Reprint of "EXOSOME LEVELS IN HUMAN BODY FLUIDS: A TUMOR MARKER BY THEMSELVES?"

PubMed

Cappello, Francesco; Logozzi, Mariantonia; Campanella, Claudia; Bavisotto, Celeste Caruso; Marcilla, Antonio; Properzi, Francesca; Fais, Stefano

2017-02-15

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once provide with several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may by themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up. Copyright © 2016 Elsevier B.V. All rights reserved.

Dementia in the Oldest Old

PubMed Central

Bullain, Szófia S.; Corrada, María M.

2013-01-01

Purpose of Review: This article discusses some of the unique features of dementia in the oldest old, including some of the most common diagnostic challenges, and potential strategies to overcome them. Recent Findings: Advances include new insight into the role of common risk factors and the effects of multiple underlying neuropathologic features for dementia in the oldest old. In addition, this article contains the latest age-specific normative data for commonly used neuropsychological tests for the oldest old. Summary: The oldest old—people aged 90 years and older—are the fastest-growing segment of society and have the highest rates of dementia in the population. The risk factors, diagnostic challenges, and underlying neuropathologic features of dementia are strikingly different in the 90-years-and-older population compared to younger elderly. Special consideration of these unique features of dementia is necessary when evaluating oldest-old subjects with cognitive impairment. PMID:23558489

Diagnostic pitfalls in newborns and babies with blisters and erosions.

PubMed

Nischler, Elke; Klausegger, Alfred; Hüttner, Clemens; Pohla-Gubo, Gabriele; Diem, Anja; Bauer, Johann W; Hintner, Helmut

2009-01-01

Establishing the correct diagnosis in newborns presenting with blisters and erosions is not always a straightforward process. Many different disease entities including acquired (i.e., infectious, immunobullous, traumatic) and inherited disorders have to be taken into consideration. Similarities in clinical appearance, colonization and/or superinfections of preexisting skin lesions, as well as the absence of late changes in the neonate often pose significant diagnostic challenges. In this paper we discuss by giving examples the process of making an accurate diagnosis of blistering skin diseases in the neonatal period on the basis of a diagnostic algorithm. In addition, we provide an overview of the rational use and the limitations of laboratory procedures such as microbial testing, routine light microscopy, immunofluorescence antigen mapping, transmission electron microscopy, and molecular genetic analysis.

49 CFR Appendix F to Part 222 - Diagnostic Team Considerations

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Diagnostic Team Considerations F Appendix F to.... 222, App. F Appendix F to Part 222—Diagnostic Team Considerations For purposes of this part, a diagnostic team is a group of knowledgeable representatives of parties of interest in a highway-rail grade...

49 CFR Appendix F to Part 222 - Diagnostic Team Considerations

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Diagnostic Team Considerations F Appendix F to.... 222, App. F Appendix F to Part 222—Diagnostic Team Considerations For purposes of this part, a diagnostic team is a group of knowledgeable representatives of parties of interest in a highway-rail grade...

49 CFR Appendix F to Part 222 - Diagnostic Team Considerations

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Diagnostic Team Considerations F Appendix F to.... 222, App. F Appendix F to Part 222—Diagnostic Team Considerations For purposes of this part, a diagnostic team is a group of knowledgeable representatives of parties of interest in a highway-rail grade...

49 CFR Appendix F to Part 222 - Diagnostic Team Considerations

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Diagnostic Team Considerations F Appendix F to.... 222, App. F Appendix F to Part 222—Diagnostic Team Considerations For purposes of this part, a diagnostic team is a group of knowledgeable representatives of parties of interest in a highway-rail grade...

49 CFR Appendix F to Part 222 - Diagnostic Team Considerations

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Diagnostic Team Considerations F Appendix F to.... 222, App. F Appendix F to Part 222—Diagnostic Team Considerations For purposes of this part, a diagnostic team is a group of knowledgeable representatives of parties of interest in a highway-rail grade...

Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

PubMed

Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

2015-12-28

Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

Implementation of HIV and Tuberculosis Diagnostics: The Importance of Context.

PubMed

Dominique, Joyelle K; Ortiz-Osorno, Alberto A; Fitzgibbon, Joseph; Gnanashanmugam, Devasena; Gilpin, Christopher; Tucker, Timothy; Peel, Sheila; Peter, Trevor; Kim, Peter; Smith, Steven

2015-10-15

Novel diagnostics have been widely applied across human immunodeficiency virus (HIV) and tuberculosis prevention and treatment programs. To achieve the greatest impact, HIV and tuberculosis diagnostic programs must carefully plan and implement within the context of a specific healthcare system and the laboratory capacity. A workshop was convened in Cape Town in September 2014. Participants included experts from laboratory and clinical practices, officials from ministries of health, and representatives from industry. The article summarizes best practices, challenges, and lessons learned from implementation experiences across sub-Saharan Africa for (1) building laboratory programs within the context of a healthcare system; (2) utilizing experience of clinicians and healthcare partners in planning and implementing the right diagnostic; and (3) evaluating the effects of new diagnostics on the healthcare system and on patient health outcomes. The successful implementation of HIV and tuberculosis diagnostics in resource-limited settings relies on careful consideration of each specific context. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach.

PubMed

Thompson, Lester Dr

2017-01-01

One of the most challenging diagnostic categories within tumors of the sinonasal tract is the small round blue cell tumors. Biopsies are usually small and limited, resulting in considerable diagnostic difficulty for practicing surgical pathologists. These tumors share several overlapping histologic and immunophenotypic findings while also showing considerable variation within and between cases. Specific tumor site of origin, imaging findings, and clinical findings must be combined with the histology and pertinent ancillary studies if the correct diagnosis is to be reached. Discrimination between neoplasms is critical as there are significant differences in therapy and overall outcome. It is important to have a well developed differential diagnosis for this category of tumors, where each of the diagnoses is considered, evaluated, and either confirmed or excluded from further consideration. In an undifferentiated tumor, showing a small round blue cell morphology, using the mnemonic 'MR SLEEP' helps to highlight tumors to consider: melanoma, mesenchymal chondrosarcoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, squamous cell carcinoma (including NUT carcinoma), small cell osteosarcoma, lymphoma, esthesioneuroblastoma (olfactory neuroblastoma), Ewing sarcoma/primitive neuroectodermal tumor, pituitary adenoma, and plasmacytoma. A panel of pertinent immunohistochemistry studies, histochemistries and/or molecular tests should aid in reaching a diagnosis, especially when taking the pattern and intensity of reactions into consideration.

Fever, petechiae, and pulmonary infiltrates in an immunocompromised Peruvian man.

PubMed Central

Berenson, C. S.; Dobuler, K. J.; Bia, F. J.

1987-01-01

The diagnostic considerations raised by immunocompromised patients with opportunistic infection continue to expand. When such patients harbor latent or persistent infection acquired in a tropical environment, the diagnostic challenge is even greater. The Infectious Disease Service at Yale-New Haven Hospital was asked to see a middle-aged man from Peru with known T-cell lymphoma who had recently completed a course of chemotherapy. He presented to the hospital with fever, petechial skin rash, pulmonary infiltrates, and neutropenia. Ultimately this case illustrated the necessity for careful evaluation of such patients, looking, in particular, for evidence of opportunistic parasitic infection. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:3424876

Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges

PubMed Central

2013-01-01

Tremendous efforts have been made over the past few decades to discover novel cancer biomarkers for use in clinical practice. However, a striking discrepancy exists between the effort directed toward biomarker discovery and the number of markers that make it into clinical practice. One of the confounding issues in translating a novel discovery into clinical practice is that quite often the scientists working on biomarker discovery have limited knowledge of the analytical, diagnostic, and regulatory requirements for a clinical assay. This review provides an introduction to such considerations with the aim of generating more extensive discussion for study design, assay performance, and regulatory approval in the process of translating new proteomic biomarkers from discovery into cancer diagnostics. We first describe the analytical requirements for a robust clinical biomarker assay, including concepts of precision, trueness, specificity and analytical interference, and carryover. We next introduce the clinical considerations of diagnostic accuracy, receiver operating characteristic analysis, positive and negative predictive values, and clinical utility. We finish the review by describing components of the FDA approval process for protein-based biomarkers, including classification of biomarker assays as medical devices, analytical and clinical performance requirements, and the approval process workflow. While we recognize that the road from biomarker discovery, validation, and regulatory approval to the translation into the clinical setting could be long and difficult, the reward for patients, clinicians and scientists could be rather significant. PMID:24088261

Severe Pneumonia Caused by Legionella pneumophila: Differential Diagnosis and Therapeutic Considerations.

PubMed

Chahin, Abdullah; Opal, Steven M

2017-03-01

Severe legionella pneumonia poses a diagnostic challenge and requires early intervention. Legionnaire's disease can have several presenting signs, symptoms, and laboratory abnormalities that suggest that Legionella pneumophila is the pathogen, but none of these are sufficient to distinguish L pneumophila pneumonia from other respiratory pathogens. L pneumophila is primarily an intracellular pathogen and needs treatment with antibiotics that efficiently enter the intracellular space. Copyright © 2016 Elsevier Inc. All rights reserved.

The diagnostic challenge of dizziness: computed tomography and magnetic resonance imaging findings

PubMed Central

Ribeiro, Bruno Niemeyer de Freitas; Correia, Rafael Santos; Antunes, Lívia de Oliveira; Salata, Tiago Medina; Rosas, Heraldo Belmont; Marchiori, Edson

2017-01-01

Dizziness is a prevalent symptom in the general population, accounting for a considerable share of physician office visits, and most causes are clinically treatable. It is also a common indication for neuroimaging studies, in order to identify a specific etiology and exclude surgical causes. Here, we illustrate the main peripheral and central causes of dizziness, discussing their possible differential diagnoses, as well as their most important image aspects. PMID:29085167

Algorithm for Video Summarization of Bronchoscopy Procedures

PubMed Central

2011-01-01

Background The duration of bronchoscopy examinations varies considerably depending on the diagnostic and therapeutic procedures used. It can last more than 20 minutes if a complex diagnostic work-up is included. With wide access to videobronchoscopy, the whole procedure can be recorded as a video sequence. Common practice relies on an active attitude of the bronchoscopist who initiates the recording process and usually chooses to archive only selected views and sequences. However, it may be important to record the full bronchoscopy procedure as documentation when liability issues are at stake. Furthermore, an automatic recording of the whole procedure enables the bronchoscopist to focus solely on the performed procedures. Video recordings registered during bronchoscopies include a considerable number of frames of poor quality due to blurry or unfocused images. It seems that such frames are unavoidable due to the relatively tight endobronchial space, rapid movements of the respiratory tract due to breathing or coughing, and secretions which occur commonly in the bronchi, especially in patients suffering from pulmonary disorders. Methods The use of recorded bronchoscopy video sequences for diagnostic, reference and educational purposes could be considerably extended with efficient, flexible summarization algorithms. Thus, the authors developed a prototype system to create shortcuts (called summaries or abstracts) of bronchoscopy video recordings. Such a system, based on models described in previously published papers, employs image analysis methods to exclude frames or sequences of limited diagnostic or education value. Results The algorithm for the selection or exclusion of specific frames or shots from video sequences recorded during bronchoscopy procedures is based on several criteria, including automatic detection of "non-informative", frames showing the branching of the airways and frames including pathological lesions. Conclusions The paper focuses on the challenge of generating summaries of bronchoscopy video recordings. PMID:22185344

Progress and challenges of disaster health management in China: a scoping review.

PubMed

Zhong, Shuang; Clark, Michele; Hou, Xiang-Yu; Zang, Yuli; FitzGerald, Gerard

2014-01-01

Despite the importance of an effective health system response to various disasters, relevant research is still in its infancy, especially in middle- and low-income countries. This paper provides an overview of the status of disaster health management in China, with its aim to promote the effectiveness of the health response for reducing disaster-related mortality and morbidity. A scoping review method was used to address the recent progress of and challenges to disaster health management in China. Major health electronic databases were searched to identify English and Chinese literature that were relevant to the research aims. The review found that since 2003 considerable progress has been achieved in the health disaster response system in China. However, there remain challenges that hinder effective health disaster responses, including low standards of disaster-resistant infrastructure safety, the lack of specific disaster plans, poor emergency coordination between hospitals, lack of portable diagnostic equipment and underdeveloped triage skills, surge capacity, and psychological interventions. Additional challenges include the fragmentation of the emergency health service system, a lack of specific legislation for emergencies, disparities in the distribution of funding, and inadequate cost-effective considerations for disaster rescue. One solution identified to address these challenges appears to be through corresponding policy strategies at multiple levels (e.g. community, hospital, and healthcare system level).

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

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.

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.

Graphene-based nanoprobes for molecular diagnostics.

PubMed

Chen, Shixing; Li, Fuwu; Fan, Chunhai; Song, Shiping

2015-10-07

In recent years, graphene has received widespread attention owing to its extraordinary electrical, chemical, optical, mechanical and structural properties. Lately, considerable interest has been focused on exploring the potential applications of graphene in life sciences, particularly in disease-related molecular diagnostics. In particular, the coupling of functional molecules with graphene as a nanoprobe offers an excellent platform to realize the detection of biomarkers, such as nucleic acids, proteins and other bioactive molecules, with high performance. This article reviews emerging graphene-based nanoprobes in electrical, optical and other assay methods and their application in various strategies of molecular diagnostics. In particular, this review focuses on the construction of graphene-based nanoprobes and their special advantages for the detection of various bioactive molecules. Properties of graphene-based materials and their functionalization are also comprehensively discussed in view of the development of nanoprobes. Finally, future challenges and perspectives of graphene-based nanoprobes are discussed.

Factitious Disorder as Repeated Diabetic Ketoacidosis

PubMed Central

Oettel, David J.

2011-01-01

Factitious disorder is a challenging entity, both in diagnosis and treatment. The clinical presentation is variable in feigned symptoms and spans virtually all organ systems. The diagnostic criteria are simple, yet making the diagnosis is often complicated and can be delayed by focusing on the urgent or readily observable diagnosis. In this article, the authors present a case of factitious diabetic ketoacidosis resulting from the deliberate withholding of exogenous insulin. This particular case is dissected in order to portray the underlying psychopathology. In doing so, the authors illustrate how a patient with factitious disorder might fulfill unmet, presumably unrealized needs. The authors also discuss the diagnostic criteria and treatment strategies of factitious disorder, both of which are of considerable debate within the psychiatric community. PMID:21468297

Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies.

PubMed

Waddington, Claire S; Darton, Thomas C; Woodward, William E; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2014-05-01

Typhoid infection causes considerable morbidity and mortality worldwide, particularly in settings where lack of clean water and inadequate sanitation facilitate disease spread through faecal-oral transmission. Improved understanding of the pathogenesis, immune control and microbiology of Salmonella Typhi infection can help accelerate the development of improved vaccines and diagnostic tests necessary for disease control. S. Typhi is a human-restricted pathogen; therefore animal models are limited in their relevance to human infection. During the latter half of the 20th century, induced human infection ("challenge") studies with S. Typhi were used effectively to assess quantitatively the human host response to challenge and to measure directly the efficacy of typhoid vaccines in preventing clinical illness. Here, the findings of these historic challenge studies are reviewed, highlighting the pivotal role that challenge studies have had in improving our understanding of the host-pathogen interaction, and illustrating issues relevant to modern typhoid challenge model design. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Ana o 3-specific IgE is a good predictor for clinically relevant cashew allergy in children.

PubMed

Lange, L; Lasota, L; Finger, A; Vlajnic, D; Büsing, S; Meister, J; Broekaert, I; Pfannenstiel, C; Friedrichs, F; Price, M; Trendelenburg, V; Niggemann, B; Beyer, K

2017-04-01

Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the ImmunoCAP-FEIA and a standardized diagnostic procedure including oral challenges where indicated. A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mandible Fractures

PubMed Central

Pickrell, Brent B.; Serebrakian, Arman T.; Maricevich, Renata S.

2017-01-01

Mandible fractures account for a significant portion of maxillofacial injuries and the evaluation, diagnosis, and management of these fractures remain challenging despite improved imaging technology and fixation techniques. Understanding appropriate surgical management can prevent complications such as malocclusion, pain, and revision procedures. Depending on the type and location of the fractures, various open and closed surgical reduction techniques can be utilized. In this article, the authors review the diagnostic evaluation, treatment options, and common complications of mandible fractures. Special considerations are described for pediatric and atrophic mandibles. PMID:28496390

Mandible Fractures.

PubMed

Pickrell, Brent B; Serebrakian, Arman T; Maricevich, Renata S

2017-05-01

Mandible fractures account for a significant portion of maxillofacial injuries and the evaluation, diagnosis, and management of these fractures remain challenging despite improved imaging technology and fixation techniques. Understanding appropriate surgical management can prevent complications such as malocclusion, pain, and revision procedures. Depending on the type and location of the fractures, various open and closed surgical reduction techniques can be utilized. In this article, the authors review the diagnostic evaluation, treatment options, and common complications of mandible fractures. Special considerations are described for pediatric and atrophic mandibles.

Progress and challenges of disaster health management in China: a scoping review

PubMed Central

Zhong, Shuang; Clark, Michele; Hou, Xiang-Yu; Zang, Yuli; FitzGerald, Gerard

2014-01-01

Background Despite the importance of an effective health system response to various disasters, relevant research is still in its infancy, especially in middle- and low-income countries. Objective This paper provides an overview of the status of disaster health management in China, with its aim to promote the effectiveness of the health response for reducing disaster-related mortality and morbidity. Design A scoping review method was used to address the recent progress of and challenges to disaster health management in China. Major health electronic databases were searched to identify English and Chinese literature that were relevant to the research aims. Results The review found that since 2003 considerable progress has been achieved in the health disaster response system in China. However, there remain challenges that hinder effective health disaster responses, including low standards of disaster-resistant infrastructure safety, the lack of specific disaster plans, poor emergency coordination between hospitals, lack of portable diagnostic equipment and underdeveloped triage skills, surge capacity, and psychological interventions. Additional challenges include the fragmentation of the emergency health service system, a lack of specific legislation for emergencies, disparities in the distribution of funding, and inadequate cost-effective considerations for disaster rescue. Conclusions One solution identified to address these challenges appears to be through corresponding policy strategies at multiple levels (e.g. community, hospital, and healthcare system level). PMID:25215910

Update on the status of the ITER ECE diagnostic design

NASA Astrophysics Data System (ADS)

Taylor, G.; Austin, M. E.; Basile, A.; Beno, J. H.; Danani, S.; Feder, R.; Houshmandyar, S.; Hubbard, A. E.; Johnson, D. W.; Khodak, A.; Kumar, R.; Kumar, S.; Ouroua, A.; Padasalagi, S. B.; Pandya, H. K. B.; Phillips, P. E.; Rowan, W. L.; Stillerman, J.; Thomas, S.; Udintsev, V. S.; Vayakis, G.; Walsh, M.; Weeks, D.

