a central analytical center at Group Health Cooperative. A two-sided P value with α = .05 was considered to show statistical significance in all analyses. RESULTS Forty-five of 53 eligible mammography facilities (85%) returned the survey. Shortages of radiologists relative to the mammographic volume were found in 44% of mammography facilities overall, with shortages of radiologists higher in not-for-profit versus for-profit facilities (60% vs 28% reported). Shortages of Mammography Quality Standards Act–qualified technologists were reported by 20% of facilities, with 46% reporting some level of difficulty in maintaining qualified technologists. Waiting times for diagnostic mammography ranged from less than 1 week to 4 weeks, with 85% performed within 1 week. Waiting times for screening mammography ranged from less than 1 week to 8 weeks, with 59% performed between 1 week and 4 weeks. Waiting times for both diagnostic and screening services were two to three times higher in high-volume compared with low-volume facilities. CONCLUSION Survey results show shortages of radiologists and certified mammography technologists. PMID:15798153

Recommendations for provoked challenge urine testing.

PubMed

Ruha, Anne-Michelle

2013-12-01

"Urine mobilization test," "challenge test," and "provoked urine test" are all terms used to describe the administration of a chelating agent to a person prior to collection of their urine to test for metals. There is no standard, validated challenge test. Despite recommendations by professional and government organizations against the use of provoked urine testing, the tests are still commonly used and recommended by some practitioners. Challenge testing utilizes a variety of chelating agents, including dimercaptosuccinic acid (DMSA), dimercaptopropanesulfonate (DMPS), and ethylenediaminetetraacetic acid (EDTA). The agents are given by a variety of routes of administration, doses used are inconsistent, and urine collection procedures vary. Additional problems with challenge tests include comparison of results to inappropriate reference ranges and creatinine correction of urine obtained within hours of chelator administration. Human volunteer studies demonstrate that mercury is detected in the urine of most people even in the absence of known exposure or chelator administration, and that urinary mercury excretion rises after administration of a chelator, regardless of exposure history and in an unpredictable fashion. Studies also demonstrate that challenge testing fails to reveal a "body burden" of mercury due to remote exposure. Chelating agents have been associated with adverse reactions. Current evidence does not support the use of DMPS, DMSA, or other chelation challenge tests for the diagnosis of metal toxicity. Since there are no established reference ranges for provoked urine samples in healthy subjects, no reliable evidence to support a diagnostic value for the tests, and potential harm, these tests should not be utilized.

Measurements of high-current electron beams from X pinches and wire array Z pinches.

PubMed

Shelkovenko, T A; Pikuz, S A; Blesener, I C; McBride, R D; Bell, K S; Hammer, D A; Agafonov, A V; Romanova, V M; Mingaleev, A R

2008-10-01

Some issues concerning high-current electron beam transport from the X pinch cross point to the diagnostic system and measurements of the beam current by Faraday cups are discussed. Results of computer simulation of electron beam propagation from the pinch to the Faraday cup give limits for the measured current for beams having different energy spreads. The beam is partially neutralized as it propagates from the X pinch to a diagnostic system, but within a Faraday cup diagnostic, space charge effects can be very important. Experimental results show evidence of such effects.

Core-Noise

NASA Technical Reports Server (NTRS)

Hultgren, Lennart S.

2010-01-01

This presentation is a technical progress report and near-term outlook for NASA-internal and NASA-sponsored external work on core (combustor and turbine) noise funded by the Fundamental Aeronautics Program Subsonic Fixed Wing (SFW) Project. Sections of the presentation cover: the SFW system level noise metrics for the 2015, 2020, and 2025 timeframes; the emerging importance of core noise and its relevance to the SFW Reduced-Noise-Aircraft Technical Challenge; the current research activities in the core-noise area, with some additional details given about the development of a high-fidelity combustion-noise prediction capability; the need for a core-noise diagnostic capability to generate benchmark data for validation of both high-fidelity work and improved models, as well as testing of future noise-reduction technologies; relevant existing core-noise tests using real engines and auxiliary power units; and examples of possible scenarios for a future diagnostic facility. The NASA Fundamental Aeronautics Program has the principal objective of overcoming today's national challenges in air transportation. The SFW Reduced-Noise-Aircraft Technical Challenge aims to enable concepts and technologies to dramatically reduce the perceived aircraft noise outside of airport boundaries. This reduction of aircraft noise is critical for enabling the anticipated large increase in future air traffic. Noise generated in the jet engine core, by sources such as the compressor, combustor, and turbine, can be a significant contribution to the overall noise signature at low-power conditions, typical of approach flight. At high engine power during takeoff, jet and fan noise have traditionally dominated over core noise. However, current design trends and expected technological advances in engine-cycle design as well as noise-reduction methods are likely to reduce non-core noise even at engine-power points higher than approach. In addition, future low-emission combustor designs could increase the combustion-noise component. The trend towards high-power-density cores also means that the noise generated in the low-pressure turbine will likely increase. Consequently, the combined result from these emerging changes will be to elevate the overall importance of turbomachinery core noise, which will need to be addressed in order to meet future noise goals.

Systematic Benchmarking of Diagnostic Technologies for an Electrical Power System

NASA Technical Reports Server (NTRS)

Kurtoglu, Tolga; Jensen, David; Poll, Scott

2009-01-01

Automated health management is a critical functionality for complex aerospace systems. A wide variety of diagnostic algorithms have been developed to address this technical challenge. Unfortunately, the lack of support to perform large-scale V&V (verification and validation) of diagnostic technologies continues to create barriers to effective development and deployment of such algorithms for aerospace vehicles. In this paper, we describe a formal framework developed for benchmarking of diagnostic technologies. The diagnosed system is the Advanced Diagnostics and Prognostics Testbed (ADAPT), a real-world electrical power system (EPS), developed and maintained at the NASA Ames Research Center. The benchmarking approach provides a systematic, empirical basis to the testing of diagnostic software and is used to provide performance assessment for different diagnostic algorithms.

Optimising molecular diagnostic capacity for effective control of tuberculosis in high-burden settings.

PubMed

Sabiiti, W; Mtafya, B; Kuchaka, D; Azam, K; Viegas, S; Mdolo, A; Farmer, E C W; Khonga, M; Evangelopoulos, D; Honeyborne, I; Rachow, A; Heinrich, N; Ntinginya, N E; Bhatt, N; Davies, G R; Jani, I V; McHugh, T D; Kibiki, G; Hoelscher, M; Gillespie, S H

2016-08-01

The World Health Organization's 2035 vision is to reduce tuberculosis (TB) associated mortality by 95%. While low-burden, well-equipped industrialised economies can expect to see this goal achieved, it is challenging in the low- and middle-income countries that bear the highest burden of TB. Inadequate diagnosis leads to inappropriate treatment and poor clinical outcomes. The roll-out of the Xpert(®) MTB/RIF assay has demonstrated that molecular diagnostics can produce rapid diagnosis and treatment initiation. Strong molecular services are still limited to regional or national centres. The delay in implementation is due partly to resources, and partly to the suggestion that such techniques are too challenging for widespread implementation. We have successfully implemented a molecular tool for rapid monitoring of patient treatment response to anti-tuberculosis treatment in three high TB burden countries in Africa. We discuss here the challenges facing TB diagnosis and treatment monitoring, and draw from our experience in establishing molecular treatment monitoring platforms to provide practical insights into successful optimisation of molecular diagnostic capacity in resource-constrained, high TB burden settings. We recommend a holistic health system-wide approach for molecular diagnostic capacity development, addressing human resource training, institutional capacity development, streamlined procurement systems, and engagement with the public, policy makers and implementers of TB control programmes.

Global-to-local policy transfer in the introduction of new molecular tuberculosis diagnostics in South Africa.

PubMed

Colvin, C J; Leon, N; Wills, C; van Niekerk, M; Bissell, K; Naidoo, P

2015-11-01

Lack of innovation in diagnostics has contributed to tuberculosis (TB) remaining a global health challenge. It is critical to understand how new diagnostic technologies are translated into policies and how these are implemented. To examine policy transfer for two rapid molecular diagnostic tests, GenoType(®) MDRTBplus and Xpert(®) MTB/RIF, to understand policy development, uptake and implementation in South Africa. A policy transfer analysis framework integrating the key dimensions of policy transfer into one coherent model was used. Two phases of key informant interviews were undertaken with a wide range of stakeholders. Both tests were developed through innovative partnerships and responded to urgent public health needs. GenoType was introduced through a process that was more inclusive than that for Xpert. National policy and planning processes were opaque for both tests. Their implementation, maintenance and expansion suffered from poor communication and coordination, insufficient attention to resource implications, technical challenges and a lack of broader health systems thinking. Our analysis identified the risks and benefits of partnerships for technological innovation, the complex intersections between global and national actors and the impact of health systems on policy transfer, and the risks of rescue- and technology-focused thinking in addressing public health challenges.

Proceedings of the 2015 National Toxicology Program Satellite Symposium.

PubMed

Elmore, Susan A; Farman, Cindy A; Hailey, James R; Kovi, Ramesh C; Malarkey, David E; Morrison, James P; Neel, Jennifer; Pesavento, Patricia A; Porter, Brian F; Szabo, Kathleen A; Teixeira, Leandro B C; Quist, Erin M

2016-06-01

The 2015 Annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri" was held in Minneapolis, Minnesota, at the American College of Veterinary Pathologists/American Society for Veterinary Clinical Pathology/Society of Toxicologic Pathology combined meeting. The goal of this symposium is to present and discuss diagnostic pathology challenges or nomenclature issues. Because of the combined meeting, both laboratory and domestic animal cases were presented. This article presents summaries of the speakers' talks, including challenging diagnostic cases or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included hepatocellular lesions, a proposed harmonized diagnostic approach to rat cardiomyopathy, crop milk in a bird, avian feeding accoutrement, heat exchanger in a tuna, metastasis of a tobacco carcinogen-induced pulmonary carcinoma, neurocytoma in a rat, pituicytoma in a rat, rodent mammary gland whole mounts, dog and rat alveolar macrophage ultrastructure, dog and rat pulmonary phospholipidosis, alveolar macrophage aggregation in a dog, degenerating yeast in a cat liver aspirate, myeloid leukemia in lymph node aspirates from a dog, Trypanosoma cruzi in a dog, solanum toxicity in a cow, bovine astrovirus, malignant microglial tumor, and nomenclature challenges from the Special Senses International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Group. © The Author(s) 2016.

An international comparative family medicine study of the Transition Project data from the Netherlands, Malta and Serbia. Is family medicine an international discipline? Comparing diagnostic odds ratios across populations.