2017-07-01

Considerable progress has been made on the design of the ITER electron cyclotron emission (ECE) diagnostic over the past two years. Radial and oblique views are still included in the design in order to measure distortions in the electron momentum distribution, but the oblique view has been redirected to reduce stray millimeter radiation from the electron cyclotron heating system. A major challenge has been designing the 1000 K calibration sources and remotely activated mirrors located in the ECE diagnostic shield module (DSM) in the equatorial port plug #09. These critical systems are being modeled and prototypes are being developed. Providing adequate neutron shielding in the DSM while allowing sufficient space for optical components is also a significant challenge. Four 45-meter long low-loss transmission lines transport the 70-1000 GHz ECE from the DSM to the ECE instrumentation room. Prototype transmission lines are being tested, as are the polarization splitter modules that separate O-mode and X-mode polarized ECE. A highly integrated prototype 200-300 GHz radiometer is being tested on the DIII-D tokamak in the USA. Design activities also include integration of ECE signals into the ITER plasma control system and determining the hardware and software architecture needed to control and calibrate the ECE instruments.

Advancements in Nanomedicine for Multiple Myeloma.

PubMed

Detappe, Alexandre; Bustoros, Mark; Mouhieddine, Tarek H; Ghoroghchian, P Peter

2018-06-01

In the past decades, considerable progress has been made in our understanding and treatment of multiple myeloma. Several challenges remain including our abilities to longitudinally image tumor responses to treatment, to combine various therapeutic agents with different mechanisms of action but with overlapping toxicities, and to efficiently harness the power of the immune system to augment remission and/or to induce permanent cures. Nanomedicine may help to address many of these outstanding issues, affording novel diagnostic capabilities and offering disruptive technologies that promise to revolutionize treatment. Here, we review recent developments and the future of nanomedicine for multiple myeloma, highlighting new considerations in nanoparticle designs that may help to augment active targeting, to facilitate longitudinal imaging, and to improve drug delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Controversies in the Management of Asymptomatic Patients Sustaining Penetrating Thoracoabdominal Wounds

PubMed Central

Parreira, Jose Gustavo; Rasslan, Samir; Utiyama, Edivaldo M.

2008-01-01

The most challenging diagnostic issue in the management of thoracoabdominal wounds concerns the assessment of asymptomatic patients. In almost one-third of such cases, diaphragmatic injuries are present even in the absence of any clear clinical signs. The sensitivity of noninvasive diagnostic tests is very low in this situation, and acceptable methods for diagnosis are limited to videolaparoscopy or videothoracoscopy. However, these procedures are performed under general anesthesia and present real, and potentially unnecessary, risks for the patient. On the other hand, diaphragmatic hernias, which can result from unsutured diaphragmatic lesions, are associated with considerable morbidity and mortality. In this paper, the management of asymptomatic patients sustaining wounds to the lower chest is discussed, with a focus on the diagnosis of diaphragmatic injuries and the necessity of suturing them. PMID:18925332

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

PubMed

Feikin, Daniel R; Hammitt, Laura L; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G

2017-06-15

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Bone density in the obese child - clinical considerations and diagnostic challenges

PubMed Central

Kelley, Jennifer; Crabtree, Nicola; Zemel, Babette S.

2017-01-01

The prevalence of obesity in children has reached epidemic proportions. Concern about bone health in obese children, in part, derives from the potentially increased fracture risk associated with obesity. Additional risk factors that affect bone mineral accretion, may also contribute to obesity, such as low physical activity and nutritional factors. Consequences of obesity, such as inflammation, insulin resistance and non-alcoholic fatty liver disease, may also affect bone mineral acquisition, especially during the adolescent years when rapid increases in bone contribute to attaining peak bone mass. Further, numerous pediatric health conditions are associated with excess adiposity, altered body composition or endocrine disturbances that can affect bone accretion. Thus, there is a multitude of reasons for considering clinical assessment of bone health in an obese child. Multiple diagnostic challenges affect the measurement of bone density and its interpretation. These include greater precision error, difficulty in positioning, and the effects of increased lean and fat tissue on bone health outcomes. Future research is required to address these issues to improve bone health assessment in obese children. PMID:28105511

The AcCell series 2000 as a support system for training and evaluation in educational and clinical settings.

PubMed

Greening, S E; Grohs, D H; Guidos, B J

1997-01-01

Providing effective training, retraining and evaluation programs, including proficiency testing programs, for cytoprofessionals is a challenge shared by many academic and clinical educators internationally. In cytopathology the quality of training has immediately transferable and critically important impacts on satisfactory performance in the clinical setting. Well-designed interactive computer-assisted instruction and testing programs have been shown to enhance initial learning and to reinforce factual and conceptual knowledge. Computer systems designed not only to promote diagnostic accuracy but to integrate and streamline work flow in clinical service settings are candidates for educational adaptation. The AcCell 2000 system, designed as a diagnostic screening support system, offers technology that is adaptable to educational needs during basic and in-service training as well as testing of screening proficiency in both locator and identification skills. We describe the considerations, approaches and applications of the AcCell 2000 system in education programs for both training and evaluation of gynecologic diagnostic screening proficiency.

Endodontic management of mandibular third molar with three mesial roots using spiral computed tomography scan as a diagnostic aid: a case report.

PubMed

Tomar, Deepak; Dhingra, Anil; Tomer, Anil; Sharma, Shalini; Sharma, Vivek; Miglani, Anjali

2013-05-01

Aberrant root canal anatomy is diagnostically and clinically challenging for clinicians. The most common root canal configuration of human molars is 2 roots and 3 canals, but various combinations may still exist. Third molars are known to have the most unusual anatomy among human teeth. Restorative, prosthetic, and orthodontic considerations often require endodontic treatment of third molars in order for them to be retained as functional components of the dental arch. The present case report demonstrates unusual root canal morphology of the mandibular third molar. Roentgenographic examination, which included spiral CT scan, revealed 3 separate mesial roots in tooth #48 with 3 independent canals and 3 canal orifices, indicating an endodontic rarity. The present case report puts impetus on exploration of additional canals using advanced diagnostic aids, such as spiral computed tomography, which can have a huge impact on the successful outcome of endodontic therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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.

Renal lesions associated with plasma cell dyscrasias: practical approach to diagnosis, new concepts, and challenges.

PubMed

Herrera, Guillermo A

2009-02-01

Patients with plasma cell dyscrasias (myeloma) may exhibit a variety of renal manifestations as a result of damage from circulating light- and heavy-chain immunoglobulin components produced by the neoplastic plasma cells. The renal alterations can occur in any of the renal compartments, and in a significant number of the cases more than one compartment is affected. Research in the laboratory has helped considerably in providing a solid conceptual understanding of how renal damage occurs. To detail advances that have been made in the diagnosis of these conditions and to provide an account of research accomplishments that have solidified diagnostic criteria. The new knowledge that has been acquired serves to provide a solid platform for the future design of new therapeutic interventions aimed at ameliorating or abolishing the progressive renal damage that typically takes place. Translational efforts have substantially contributed to elucidate mechanistically the molecular events responsible for the renal damage. The spectrum of renal manifestations associated with plasma cell dyscrasias has expanded significantly in the last 10 years. Diagnostic criteria have also been refined. This information has been summarized from work done at several institutions. A number of significant challenges remain in the diagnosis of these conditions, some of which will be discussed in this article. Dealing with these challenges will require additional translational efforts and close cooperation between basic researchers, clinicians, and pathologists in order to improve the diagnostic tools available to renal pathologists and to acquire a more complete understanding of clinical and pathologic manifestations associated with these conditions.

U-shaped development: an old but unsolved problem.

PubMed

Pauls, Franz; Macha, Thorsten; Petermann, Franz

2013-01-01

Even today the investigation of U-shaped functions in human development is of considerable importance for different domains of Developmental Psychology. More and more scientific researchers focus their efforts on the challenge to describe and explain the phenomenon by identifying those skills and abilities being affected. The impact of U-shaped functions on diagnostic decision-making and on therapeutic treatment programs highlights the importance of understanding the nature of non-monotonic development. The present article therefore addresses the relevant questions of how U-shaped functions are defined in theory, in which developmental domains such non-monotonic growth curves are suggested to occur, and which implications there are for future methodology and diagnostic practice. Finally, it is recommended to clearly identify those interactions between proximal and distal subcomponents which are expected to contribute to a U-shaped development.

U-Shaped Development: An Old but Unsolved Problem

PubMed Central

Pauls, Franz; Macha, Thorsten; Petermann, Franz

2013-01-01

Even today the investigation of U-shaped functions in human development is of considerable importance for different domains of Developmental Psychology. More and more scientific researchers focus their efforts on the challenge to describe and explain the phenomenon by identifying those skills and abilities being affected. The impact of U-shaped functions on diagnostic decision-making and on therapeutic treatment programs highlights the importance of understanding the nature of non-monotonic development. The present article therefore addresses the relevant questions of how U-shaped functions are defined in theory, in which developmental domains such non-monotonic growth curves are suggested to occur, and which implications there are for future methodology and diagnostic practice. Finally, it is recommended to clearly identify those interactions between proximal and distal subcomponents which are expected to contribute to a U-shaped development. PMID:23750146

Bench-top validation testing of selected immunological and molecular Renibacterium salmoninarum diagnostic assays by comparison with quantitative bacteriological culture

USGS Publications Warehouse

Elliott, D.G.; Applegate, L.J.; Murray, A.L.; Purcell, M.K.; McKibben, C.L.

2013-01-01

No gold standard assay exhibiting error-free classification of results has been identified for detection of Renibacterium salmoninarum, the causative agent of salmonid bacterial kidney disease. Validation of diagnostic assays for R. salmoninarum has been hindered by its unique characteristics and biology, and difficulties in locating suitable populations of reference test animals. Infection status of fish in test populations is often unknown, and it is commonly assumed that the assay yielding the most positive results has the highest diagnostic accuracy, without consideration of misclassification of results. In this research, quantification of R. salmoninarum in samples by bacteriological culture provided a standardized measure of viable bacteria to evaluate analytical performance characteristics (sensitivity, specificity and repeatability) of non-culture assays in three matrices (phosphate-buffered saline, ovarian fluid and kidney tissue). Non-culture assays included polyclonal enzyme-linked immunosorbent assay (ELISA), direct smear fluorescent antibody technique (FAT), membrane-filtration FAT, nested polymerase chain reaction (nested PCR) and three real-time quantitative PCR assays. Injection challenge of specific pathogen-free Chinook salmon, Oncorhynchus tshawytscha (Walbaum), with R. salmoninarum was used to estimate diagnostic sensitivity and specificity. Results did not identify a single assay demonstrating the highest analytical and diagnostic performance characteristics, but revealed strengths and weaknesses of each test.

Ethical challenges in developing drugs for psychiatric disorders.

PubMed

Carrier, Felix; Banayan, David; Boley, Randy; Karnik, Niranjan

2017-05-01

As the classification of mental disorders advances towards a disease model as promoted by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC), there is hope that a more thorough neurobiological understanding of mental illness may allow clinicians and researchers to determine treatment efficacy with less diagnostic variability. This paradigm shift has presented a variety of ethical issues to be considered in the development of psychiatric drugs. These challenges are not limited to informed consent practices, industry funding, and placebo use. The consideration for alternative research models and quality of research design also present ethical challenges in the development of psychiatric drugs. The imperatives to create valid and sound research that justify the human time, cost, risk and use of limited resources must also be considered. Clinical innovation, and consideration for special populations are also important aspects to take into account. Based on the breadth of these ethical concerns, it is particularly important that scientific questions regarding the development of psychiatric drugs be answered collaboratively by a variety of stakeholders. As the field expands, new ethical considerations will be raised with increased focus on genetic markers, personalized medicine, patient-centered outcomes research, and tension over funding. We suggest that innovation in trial design is necessary to better reflect practices in clinical settings and that there must be an emphasized focus on expanding the transparency of consent processes, regard for suicidality, and care in working with special populations to support the goal of developing sound psychiatric drug therapies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evidence-Based Toxicology.

PubMed

Hoffmann, Sebastian; Hartung, Thomas; Stephens, Martin

Evidence-based toxicology (EBT) was introduced independently by two groups in 2005, in the context of toxicological risk assessment and causation as well as based on parallels between the evaluation of test methods in toxicology and evidence-based assessment of diagnostics tests in medicine. The role model of evidence-based medicine (EBM) motivated both proposals and guided the evolution of EBT, whereas especially systematic reviews and evidence quality assessment attract considerable attention in toxicology.Regarding test assessment, in the search of solutions for various problems related to validation, such as the imperfectness of the reference standard or the challenge to comprehensively evaluate tests, the field of Diagnostic Test Assessment (DTA) was identified as a potential resource. DTA being an EBM discipline, test method assessment/validation therefore became one of the main drivers spurring the development of EBT.In the context of pathway-based toxicology, EBT approaches, given their objectivity, transparency and consistency, have been proposed to be used for carrying out a (retrospective) mechanistic validation.In summary, implementation of more evidence-based approaches may provide the tools necessary to adapt the assessment/validation of toxicological test methods and testing strategies to face the challenges of toxicology in the twenty first century.

Continuous Wave Ring-Down Spectroscopy Diagnostic for Measuring Argon Ion and Neutral Velocity Distribution Functions in a Helicon Plasma

NASA Astrophysics Data System (ADS)

McCarren, Dustin; Vandervort, Robert; Soderholm, Mark; Carr, Jerry, Jr.; Galante, Matthew; Magee, Richard; Scime, Earl

2013-10-01

Cavity Ring-Down Spectroscopy CRDS is a proven, ultra-sensitive, cavity enhanced absorption spectroscopy technique. When combined with a continuous wavelength (CW) diode laser that has a sufficiently narrow line width, the Doppler broadened absorption line, i.e., the velocity distribution functions (IVDFs), can be measured. Measurements of IVDFS can be made using established techniques, such as laser induced fluorescence (LIF). However, LIF suffers from the requirement that the initial state of the LIF sequence have a substantial density. This usually limits LIF to ions and atoms with large metastable state densities for the given plasma conditions. CW-CRDS is considerably more sensitive than LIF and can potentially be applied to much lower density populations of ion and atom states. In this work we present ongoing measurements of the CW-CRDS diagnostic and discuss the technical challenges of using CW-CRDS to make measurements in a helicon plasma.

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.

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

Persistent regurgitation in four dogs with caudal esophageal neoplasia.

PubMed

Arnell, Katharine; Hill, Steve; Hart, John; Richter, Keith

2013-01-01

Esophageal neoplasia is an uncommon, but important, consideration for acute and chronic regurgitation and megaesophagus in dogs. The diagnosis can be challenging, and treatment options are often limited. This case series describes four dogs with regurgitation secondary to caudal esophageal masses. All dogs presented with regurgitation, and three of the four dogs had radiographically apparent megaesophagus. In all dogs, ancillary diagnostics revealed the presence of a caudal esophageal mass resulting in esophageal obstruction, and all mass lesions were histopathologically confirmed to be neoplastic. Treatment responses were variable, with one dog still alive 37 mo postdiagnosis at the time of manuscript preparation.

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

W(h)ither human cardiac and body magnetic resonance at ultrahigh fields? technical advances, practical considerations, applications, and clinical opportunities.

PubMed

Niendorf, Thoralf; Paul, Katharina; Oezerdem, Celal; Graessl, Andreas; Klix, Sabrina; Huelnhagen, Till; Hezel, Fabian; Rieger, Jan; Waiczies, Helmar; Frahm, Jens; Nagel, Armin M; Oberacker, Eva; Winter, Lukas

2016-09-01

The objective of this study was to document and review advances and groundbreaking progress in cardiac and body MR at ultrahigh fields (UHF, B0 ≥ 7.0 T) with the goal to attract talent, clinical adopters, collaborations and resources to the biomedical and diagnostic imaging communities. This review surveys traits, advantages and challenges of cardiac and body MR at 7.0 T. The considerations run the gamut from technical advances to clinical opportunities. Key concepts, emerging technologies, practical considerations, frontier applications and future directions of UHF body and cardiac MR are provided. Examples of UHF cardiac and body imaging strategies are demonstrated. Their added value over the kindred counterparts at lower fields is explored along with an outline of research promises. The achievements of cardiac and body UHF-MR are powerful motivators and enablers, since extra speed, signal and imaging capabilities may be invested to overcome the fundamental constraints that continue to hamper traditional cardiac and body MR applications. If practical obstacles, concomitant physics effects and technical impediments can be overcome in equal measure, sophisticated cardiac and body UHF-MR will help to open the door to new MRI and MRS approaches for basic research and clinical science, with the lessons learned at 7.0 T being transferred into broad clinical use including diagnostics and therapy guiding at lower fields. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The Proposed MACRA/MIPS Threshold for Patient-Facing Encounters: What It Means for Radiologists.

PubMed

Rosenkrantz, Andrew B; Hirsch, Joshua A; Allen, Bibb; Wang, Wenyi; Hughes, Danny R; Nicola, Gregory N

2017-03-01

In implementing the Merit-Based Incentive Payment System (MIPS), CMS will provide special considerations to physicians with infrequent face-to-face patient encounters by reweighting MIPS performance categories to account for the unique circumstances facing these providers. The aim of this study was to determine the impact of varying criteria on the fraction of radiologists who are likely to receive special considerations for performance assessment under MIPS. Data from the 2014 Medicare Physician and Other Supplier file for 28,710 diagnostic radiologists were used to determine the fraction of radiologists meeting various proposed criteria for receiving special considerations. For each definition, the fraction of patient-facing encounters among all billed codes was determined for those radiologists not receiving special considerations. When using the criterion proposed by CMS that physicians will receive special considerations if billing ≤25 evaluation and management services or surgical codes, 72.0% of diagnostic radiologists would receive special considerations, though such encounters would represent only 2.1% of billed codes among remaining diagnostic radiologists without special considerations. If CMS were to apply an alternative criterion of billing ≤100 evaluation and management codes exclusively, 98.8% of diagnostic radiologists would receive special considerations. At this threshold, patient-facing encounters would represent approximately 10% of billed codes among remaining radiologists without special considerations. The current CMS proposed criterion for special considerations would result in a considerable fraction of radiologists being evaluated on the basis of measures that are not reflective of their practice and beyond their direct control. Alternative criteria could help ensure that radiologists are provided a fair opportunity for success in performance review under the MIPS. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics

PubMed Central

Vu, Dung M.; Mendez, Heather M.; Jakhar, Shailja; Mukundan, Harshini

2017-01-01

Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential for their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. The biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review. PMID:28677660

Economic challenges associated with tuberculosis diagnostic development

PubMed Central

Hanrahan, Colleen F.; Shah, Maunank

2015-01-01

Tuberculosis remains a global health crisis in part due to underdiagnosis. Technological innovations are needed to improve diagnostic test accuracy and reduce the reliance on expensive laboratory infrastructure. However, there are significant economic challenges impeding the development and implementation of new diagnostics. The aim of this piece is to examine the current state of TB diagnostics, outline the unmet needs for new tests, and detail the economic challenges associated with development of new tests from the perspective of developers, policy makers and implementers. PMID:24766367

Economic challenges associated with tuberculosis diagnostic development.