PubMed

Soler, Jean K; Okkes, Inge; Oskam, Sibo; van Boven, Kees; Zivotic, Predrag; Jevtic, Milan; Dobbs, Frank; Lamberts, Henk

2012-06-01

This is an international study of the epidemiology of family medicine (FM) in three practice populations from the Netherlands, Malta and Serbia. Diagnostic associations between common reasons for encounter (RfEs) and episodes titles are compared and similarities and differences are described and analysed. Participating family doctors (FDs) recorded details of all their patient contacts in an 'episode of care (EoC)' structure using the International Classification of Primary Care (ICPC). RfEs presented by the patient and episode titles (diagnostic labels of EoCs) were classified with ICPC. The relationships between RfEs and episode titles were studied with Bayesian methods. Distributions of diagnostic odds ratios (ORs) from the three population databases are presented and compared. ICPC, the RfE and the EoC data model are appropriate tools to study the process of diagnosis in FM. Distributions of diagnostic associations between RfEs and episode titles in the Transition Project international populations show remarkable similarities and congruencies in the process of diagnosis from both the RfE and the episode title perspectives. The congruence of diagnostic associations between populations supports the use of such data from one population to inform diagnostic decisions in another. Differences in the magnitude of such diagnostic associations are significant, and population-specific data are therefore desirable. We propose that both an international (common) and a local (health care system specific) content of FM exist and that the empirical distributions of diagnostic associations presented in this paper are a reflection of both these effects. We also observed that the frequency of exposure to such diagnostic challenges had a strong effect on the confidence intervals of diagnostic ORs reflecting these diagnostic associations. We propose that this constitutes evidence that expertise in FM is associated with frequency of exposure to diagnostic challenges.

Diagnostic microbiology in veterinary dermatology: present and future.

PubMed

Guardabassi, Luca; Damborg, Peter; Stamm, Ivonne; Kopp, Peter A; Broens, Els M; Toutain, Pierre-Louis

2017-02-01

The microbiology laboratory can be perceived as a service provider rather than an integral part of the healthcare team. The aim of this review is to discuss the current challenges of providing a state-of-the-art diagnostic veterinary microbiology service including the identification (ID) and antimicrobial susceptibility testing (AST) of key pathogens in veterinary dermatology. The Study Group for Veterinary Microbiology (ESGVM) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) identified scientific, technological, educational and regulatory issues impacting the predictive value of AST and the quality of the service offered by microbiology laboratories. The advent of mass spectrometry has significantly reduced the time required for ID of key pathogens such as Staphylococcus pseudintermedius. However, the turnaround time for validated AST methods has remained unchanged for many years. Beyond scientific and technological constraints, AST methods are not harmonized and clinical breakpoints for some antimicrobial drugs are either missing or inadequate. Small laboratories, including in-clinic laboratories, are usually not adequately equipped to run up-to-date clinical microbiologic diagnostic tests. ESGVM recommends the use of laboratories employing mass spectrometry for ID and broth micro-dilution for AST, and offering assistance by expert microbiologists on pre- and post-analytical issues. Setting general standards for veterinary clinical microbiology, promoting antimicrobial stewardship, and the development of new, validated and rapid diagnostic methods, especially for AST, are among the missions of ESGVM. © 2017 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and ACVD.

A diagnostic nomogram for delayed hemolytic transfusion reaction in sickle cell disease.

PubMed

Mekontso Dessap, Armand; Pirenne, France; Razazi, Keyvan; Moutereau, Stéphane; Abid, Shariq; Brun-Buisson, Christian; Maitre, Bernard; Michel, Marc; Galacteros, Frederic; Bartolucci, Pablo; Habibi, Anoosha

2016-12-01

Diagnosis of delayed hemolytic transfusion reactions (DHTR), one of the most dreaded complications of transfusion in patients with sickle cell disease (SCD), is challenging and not straightforward. Current diagnostic approaches are complex and not consensual; they are based on assessment of hemoglobin (Hb) drop and enhanced hemolysis, features also seen during classical vaso-occlusive events. In this observational study, we tested the hypothesis that the rate of decline in HbA after an index transfusion is a surrogate marker for the destruction of transfused RBC, which could be used diagnostically. We examined 421 transfusion episodes (in 128 patients of a French referral center for SCD) for which an Hb electrophoresis was obtained within 1 week following an index transfusion and repeated within 2 months (before a subsequent scheduled transfusion or during an acute complication). Chart review found DHTR to be present in 26 cases (6.2%), absent in 389 cases (92.4%), and possible in six cases (1.4%). As expected, DHTR was associated with accelerated hemolysis (increased serum bilirubin and lactic dehydrogenase concentrations) and a decline in total Hb as compared to the early post-transfusion value. However, the decline in HbA concentration appeared more effective in segregating between patients without DHTR and others. We propose a diagnostic nomogram for DHTR based on Hb A as a biologic marker of the survival of transfused RBCs. Am. J. Hematol. 91:1181-1184, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A Vision for Better Health: Mass Spectrometry Imaging for Clinical Diagnostics

PubMed Central

Ye, Hui; Gemperline, Erin; Li, Lingjun

2012-01-01

Background Mass spectrometry imaging (MSI) is a powerful tool that grants the ability to investigate a broad mass range of molecules from small molecules to large proteins by creating detailed distribution maps of selected compounds. Its usefulness in biomarker discovery towards clinical applications has obtained success by correlating the molecular expression of tissues acquired from MSI with well-established histology. Results To date, MSI has demonstrated its versatility in clinical applications, such as biomarker diagnostics of different diseases, prognostics of disease severities and metabolic response to drug treatment, etc. These studies have provided significant insight in clinical studies over the years and current technical advances are further facilitating the improvement of this field. Although the underlying concept is simple, factors such as choice of ionization method, sample preparation, instrumentation and data analysis must be taken into account for successful applications of MSI. Herein, we briefly reviewed these key elements yet focused on the clinical applications of MSI that cannot be addressed by other means. Conclusions Challenges and future perspectives in this field are also discussed to conclude that the ever-growing applications with continuous development of this powerful analytical tool will lead to a better understanding of the biology of diseases and improvements in clinical diagnostics. PMID:23078851

Early Detection of Lung Cancer Using Nano-Nose - A Review

PubMed Central

Fernandes, M. P.; Venkatesh, S; Sudarshan, B. G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer. PMID:26628933

Pulmonary infections in critical/intensive care - rapid diagnosis and optimizing antimicrobial usage.