PubMed

Hanrahan, Colleen F; Shah, Maunank

2014-08-01

Tuberculosis remains a global health crisis in part due to underdiagnosis. Technological innovations are needed to improve diagnostic test accuracy and reduce the reliance on expensive laboratory infrastructure. However, there are significant economic challenges impeding the development and implementation of new diagnostics. The aim of this piece is to examine the current state of TB diagnostics, outline the unmet needs for new tests, and detail the economic challenges associated with development of new tests from the perspective of developers, policy makers and implementers.

Operational challenges in delivering CD4 diagnostics in sub-Saharan Africa.

PubMed

Thairu, L; Katzenstein, D; Israelski, D

2011-07-01

Access to reliable and low cost CD4 T-cell enumeration to stage illness and monitor anti-retroviral therapy remains elusive in resource-limited settings. We report challenges in delivering CD4 testing using the microcapillary Fluorescence-Activated Cell Sorter (FACS) methodology (Guava EasyCD4 instrument Guava Technologies, Hayward) in Burkina Faso and Zimbabwe. Resources, instruments, reagents, and training were provided to local laboratories within the existing infrastructure and data on CD4 were collected from routine laboratory testing. Challenges encountered included frequent instrument breakdown; poor manufacturer maintenance; difficulties in managing reagent stocks; high technician turnover; reliance on antiquated data management systems; redundant service provision; and lack of repeat testing in male HIV+ patients and in patients with higher CD4 counts after initial staging. While adopting newer, less expensive technologies such as fluorescent platforms and point of care tests can facilitate access to lower cost CD4 testing, our experience suggests that supply chain, corporate commitment to implementation, and community factors also require consideration.

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.

Challenges and regulatory considerations in the acoustic measurement of high-frequency (>20 MHz) ultrasound.

PubMed

Nagle, Samuel M; Sundar, Guru; Schafer, Mark E; Harris, Gerald R; Vaezy, Shahram; Gessert, James M; Howard, Samuel M; Moore, Mary K; Eaton, Richard M

2013-11-01

This article examines the challenges associated with making acoustic output measurements at high ultrasound frequencies (>20 MHz) in the context of regulatory considerations contained in the US Food and Drug Administration industry guidance document for diagnostic ultrasound devices. Error sources in the acoustic measurement, including hydrophone calibration and spatial averaging, nonlinear distortion, and mechanical alignment, are evaluated, and the limitations of currently available acoustic measurement instruments are discussed. An uncertainty analysis of acoustic intensity and power measurements is presented, and an example uncertainty calculation is done on a hypothetical 30-MHz high-frequency ultrasound system. This analysis concludes that the estimated measurement uncertainty of the acoustic intensity is +73%/-86%, and the uncertainty in the mechanical index is +37%/-43%. These values exceed the respective levels in the Food and Drug Administration guidance document of 30% and 15%, respectively, which are more representative of the measurement uncertainty associated with characterizing lower-frequency ultrasound systems. Recommendations made for minimizing the measurement uncertainty include implementing a mechanical positioning system that has sufficient repeatability and precision, reconstructing the time-pressure waveform via deconvolution using the hydrophone frequency response, and correcting for hydrophone spatial averaging.

Primary tuberculosis of the middle ear cleft: diagnostic and therapeutic considerations.

PubMed

Liktor, Balázs; Liktor, Bálint; Liktor, Bálint; Kálmán, Judit; Horváth, Barnabás; Sziklai, István; Karosi, Tamás

2014-07-01

Tuberculosis remains one of the most challenging infectious diseases, which rarely manifests in the middle ear cleft exclusively. Typical symptoms of tuberculosis have become more and more confusing due to the genetic evolution of different Mycobacterium species. In the diagnosis of tuberculous otitis media (TOM), clinical suspicion plays a fundamental role, when topical and/or systemic antibiotic treatment cannot lead to improvement in ear discharge and inflammation. If there is no other reason of persisting otorrhea, microbiological sampling and culturing are the subsequent steps of diagnosis. These investigations, however, have low sensitivity; therefore a canal wall-up mastoidectomy is recommended, which includes the removal of necrotic bone and multiple histological sampling from various locations. Currently, histopathological analysis is the most robust and reliable method in the diagnosis of TOM. Tuberculin skin test, Mycobacterium-specific PCR and interferon-gamma release assay cannot distinguish between active, inactive or post-infective conditions. According to these considerations, these methods may serve as supplementary assays for the final diagnosis. Having the appropriate diagnosis after surgical intervention and laboratory analysis, medical management should be continued by anti-tuberculosis chemotherapy. Hereby, we demonstrate two cases with primary TOM and provide an overview of the literature in the light of diagnostic and therapeutic guidelines in the management of TOM.

Design standards for experimental and field studies to evaluate diagnostic accuracy of tests for infectious diseases in aquatic animals.

PubMed

Laurin, E; Thakur, K K; Gardner, I A; Hick, P; Moody, N J G; Crane, M S J; Ernst, I

2018-05-01

Design and reporting quality of diagnostic accuracy studies (DAS) are important metrics for assessing utility of tests used in animal and human health. Following standards for designing DAS will assist in appropriate test selection for specific testing purposes and minimize the risk of reporting biased sensitivity and specificity estimates. To examine the benefits of recommending standards, design information from published DAS literature was assessed for 10 finfish, seven mollusc, nine crustacean and two amphibian diseases listed in the 2017 OIE Manual of Diagnostic Tests for Aquatic Animals. Of the 56 DAS identified, 41 were based on field testing, eight on experimental challenge studies and seven on both. Also, we adapted human and terrestrial-animal standards and guidelines for DAS structure for use in aquatic animal diagnostic research. Through this process, we identified and addressed important metrics for consideration at the design phase: study purpose, targeted disease state, selection of appropriate samples and specimens, laboratory analytical methods, statistical methods and data interpretation. These recommended design standards for DAS are presented as a checklist including risk-of-failure points and actions to mitigate bias at each critical step. Adherence to standards when designing DAS will also facilitate future systematic review and meta-analyses of DAS research literature. © 2018 John Wiley & Sons Ltd.

Surveillance of wild birds for avian influenza virus.

PubMed

Hoye, Bethany J; Munster, Vincent J; Nishiura, Hiroshi; Klaassen, Marcel; Fouchier, Ron A M

2010-12-01

Recent demand for increased understanding of avian influenza virus in its natural hosts, together with the development of high-throughput diagnostics, has heralded a new era in wildlife disease surveillance. However, survey design, sampling, and interpretation in the context of host populations still present major challenges. We critically reviewed current surveillance to distill a series of considerations pertinent to avian influenza virus surveillance in wild birds, including consideration of what, when, where, and how many to sample in the context of survey objectives. Recognizing that wildlife disease surveillance is logistically and financially constrained, we discuss pragmatic alternatives for achieving probability-based sampling schemes that capture this host-pathogen system. We recommend hypothesis-driven surveillance through standardized, local surveys that are, in turn, strategically compiled over broad geographic areas. Rethinking the use of existing surveillance infrastructure can thereby greatly enhance our global understanding of avian influenza and other zoonotic diseases.

Bilateral isolated submandibular gland mumps.

PubMed

Cheung, Linnea; Henderson, Arthur Harry; Banfield, Graham; Carswell, Andrew

2017-06-05

Isolated submandibular swellings pose a diagnostic challenge to the practising otolaryngologist. We report an unusual case of mumps isolated to bilateral submandibular glands. We discuss the case and the literature surrounding this condition and remind clinicians that mumps should be considered as a diagnosis in the presence of submandibular gland swelling in the absence of typical parotid swelling associated with mumps. Early consideration of this differential diagnosis, serological testing and a multidisciplinary approach may help to clinch the diagnosis earlier and prevent spread of the virus. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Nano-technology contributions towards the development of high performance radioisotope generators: The future promise to meet the continuing clinical demand.

PubMed

Sakr, Tamer M; Nawar, Mohamed F; Fasih, T W; El-Bayoumy, S; Abd El-Rehim, H A

2017-11-01

Nanostructured materials attracted considerable attention because of its high surface area to volume ratio resulting from their nano-scale dimensions. This class of sorbents is expected to have a potential impact on enhancement the efficacy of radioisotope generators for diagnostic and therapeutic applications in nuclear medicine. This review provides a summary on the importance of nanostructured materials as effective sorbents for the development of clinical-scale radioisotope generators and outlining the assessment of recent developments, key challenges and promising access to the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Conjunctival malignant melanoma: A rare variant and review of important diagnostic and therapeutic considerations

PubMed Central

Albreiki, Danah H.; Gilberg, Steven M.; Farmer, James P.

2012-01-01

Malignant melanoma of the conjunctiva is a relatively infrequent neoplasm that can be associated with significant morbidity and cause diagnostic difficulty to both the ophthalmologist and pathologist. We herein describe the first reported case in North American and European databases of a rare variant-signet ring cell melanoma – arising in the background of primary acquired melanosis (PAM) and use this case as a review of important diagnostic and therapeutic considerations when faced with this condition. PMID:23960986

A portable microscopy system for fluorescence, polarized, and brightfield imaging

NASA Astrophysics Data System (ADS)

Gordon, Paul; Wattinger, Rolla; Lewis, Cody; Venancio, Vinicius Paula; Mertens-Talcott, Susanne U.; Coté, Gerard

2018-02-01

The use of mobile phones to conduct diagnostic microscopy at the point-of-care presents intriguing possibilities for the advancement of high-quality medical care in remote settings. However, it is challenging to create a single device that can adapt to the ever-varying camera technologies in phones or that can image with the customization that multiple modalities require for applications such as malaria diagnosis. A portable multi-modal microscope system is presented that utilizes a Raspberry Pi to collect and transmit data wirelessly to a myriad of electronic devices for image analysis. The microscopy system is capable of providing to the user correlated brightfield, polarized, and fluorescent images of samples fixed on traditional microscopy slides. The multimodal diagnostic capabilities of the microscope were assessed by measuring parasitemia of Plasmodium falciparum-infected thin blood smears. The device is capable of detecting fluorescently-labeled DNA using FITC excitation (490 nm) and emission (525 nm), the birefringent P. falciparum byproduct hemozoin, and detecting brightfield absorption with a resolution of 0.78 micrometers (element 9-3 of a 1951 Air Force Target). This microscopy system is a novel portable imaging tool that may be a viable candidate for field implementation if challenges of system durability, cost considerations, and full automation can be overcome.

Nanotechnology in dentistry: prevention, diagnosis, and therapy.

PubMed

Abou Neel, Ensanya Ali; Bozec, Laurent; Perez, Roman A; Kim, Hae-Won; Knowles, Jonathan C

2015-01-01

Nanotechnology has rapidly expanded into all areas of science; it offers significant alternative ways to solve scientific and medical questions and problems. In dentistry, nanotechnology has been exploited in the development of restorative materials with some significant success. This review discusses nanointerfaces that could compromise the longevity of dental restorations, and how nanotechnolgy has been employed to modify them for providing long-term successful restorations. It also focuses on some challenging areas in dentistry, eg, oral biofilm and cancers, and how nanotechnology overcomes these challenges. The recent advances in nanodentistry and innovations in oral health-related diagnostic, preventive, and therapeutic methods required to maintain and obtain perfect oral health, have been discussed. The recent advances in nanotechnology could hold promise in bringing a paradigm shift in dental field. Although there are numerous complex therapies being developed to treat many diseases, their clinical use requires careful consideration of the expense of synthesis and implementation.

Nanotechnology in dentistry: prevention, diagnosis, and therapy

PubMed Central

Abou Neel, Ensanya Ali; Bozec, Laurent; Perez, Roman A; Kim, Hae-Won; Knowles, Jonathan C

2015-01-01

Nanotechnology has rapidly expanded into all areas of science; it offers significant alternative ways to solve scientific and medical questions and problems. In dentistry, nanotechnology has been exploited in the development of restorative materials with some significant success. This review discusses nanointerfaces that could compromise the longevity of dental restorations, and how nanotechnolgy has been employed to modify them for providing long-term successful restorations. It also focuses on some challenging areas in dentistry, eg, oral biofilm and cancers, and how nanotechnology overcomes these challenges. The recent advances in nanodentistry and innovations in oral health-related diagnostic, preventive, and therapeutic methods required to maintain and obtain perfect oral health, have been discussed. The recent advances in nanotechnology could hold promise in bringing a paradigm shift in dental field. Although there are numerous complex therapies being developed to treat many diseases, their clinical use requires careful consideration of the expense of synthesis and implementation. PMID:26504385

Drug safety assurance through clinical genotyping: near-term considerations for a system-wide implementation of personalized medicine.

PubMed

Kane, Michael D; Springer, John A; Sprague, Jon E

2008-07-01

The rationale and overall system-wide behavior of a clinical genotyping information system (both DNA analysis and data management) requires a near-term, scalable approach, which is emerging in the focused implementation of pharmacogenomics and drug safety assurance. The challenges to implementing a successful clinical genotyping system are described, as are how the benefits of a focused, near-term system for drug safety assessment and assurance overcome the logistical and operational challenges that perpetually hinder the development of a societal-scale clinical genotyping system. This rationale is based on the premise that a focused application domain for clinical genotyping, specifically drug safety assurance, provides a transition paradigm for both professionals and consumers of healthcare, thereby facilitating the movement of genotyping from bench to bedside and paving the way for the adoption of prognostic and diagnostic applications in clinical genomics.

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

Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin.

PubMed

Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo

2017-10-01

Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

The role of managed care in improving outcomes in epilepsy.

PubMed

Stern, John M

2011-07-01

The burden of epilepsy for patients and payers is large and onerous. The heterogeneous nature of the condition and the lack of diagnostic or treatment biomarkers present considerable clinical challenge. Despite expansion of the treatment armamentarium, selection of maximally appropriate therapy for individual patients remains a challenge, especially in those with treatment-refractory epilepsy. While numerous factors play a role in resolving these uncertainties, 3 key factors stand out. An overwhelming quantity of clinical data support the notion that the most effective therapies-measured by the ability to control seizures while minimizing adverse effects-are typically the most cost-effective. A second consideration is maximizing adherence to prescribed therapies, which has been an ongoing dilemma in the treatment of epilepsy because the condition occurs episodically. Poor adherence has a profound effect on treatment and costs, and several strategies for improving adherence have been identified. If properly observed, these can improve outcomes and lower expenditures. The third consideration is the monitoring of therapeutic response. This is essentially through ongoing care by the prescriber with careful assessment of seizures, patient satisfaction with treatment, dose-related adverse effects, and the subjective aspects of idiosyncratic toxicity; however, laboratory testing can also have a role. The resources needed to provide this monitoring vary across treatments. From a systemic point of view, engagement of all stakeholders-patients, payers, and physicians-in overseeing the effective and efficient use of healthcare resources will benefit all parties involved.

Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.

PubMed

Uneke, C J

2008-06-01

Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987-2007), to highlight the diagnostic challenges and the public health implications. Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

Lost in Translation? Ethical Challenges of Implementing a New Diagnostic Procedure.

PubMed

Schmitz, Dagmar

2016-01-01

Since cell-free DNA (cfDNA) fragments of placental origin can be isolated and analyzed from the blood of pregnant women. Applications of this finding have been developed and implemented in clinical care pathways worldwide at an unprecedented pace and manner. Implementation patterns, however, exhibit considerable insufficiencies. Different "motors" of implementation processes, like the market or various regulatory institutions, can be identified at a national level. Each "motor" entails characteristic ethical challenges which are exemplified impressively by a rising number of case reports.Empirical data demonstrate that there are significant "losses" in the respective translational processes, especially when the results from clinical research are to be translated into the clinical reality of NIPT (the so called "second roadblock" (T2)). These "losses" are perceived in the fields of knowledge transfer, professional standardization and ethical debate. Recommendations of professional organizations often fail to reach general practitioners. Blindsided by the new diagnostic procedure in their clinical practice, professionals in prenatal care express their insecurities with regard to its handling. Ethical debate appears to adhere to pre-existing (and partly already proven to be insufficient) normative frameworks for prenatal testing. While all of these deficits are typical for the implementation processes of many new molecular diagnostic procedures, especially in NIPT, they show a high variability between different nations.A critical assessment of the preferred strategy of implementation against the background of already existing national ethical frameworks is indispensable, if potential adverse effects are to be diminished. The described translational losses seem to be significantly reducible by granting the translational process in roadblock T2 more time.

Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics

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

Kubicek-Sutherland, Jessica Z.; Vu, Dung M.; Mendez, Heather M.

Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential formore » their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. Furthermore, the biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review.« less

Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics

DOE PAGES

Kubicek-Sutherland, Jessica Z.; Vu, Dung M.; Mendez, Heather M.; ...

2017-07-04

Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential formore » their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. Furthermore, the biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review.« less

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.

Faulty judgment, expert opinion, and decision-making capacity.

PubMed

Silberfeld, M; Checkland, D

1999-08-01

An assessment of decision-making capacity is the accepted procedure for determining when a person is not competent. An inferential gap exists between the criteria for capacity specific abilities and the legal requirements to understand relevant information and appreciate the consequences of a decision. This gap extends to causal influences on a person's capacity to decide. Using a published case of depression, we illustrate that assessors' uses of diagnostic information is frequently not up to the task of bridging this inferential gap in a justifiable way. We then describe cases of faulty judgement which challenge the understanding of diagnostic causal influences. These cases help to clarify the nature of the expertise required for capacity assessments. In practice, the requirements of decision-making capacity are often abandoned to other considerations due to a lack of requisite expertise. The legal policy supporting decision-making capacity as a means to protective intervention is justified only if the requisite expertise is developed. We propose the requisite expertise to be developed in the long term as a distinct multidisciplinary endeavour.

The private-practice perspective of the manpower crisis in radiology: greener pastures?