PubMed

Douglas, Ivor S

2017-05-01

Diagnosis of pulmonary infection, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in the critically ill patient remains a common and therapeutically challenging diagnosis with significant attributable morbidity, mortality, and cost. Current clinical approaches to surveillance, early detection and, conventional culture-based microbiology are inadequate for optimal targeted antibiotic treatment and stewardship. Efforts to enhance diagnosis of HAP and VAP and the impact of these novel approaches on rational antimicrobial selection and stewardship are the focus of recent studies reviewed here. Recent consensus guidelines for diagnosis and management of HAP and VAP are relatively silent on the potential role of novel rapid microbiological techniques and reply heavily on conventional culture strategies of noninvasively obtained (including endotracheal aspirate samples). Novel rapid microbiological diagnostics, including nucleic acid amplification, mass spectrometry, and fluorescence microscopy-based technologies are promising approaches for the future. Exhaled breath biomarkers, including measurement of VOC represent a future approach. Further validation of novel diagnostic technology platforms will be required to evaluate their utility for enhancing diagnosis and guiding treatment of pulmonary infections in the critically ill. However, the integration of novel diagnostics for rapid microbial identification, resistance phenotyping, and antibiotic sensitivity testing into usual care practice could significantly transform the care of patients and potentially inform improved targeted antimicrobial selection, de-escalation, and stewardship.

First step toward translation of thermophotonic lock-in imaging to dentistry as an early caries detection technology

NASA Astrophysics Data System (ADS)

Ojaghi, Ashkan; Parkhimchyk, Artur; Tabatabaei, Nima

2016-09-01

Early detection of the most prevalent oral disease worldwide, i.e., dental caries, still remains as one of the major challenges in dentistry. The current dental standard of care relies on caries detection methods, such as visual inspection and x-ray radiography, which lack the sufficient specificity and sensitivity to detect caries at early stages of formation when they can be healed. We report on the feasibility of early caries detection in a clinically and commercially viable thermophotonic imaging system. The system incorporates intensity-modulated laser light along with a low-cost long-wavelength infrared (LWIR; 8 to 14 μm) camera, providing diagnostic contrast based on the enhanced light absorption of early caries. The LWIR camera is highly suitable for integration into clinical platforms because of its low weight and cost. In addition, through theoretical modeling, we show that LWIR detection enhances the diagnostic contrast due to the minimal LWIR transmittance of enamel and suppression of the masking effect of the direct thermal Planck emission. Diagnostic performance of the system and its detection threshold are experimentally evaluated by monitoring the inception and progression of artificially induced occlusal and smooth surface caries. The results are suggestive of the suitability of the developed LWIR system for detecting early dental caries.

Imaging of thoracic tuberculosis in children: current and future directions.

PubMed

Sodhi, Kushaljit Singh; Bhalla, Ashu S; Mahomed, Nasreen; Laya, Bernard F

2017-09-01

Tuberculosis continues to be an important cause of morbidity and mortality worldwide. It is the leading cause of infection-related deaths worldwide. Children are amongst the high-risk groups for developing tuberculosis and often pose a challenge to the clinicians in making a definitive diagnosis. The newly released global tuberculosis report from World Health Organization reveals a 50% increase in fatality from tuberculosis in children. Significantly, diagnostic and treatment algorithms of tuberculosis for children differ from those of adults. Bacteriologic confirmation of the disease is often difficult in children; hence radiologists have an important role to play in early diagnosis of this disease. Despite advancing technology, the key diagnostic imaging modalities for primary care and emergency services, especially in rural and low-resource areas, are chest radiography and ultrasonography. In this article, we discuss various diagnostic imaging modalities used in diagnosis and treatment of tuberculosis and their indications. We highlight the use of US as point-of-care service along with mediastinal US and rapid MRI protocols, especially in mediastinal lymphadenopathy and thoracic complications. MRI is the ideal modality in high-resource areas when adequate infrastructure is available. Because the prevalence of tuberculosis is highest in lower-resource countries, we also discuss global initiatives in low-resource settings.

Early Detection of Lung Cancer Using Nano-Nose - A Review.

PubMed

Fernandes, M P; Venkatesh, S; Sudarshan, B G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer.

Proceedings of the 2014 National Toxicology Program Satellite Symposium

PubMed Central

Elmore, Susan A.; Cora, Michelle C.; Gruebbel, Margarita M.; Hayes, Schantel A.; Hoane, Jessica S.; Koizumi, Haruko; Peters, Rachel; Rosol, Thomas J.; Singh, Bhanu P.; Szabo, Kathleen A.

2014-01-01

The 2014 annual National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri” was held in Washington DC, in advance of the Society of Toxicologic Pathology’s 33rd annual meeting. The goal of this annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a pulmonary mucinous adenocarcinoma in a male B6C3F1 mouse; plexiform vasculopathy in Wistar Han rats; staging of the estrous cycle in rats and mice; peri-islet fibrosis, hemorrhage, lobular atrophy and inflammation in male Sprague Dawley rats; retinal dysplasia in Wistar Han rats and B6C3F1 mice; multicentric lymphoma with intravascular microemboli and tumor lysis syndrome, and two cases of myopathy and vascular anomaly in Tg.rasH2 mice; benign thymomas in Wistar Han rats; angiomatous lesions in the mesenteric lymph nodes of Wistar Han rats; an unusual foveal lesion in a cynomolgous monkey; and finally a series of nomenclatures challenges from the endocrine International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) organ working group (OWG). PMID:25385331

Role of gastrografin challenge in early postoperative small bowel obstruction.

PubMed

Khasawneh, Mohammad A; Ugarte, Maria L Martinez; Srvantstian, Boris; Dozois, Eric J; Bannon, Michael P; Zielinski, Martin D

2014-02-01

Early small bowel obstruction following abdominal surgery presents a diagnostic and therapeutic challenge. Abdominal imaging using Gastrografin has been shown to have diagnostic and therapeutic properties when used in the setting of small bowel obstruction outside the early postoperative period (>6 weeks). We hypothesize that a GG challenge will reduce need for re-exploration. Patients with early small bowel obstruction who underwent a Gastrografin challenge between 2010 and 2012 were case controlled, based on age ±5 years, sex, and operative approach to an equal number of patients that did not receive the challenge. One hundred sixteen patients received a Gastrografin challenge. There were 87 males in each group with an average age of 62 years. A laparoscopic approach in the index operation was done equally between groups (18 vs. 18 %). There was no difference between groups in operative re-exploration rates (14 vs. 10 %); however, hospital duration of stay was greater in patients who received Gastrografin challenge (17 vs. 13 days). Two in hospital deaths occurred, one in each group, both of infectious complications. Use of the Gastrografin challenge in the immediate postoperative period appeared to be safe. There was no difference, however, in the rate of re-exploration between groups.

The challenges of oral-based diagnostics in extending the role of dentistry as a health care profession: property rights, privacy, and informed consent.

PubMed

Vernillo, Anthony; Welie, Jos V M; Naidoo, Sudeshni; Malamud, Daniel

2011-01-01

Saliva may be a legal and ethical counterpart of other bodily fluids in diagnostic testing to blood and urine, with regard to its role in diagnostic testing. Two paradigms that have been proposed in the literature to address these challenges are reviewed in this paper. The first is centered on ownership and property rights to saliva, including financial compensation from commercially developed products using saliva. The commodification of saliva as property is also discussed. The second paradigm is related to privacy and the potential for genetic discrimination, given the unwarranted disclosure of confidential information. The management of saliva specimens from dental patients and research participants will also require the implementation of innovative approaches to obtain informed consent.

Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics-Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer.

PubMed

Plönes, Till; Engel-Riedel, Walburga; Stoelben, Erich; Limmroth, Christina; Schildgen, Oliver; Schildgen, Verena

2016-01-15

Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

Strategies in Interventional Radiology: Formation of an Interdisciplinary Center of Vascular Anomalies - Chances and Challenges for Effective and Efficient Patient Management.

PubMed

Sadick, Maliha; Dally, Franz Josef; Schönberg, Stefan O; Stroszczynski, Christian; Wohlgemuth, Walter A

2017-10-01

Background  Radiology is an interdisciplinary field dedicated to the diagnosis and treatment of numerous diseases and is involved in the development of multimodal treatment concepts. Method  Interdisciplinary case management, a broad spectrum of diagnostic imaging facilities and dedicated endovascular radiological treatment options are valuable tools that allow radiology to set up an interdisciplinary center for vascular anomalies. Results  Image-based diagnosis combined with endovascular treatment options is an essential tool for the treatment of patients with highly complex vascular diseases. These vascular anomalies can affect numerous parts of the body so that a multidisciplinary treatment approach is required for optimal patient care. Conclusion  This paper discusses the possibilities and challenges regarding effective and efficient patient management in connection with the formation of an interdisciplinary center for vascular anomalies with strengthening of the clinical role of radiologists. Key points   · Vascular anomalies, which include vascular tumors and malformations, are complex to diagnose and treat.. · There are far more patients with vascular anomalies requiring therapy than interdisciplinary centers for vascular anomalies - there is currently a shortage of dedicated interdisciplinary centers for vascular anomalies in Germany that can provide dedicated care for affected patients.. · Radiology includes a broad spectrum of diagnostic and minimally invasive therapeutic tools which allow the formation of an interdisciplinary center for vascular anomalies for effective, efficient and comprehensive patient management.. Citation Format · Sadick M, Dally FJ, Schönberg SO et al. Strategies in Interventional Radiology: Formation of an Interdisciplinary Center of Vascular Anomalies - Chances and Challenges for Effective and Efficient Patient Management. Fortschr Röntgenstr 2017; 189: 957 - 966. © Georg Thieme Verlag KG Stuttgart · New York.

LAMP detection assays for boxwood blight pathogens: a comparative genomics approach

USDA-ARS?s Scientific Manuscript database

Rapid and accurate molecular diagnostic tools are critical to efforts to minimize the impact and spread of emergent pathogens. The identification of diagnostic markers for novel pathogens presents several challenges, especially in the absence of information about population diversity, and where gen...

DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES II

EPA Science Inventory

Thyroid proliferative lesions are rather common in bony fishes but diagnostic terminology and criteria for these lesions are inconsistent in the literature. The diagnosis of proliferative thyroid lesions is especially challenging in fish due to the fact that the thyroid is not a ...

Current insights into the laboratory diagnosis of HIT.

PubMed

Bakchoul, T; Zöllner, H; Greinacher, A

2014-06-01

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune-mediated disorders, the currently available laboratory tests for anti-PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations. © 2014 John Wiley & Sons Ltd.

Saliva as a Diagnostic Fluid

PubMed Central

Malamud, Daniel; Rodriguez-Chavez, Isaac R.

2010-01-01

Synopsis Salivary diagnostics is a dynamic and emerging field utilizing nanotechnology and molecular diagnostics to aid in the diagnosis of oral and systemic diseases. Here, we critically review the latest advances using oral biomarkers for disease detection. The use of oral fluids is broadening perspectives in clinical diagnosis, disease monitoring and decision making for patient care. Important elements determining the future possibilities and challenges in this field are also discussed. PMID:21094724

Quality of Diagnosis and Treatment Plans After Using the 'Diagnostic Guideline for Anxiety and Challenging Behaviours' in People with Intellectual Disabilities: A Comparative Multiple Case Study Design.

PubMed

Pruijssers, Addy; van Meijel, Berno; Maaskant, Marian; Keeman, Noortje; van Achterberg, Theo

2016-07-01

People with intellectual disabilities often have a multitude of concurrent problems due to the combination of cognitive impairments, psychiatric disorders (particularly anxiety) and related challenging behaviours. Diagnoses in people with intellectual disabilities are complicated. This study evaluates the quality of the diagnoses and treatment plans after using a guideline that was developed to support professionals in their diagnostic tasks. A comparative multiple case study with an experimental and control condition, applying deductive analyses of diagnoses and treatment plans. The analyses revealed that the number of diagnostic statements and planned treatment actions in the experimental group was significantly larger and more differentiated than in the control condition. In the control group, consequential harm and protective factors were hardly mentioned in diagnoses and treatment plans. Working with the 'Diagnostic Guideline for Anxiety and CB' leads to improved diagnoses and treatment plans compared with care as usual. © 2015 John Wiley & Sons Ltd.

Democratizing molecular diagnostics for the developing world.

PubMed

Abou Tayoun, Ahmad N; Burchard, Paul R; Malik, Imran; Scherer, Axel; Tsongalis, Gregory J

2014-01-01

Infectious diseases that are largely treatable continue to pose a tremendous burden on the developing world despite the availability of highly potent drugs. The high mortality and morbidity rates of these diseases are largely due to a lack of affordable diagnostics that are accessible to resource-limited areas and that can deliver high-quality results. In fact, modified molecular diagnostics for infectious diseases were rated as the top biotechnology to improve health in developing countries. In this review, we describe the characteristics of accessible molecular diagnostic tools and discuss the challenges associated with implementing such tools at low infrastructure sites. We highlight our experience as part of the "Grand Challenge" project supported by the Gates Foundation for addressing global health inequities and describe issues and solutions associated with developing adequate technologies or molecular assays needed for broad access in the developing world. We believe that sharing this knowledge will facilitate the development of new molecular technologies that are extremely valuable for improving global health.

Are there financial savings associated with supplementing current diagnostic practice for preeclampsia with a novel test? Learnings from a modeling analysis from a German payer perspective.

PubMed

Hadker, Nandini; Garg, Suchita; Costanzo, Cory; van der Helm, Wim; Creeden, James

2013-05-01

To quantify the financial impact of adding a novel serum test to the current diagnostic toolkit for preeclampsia (PE) detection in Germany. A decision-analytic model was created to quantify the economic impact of adding a recently developed novel diagnostic test for PE (Roche Diagnostics, Rotkreuz, Switzerland) to current diagnostic practice in Germany. The model simulated a cohort of 1000 pregnant patients receiving obstetric care and quantified the budget impact of adding the novel test to current German PE detection and management practices. The model estimates that the costs associated with managing a typical pregnancy in Germany are €941 when the novel test is used versus €1579 with standard practice. This represents savings of €637 per pregnant woman, even when the test is used as a supplementary diagnostic tool. The savings are attributed to the novel test's ability to better classify patients relative to current practice, specifically, its ability to reduce false negatives by 67% and false positives by 71%. The novel PE test has the potential to provide substantial cost savings to German healthcare payers, even when used as an addition to standard practice. Better classification of patients at risk for developing PE and declassification of those that are not compared to current practice leads to economic savings for the healthcare system. Furthermore, by reducing the rates of false-positive and false-negative classification relative to current standard of care, the test helps better target healthcare spending and lowers overall costs associated with PE care.

Implementation of Point-of-Care Diagnostics in Rural Primary Healthcare Clinics in South Africa: Perspectives of Key Stakeholders.