PubMed

Swayne, Lawrence C

2004-11-01

Rising consumer expectations and a rapidly aging population point to a long-term shortage of all physicians, including radiologists. While attention has been drawn to the escalating manpower crisis in academic radiology departments, the private-practice perspective has been generally overlooked. Although clinical workloads and income are higher in private practice, studies have shown higher satisfaction levels (likely because of a greater variety of work) among academic radiologists. As the distinction between community and teaching hospitals has become increasingly blurred, there is now considerable overlap in the skill sets, sources of job satisfaction, and stresses that are encountered in both practice settings. Perhaps more than at any time in the recent past, diagnostic radiologists in academic and private practice share more in common than any perceived differences. Both groups must work together in concert with the ACR to address the growing manpower shortage, as well as the other challenges that confront diagnostic radiology at the beginning of the 21st century.

Laboratory Approach to the Diagnosis of Culture-Negative Infective Endocarditis.

PubMed

Subedi, S; Jennings, Z; Chen, S C-A

2017-08-01

Blood-culture negative endocarditis (BCNE) accounts for up to 35% of all cases of infective endocarditis (IE) and is a serious life-threatening condition with considerable morbidity and mortality. Rapid detection and identification of the causative pathogen is essential for timely, directed therapy. Blood-culture negative endocarditis presents a diagnostic and therapeutic challenge. Causes of BCNE are varied including: treatment with antibiotic agents prior to blood culture collection; sub-optimal specimen collection; and/or infection due to fastidious (eg. nutritionally variant streptococci), intracellular (eg. Coxiella burnetii, Bartonella species) or non-culturable or difficult to culture organisms (eg. Mycobacteria, Tropheryma whipplei and fungi); as well as non-infective aetiologies. Here, we review aetiological and diagnostic approaches to BCNE including newer molecular based techniques, with a brief summary of imaging investigation and treatment principles. Copyright © 2017 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.

Trichomonas vaginalis Genital Infections: Progress and Challenges

PubMed Central

Hobbs, Marcia M.; Seña, Arlene C.; Sobel, Jack D.; Schwebke, Jane R.; Krieger, John N.; McClelland, R. Scott; Workowski, Kimberly A.

2011-01-01

Trichomonas vaginalis (TV) infection is the most prevalent curable sexually transmitted infection in the United States and worldwide. Most TV infections are asymptomatic, and the accurate diagnosis of this infection has been limited by lack of sufficiently sensitive and specific diagnostic tests, particularly for men. To provide updates for the 2010 Centers for Disease Control and Prevention’s Sexually Transmitted Diseases Treatment Guidelines, a PubMed search was conducted of all TV literature published from 9 January 2004 through 24 September 2008. Approximately 175 pertinent abstracts and articles were reviewed and discussed with national experts. This article describes advances in TV diagnostics which have led to an improved understanding of the epidemiology of this pathogen, as well as potential biologic and epidemiological interactions between TV and human immunodeficiency virus (HIV). New data on treatment outcomes, metronidazole-resistant TV, management of nitroimidazole-allergic patients, frequency of recurrent TV infection following treatment, and screening considerations for TV in certain populations are also presented. PMID:22080269

Non-Alzheimer’s dementia 2

PubMed Central

Walker, Zuzana; Possin, Katherine L; Boeve, Bradley F; Aarsland, Dag

2018-01-01

The broad importance of dementia is undisputed, with Alzheimer’s disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson’s disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson’s disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments. PMID:26595642

Ribosomal DNA analysis of tsetse and non-tsetse transmitted Ethiopian Trypanosoma vivax strains in view of improved molecular diagnosis.

PubMed

Fikru, Regassa; Matetovici, Irina; Rogé, Stijn; Merga, Bekana; Goddeeris, Bruno Maria; Büscher, Philippe; Van Reet, Nick

2016-04-15

Animal trypanosomosis caused by Trypanosoma vivax (T. vivax) is a devastating disease causing serious economic losses. Most molecular diagnostics for T. vivax infection target the ribosomal DNA locus (rDNA) but are challenged by the heterogeneity among T. vivax strains. In this study, we investigated the rDNA heterogeneity of Ethiopian T. vivax strains in relation to their presence in tsetse-infested and tsetse-free areas and its effect on molecular diagnosis. We sequenced the rDNA loci of six Ethiopian (three from tsetse-infested and three from tsetse-free areas) and one Nigerian T. vivax strain. We analysed the obtained sequences in silico for primer-mismatches of some commonly used diagnostic PCR assays and for GC content. With these data, we selected some rDNA diagnostic PCR assays for evaluation of their diagnostic accuracy. Furthermore we constructed two phylogenetic networks based on sequences within the smaller subunit (SSU) of 18S and within the 5.8S and internal transcribed spacer 2 (ITS2) to assess the relatedness of Ethiopian T. vivax strains to strains from other African countries and from South America. In silico analysis of the rDNA sequence showed important mismatches of some published diagnostic PCR primers and high GC content of T. vivax rDNA. The evaluation of selected diagnostic PCR assays with specimens from cattle under natural T. vivax challenge showed that this high GC content interferes with the diagnostic accuracy of PCR, especially in cases of mixed infections with T. congolense. Adding betain to the PCR reaction mixture can enhance the amplification of T. vivax rDNA but decreases the sensitivity for T. congolense and Trypanozoon. The networks illustrated that Ethiopian T. vivax strains are considerably heterogeneous and two strains (one from tsetse-infested and one from tsetse-free area) are more related to the West African and South American strains than to the East African strains. The rDNA locus sequence of six Ethiopian T. vivax strains showed important differences and higher GC content compared to other animal trypanosomes but could not be related to their origin from tsetse-infested or tsetse-free area. The high GC content of T. vivax DNA renders accurate diagnosis of all pathogenic animal trypanosomes with one single PCR problematic. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Childhood Gender Identity...Disorder? Developmental, Cultural, and Diagnostic Concerns

ERIC Educational Resources Information Center

Dragowski, Eliza A.; Scharron-del Rio, Maria R.; Sandigorsky, Amy L.

2011-01-01

Childhood gender identity development is reviewed in the context of biological, environmental, cultural, and diagnostic factors. With the upcoming 5th revision of the "Diagnostic and Statistical Manual of Mental Disorders," the authors offer a critical consideration of childhood gender identity disorder, along with proposed diagnostic changes.…

Quantitative imaging biomarkers: the application of advanced image processing and analysis to clinical and preclinical decision making.

PubMed

Prescott, Jeffrey William

2013-02-01

The importance of medical imaging for clinical decision making has been steadily increasing over the last four decades. Recently, there has also been an emphasis on medical imaging for preclinical decision making, i.e., for use in pharamaceutical and medical device development. There is also a drive towards quantification of imaging findings by using quantitative imaging biomarkers, which can improve sensitivity, specificity, accuracy and reproducibility of imaged characteristics used for diagnostic and therapeutic decisions. An important component of the discovery, characterization, validation and application of quantitative imaging biomarkers is the extraction of information and meaning from images through image processing and subsequent analysis. However, many advanced image processing and analysis methods are not applied directly to questions of clinical interest, i.e., for diagnostic and therapeutic decision making, which is a consideration that should be closely linked to the development of such algorithms. This article is meant to address these concerns. First, quantitative imaging biomarkers are introduced by providing definitions and concepts. Then, potential applications of advanced image processing and analysis to areas of quantitative imaging biomarker research are described; specifically, research into osteoarthritis (OA), Alzheimer's disease (AD) and cancer is presented. Then, challenges in quantitative imaging biomarker research are discussed. Finally, a conceptual framework for integrating clinical and preclinical considerations into the development of quantitative imaging biomarkers and their computer-assisted methods of extraction is presented.

Molecular allergy diagnostics using multiplex assays: methodological and practical considerations for use in research and clinical routine: Part 21 of the Series Molecular Allergology.

PubMed

Jakob, Thilo; Forstenlechner, Peter; Matricardi, Paolo; Kleine-Tebbe, Jörg

The availability of single allergens and their use in microarray technology enables the simultaneous determination of specific IgE (sIgE) to a multitude of different allergens (> 100) in a multiplex procedure requiring only minute amounts of serum. This allows extensive individual sensitization profiles to be determined from a single analysis. Combined with a patient's medical history, these profiles simplify identification of cross-reactivity; permit a more accurate estimation of the risk of severe reactions; and enable the indication for specific immunotherapy to be more precisely established, particularly in cases of polysensitization. Strictly speaking, a multiplex assay is not a single test, but instead more than 100 simultaneous tests. This places considerable demands on the production, quality assurance, and interpretation of data. The following chapter describes the multiplex test systems currently available and discusses their characteristics. Performance data are presented and the sIgE values obtained from multiplex and singleplex assays are compared. Finally, the advantages and limitations of molecular allergy diagnostics using multiplex assays in clinical routine are discussed, and innovative possibilities for clinical research are described. The multiplex diagnostic tests available for clinical routine have now become well established. The interpretation of test results is demanding, particularly since all individual results need to be checked for their plausibility and clinical relevance on the basis of previous history (patient history, clinical symptoms, challenge test results). There is still room for improvement in certain areas, for example with respect to the overall test sensitivity of the method, as well as the availability and quality of particular allergens. The current test systems are just the beginning of a continuous development that will influence and most likely change clinical allergology in the coming years.

The Impact of Living with Klinefelter Syndrome: A Qualitative Exploration of Adolescents and Adults.

PubMed

Turriff, Amy; Macnamara, Ellen; Levy, Howard P; Biesecker, Barbara

2017-08-01

Klinefelter syndrome (XXY) is a common yet significantly underdiagnosed condition with considerable medical, psychological and social implications. Many health care providers lack familiarity with XXY, resulting in medical management challenges and a limited understanding of the personal impact of the condition. Genetic counselors benefit from understanding the challenges adolescents and men with XXY face to effectively address their medical and psychosocial needs. The purpose of this study was to understand the impact of living with XXY as an adolescent or an adult. Individuals aged 14 to 75 years with self-reported XXY were recruited from online support networks to complete a web-based survey that included open-ended questions. Open-ended responses were coded and analyzed thematically (n = 169 to 210 for each open-ended question). Over half of respondents to the open-ended questions reported challenges in finding health care providers who are knowledgeable about XXY, with many describing an extensive diagnostic odyssey and relief when receiving a diagnosis. Individuals sought support coping with the challenges they face and acknowledgement of the positive aspects of XXY. Recommendations are made for how genetic counseling can enhance quality of life for individuals living with XXY.

Microfluidics-Enabled Diagnostic Systems: Markets, Challenges, and Examples.

PubMed

Becker, Holger; Gärtner, Claudia

2017-01-01

Microfluidics has become an important tool for the commercial product development in diagnostics. This article will focus on current technical demands during the development process such as material and integration challenges. Furthermore, we present data on the diagnostics market as well as examples of microfluidics-enabled systems currently under commercial development or already on the market.

Paranoid personality disorder and the schizophrenia spectrum-Where to draw the line?

PubMed

Birkeland, Søren Fryd

2013-08-01

By means of a case vignette, this study explores the clinical intersection between paranoid personality disorder and other schizophrenia-spectrum illness. Even though the patient described had paramount signs of a paranoid personality disorder and was diagnosed as such, psychopathological symptoms extended considerably beyond the common concept and diagnostic criteria of the disorder. Management strategies included psychopharmacological and non-pharmacological interventions, yet psychosocial functioning permanently appeared defective. While there is a persistent need for an opportunity to distinguish the characteristic syndromal pattern of paranoid personality attributes, the case exemplifies the challenges associated with classifying some largely suspicious and distrustful eccentrics within the schizophrenia spectrum. Copyright © 2013 John Wiley & Sons, Ltd.

Managing Innovation to Maximize Value Along the Discovery-Translation-Application Continuum.

PubMed

Waldman, S A; Terzic, A

2017-01-01

Success in pharmaceutical development led to a record 51 drugs approved in the past year, surpassing every previous year since 1950. Technology innovation enabled identification and exploitation of increasingly precise disease targets ensuring next generation diagnostic and therapeutic products for patient management. The expanding biopharmaceutical portfolio stands, however, in contradistinction to the unsustainable costs that reflect remarkable challenges of clinical development programs. This annual Therapeutic Innovations issue juxtaposes advances in translating molecular breakthroughs into transformative therapies with essential considerations for lowering attrition and improving the cost-effectiveness of the drug-development paradigm. Realizing the discovery-translation-application continuum mandates a congruent approval, adoption, and access triad. © 2016 ASCPT.

Managing Innovation to Maximize Value Along the Discovery-Translation-Application Continuum

PubMed Central

Waldman, SA; Terzic, A

2017-01-01

Success in pharmaceutical development led to a record 51 drug approved in the past year, surpassing every previous year since 1950. Technology innovation enabled identification and exploitation of increasingly precise disease targets ensuring a next generation diagnostic and therapeutic products for patient management. The expanding biopharmaceutical portfolio stands however in contradistinction to the unsustainable costs that reflect remarkable challenges of clinical development programs. This annual Therapeutic Innovations issue juxtaposes advances in translating molecular breakthroughs into transformative therapies with essential considerations for lowering attrition and improving the cost-effectiveness of the drug development paradigm. Realizing the discovery-translation-application continuum mandates a congruent approval, adoption and access triad. PMID:27869291

Caring for homeless persons with serious mental illness in general hospitals.

PubMed

Bauer, Leah K; Baggett, Travis P; Stern, Theodore A; O'Connell, Jim J; Shtasel, Derri

2013-01-01

The care of homeless persons with serious mental illness remains a common and challenging problem in general hospital settings. This article aims to review data on homelessness and its psychiatric comorbidities, and to expand the skills of providers who encounter homeless individuals in general hospital settings. Literature review reveals patient, provider, and systems factors that contribute to suboptimal health outcomes in homeless individuals. Diagnostic rigor, integrated medical and psychiatric care, trauma-informed interventions, special considerations in capacity evaluations, and health care reform initiatives can improve the treatment of homeless persons with serious mental illness. Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Privacy considerations in the context of an Australian observational database.

PubMed

Duszynski, K M; Beilby, J J; Marley, J E; Walker, D C; Pratt, N L

2001-12-01

Observational databases are increasingly acknowledged for their value in clinical investigation. Australian general practice in particular presents an exciting opportunity to examine treatment in a natural setting. The paper explores issues such as privacy and confidentiality--foremost considerations when conducting this form of pharmacoepidemiological research. Australian legislation is currently addressing these exact issues in order to establish clear directives regarding ethical concerns. The development of a pharmacoepidemiological database arising from the integration of computerized Australian general practice records is described in addition, to the challenges associated with creating a database which considers patient privacy. The database known as 'Medic-GP', presently contains more than 950,000 clinical notes (including consultations, pathology, diagnostic imaging and adverse reactions) over a 5-year time period and relates to 55,000 patients. The paper then details a retrospective study which utilized the database to examine the interaction between antibiotic prescribing and patient outcomes from a community perspective, following a policy intervention. This study illustrates the application of computerized general practice records in research.

Comprehensive Identification of Proteins from MALDI Imaging*

PubMed Central

Maier, Stefan K.; Hahne, Hannes; Gholami, Amin Moghaddas; Balluff, Benjamin; Meding, Stephan; Schoene, Cédrik; Walch, Axel K.; Kuster, Bernhard

2013-01-01

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful tool for the visualization of proteins in tissues and has demonstrated considerable diagnostic and prognostic value. One main challenge is that the molecular identity of such potential biomarkers mostly remains unknown. We introduce a generic method that removes this issue by systematically identifying the proteins embedded in the MALDI matrix using a combination of bottom-up and top-down proteomics. The analyses of ten human tissues lead to the identification of 1400 abundant and soluble proteins constituting the set of proteins detectable by MALDI IMS including >90% of all IMS biomarkers reported in the literature. Top-down analysis of the matrix proteome identified 124 mostly N- and C-terminally fragmented proteins indicating considerable protein processing activity in tissues. All protein identification data from this study as well as the IMS literature has been deposited into MaTisse, a new publically available database, which we anticipate will become a valuable resource for the IMS community. PMID:23782541

Intellectual property considerations for molecular diagnostic development with emphasis on companion diagnostics.

PubMed

Glorikian, Harry; Warburg, Richard Jeremy; Moore, Kelly; Malinowski, Jennifer

2018-02-01

The development of molecular diagnostics is a complex endeavor, with multiple regulatory pathways to consider and numerous approaches to development and commercialization. Companion diagnostics, devices which are "essential for the safe and effective use of a corresponding drug or diagnostic product" (see U.S. Food & Drug Administration, In Vitro Diagnostics - Companion Diagnostics, U.S. Dept. of Health & Human Services(2016), available at https://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm407297.htm ) and complementary diagnostics, which are more broadly associated with a class of drug, are becoming increasingly important as integral components of the implementation of precision medicine. Areas covered: The following article will highlight the intellectual property ('IP') considerations pertinent to molecular diagnostics development with special emphasis on companion diagnostics. Expert opinion/commentary Summary: For all molecular diagnostics, intellectual property (IP) concerns are of paramount concern, whether the device will be marketed only in the United States or abroad. Taking steps to protect IP at each stage of product development is critical to optimize profitability of a diagnostic product. Also the legal framework around IP protection of diagnostic technologies has been changing over the previous few years and can be expected to continue to change in the foreseeable near future, thus, a comprehensive IP strategy should take into account the fact that changes in the law can be expected.

21 CFR 601.32 - General factors relevant to safety and effectiveness.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) BIOLOGICS LICENSING Diagnostic Radiopharmaceuticals § 601.32 General factors relevant to safety and effectiveness. FDA's determination of the safety and effectiveness of a diagnostic radiopharmaceutical includes consideration of the following: (a) The proposed use of the diagnostic...

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.

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.

77 FR 12318 - National Cancer Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... potential new cancer diagnostics. The outcome of the evaluation will provide information for consideration... available contract resources for development of the potential diagnostics to improve the treatment of cancer... development resources for potential new diagnostics for cancer. Place: National Cancer Institute, NIH, 6001...