PubMed

Mashamba-Thompson, Tivani P; Jama, Ngcwalisa A; Sartorius, Benn; Drain, Paul K; Thompson, Rowan M

2017-01-08

Key stakeholders' involvement is crucial to the sustainability of quality point-of-care (POC) diagnostics services in low-and-middle income countries. The aim of this study was to explore key stakeholder perceptions on the implementation of POC diagnostics in rural primary healthcare (PHC) clinics in South Africa. We conducted a qualitative study encompassing in-depth interviews with multiple key stakeholders of POC diagnostic services for rural and resource-limited PHC clinics. Interviews were digitally recorded and transcribed verbatim prior to thematic content analysis. Thematic content analysis was conducted using themes guided by the World Health Organisation (WHO) quality-ASSURED (Affordable, Sensitive, Specific, User friendly, Rapid and to enable treatment at first visit and Robust, Equipment free and Delivered to those who need it) criteria for POC diagnostic services in resource-limited settings. 11 key stakeholders participated in the study. All stakeholders perceived the main advantage of POC diagnostics as enabling access to healthcare for rural patients. Stakeholders perceived the current POC diagnostic services to have an ability to meet patients' needs, but recommended further improvement of the following areas: research on cost-effectiveness; improved quality management systems; development of affordable POC diagnostic and clinic-based monitoring and evaluation. Key stakeholders of POC diagnostics in rural PHC clinics in South Africa highlighted the need to assess affordability and ensure quality assurance of current services before adopting new POC diagnostics and scaling up current POC diagnostics.

Implementation of Point-of-Care Diagnostics in Rural Primary Healthcare Clinics in South Africa: Perspectives of Key Stakeholders

PubMed Central

Mashamba-Thompson, Tivani P.; Jama, Ngcwalisa A.; Sartorius, Benn; Drain, Paul K.; Thompson, Rowan M.

2017-01-01

Introduction: Key stakeholders’ involvement is crucial to the sustainability of quality point-of-care (POC) diagnostics services in low-and-middle income countries. The aim of this study was to explore key stakeholder perceptions on the implementation of POC diagnostics in rural primary healthcare (PHC) clinics in South Africa. Method: We conducted a qualitative study encompassing in-depth interviews with multiple key stakeholders of POC diagnostic services for rural and resource-limited PHC clinics. Interviews were digitally recorded and transcribed verbatim prior to thematic content analysis. Thematic content analysis was conducted using themes guided by the World Health Organisation (WHO) quality-ASSURED (Affordable, Sensitive, Specific, User friendly, Rapid and to enable treatment at first visit and Robust, Equipment free and Delivered to those who need it) criteria for POC diagnostic services in resource-limited settings. Results: 11 key stakeholders participated in the study. All stakeholders perceived the main advantage of POC diagnostics as enabling access to healthcare for rural patients. Stakeholders perceived the current POC diagnostic services to have an ability to meet patients’ needs, but recommended further improvement of the following areas: research on cost-effectiveness; improved quality management systems; development of affordable POC diagnostic and clinic-based monitoring and evaluation. Conclusions: Key stakeholders of POC diagnostics in rural PHC clinics in South Africa highlighted the need to assess affordability and ensure quality assurance of current services before adopting new POC diagnostics and scaling up current POC diagnostics. PMID:28075337

Autoimmune diagnostics: the technology, the strategy and the clinical governance.

PubMed

Bizzaro, Nicola; Tozzoli, Renato; Villalta, Danilo

2015-02-01

In recent years, there has been a profound change in autoimmune diagnostics. From long, tiring and inaccurate manual methods, the art of diagnostics has turned to modern, rapid and automated technology. New antibody tests have been developed, and almost all autoimmune diseases now have some specific diagnostic markers. The current need to make the most of available economic and human resources has led to the production of diagnostic algorithms and guidelines designated for optimal strategic use of the tests and to increase the diagnostic appropriateness. An important role in this scenario was assumed by the laboratory autoimmunologist, whose task is not only to govern the analytical phase, but also to help clinicians in correctly choosing the most suitable test for each clinical situation and provide consultancy support. In this review, we summarize recent advances in technology, describe the diagnostic strategies and highlight the current role of the laboratory autoimmunologist in the clinical governance of autoimmune diagnostics.

Design and testing of a magnetically driven implosion peak current diagnostic

NASA Astrophysics Data System (ADS)

Hess, M. H.; Peterson, K. J.; Ampleford, D. J.; Hutsel, B. T.; Jennings, C. A.; Gomez, M. R.; Dolan, D. H.; Robertson, G. K.; Payne, S. L.; Stygar, W. A.; Martin, M. R.; Sinars, D. B.

2018-04-01

A critical component of the magnetically driven implosion experiments at Sandia National Laboratories is the delivery of high-current, 10s of MA, from the Z pulsed power facility to a target. In order to assess the performance of the experiment, it is necessary to measure the current delivered to the target. Recent Magnetized Liner Inertial Fusion (MagLIF) experiments have included velocimetry diagnostics, such as PDV (Photonic Doppler Velocimetry) or Velocity Interferometer System for Any Reflector, in the final power feed section in order to infer the load current as a function of time. However, due to the nonlinear volumetrically distributed magnetic force within a velocimetry flyer, a complete time-dependent load current unfold is typically a time-intensive process and the uncertainties in the unfold can be difficult to assess. In this paper, we discuss how a PDV diagnostic can be simplified to obtain a peak current by sufficiently increasing the thickness of the flyer. This effectively keeps the magnetic force localized to the flyer surface, resulting in fast and highly accurate measurements of the peak load current. In addition, we show the results of experimental peak load current measurements from the PDV diagnostic in recent MagLIF experiments.

PTSD, Optimism, Religious Commitment, and Growth as Post-Trauma Trajectories: A Structural Equation Modeling of Former Refugees

ERIC Educational Resources Information Center

Acquaye, Hannah E.

2017-01-01

Refugees report several mental health challenges associated with pre-, peri-, and post-flight conditions. Some of these challenges include fear, anxiety, hypervigilance, hyperarousal, and nightmares--symptoms that could meet the diagnostic criteria for post-traumatic stress disorder (PTSD). Despite these challenges, some refugees also report…

Nasal juvenile angiofibroma: Current perspectives with emphasis on management.