KS-Detect – Validation of Solar Thermal PCR for the Diagnosis of Kaposi’s Sarcoma Using Pseudo-Biopsy Samples

PubMed Central

Snodgrass, Ryan; Gardner, Andrea; Jiang, Li; Fu, Cheng; Cesarman, Ethel; Erickson, David

2016-01-01

Resource-limited settings present unique engineering challenges for medical diagnostics. Diagnosis is often needed for those unable to reach central healthcare systems, making portability and independence from traditional energy infrastructure essential device parameters. In 2014, our group presented a microfluidic device that performed a solar-powered variant of the polymerase chain reaction, which we called solar thermal PCR. In this work, we expand on our previous effort by presenting an integrated, portable, solar thermal PCR system targeted towards the diagnosis of Kaposi’s sarcoma. We call this system KS-Detect, and we now report the system’s performance as a diagnostic tool using pseudo-biopsy samples made from varying concentrations of human lymphoma cell lines positive for the KS herpesvirus (KSHV). KS-Detect achieved 83% sensitivity and 70% specificity at high (≥10%) KSHV+ cell concentrations when diagnosing pseudo-biopsy samples by smartphone image. Using histology, we confirm that our prepared pseudo-biopsies contain similar KSHV+ cell concentrations as human biopsies positive for KS. Through our testing of samples derived from human cell lines, we validate KS-Detect as a viable, portable KS diagnostic tool, and we identify critical engineering considerations for future solar-thermal PCR devices. PMID:26799834

Rapid molecular TB diagnosis: evidence, policy making and global implementation of Xpert MTB/RIF.

PubMed

Weyer, Karin; Mirzayev, Fuad; Migliori, Giovanni Battista; Van Gemert, Wayne; D'Ambrosio, Lia; Zignol, Matteo; Floyd, Katherine; Centis, Rosella; Cirillo, Daniela M; Tortoli, Enrico; Gilpin, Chris; de Dieu Iragena, Jean; Falzon, Dennis; Raviglione, Mario

2013-07-01

If tuberculosis (TB) is to be eliminated as a global health problem in the foreseeable future, improved detection of patients, earlier diagnosis and timely identification of rifampicin resistance will be critical. New diagnostics released in recent years have improved this perspective but they require investments in laboratory infrastructure, biosafety and staff specialisation beyond the means of many resource-constrained settings where most patients live. Xpert MTB/RIF, a new assay employing automated nucleic acid amplification to detect Mycobacterium tuberculosis, as well as mutations that confer rifampicin resistance, holds the promise to largely overcome these operational challenges. In this article we position Xpert MTB/RIF in today's TB diagnostic landscape and describe its additional potential as an adjunct to surveillance and surveys, taking into account considerations of pricing and ethics. In what could serve as a model for the future formulation of new policy on diagnostics, we trace the unique process by which the World Health Organization consulted international expertise and systematically assessed published evidence and freshly emerging experience from the field ahead of its endorsement of the Xpert MTB/RIF technology in 2010, summarise subsequent research findings and guidance on who to test and how, and provide perspectives on scaling up the new technology.

Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different.

PubMed

Lee, Roy E; Henricks, Walter H; Sirintrapun, Sahussapont J

2016-03-01

Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory.

78 FR 36201 - National Cancer Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... potential new cancer diagnostics. The outcome of the evaluation will be information for consideration by an... contract resources for development of the potential diagnostics to improve the treatment of cancer. The... development resources for potential new diagnostics for cancer. Place: National Cancer Institute, 9609 Medical...

Design control considerations for biologic-device combination products.

PubMed

Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

2017-03-01

Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting development of innovative, safe and effective combination products. It remains the manufacturer's responsibility to comply with the relevant requirements and regulations, and develop good business practices that clearly describe how these practices comply with FDA's final rule (21 CFR Part 4) and aligns with the company's already established quality system. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-invasive diagnostic platforms in management of non-small cell lung cancer: opportunities and challenges

PubMed Central

Pennell, Nathan A.

2017-01-01

Several non-invasive diagnostic platforms are already being incorporated in routine clinical practice in the work up and monitoring of patients with lung cancer. These approaches have great potential to improve patient selection and monitor patients while on therapy, however several challenges exist in clinical validation and standardization of such platforms. In this review, we summarize the current technologies available for non-invasive diagnostic evaluation from the blood of patients with non-small cell lung cancer (NSCLC), and discuss the technical and logistical challenges associated incorporating such testing in clinical practice. PMID:29057238

Mucosal melanoma: a clinically and biologically unique disease entity.

PubMed

Carvajal, Richard D; Spencer, Sharon A; Lydiatt, William

2012-03-01

Mucosal melanoma (MM) is an aggressive and clinically complex malignancy made more challenging by its relative rarity. Because of the rarity of MM as a whole, and because of the unique biology and clinical challenges of MM arising from each anatomic location, understanding of this disease and its optimal management remains limited. The impact of various treatment strategies on disease control and survival has been difficult to assess because of the small size of most reported series of MM arising from any one particular site, the retrospective nature of most series, and the lack of a uniform comprehensive staging system for this disease. This article summarizes the clinical, pathologic, and molecular features, and the diagnostic and therapeutic considerations for the management of MM, underscoring the similarities and differences from cutaneous melanoma. Furthermore, the distinct clinical features and management implications unique to melanoma arising from the mucosal surfaces of the head and neck, the anorectal region, and the female genital tract are highlighted.

CT Angiography after 20 Years

PubMed Central

Rubin, Geoffrey D.; Leipsic, Jonathon; Schoepf, U. Joseph; Fleischmann, Dominik; Napel, Sandy

2015-01-01

Through a marriage of spiral computed tomography (CT) and graphical volumetric image processing, CT angiography was born 20 years ago. Fueled by a series of technical innovations in CT and image processing, over the next 5–15 years, CT angiography toppled conventional angiography, the undisputed diagnostic reference standard for vascular disease for the prior 70 years, as the preferred modality for the diagnosis and characterization of most cardiovascular abnormalities. This review recounts the evolution of CT angiography from its development and early challenges to a maturing modality that has provided unique insights into cardiovascular disease characterization and management. Selected clinical challenges, which include acute aortic syndromes, peripheral vascular disease, aortic stent-graft and transcatheter aortic valve assessment, and coronary artery disease, are presented as contrasting examples of how CT angiography is changing our approach to cardiovascular disease diagnosis and management. Finally, the recently introduced capabilities for multispectral imaging, tissue perfusion imaging, and radiation dose reduction through iterative reconstruction are explored with consideration toward the continued refinement and advancement of CT angiography. PMID:24848958

Rural and remote care

PubMed Central

Marciniuk, Darcy

2016-01-01

The challenges of providing quality respiratory care to persons living in rural or remote communities can be daunting. These populations are often vulnerable in terms of both health status and access to care, highlighting the need for innovation in service delivery. The rapidly expanding options available using telehealthcare technologies have the capacity to allow patients in rural and remote communities to connect with providers at distant sites and to facilitate the provision of diagnostic, monitoring, and therapeutic services. Successful implementation of telehealthcare programs in rural and remote settings is, however, contingent upon accounting for key technical, organizational, social, and legal considerations at the individual, community, and system levels. This review article discusses five types of telehealthcare delivery that can facilitate respiratory care for residents of rural or remote communities: remote monitoring (including wearable and ambient systems; remote consultations (between providers and between patients and providers), remote pulmonary rehabilitation, telepharmacy, and remote sleep monitoring. Current and future challenges related to telehealthcare are discussed. PMID:26902542

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.

From Cleanroom to Desktop: Emerging Micro-Nanofabrication Technology for Biomedical Applications

PubMed Central

Wang, Wei

2010-01-01

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities. PMID:21161384

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.

Early lessons from schistosomiasis mass drug administration programs

PubMed Central

Secor, W. Evan

2015-01-01

Mass drug administration using praziquantel is the backbone of the current strategy for the control of schistosomiasis. As the theoretical plans have moved into practical application, certain challenges with this approach have surfaced, and it is likely that annual mass drug administration alone may not be sufficient to achieve program goals. However, mass drug administration is still the only available intervention that can be readily used in the wide variety of settings where schistosomiasis is endemic. The task then becomes how to improve this approach and identify what adjuncts to mass drug administration are effective, as programs move from morbidity control to elimination goals. Other aspects worthy of consideration include how best to employ new diagnostic tools to more easily identify where treatment is needed, and new formulations of praziquantel to extend the availability of treatment to all age groups. The aim of this review is to highlight both areas of challenge and of opportunity to improve the public health impact of schistosomiasis control programs. PMID:26937275

From cleanroom to desktop: emerging micro-nanofabrication technology for biomedical applications.

PubMed

Pan, Tingrui; Wang, Wei

2011-02-01

This review is motivated by the growing demand for low-cost, easy-to-use, compact-size yet powerful micro-nanofabrication technology to address emerging challenges of fundamental biology and translational medicine in regular laboratory settings. Recent advancements in the field benefit considerably from rapidly expanding material selections, ranging from inorganics to organics and from nanoparticles to self-assembled molecules. Meanwhile a great number of novel methodologies, employing off-the-shelf consumer electronics, intriguing interfacial phenomena, bottom-up self-assembly principles, etc., have been implemented to transit micro-nanofabrication from a cleanroom environment to a desktop setup. Furthermore, the latest application of micro-nanofabrication to emerging biomedical research will be presented in detail, which includes point-of-care diagnostics, on-chip cell culture as well as bio-manipulation. While significant progresses have been made in the rapidly growing field, both apparent and unrevealed roadblocks will need to be addressed in the future. We conclude this review by offering our perspectives on the current technical challenges and future research opportunities.

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

Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis.

PubMed

Pfaller, Michael A; Castanheira, Mariana

2016-01-01

Candidemia and other forms of candidiasis are associated with considerable excess mortality and costs. Despite the addition of several new antifungal agents with improved spectrum and potency, the frequency of Candida infection and associated mortality have not decreased in the past two decades. The lack of rapid and sensitive diagnostic tests has led to considerable overuse of antifungal agents resulting in increased costs, selection pressure for resistance, unnecessary drug toxicity, and adverse drug interactions. Both the lack of timely diagnostic tests and emergence of antifungal resistance pose considerable problems for antifungal stewardship. Whereas antifungal stewardship with a focus on nosocomial candidiasis should be able to improve the administration of antifungal therapy in terms of drug selection, proper dose and duration, source control and de-escalation therapy, an important parameter, timeliness of antifungal therapy, remains a victim of slow and insensitive diagnostic tests. Fortunately, new proteomic and molecular diagnostic tools are improving the time to species identification and detection. In this review we will describe the potential impact that rapid diagnostic testing and antifungal stewardship can have on the management of nosocomial candidiasis. © 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.

Sacro-anterior haemangiopericytoma: a case report

PubMed Central

Ge, Xiu-Hong; Liu, Shuai-Shuai; Shan, Hu-Sheng; Wang, Zhi-Min; Li, Qian-Wen

2014-01-01

Haemangiopericytoma (HPC) is a rare vascular tumor with borderline malignancy, considerable histological variability, and unpredictable clinical and biological behavior. HPC can present a diagnostic challenge because of its indeterminate clinical, radiological, and pathological features. HPC generally presents in adulthood and is equally frequent in both sexes. HPC can arise in any site in the body as a slowly growing and painless mass. The precise cell type origin of HPC is uncertain. One third of HPCs occur in the head and neck areas. Exceptional cases of hemangioblastoma arising outside the head and neck areas have been reported, but little is known about their clinicopathologic and immunohistochemical features. This study reports on a case of a large sacro-anterior HPC in a 65-year-old male. PMID:25009757

Percutaneous Biopsy of Retrobulbar Masses: Anatomical Considerations and MRI Guidance

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

Edalat, Faramarz, E-mail: faramarz.edalat@gmail.com; Cazzato, Roberto Luigi; Garnon, Julien

2017-04-15

PurposeObtaining adequate tissue from retrobulbar masses remains a challenge. To this end, a new method of retrobulbar mass biopsy using MRI guidance is presented.Materials and MethodsTwo patients (7- and 71-year-old male) with indeterminate retrobulbar masses underwent bioptic and cytological samplings using MR-compatible 18G and 20–22G needles, and multi-planar MR fluoroscopy. An inferior approach was taken to avoid injury to the optic nerve and ophthalmic arteries.ResultsThe two biopsies were completed without complication. The core biopsy resulted in a final diagnosis, whereas the cytological sampling was non-diagnostic.ConclusionPercutaneous MR-guided retrobulbar mass biopsy proved to be feasible and safe in the two cases describedmore » in this report.« less

Advances in Candida detection platforms for clinical and point-of-care applications

PubMed Central

Safavieh, Mohammadali; Coarsey, Chad; Esiobu, Nwadiuto; Memic, Adnan; Vyas, Jatin Mahesh; Shafiee, Hadi; Asghar, Waseem

2016-01-01

Invasive candidiasis remains one of the most serious community and healthcare-acquired infections worldwide. Conventional Candida detection methods based on blood and plate culture are time-consuming and require at least 2–4 days to identify various Candida species. Despite considerable advances for candidiasis detection, the development of simple, compact and portable point-of-care diagnostics for rapid and precise testing that automatically performs cell lysis, nucleic acid extraction, purification and detection still remains a challenge. Here, we systematically review most prominent conventional and nonconventional techniques for the detection of various Candida species, including Candida staining, blood culture, serological testing and nucleic acid-based analysis. We also discuss the most advanced lab on a chip devices for candida detection. PMID:27093473

Diagnosis and management of functional symptoms in inflammatory bowel disease in remission

PubMed Central

Teruel, Carlos; Garrido, Elena; Mesonero, Francisco

2016-01-01

Inflammatory bowel disease (IBD) patients in remission may suffer from gastrointestinal symptoms that resemble irritable bowel syndrome (IBS). Knowledge on this issue has increased considerably in the last decade, and it is our intention to review and summarize it in the present work. We describe a problematic that comprises physiopathological uncertainties, diagnostic difficulties, as IBS-like symptoms are very similar to those produced by an inflammatory flare, and the necessity of appropriate management of these patients, who, although in remission, have impaired quality of life. Ultimately, from almost a philosophical point of view, the presence of IBS-like symptoms in IBD patients in remission supposes a challenge to the traditional functional-organic dichotomy, suggesting the need for a change of paradigm. PMID:26855814

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

Ectopic Thymic Cyst of the Subglottis: Considerations for Diagnosis and Management.

PubMed

Ahmad, Iram; Kirby, Patricia; Liming, Bryan

2018-03-01

To share the diagnostic and management challenges created by an extremely rare airway lesion-the subglottic ectopic thymic cyst. Case report and literature review. We review the presentation, management, and clinical course of an infant who presented with a subglottic mass that was histologically confirmed as a thymic cyst. A brief literature review supplements the case presentation Results: We present the third described case of an ectopic thymic cyst presenting as a subglottic mass. The differential diagnosis of subglottic masses in neonates consists primarily of subglottic hemangioma and mucous retention cysts. Otolaryngologists must be prepared for unexpected findings when dealing with critical airways. We compare the presentation and management of our patient with the 2 previously described cases. We propose an embryologic theory for the origin of these rare lesions. An ectopic thymic cyst is a rare and unexpected cause of neonatal stridor. Management of pediatric airway lesions must allow for unexpected findings at the time of diagnostic and therapeutic endoscopy. The appropriate management of subglottic thymic cysts is poorly defined, but close surveillance for recurrence is mandatory.

Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point

NASA Astrophysics Data System (ADS)

Bose, Tanima; Latawiec, Diane; Mondal, Partha Pratim; Mandal, Subhra

2014-08-01

The ever-increasing number of diseases worldwide requires comprehensive, efficient, and cost-effective modes of treatments. Among various strategies, nanomaterials fulfill most of these criteria. The unique physicochemical properties of nanoparticles have made them a premier choice as a drug or a drug delivery system for the purpose of treatment, and as bio-detectors for disease prognosis. However, the main challenge is the proper consideration of the physical properties of these nanomaterials, while developing them as potential tools for therapeutics and/or diagnostics. In this review, we focus mainly on the characteristics of nanoparticles to develop an effective and sensitive system for clinical purposes. This review will present an overview of the important properties of nanoparticles, through their journey from its route of administration until disposal from the human body after accomplishing targeted functionality. We have chosen cancer as our model disease to explain the potentiality of nano-systems for therapeutics and diagnostics in relation to several organs (intestine, lung, brain, etc.). Furthermore, we have discussed their biodegradability and accumulation probability which can cause unfavorable side effects in healthy human subjects.

Research Domain Criteria versus DSM V: How does this debate affect attempts to model corticostriatal dysfunction in animals?

PubMed

Young, Jared W; Winstanley, Catharine A; Brady, Anne Marie; Hall, Frank Scott

2017-05-01

For decades, the nosology of mental illness has been based largely upon the descriptions in the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM). A recent challenge to the DSM approach to psychiatric nosology from the National Institute on Mental Health (USA) defines Research Domain Criteria (RDoC) as an alternative. For RDoC, psychiatric illnesses are not defined as discrete categories, but instead as specific behavioral dysfunctions irrespective of DSM diagnostic categories. This approach was driven by two primary weaknesses noted in the DSM: (1) the same symptoms occur in very different disease states; and (2) DSM criteria lack grounding in the underlying biological causes of mental illness. RDoC intends to ground psychiatric nosology in those underlying mechanisms. This review addresses the suitability of RDoC vs. DSM from the view of modeling mental illness in animals. A consideration of all types of psychiatric dysfunction is beyond the scope of this review, which will focus on models of conditions associated with frontostriatal dysfunction. Copyright © 2016. Published by Elsevier Ltd.

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

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 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.

Posttraumatic Stress Disorder in the DSM-5: Controversy, Change, and Conceptual Considerations.

PubMed

Pai, Anushka; Suris, Alina M; North, Carol S

2017-02-13

The criteria for posttraumatic stress disorder PTSD have changed considerably with the newest edition of the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders ( DSM-5 ). Changes to the diagnostic criteria from the DSM-IV to DSM-5 include: the relocation of PTSD from the anxiety disorders category to a new diagnostic category named "Trauma and Stressor-related Disorders", the elimination of the subjective component to the definition of trauma, the explication and tightening of the definitions of trauma and exposure to it, the increase and rearrangement of the symptoms criteria, and changes in additional criteria and specifiers. This article will explore the nosology of the current diagnosis of PTSD by reviewing the changes made to the diagnostic criteria for PTSD in the DSM-5 and discuss how these changes influence the conceptualization of PTSD.

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.

Fear of knowledge: Clinical hypotheses in diagnostic and prognostic reasoning.

PubMed

Chiffi, Daniele; Zanotti, Renzo

2017-10-01

Patients are interested in receiving accurate diagnostic and prognostic information. Models and reasoning about diagnoses have been extensively investigated from a foundational perspective; however, for all its importance, prognosis has yet to receive a comparable degree of philosophical and methodological attention, and this may be due to the difficulties inherent in accurate prognostics. In the light of these considerations, we discuss a considerable body of critical thinking on the topic of prognostication and its strict relations with diagnostic reasoning, pointing out the distinction between nosographic and pathophysiological types of diagnosis and prognosis, underlying the importance of the explication and explanation processes. We then distinguish between various forms of hypothetical reasoning applied to reach diagnostic and prognostic judgments, comparing them with specific forms of abductive reasoning. The main thesis is that creative abduction regarding clinical hypotheses in diagnostic process is very unlikely to occur, whereas this seems to be often the case for prognostic judgments. The reasons behind this distinction are due to the different types of uncertainty involved in diagnostic and prognostic judgments. © 2016 John Wiley & Sons, Ltd.

Perspectives on Introduction and Implementation of New Point-of-Care Diagnostic Tests

PubMed Central

Palamountain, Kara M.; Baker, Jeff; Cowan, Elliot P.; Essajee, Shaffiq; Mazzola, Laura T.; Metzler, Mutsumi; Schito, Marco; Stevens, Wendy S.; Young, Gloria J.

2012-01-01

In recent years, there has been significant investment from both the private and public sectors in the development of diagnostic technologies to meet the need for human immunodeficiency virus (HIV) and tuberculosis testing in low-resource settings. Future investments should ensure that the most appropriate technologies are adopted in settings where they will have a sustainable impact. Achieving these aims requires the involvement of many stakeholders, as their needs, operational constraints, and priorities are often distinct. Here, we discuss these considerations from different perspectives representing those of various stakeholders involved in the development, introduction, and implementation of diagnostic tests. We also discuss some opportunities to address these considerations. PMID:22402038

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.

ATR spectra on boundary with mixture containing organic substances

NASA Astrophysics Data System (ADS)

Schelokov, R. V.; Yatsishen, V. V.

2005-02-01

The problem of not destroying diagnostics and dosing of radiation at laser therapy is one of important in medicine. Therefore the purpose of our work is development of method ATR for diagnostics and researches in biomedicine. In this work as objects of consideration were: a mixture of nicotine with water, a mixture of an ascorbic acid with water and surface lesions of an eye cornea by a herpes virus. Results of our consideration are the ATR spectra defined at different concentration of organic substances and virions.

DNA-informed breeding of rosaceous crops: promises, progress and prospects

PubMed Central

Peace, Cameron P

2017-01-01

Crops of the Rosaceae family provide valuable contributions to rural economies and human health and enjoyment. Sustained solutions to production challenges and market demands can be met with genetically improved new cultivars. Traditional rosaceous crop breeding is expensive and time-consuming and would benefit from improvements in efficiency and accuracy. Use of DNA information is becoming conventional in rosaceous crop breeding, contributing to many decisions and operations, but only after past decades of solved challenges and generation of sufficient resources. Successes in deployment of DNA-based knowledge and tools have arisen when the ‘chasm’ between genomics discoveries and practical application is bridged systematically. Key steps are establishing breeder desire for use of DNA information, adapting tools to local breeding utility, identifying efficient application schemes, accessing effective services in DNA-based diagnostics and gaining experience in integrating DNA information into breeding operations and decisions. DNA-informed germplasm characterization for revealing identity and relatedness has benefitted many programs and provides a compelling entry point to reaping benefits of genomics research. DNA-informed germplasm evaluation for predicting trait performance has enabled effective reallocation of breeding resources when applied in pioneering programs. DNA-based diagnostics is now expanding from specific loci to genome-wide considerations. Realizing the full potential of this expansion will require improved accuracy of predictions, multi-trait DNA profiling capabilities, streamlined breeding information management systems, strategies that overcome plant-based features that limit breeding progress and widespread training of current and future breeding personnel and allied scientists. PMID:28326185

Practical Considerations for Clinical PET/MR Imaging.

PubMed

Galgano, Samuel; Viets, Zachary; Fowler, Kathryn; Gore, Lael; Thomas, John V; McNamara, Michelle; McConathy, Jonathan

2018-01-01

Clinical PET/MR imaging is currently performed at a number of centers around the world as part of routine standard of care. This article focuses on issues and considerations for a clinical PET/MR imaging program, focusing on routine standard-of-care studies. Although local factors influence how clinical PET/MR imaging is implemented, the approaches and considerations described here intend to apply to most clinical programs. PET/MR imaging provides many more options than PET/computed tomography with diagnostic advantages for certain clinical applications but with added complexity. A recurring theme is matching the PET/MR imaging protocol to the clinical application to balance diagnostic accuracy with efficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Practical Considerations for Clinical PET/MR Imaging.

PubMed

Galgano, Samuel; Viets, Zachary; Fowler, Kathryn; Gore, Lael; Thomas, John V; McNamara, Michelle; McConathy, Jonathan

2017-05-01

Clinical PET/MR imaging is currently performed at a number of centers around the world as part of routine standard of care. This article focuses on issues and considerations for a clinical PET/MR imaging program, focusing on routine standard-of-care studies. Although local factors influence how clinical PET/MR imaging is implemented, the approaches and considerations described here intend to apply to most clinical programs. PET/MR imaging provides many more options than PET/computed tomography with diagnostic advantages for certain clinical applications but with added complexity. A recurring theme is matching the PET/MR imaging protocol to the clinical application to balance diagnostic accuracy with efficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Preliminary consideration of CFETR ITER-like case diagnostic system.

PubMed

Li, G S; Yang, Y; Wang, Y M; Ming, T F; Han, X; Liu, S C; Wang, E H; Liu, Y K; Yang, W J; Li, G Q; Hu, Q S; Gao, X

2016-11-01

Chinese Fusion Engineering Test Reactor (CFETR) is a new superconducting tokamak device being designed in China, which aims at bridging the gap between ITER and DEMO, where DEMO is a tokamak demonstration fusion reactor. Two diagnostic cases, ITER-like case and towards DEMO case, have been considered for CFETR early and later operating phases, respectively. In this paper, some preliminary consideration of ITER-like case will be presented. Based on ITER diagnostic system, three versions of increased complexity and coverage of the ITER-like case diagnostic system have been developed with different goals and functions. Version A aims only machine protection and basic control. Both of version B and version C are mainly for machine protection, basic and advanced control, but version C has an increased level of redundancy necessary for improved measurements capability. The performance of these versions and needed R&D work are outlined.

Preliminary consideration of CFETR ITER-like case diagnostic system

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

Li, G. S.; Liu, Y. K.; Gao, X.

2016-11-15

Chinese Fusion Engineering Test Reactor (CFETR) is a new superconducting tokamak device being designed in China, which aims at bridging the gap between ITER and DEMO, where DEMO is a tokamak demonstration fusion reactor. Two diagnostic cases, ITER-like case and towards DEMO case, have been considered for CFETR early and later operating phases, respectively. In this paper, some preliminary consideration of ITER-like case will be presented. Based on ITER diagnostic system, three versions of increased complexity and coverage of the ITER-like case diagnostic system have been developed with different goals and functions. Version A aims only machine protection and basicmore » control. Both of version B and version C are mainly for machine protection, basic and advanced control, but version C has an increased level of redundancy necessary for improved measurements capability. The performance of these versions and needed R&D work are outlined.« less

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.

Post-traumatic stress disorder--a diagnostic and therapeutic challenge.

PubMed

Frommberger, Ulrich; Angenendt, Jörg; Berger, Mathias

2014-01-31

In Germany, the one-month prevalence of post-traumatic stress disorder (PTSD) is in the range of 1% to 3%. Soldiers, persons injured in accidents, and victims of domestic violence increasingly seek medical help for symptoms of emotional stress. Days lost from work and monetary compensation for emotional disturbances are markedly on the rise. The term "PTSD" is commonly used uncritically and imprecisely, with too little regard for the existing diagnostic criteria. It is at risk of turning into a nonspecific collective term for emotional stress of any kind. We selectively reviewed the literature in the PubMed database and pertinent journals, with additional consideration of the recommendations and guidelines of medical societies from Germany and abroad. The characteristic types of reactions seen in PTSD are nightmares and an intense, repetitive, intrusive "reliving" of the traumatic event(s). Emotional traumatization manifests itself not only as PTSD but also through major effects on other mental and somatic diseases. An early, trauma-focused behavioral therapeutic intervention involving several sessions, generally on an outpatient basis, can prevent the development of PTSD. The most important components of effective treatment are a focus on the particular trauma experienced and confrontation with the patient's memories of the trauma. The best existing evidence is for cognitive therapy, behavioral therapy according to the exposure paradigm of Foa, and eye movement desensitization and reprocessing therapy. The most recent meta-analysis reveals effect strengths of g = 1.14 for all types of psychotherapy and g = 0.42 for all types of pharmacotherapy taken together (with considerable differences among psychotherapeutic methods and among drugs). The efficacy of psychodynamic therapy, systemic therapy, body-oriented therapy, and hypnotherapy has not been adequately documented in randomized controlled trials. PTSD can be precisely diagnosed and effectively treated when the diagnostic criteria and guideline recommendations are taken into account. Referral for trauma-focused psychotherapy should be considered if the acute symptoms persist for several weeks.

State of the art diagnostic of mold diseases: a practical guide for clinicians.

PubMed

Beirão, F; Araujo, R

2013-01-01

The epidemiology of fungal diseases changed, and molds have been increasingly associated with high mortality in severe immunocompromised patients. Invasive mold diseases may originate from the airborne conidia through inhalation or inoculation in skin fissures associated with indwelling catheters, wounds, burns, or onychomycosis. The diagnosis and treatment of fungal diseases is problematic and raises considerable challenges. Diagnosis of invasive mold diseases includes several methodologies, of which the most commonly used are the cultural methods, antigen testing, nucleic acid detection, and radiological imaging. Galactomannan and (1 → 3)-β-D-glucan detection significantly improved mold diagnosis in the last decade. Several molecular strategies have been proposed over the years but no consensus was achieved for standardized protocols or cut-off values. Recently, the first commercially available molecular assay for detection of Aspergillus was tested and the results were highly reproducible. In addition, blood cultures may also be helpful for invasive aspergillosis by following a novel procedure for the recovery of Aspergillus spp. from blood cultures. The association of distinct diagnostic methods, particularly molecular tests, galactomannan, and/or (1 → 3)-β-D-glucan detection, may provide earlier and more sensitive diagnosis of mold diseases and be indicative for early antifungal treatment. Accurate routine use of diagnostic tests can be cost-effective for laboratories and be of great value to patients.

Toxocariasis: a silent threat with a progressive public health impact.

PubMed

Chen, Jia; Liu, Quan; Liu, Guo-Hua; Zheng, Wen-Bin; Hong, Sung-Jong; Sugiyama, Hiromu; Zhu, Xing-Quan; Elsheikha, Hany M

2018-06-13

Toxocariasis is a neglected parasitic zoonosis that afflicts millions of the pediatric and adolescent populations worldwide, especially in impoverished communities. This disease is caused by infection with the larvae of Toxocara canis and T. cati, the most ubiquitous intestinal nematode parasite in dogs and cats, respectively. In this article, recent advances in the epidemiology, clinical presentation, diagnosis and pharmacotherapies that have been used in the treatment of toxocariasis are reviewed. Over the past two decades, we have come far in our understanding of the biology and epidemiology of toxocariasis. However, lack of laboratory infrastructure in some countries, lack of uniform case definitions and limited surveillance infrastructure are some of the challenges that hindered the estimation of global disease burden. Toxocariasis encompasses four clinical forms: visceral, ocular, covert and neural. Incorrect or misdiagnosis of any of these disabling conditions can result in severe health consequences and considerable medical care spending. Fortunately, multiple diagnostic modalities are available, which if effectively used together with the administration of appropriate pharmacologic therapies, can minimize any unnecessary patient morbidity. Although progress has been made in the management of toxocariasis patients, there remains much work to be done. Implementation of new technologies and better understanding of the pathogenesis of toxocariasis can identify new diagnostic biomarkers, which may help in increasing diagnostic accuracy. Also, further clinical research breakthroughs are needed to develop better ways to effectively control and prevent this serious disease.

Questioning diagnoses in clinical practice: a thematic analysis of clinical psychologists' accounts of working beyond diagnosis in the United Kingdom.

PubMed

Randall-James, James; Coles, Steven

2018-02-08

The British Psychological Society proposes that clinical psychologists are well placed to move beyond psychiatric diagnoses and develop alternative practices. This study sought to explore what the application of these guiding principles looks like in clinical practice, the challenges faced and possible routes forward. A purpose-designed survey was completed by 305 respondents and a thematic analysis completed. Thematic analysis was used to identify five superordinate themes relating to individuals, relational, others, structures and society, comprising of a total of 21 group themes. The presented group themes highlight an array of approaches to practicing beyond diagnosis and factors that help and hinder such action; from scaffolding change, becoming leaders, relating to the multi-disciplinary team, restructuring services and the processes of change. A key concept was "playing the diagnostic game". "Playing the diagnostic game" enables psychologists to manage an array of tensions and anxieties: conflicts between belief and practice, relationships with colleagues, and dilemmas of position and power. It also potentially limits a concerted questioning of diagnosis and consideration of alternatives. An alternative conceptual framework for non-diagnostic practice is needed to aid the collective efforts of clinical psychologists developing their practice beyond diagnosis, some of which have been highlighted in this study. Until then, ways of mitigating the perceived threats to questioning diagnosis need further exploration, theorising and backing.

Obese patients and radiography literature: what do we know about a big issue?

PubMed Central

Le, Nhat Tan Thanh; Robinson, John; Lewis, Sarah J

2015-01-01

Obesity is a global health issue with obese patients requiring specialised diagnosis, treatment and care through the health service. The practical and social difficulties associated with medical imaging of obese patients are an increasingly common problem and it is currently unknown how student and qualified radiographers perceive and respond to these challenges. By better understanding challenges presented in providing quality imaging and care of imaging obese patients, education for both qualified and student radiographers can be enhanced. Radiographers are heavily reliant on visual and tactile senses to locate the position of anatomical structures for diagnostic imaging and determine radiation exposure through a delicate consideration of dose, image quality and anatomical attenuation. However, obese patients require modifications to routine radiographic practice in terms of movement/assisted positioning, equipment capabilities to take increased weight or coverage. These patients may also be subject to compromised radiological diagnosis through poor visualisation of structures. In this paper, the professional and educational literature was narratively reviewed to assess gaps in the evidence base related to the skill and care knowledge for obese patients. Literature was sourced relating to discrete radiographic considerations such as the technical factors of imaging obese patients, exposure and the impact of obesity on imaging departments’ service provisions. The recent literature (post-2000 to coincide with the sharp increase in global obesity) on the perceptions of health professionals and student health practitioners has also been explored because there are no specific radiographer studies to report. By understanding the research in similar fields, we may identify what common attitudes qualified and student radiographer's hold and what challenges, technical and care related, can be prepared for. PMID:26229678

Developing the radiation protection safety culture in the UK.

PubMed

Cole, P; Hallard, R; Broughton, J; Coates, R; Croft, J; Davies, K; Devine, I; Lewis, C; Marsden, P; Marsh, A; McGeary, R; Riley, P; Rogers, A; Rycraft, H; Shaw, A

2014-06-01

In the UK, as elsewhere, there is potential to improve how radiological challenges are addressed through improvement in, or development of, a strong radiation protection (RP) safety culture. In preliminary work in the UK, two areas have been identified as having a strong influence on UK society: the healthcare and nuclear industry sectors. Each has specific challenges, but with many overlapping common factors. Other sectors will benefit from further consideration.In order to make meaningful comparisons between these two principal sectors, this paper is primarily concerned with cultural aspects of RP in the working environment and occupational exposures rather than patient doses.The healthcare sector delivers a large collective dose to patients each year, particularly for diagnostic purposes, which continues to increase. Although patient dose is not the focus, it must be recognised that collective patient dose is inevitably linked to collective occupational exposure, especially in interventional procedures.The nuclear industry faces major challenges as work moves from operations to decommissioning on many sites. This involves restarting work in the plants responsible for the much higher radiation doses of the 1960/70s, but also performing tasks that are considerably more difficult and hazardous than those original performed in these plants.Factors which influence RP safety culture in the workplace are examined, and proposals are considered for a series of actions that may lead to an improvement in RP culture with an associated reduction in dose in many work areas. These actions include methods to improve knowledge and awareness of radiation safety, plus ways to influence management and colleagues in the workplace. The exchange of knowledge about safety culture between the nuclear industry and medical areas may act to develop RP culture in both sectors, and have a wider impact in other sectors where exposures to ionising radiations can occur.

Obese patients and radiography literature: what do we know about a big issue?

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

Le, Nhat Tan Thanh; Robinson, John; Lewis, Sarah J, E-mail: sarah.lewis@sydney.edu.au

Obesity is a global health issue with obese patients requiring specialised diagnosis, treatment and care through the health service. The practical and social difficulties associated with medical imaging of obese patients are an increasingly common problem and it is currently unknown how student and qualified radiographers perceive and respond to these challenges. By better understanding challenges presented in providing quality imaging and care of imaging obese patients, education for both qualified and student radiographers can be enhanced. Radiographers are heavily reliant on visual and tactile senses to locate the position of anatomical structures for diagnostic imaging and determine radiation exposuremore » through a delicate consideration of dose, image quality and anatomical attenuation. However, obese patients require modifications to routine radiographic practice in terms of movement/assisted positioning, equipment capabilities to take increased weight or coverage. These patients may also be subject to compromised radiological diagnosis through poor visualisation of structures. In this paper, the professional and educational literature was narratively reviewed to assess gaps in the evidence base related to the skill and care knowledge for obese patients. Literature was sourced relating to discrete radiographic considerations such as the technical factors of imaging obese patients, exposure and the impact of obesity on imaging departments’ service provisions. The recent literature (post-2000 to coincide with the sharp increase in global obesity) on the perceptions of health professionals and student health practitioners has also been explored because there are no specific radiographer studies to report. By understanding the research in similar fields, we may identify what common attitudes qualified and student radiographer's hold and what challenges, technical and care related, can be prepared for.« less

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…

Familial diagnostic experiences in paediatric oncology.

PubMed

Evans, N T; Wakefield, C E; McLoone, J K; Cohn, R J

2015-01-06

Diagnostic delays may not have significant prognostic implications in paediatric oncology, but psychological impacts remain understudied. Interviews exploring diagnostic experiences were conducted with childhood cancer survivors (n=19), parents (n=78) and siblings (n=15). Median diagnostic time was 3 weeks. Participants described a mixture of rapid diagnoses (28.9%), plus delayed appraisal intervals (that is, parent- or patient-associated diagnostic delays; 40.0%) and diagnostic intervals (that is, healthcare-associated delays; 46.7%). Families experiencing delays described guilt and anger and deleterious impacts on the family-clinician relationship. Some believed delays impacted on treatment and prognosis. The effect of the diagnostic experience can be considerable.