PubMed

López, Fernando; Triantafyllou, Asterios; Snyderman, Carl H; Hunt, Jennifer L; Suárez, Carlos; Lund, Valerie J; Strojan, Primož; Saba, Nabil F; Nixon, Iain J; Devaney, Kenneth O; Alobid, Isam; Bernal-Sprekelsen, Manuel; Hanna, Ehab Y; Rinaldo, Alessandra; Ferlito, Alfio

2017-05-01

Juvenile angiofibroma is an uncommon, benign, locally aggressive vascular tumor. It is found almost exclusively in young men. Common presenting symptoms include nasal obstruction and epistaxis. More advanced tumors may present with facial swelling and visual or neurological disturbances. The evaluation of patients with juvenile angiofibroma relies on diagnostic imaging. Preoperative biopsy is not recommended. The mainstay of treatment is resection combined with preoperative embolization. Endoscopic surgery is the approach of choice in early stages, whereas, in advanced stages, open or endoscopic approaches are feasible in expert hands. Postoperative radiotherapy (RT) or stereotactic radiosurgery seem valuable in long-term control of juvenile angiofibroma, particularly those that extend to anatomically critical areas unsuitable for complete resection. Chemotherapy and hormone therapy are ineffective. The purpose of the present review was to update current aspects of knowledge related to this rare and challenging disease. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1033-1045, 2017. © 2017 Wiley Periodicals, Inc.

Clinical Adoption of Prognostic Biomarkers The Case for Heart Failure

PubMed Central

Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Butler, Javed

2013-01-01

The recent explosion of scientific knowledge and technological progress has led to the discovery of a large array of circulating molecules commonly referred to as biomarkers. Biomarkers in heart failure research have been used to provide pathophysiological insights, aid in establishing the diagnosis, refine prognosis, guide management, and target treatment. However, beyond diagnostic applications of natriuretic peptides, there are currently few widely recognized applications for biomarkers in heart failure. This represents a remarkable discordance considering the number of molecules that have been shown to correlate with outcomes, refine risk prediction, or track disease severity in heart failure in the past decade. In this article, we use a broad framework proposed for cardiovascular risk markers to summarize the current state of biomarker development for heart failure patients. We utilize this framework to identify the challenges of biomarker adoption for risk prediction, disease management, and treatment selection for heart failure and suggest considerations for future research. PMID:22824105

An Update on the Current Management of Perforated Diverticulitis.

PubMed

Zoog, Evon; Giles, W Heath; Maxwell, Robert A

2017-12-01

The management of perforated diverticulitis is a challenging aspect of general surgery. The prevalence of colonic diverticular disease has increased over the last decade and will continue to increase as the baby boomers add to the elderly population. Improvements in diagnostic imaging modalities, efforts to maintain intestinal continuity, and percutaneous drainage procedures now result in several alternatives when selecting a management strategy for complicated presentations. Specifically, laparoscopic lavage and resection with primary anastomosis have emerged as options for treatment of Hinchey III and IV diverticulitis in place of diversion in the appropriately selected patient. Percutaneous drainage of Hinchey II diverticulitis in centers equipped with interventional radiology provides another minimally invasive adjunct. The objective of this paper is to provide an update on the current management of perforated diverticulitis, with a focus on the advantages and disadvantages of the surgical options for the treatment of Hinchey III and IV diverticulitis.

Radiological and Radionuclide Imaging of Degenerative Disease of the Facet Joints

PubMed Central

Shur, Natalie; Corrigan, Alexis; Agrawal, Kanhaiyalal; Desai, Amidevi; Gnanasegaran, Gopinath

2015-01-01

The facet joint has been increasingly implicated as a potential source of lower back pain. Diagnosis can be challenging as there is not a direct correlation between facet joint disease and clinical or radiological features. The purpose of this article is to review the diagnosis, treatment, and current imaging modality options in the context of degenerative facet joint disease. We describe each modality in turn with a pictorial review using current evidence. Newer hybrid imaging techniques such as single photon emission computed tomography/computed tomography (SPECT/CT) provide additional information relative to the historic gold standard magnetic resonance imaging. The diagnostic benefits of SPECT/CT include precise localization and characterization of spinal lesions and improved diagnosis for lower back pain. It may have a role in selecting patients for local therapeutic injections, as well as guiding their location with increased precision. PMID:26170560

Brucellosis in Sub-Saharan Africa: Current challenges for management, diagnosis and control.

PubMed

Ducrotoy, M; Bertu, W J; Matope, G; Cadmus, S; Conde-Álvarez, R; Gusi, A M; Welburn, S; Ocholi, R; Blasco, J M; Moriyón, I

2017-01-01

Brucellosis is a highly contagious zoonosis caused by bacteria of the genus Brucella and affecting domestic and wild mammals. In this paper, the bacteriological and serological evidence of brucellosis in Sub-Saharan Africa (SSA) and its epidemiological characteristics are discussed. The tools available for the diagnosis and treatment of human brucellosis and for the diagnosis and control of animal brucellosis and their applicability in the context of SSA are presented and gaps identified. These gaps concern mostly the need for simpler and more affordable antimicrobial treatments against human brucellosis, the development of a B. melitensis vaccine that could circumvent the drawbacks of the currently available Rev 1 vaccine, and the investigation of serological diagnostic tests for camel brucellosis and wildlife. Strategies for the implementation of animal vaccination are also discussed. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.