Status of US ITER Diagnostics

NASA Astrophysics Data System (ADS)

Stratton, B.; Delgado-Aparicio, L.; Hill, K.; Johnson, D.; Pablant, N.; Barnsley, R.; Bertschinger, G.; de Bock, M. F. M.; Reichle, R.; Udintsev, V. S.; Watts, C.; Austin, M.; Phillips, P.; Beiersdorfer, P.; Biewer, T. M.; Hanson, G.; Klepper, C. C.; Carlstrom, T.; van Zeeland, M. A.; Brower, D.; Doyle, E.; Peebles, A.; Ellis, R.; Levinton, F.; Yuh, H.

2013-10-01

The US is providing 7 diagnostics to ITER: the Upper Visible/IR cameras, the Low Field Side Reflectometer, the Motional Stark Effect diagnostic, the Electron Cyclotron Emission diagnostic, the Toroidal Interferometer/Polarimeter, the Core Imaging X-Ray Spectrometer, and the Diagnostic Residual Gas Analyzer. The front-end components of these systems must operate with high reliability in conditions of long pulse operation, high neutron and gamma fluxes, very high neutron fluence, significant neutron heating (up to 7 MW/m3) , large radiant and charge exchange heat flux (0.35 MW/m2) , and high electromagnetic loads. Opportunities for repair and maintenance of these components will be limited. These conditions lead to significant challenges for the design of the diagnostics. Space constraints, provision of adequate radiation shielding, and development of repair and maintenance strategies are challenges for diagnostic integration into the port plugs that also affect diagnostic design. The current status of design of the US ITER diagnostics is presented and R&D needs are identified. Supported by DOE contracts DE-AC02-09CH11466 (PPPL) and DE-AC05-00OR22725 (UT-Battelle, LLC).

Clinical bacteriology in low-resource settings: today's solutions.

PubMed

Ombelet, Sien; Ronat, Jean-Baptiste; Walsh, Timothy; Yansouni, Cedric P; Cox, Janneke; Vlieghe, Erika; Martiny, Delphine; Semret, Makeda; Vandenberg, Olivier; Jacobs, Jan

2018-03-05

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections. Copyright © 2018 Elsevier Ltd. All rights reserved.

Network analysis of pediatric eating disorder symptoms in a treatment-seeking, transdiagnostic sample.

PubMed

Goldschmidt, Andrea B; Crosby, Ross D; Cao, Li; Moessner, Markus; Forbush, Kelsie T; Accurso, Erin C; Le Grange, Daniel

2018-02-01

Classifying eating disorders in youth is challenging in light of developmental considerations and high rates of diagnostic migration. Understanding the transactional relationships among eating disorder symptoms, both across the transdiagnostic spectrum and within specific diagnostic categories, may clarify which core eating disorder symptoms contribute to, and maintain, eating-related psychopathology in youth. We utilized network analysis to investigate interrelationships among eating disorder symptoms in 636 treatment-seeking children and adolescents (90.3% female) ages 6-18 years (M age = 15.4 ± 2.2). An undirected, weighted network of eating disorder symptoms was created using behavioral and attitudinal items from the Eating Disorder Examination. Across diagnostic groups, symptoms reflecting appearance-related concerns (e.g., dissatisfaction with shape and weight) and dietary restraint (e.g., a desire to have an empty stomach) were most strongly associated with other eating disorder symptoms in the network. Binge eating and compensatory behaviors (e.g., self-induced vomiting) were strongly connected to one another but not to other symptoms in the network. Network connectivity was similar across anorexia nervosa, bulimia nervosa, and otherwise specified feeding or eating disorder subgroups. Among treatment-seeking children and adolescents, dietary restraint and shape- and weight-related concerns appear to play key roles in the psychopathology of eating disorders, supporting cognitive-behavioral theories of onset and maintenance. Similarities across diagnostic categories provide support for a transdiagnostic classification scheme. Clinical interventions should seek to disrupt these symptoms early in treatment to achieve maximal outcomes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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.

A Roundtable Discussion: Combination Products: Twice the Challenge?

PubMed

Baird, Nolan; Binion, Steven B; Cammack, Jon; Paine, Stephanie Del; Gonzales, Rosemary; Passut, Jena; Weiner, John Barlow Barr

2015-01-01

Combination products are therapeutic or diagnostic medical products that combine drugs, devices, and/or biological products with one another. FDA developed a regulation (final rule) on Current Good Manufacturing Practices (CGMP) for combination products that became effective July 22, 2013 (21 CFR Part 4). AAMI recently developed a technical information report (TIR) that provides information on how to effectively implement FDA's regulation. The overall goal of the TIR is to aid informed, risk-based decisions in establishing CGMP operating systems that support development, manufacture, premarket regulatory evaluation, and ultimately commercialization of combination products. This article, a result of an discussion with industry and FDA representatives, explores the landscape of combination products, highlights important considerations in developing and seeking marketing clearance for these innovative products, and provides insight on trends in the area.

[Anomalous connection of inferior vena cava to left atrium: infrequent entity that can be a diagnosis and surgical challenge].

PubMed

Archundia García, A; Gómez Alvarez, E; Ixcamparij Rosales, C; Blanco Canto, M; Hernández Ruiz, M A

2000-01-01

This is the diagnostic experiences as well as the surgical mode of treatment used in a 31 years old women suffering diversion of the inferior vena cava into the left atrium associated with atrial septal defect. The patient had been previously studied and operated thrice under conventional circumstances at different institutions in order to solve the septal defect. The hemodynamic solution had not been reached due to a missing pathological definition. The cineangiogram through the saphenous vein specified the left atrium form the inferior vena cava. Some considerations are made on the surgical methods used for the fourth operation, and in regard of the fact that the patient refused blood transfusion because of religious convictions (Jehova Witness).

Validation conform ISO-15189 of assays in the field of autoimmunity: Joint efforts in The Netherlands.

PubMed

Mulder, Leontine; van der Molen, Renate; Koelman, Carin; van Leeuwen, Ester; Roos, Anja; Damoiseaux, Jan

2018-05-01

ISO 15189:2012 requires validation of methods used in the medical laboratory, and lists a series of performance parameters for consideration to include. Although these performance parameters are feasible for clinical chemistry analytes, application in the validation of autoimmunity tests is a challenge. Lack of gold standards or reference methods in combination with the scarcity of well-defined diagnostic samples of patients with rare diseases make validation of new assays difficult. The present manuscript describes the initiative of Dutch medical immunology laboratory specialists to combine efforts and perform multi-center validation studies of new assays in the field of autoimmunity. Validation data and reports are made available to interested Dutch laboratory specialists. Copyright © 2018 Elsevier B.V. All rights reserved.

Point of care investigations in pediatric care to improve health care in rural areas.

PubMed

Walia, Kamini

2013-07-01

The good quality laboratory services in developing countries are often limited to major urban centers. As a result, many commercially available high-quality diagnostic tests for infectious diseases are neither accessible nor affordable to patients in the rural areas. Health facilities in rural areas are compromised and this limits the usability and performance of the best medical diagnostic technologies in rural areas as they are designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of samples. The advent of new technologies have allowed miniaturization and integration of complex functions, which has made it possible for sophisticated diagnostic tools to move out of the developed-world laboratory in the form of a "point of care"(POC) tests. Many diagnostic tests are being developed using these platforms. However, the challenge is to develop diagnostics which are inexpensive, rugged and well suited to the medical and social contexts of the developing world and do not compromise on accuracy and reliability. The already available POC tests which are reliable and affordable, like for HIV infection, malaria, syphilis, and some neglected tropical diseases, and POC tests being developed for other diseases if correctly used and effectively regulated after rigorous evaluation, have the potential to make a difference in clinical management and improve surveillance. In order to use these tests effectively they would need to be supported by technically competent manpower, availability of good-quality reagents, and healthcare providers who value and are able to interpret laboratory results to guide treatment; and a system for timely communication between the laboratory and the healthcare provider. Strengthening the laboratories at the rural level can enable utilization of these diagnostics for improving the diagnosis and management of infectious diseases among children which require prompt treatment and thus, considerably reduce morbidity and mortality among the pediatric age group.

Some imminent but overlooked preanalytical and analytical challenges currently facing biomarkers and companion diagnostics.

PubMed

Halim, Abdel-Baset

2015-06-01

An incredibly high failure rate in the pharmaceutical industry has positioned personalized medicine with its prerequisite drug-diagnostic codevelopment, commonly known as companion diagnostics (CDx), in the frontline as an potential rescuer. This hopefulness is potentiated by the recent major advances and competitiveness in molecular diagnostics, making laboratory tests widely accessible at affordable prices. If executed correctly, biomarkers and CDx can potentially help the drug industry by enhancing the probability of success and possibly accelerating time to market; help the diagnostics industry develop tests utilizing precious, clinically annotated human samples; and, more importantly, benefit patients by supporting accurate diagnosis and selection of the most efficacious and least toxic therapies. However, this spectacular road is not yet paved, and it faces an enormous number of challenges. This paper will list these challenges and highlight some critical problems with representative examples of imminent but still overlooked preanalytical and analytical variables that can defeat the whole purpose of biomarkers and CDx and mislead drug developers and clinicians. The paper will provide some suggestions for mitigation. © 2015 New York Academy of Sciences.

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

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.

Gender Dysphoria and Co-Occurring Autism Spectrum Disorders: Review, Case Examples, and Treatment Considerations.

PubMed

Jacobs, Laura A; Rachlin, Katherine; Erickson-Schroth, Laura; Janssen, Aron

2014-12-01

Transgender and gender nonconforming people who fulfill diagnostic criteria for autism spectrum disorders (ASDs) often present to mental health providers with concerns that are distinct from those without ASDs. Gender Dysphoria (GD) and ASDs have been proposed to share etiologic mechanisms and there is evidence that ASDs may be more common in transgender and gender nonconforming people. We explore the impact of ASD characteristics on individual gender identity, expression, and the process of psychotherapy. The authors present two case studies of high-functioning individuals with ASD and GD diagnoses. The limited ability to articulate an inner experience, deficits in Theory of Mind (ToM), along with the intolerance of ambiguity as a manifestation of the cognitive rigidity characteristic of ASDs, may present special difficulties to gender identity formation and consolidation and create challenges in psychotherapy. The authors suggest that ASDs do not preclude gender transition and that individuals with high-functioning ASDs are capable of making informed decisions regarding their medical care and life choices. The authors also consider possible challenges and suggest techniques for assisting such clients in exploring their gender identities.

Short-wavelength free-electron laser sources and science: a review.

PubMed

Seddon, E A; Clarke, J A; Dunning, D J; Masciovecchio, C; Milne, C J; Parmigiani, F; Rugg, D; Spence, J C H; Thompson, N R; Ueda, K; Vinko, S M; Wark, J S; Wurth, W

2017-11-01

This review is focused on free-electron lasers (FELs) in the hard to soft x-ray regime. The aim is to provide newcomers to the area with insights into: the basic physics of FELs, the qualities of the radiation they produce, the challenges of transmitting that radiation to end users and the diversity of current scientific applications. Initial consideration is given to FEL theory in order to provide the foundation for discussion of FEL output properties and the technical challenges of short-wavelength FELs. This is followed by an overview of existing x-ray FEL facilities, future facilities and FEL frontiers. To provide a context for information in the above sections, a detailed comparison of the photon pulse characteristics of FEL sources with those of other sources of high brightness x-rays is made. A brief summary of FEL beamline design and photon diagnostics then precedes an overview of FEL scientific applications. Recent highlights are covered in sections on structural biology, atomic and molecular physics, photochemistry, non-linear spectroscopy, shock physics, solid density plasmas. A short industrial perspective is also included to emphasise potential in this area.

Chronic hypersensitivity pneumonitis: important considerations in the work-up of this fibrotic lung disease.

PubMed

Glazer, Craig S

2015-03-01

Chronic hypersensitivity pneumonitis is increasingly recognized as an important mimic of other fibrotic lung diseases. This review will summarize recent data regarding the importance and difficulty of determining causative exposures both for accurate diagnosis and prognosis, and describe the expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis and challenges in the diagnostic evaluation. Several recent publications show the potential pathologic patterns induced by chronic hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis, interstitial infiltrates and granulomas. Other pathologic patterns include nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative antigen in fibrotic hypersensitivity pneumonitis is challenging but critically important both for accurate diagnosis and improved prognosis. The prognosis in hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains significantly better than idiopathic pulmonary fibrosis. Hypersensitivity pneumonitis is increasingly recognized as an important cause of fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed exposure history remains a cornerstone of diagnosis and management.

Challenges in the pharmacological management of epilepsy and its causes in the elderly.

PubMed

Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Aguglia, Umberto

2016-04-01

Epilepsy represents the third most common neurological disorders in the elderly after cerebrovascular disorders and dementias. The incidence of new-onset epilepsy peaks in this age group. The most peculiar aetiologies of late-onset epilepsy are stroke, dementia, and brain tumours. However, aetiology remains unknown in about half of the patients. Diagnosis of epilepsy may be challenging due to the frequent absence of ocular witnesses and the high prevalence of seizure-mimics (i.e. transient ischemic attacks, syncope, transient global amnesia or vertigo) in the elderly. The diagnostic difficulties are even greater when patients have cognitive impairment or cardiac diseases. The management of late-onset epilepsy deserves special considerations. The elderly can reach seizure control with low antiepileptic drugs (AEDs) doses, and seizure-freedom is possible in the vast majority of patients. Pharmacological management should take into account pharmacokinetics and pharmacodynamics of AEDs and the frequent occurrence of comorbidities and polytherapy in this age group. Evidences from double-blind and open-label studies indicate lamotrigine, levetiracetam and controlled-release carbamazepine as first line treatment in late-onset epilepsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contributions from personality- and psychodynamically oriented assessment to the development of the DSM-5 personality disorders.

PubMed

Huprich, Steven K

2011-07-01

Advances in personality assessment over the past 20 years have notably influenced the proposed assessment and classification of personality disorders in the Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]). However, a considerable body of personality assessment and psychodynamically oriented assessment research has significant relevance to the way in which personality disorders are evaluated that appears to have gone unrecognized in the current proposals for DSM-5. In this article, I discuss the ways in which some of these 2 bodies of literature can and should inform the DSM-5 so that the diagnostic nomenclature can be more scientifically and comprehensively informed and consequently improve the clinical utility of a diagnostic system in need of considerable revision.

Nanotechnology in respiratory medicine.

PubMed

Omlor, Albert Joachim; Nguyen, Juliane; Bals, Robert; Dinh, Quoc Thai

2015-05-29

Like two sides of the same coin, nanotechnology can be both boon and bane for respiratory medicine. Nanomaterials open new ways in diagnostics and treatment of lung diseases. Nanoparticle based drug delivery systems can help against diseases such as lung cancer, tuberculosis, and pulmonary fibrosis. Moreover, nanoparticles can be loaded with DNA and act as vectors for gene therapy in diseases like cystic fibrosis. Even lung diagnostics with computer tomography (CT) or magnetic resonance imaging (MRI) profits from new nanoparticle based contrast agents. However, the risks of nanotechnology also have to be taken into consideration as engineered nanomaterials resemble natural fine dusts and fibers, which are known to be harmful for the respiratory system in many cases. Recent studies have shown that nanoparticles in the respiratory tract can influence the immune system, can create oxidative stress and even cause genotoxicity. Another important aspect to assess the safety of nanotechnology based products is the absorption of nanoparticles. It was demonstrated that the amount of pulmonary nanoparticle uptake not only depends on physical and chemical nanoparticle characteristics but also on the health status of the organism. The huge diversity in nanotechnology could revolutionize medicine but makes safety assessment a challenging task.

Materials for Microfluidic Immunoassays: A Review.

PubMed

Mou, Lei; Jiang, Xingyu

2017-08-01

Conventional immunoassays suffer from at least one of these following limitations: long processing time, high costs, poor user-friendliness, technical complexity, poor sensitivity and specificity. Microfluidics, a technology characterized by the engineered manipulation of fluids in channels with characteristic lengthscale of tens of micrometers, has shown considerable promise for improving immunoassays that could overcome these limitations in medical diagnostics and biology research. The combination of microfluidics and immunoassay can detect biomarkers with faster assay time, reduced volumes of reagents, lower power requirements, and higher levels of integration and automation compared to traditional approaches. This review focuses on the materials-related aspects of the recent advances in microfluidics-based immunoassays for point-of-care (POC) diagnostics of biomarkers. We compare the materials for microfluidic chips fabrication in five aspects: fabrication, integration, function, modification and cost, and describe their advantages and drawbacks. In addition, we review materials for modifying antibodies to improve the performance of the reaction of immunoassay. We also review the state of the art in microfluidic immunoassays POC platforms, from the laboratory to routine clinical practice, and also commercial products in the market. Finally, we discuss the current challenges and future developments in microfluidic immunoassays. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 4: International guidelines show variability in their approaches.

PubMed

Mustafa, Reem A; Wiercioch, Wojtek; Arevalo-Rodriguez, Ingrid; Cheung, Adrienne; Prediger, Barbara; Ivanova, Liudmila; Ventresca, Matthew; Brozek, Jan; Santesso, Nancy; Bossuyt, Patrick; Garg, Amit X; Lloyd, Nancy; Lelgemann, Monika; Bühler, Diedrich; Schünemann, Holger J

2017-12-01

The objective of the study was to describe and compare current practices in developing guidelines about the use of healthcare-related tests and diagnostic strategies (HCTDS). We sampled 37 public health and clinical practice guidelines about HCTDS from various sources without language restrictions. Detailed descriptions of the systems used to assess the quality of evidence and develop recommendations were challenging to find within guidelines. We observed much variability among and within organizations with respect to how they develop recommendations about HCTDS. Twenty-four percent of the guidelines did not consider health benefits and harms but based decisions solely on test accuracy. We did not identify guidelines that described the main potential care pathways involving tests for a healthcare problem. In addition, we did not identify guidelines that systematically assessed, described, and referenced the evidence that linked test accuracy and patient-important outcomes. There is considerable variability among the processes used and factors considered in developing recommendations about the use of tests. This variability may be the cause for the disagreement we observed in recommendations about testing for the same condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Thermodynamic framework to assess low abundance DNA mutation detection by hybridization.

PubMed

Willems, Hanny; Jacobs, An; Hadiwikarta, Wahyu Wijaya; Venken, Tom; Valkenborg, Dirk; Van Roy, Nadine; Vandesompele, Jo; Hooyberghs, Jef

2017-01-01

The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics in its broadest sense. Although many methods and sensors to detect or quantify these variations are available or under development, the number of underlying physico-chemical detection principles is limited. One of these principles is the hybridization of sample target DNA versus nucleic acid probes. We introduce a novel thermodynamics approach and develop a framework to exploit the specific detection capabilities of nucleic acid hybridization, using generic principles applicable to any platform. As a case study, we detect point mutations in the KRAS oncogene on a microarray platform. For the given platform and hybridization conditions, we demonstrate the multiplex detection capability of hybridization and assess the detection limit using thermodynamic considerations; DNA containing point mutations in a background of wild type sequences can be identified down to at least 1% relative concentration. In order to show the clinical relevance, the detection capabilities are confirmed on challenging formalin-fixed paraffin-embedded clinical tumor samples. This enzyme-free detection framework contains the accuracy and efficiency to screen for hundreds of mutations in a single run with many potential applications in molecular diagnostics and the field of personalised medicine.

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.

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

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.

Early Diagnosis of Pneumonia in Severe Stroke: Clinical Features and the Diagnostic Role of C-Reactive Protein.

PubMed

Warusevitane, Anushka; Karunatilake, Dumin; Sim, Julius; Smith, Craig; Roffe, Christine

2016-01-01

Accurate diagnosis of pneumonia complicating severe stroke is challenging due to difficulties in physical examination, altered immune responses and delayed manifestations of radiological changes. The aims of this study were to describe early clinical features and to examine C-reactive protein (CRP) as a diagnostic marker of post-stroke pneumonia. Patients who required nasogastric feeding and had no evidence of pneumonia within 7 days of stroke onset were included in the study and followed-up for 21 days with a daily clinical examination. Pneumonia was diagnosed using modified British Thoracic Society criteria. 60 patients were recruited (mean age 77 years, mean National Institutes of Health Stroke Scale Score 19.47). Forty-four episodes of pneumonia were identified. Common manifestations on the day of the diagnosis were new onset crackles (43/44, 98%), tachypnoea>25/min (42/44, 95%), and oxygen saturation <90% (41/44, 93%). Cough, purulent sputum, and pyrexia >38°C were observed in 27 (61%), 25 (57%) and 15 (34%) episodes respectively. Leucocytosis (WBC>11,000/ml) and raised CRP (>10 mg/l) were observed in 38 (86%) and 43 (97%) cases of pneumonia respectively. The area under the ROC curve for CRP was 0.827 (95% CI 0.720, 0.933). The diagnostic cut-off for CRP with an acceptable sensitivity (>0.8) was 25.60 mg/L (Youden index (J) 0.515; sensitivity 0.848; specificity 0.667). A cut-off of 64.65 mg/L had the highest diagnostic accuracy (J 0.562; sensitivity 0.636; specificity 0.926). Patients with severe stroke frequently do not manifest key diagnostic features of pneumonia such as pyrexia, cough and purulent sputum early in their illness. The most common signs in this group are new-onset crackles, tachypnoea and hypoxia. Our results suggest that a CRP >25 mg/L should prompt investigations for pneumonia while values >65 mg/L have the highest diagnostic accuracy to justify consideration of this threshold as a diagnostic marker of post-stroke pneumonia.

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

[Fax Survey to Elucidate the Information Needs of General Practitioners in Lower Saxony Regarding the Topic of Medical Implants].

PubMed

Schaper, M; Berndt, M; Schrimpf, C; Wilhelmi, M; Elff, M; Haverich, A; Wilhelmi, M

2016-12-01

Background: Medial implants help a multitude of patients to gain more health, mobility and thus, quality of life. In collaboration with a still growing expectation of life especially, i.e., within Western industrial countries, this has led to an increasing use of implants over the last years. However, although biomechanical characteristics of modern implant materials have improved considerably, one big challenge still exists - the implant-associated infection. Early diagnostic and therapeutic interventions could clearly mitigate this issue, but are general practitioners sufficiently informed regarding this topic? Material and Methods: In March 2013 and in close cooperation with the Lower Saxony association of general practitioners, we initiated a survey to elucidate the information demands of general practitioners regarding the topic of medical implants. A total of 939 members of the association were contacted via fax and 101 (10.8 %) responded. Based on the obtained data, we then evaluated which topics are most interesting for this group of medical professionals. Results: The survey clearly indicates that general practitioners request more general implant-related data, e.g., type and specification of an implant as well as its location within the individual patient and contact addresses of the implanting hospital, but also want more specific information regarding diagnostic and therapeutic strategies in the case of implant-associated complications. Conclusion: The present article reports in detail on the conducted fax survey and shows some initial strategies as to how the identified challenges might be faced. Georg Thieme Verlag KG Stuttgart · New York.

78 FR 9933 - National Cancer Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute... potential new cancer diagnostics. The outcome of the evaluation will be information for consideration by an... contract resources for development of the potential diagnostics to improve the treatment of cancer. The...

77 FR 61614 - National Cancer Institute; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-10

... potential new cancer diagnostics. The outcome of the evaluation will be information for consideration by an... contract resources for development of the potential diagnostics to improve the treatment of cancer. The... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute...

Biologics industry challenges for developing diagnostic tests for the National Veterinary Stockpile.

PubMed

Hardham, J M; Lamichhane, C M

2013-01-01

Veterinary diagnostic products generated ~$3 billion US dollars in global sales in 2010. This industry is poised to undergo tremendous changes in the next decade as technological advances move diagnostic products from the traditional laboratory-based and handheld immunologic assays towards highly technical, point of care devices with increased sensitivity, specificity, and complexity. Despite these opportunities for advancing diagnostic products, the industry continues to face numerous challenges in developing diagnostic products for emerging and foreign animal diseases. Because of the need to deliver a return on the investment, research and development dollars continue to be focused on infectious diseases that have a negative impact on current domestic herd health, production systems, or companion animal health. Overcoming the administrative, legal, fiscal, and technological barriers to provide veterinary diagnostic products for the National Veterinary Stockpile will reduce the threat of natural or intentional spread of foreign diseases and increase the security of the food supply in the US.

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

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.

Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using the Mycobacterium tuberculosis Protein Array

PubMed Central

Campo, Joseph J.; Li, Lingling; Randall, Arlo; Pablo, Jozelyn; Praul, Craig A.; Raygoza Garay, Juan Antonio; Stabel, Judith R.

2017-01-01

ABSTRACT Johne's disease, a chronic gastrointestinal inflammatory disease caused by Mycobacterium avium subspecies paratuberculosis, is endemic in dairy cattle and other ruminants worldwide and remains a challenge to diagnose using traditional serological methods. Given the close phylogenetic relationship between M. avium subsp. paratuberculosis and the human pathogen Mycobacterium tuberculosis, here, we applied a whole-proteome M. tuberculosis protein array to identify seroreactive and diagnostic M. avium subsp. paratuberculosis antigens. A genome-scale pairwise analysis of amino acid identity levels between orthologous proteins in M. avium subsp. paratuberculosis and M. tuberculosis showed an average of 62% identity, with more than half the orthologous proteins sharing >75% identity. Analysis of the M. tuberculosis protein array probed with sera from M. avium subsp. paratuberculosis-infected cattle showed antibody binding to 729 M. tuberculosis proteins, with 58% of them having ≥70% identity to M. avium subsp. paratuberculosis orthologs. The results showed that only 4 of the top 40 seroreactive M. tuberculosis antigens were orthologs of previously reported M. avium subsp. paratuberculosis antigens, revealing the existence of a large number of previously unrecognized candidate diagnostic antigens. Enzyme-linked immunosorbent assay (ELISA) testing of 20 M. avium subsp. paratuberculosis recombinant proteins, representing reactive and nonreactive M. tuberculosis orthologs, further confirmed that the M. tuberculosis array has utility as a screening tool for identifying candidate antigens for Johne's disease diagnostics. Additional ELISA testing of field serum samples collected from dairy herds around the United States revealed that MAP2942c had the strongest seroreactivity with Johne's disease-positive samples. Collectively, our studies have considerably expanded the number of candidate M. avium subsp. paratuberculosis proteins with potential utility in the next generation of rationally designed Johne's disease diagnostic assays. PMID:28515134

Identification of Novel Seroreactive Antigens in Johne's Disease Cattle by Using the Mycobacterium tuberculosis Protein Array.

PubMed

Bannantine, John P; Campo, Joseph J; Li, Lingling; Randall, Arlo; Pablo, Jozelyn; Praul, Craig A; Raygoza Garay, Juan Antonio; Stabel, Judith R; Kapur, Vivek

2017-07-01

Johne's disease, a chronic gastrointestinal inflammatory disease caused by Mycobacterium avium subspecies paratuberculosis , is endemic in dairy cattle and other ruminants worldwide and remains a challenge to diagnose using traditional serological methods. Given the close phylogenetic relationship between M. avium subsp. paratuberculosis and the human pathogen Mycobacterium tuberculosis , here, we applied a whole-proteome M. tuberculosis protein array to identify seroreactive and diagnostic M. avium subsp. paratuberculosis antigens. A genome-scale pairwise analysis of amino acid identity levels between orthologous proteins in M. avium subsp. paratuberculosis and M. tuberculosis showed an average of 62% identity, with more than half the orthologous proteins sharing >75% identity. Analysis of the M. tuberculosis protein array probed with sera from M. avium subsp. paratuberculosis -infected cattle showed antibody binding to 729 M. tuberculosis proteins, with 58% of them having ≥70% identity to M. avium subsp. paratuberculosis orthologs. The results showed that only 4 of the top 40 seroreactive M. tuberculosis antigens were orthologs of previously reported M. avium subsp. paratuberculosis antigens, revealing the existence of a large number of previously unrecognized candidate diagnostic antigens. Enzyme-linked immunosorbent assay (ELISA) testing of 20 M. avium subsp. paratuberculosis recombinant proteins, representing reactive and nonreactive M. tuberculosis orthologs, further confirmed that the M. tuberculosis array has utility as a screening tool for identifying candidate antigens for Johne's disease diagnostics. Additional ELISA testing of field serum samples collected from dairy herds around the United States revealed that MAP2942c had the strongest seroreactivity with Johne's disease-positive samples. Collectively, our studies have considerably expanded the number of candidate M. avium subsp. paratuberculosis proteins with potential utility in the next generation of rationally designed Johne's disease diagnostic assays. Copyright © 2017 American Society for Microbiology.

How Should DSM-V Criteria for Schizophrenia Include Cognitive Impairment?

PubMed Central

Keefe, Richard S. E.; Fenton, Wayne S.

2007-01-01

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 with healthy controls, and almost all patients with schizophrenia demonstrate cognitive decrements compared with their expected level if they had not developed the illness. Compared with patients with affective disorders, cognitive impairment in schizophrenia appears earlier, is more severe, and tends to be more independent of clinical symptoms. While the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, description of schizophrenia includes several references to cognitive impairment, neither the diagnostic criteria nor the subtypology of schizophrenia include a requirement of cognitive impairment. We forward for consideration a proposal that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 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 and better treatment outcomes. Future research will need to address the validity of these possibilities. The reliable determination of cognitive impairment as part of a standard diagnostic evaluation may present challenges to diagnosticians with limited resources or insufficient expertise. Various 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. PMID:17567627

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.

Tuberculosis in elephants-a reemergent disease: diagnostic dilemmas, the natural history of infection, and new immunological tools.

PubMed

Maslow, J N; Mikota, S K

2015-05-01

Tuberculosis (TB) in elephants has been described since ancient times. However, it was not until 1996 when infection with Mycobacterium tuberculosis was identified in a herd of circus elephants that significant research into this disease began. The epidemiology and natural history of TB were unknown in elephants since there had been no comprehensive screening programs, and diagnostic techniques developed for cervidae and bovidae were of unknown value. And, while precepts of test and slaughter were the norm for cattle and deer, this was considered untenable for an endangered species. With no precedent for the treatment of TB in animals, treatment regimens for elephants were extrapolated from human protocols, which guided changes to the Guidelines for the Control of Tuberculosis in Elephants. In the absence of diagnostic testing to confirm cure in elephants, the efficacy of these treatment regimens is only beginning to be understood as treated elephants die and are examined postmortem. However, because of pressures arising from public relations related to elephant husbandry and the added considerations of TB infection in animals (whether real or imagined), sharing of information to aid in research and treatment has been problematic. Here we review the challenges and successes of the diagnosis of tuberculosis in elephants and discuss the natural history of the disease to put the work of Landolfi et al on the immunological response to tuberculosis in elephants in perspective. © The Author(s) 2015.

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.

Diagnosing Alzheimer's disease: a systematic review of economic evaluations.

PubMed

Handels, Ron L H; Wolfs, Claire A G; Aalten, Pauline; Joore, Manuela A; Verhey, Frans R J; Severens, Johan L

2014-03-01

The objective of this study is to systematically review the literature on economic evaluations of interventions for the early diagnosis of Alzheimer's disease (AD) and related disorders and to describe their general and methodological characteristics. We focused on the diagnostic aspects of the decision models to assess the applicability of existing decision models for the evaluation of the recently revised diagnostic research criteria for AD. PubMed and the National Institute for Health Research Economic Evaluation database were searched for English-language publications related to economic evaluations on diagnostic technologies. Trial-based economic evaluations were assessed using the Consensus on Health Economic Criteria list. Modeling studies were assessed using the framework for quality assessment of decision-analytic models. The search retrieved 2109 items, from which eight decision-analytic modeling studies and one trial-based economic evaluation met all eligibility criteria. Diversity among the study objective and characteristics was considerable and, despite considerable methodological quality, several flaws were indicated. Recommendations were focused on diagnostic aspects and the applicability of existing models for the evaluation of recently revised diagnostic research criteria for AD. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Electronic-nose devices - Potential for noninvasive early disease-detection applications

Treesearch

Alphus Dan Wilson

2017-01-01

Significant progress in the development of portable electronic devices is showing considerable promise to facilitate clinical diagnostic processes. The increasing global trend of shifts in healthcare policies and priorities toward shortening and improving the effectiveness of diagnostic procedures by utilizing non-invasive methods should provide multiple benefits of...

The Design, Development, and Evaluation of an Evaluative Computer Simulation.

ERIC Educational Resources Information Center

Ehrlich, Lisa R.

This paper discusses evaluation design considerations for a computer based evaluation simulation developed at the University of Iowa College of Medicine in Cardiology to assess the diagnostic skills of primary care physicians and medical students. The simulation developed allows for the assessment of diagnostic skills of physicians in the…

A comparative study of electrical probe techniques for plasma diagnostics

NASA Technical Reports Server (NTRS)

Szuszczewicz, E. P.

1972-01-01

Techniques for using electrical probes for plasma diagnostics are reviewed. Specific consideration is given to the simple Langmuir probe, the symmetric double probe of Johnson and Malter, the variable-area probe of Fetz and Oeschsner, and a floating probe technique. The advantages and disadvantages of each technique are discussed.

Inssues for Consideration by Mathematics Educators: Selected Papers.

ERIC Educational Resources Information Center

Denmark, Tom, Ed.

This set of papers, selected from presentations at the Fourth and Fifth Annual Conferences of the Research Council for Diagnostic and Prescriptive Mathematics, are of primary interest to mathematics educators. In the first paper, Romberg describes a model for diagnosing mathematical learning difficulties which extends the diagnostic process beyond…

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.

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.

The Diagnostic Challenge Competition: Probabilistic Techniques for Fault Diagnosis in Electrical Power Systems

NASA Technical Reports Server (NTRS)

Ricks, Brian W.; Mengshoel, Ole J.

2009-01-01

Reliable systems health management is an important research area of NASA. A health management system that can accurately and quickly diagnose faults in various on-board systems of a vehicle will play a key role in the success of current and future NASA missions. We introduce in this paper the ProDiagnose algorithm, a diagnostic algorithm that uses a probabilistic approach, accomplished with Bayesian Network models compiled to Arithmetic Circuits, to diagnose these systems. We describe the ProDiagnose algorithm, how it works, and the probabilistic models involved. We show by experimentation on two Electrical Power Systems based on the ADAPT testbed, used in the Diagnostic Challenge Competition (DX 09), that ProDiagnose can produce results with over 96% accuracy and less than 1 second mean diagnostic time.

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

Advanced imaging of the macrostructure and microstructure of bone

NASA Technical Reports Server (NTRS)

Genant, H. K.; Gordon, C.; Jiang, Y.; Link, T. M.; Hans, D.; Majumdar, S.; Lang, T. F.

2000-01-01

Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The considerable potential biological differences between the peripheral appendicular skeleton and the central axial skeleton have to be addressed further. Finally, the relative merits of these sophisticated imaging techniques have to be weighed with respect to their applications as diagnostic procedures requiring high accuracy or reliability on one hand and their monitoring applications requiring high precision or reproducibility on the other. Copyright 2000 S. Karger AG, Basel.

Challenge Activities for the Physical Education Classroom: Considerations

ERIC Educational Resources Information Center

McKenzie, Emily; Tapps, Tyler; Fink, Kevin; Symonds, Matthew L.

2018-01-01

The purpose of this article is to provide physical education teachers with the tools to develop and implement challenge course-like activities in their physical education classes. The article also covers environmental considerations for teachers who have the desire to create a challenge-based classroom setting in order to reach a wider and more…

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.

Cost analysis of breast cancer diagnostic assessment programs.

PubMed

Honein-AbouHaidar, G N; Hoch, J S; Dobrow, M J; Stuart-McEwan, T; McCready, D R; Gagliardi, A R

2017-10-01

Diagnostic assessment programs (daps) appear to improve the diagnosis of cancer, but evidence of their cost-effectiveness is lacking. Given that no earlier study used secondary financial data to estimate the cost of diagnostic tests in the province of Ontario, we explored how to use secondary financial data to retrieve the cost of key diagnostic test services in daps, and we tested the reliability of that cost-retrieving method with hospital-reported costs in preparation for future cost-effectiveness studies. We powered our sample at an alpha of 0.05, a power of 80%, and a margin of error of ±5%, and randomly selected a sample of eligible patients referred to a dap for suspected breast cancer during 1 January-31 December 2012. Confirmatory diagnostic tests received by each patient were identified in medical records. Canadian Classification of Health Intervention procedure codes were used to search the secondary financial data Web portal at the Ontario Case Costing Initiative for an estimate of the direct, indirect, and total costs of each test. The hospital-reported cost of each test received was obtained from the host-hospital's finance department. Descriptive statistics were used to calculate the cost of individual or group confirmatory diagnostic tests, and the Wilcoxon signed-rank test or the paired t-test was used to compare the Ontario Case Costing Initiative and hospital-reported costs. For the 191 identified patients with suspected breast cancer, the estimated total cost of $72,195.50 was not significantly different from the hospital-reported total cost of $72,035.52 ( p = 0.24). Costs differed significantly when multiple tests to confirm the diagnosis were completed during one patient visit and when confirmatory tests reported in hospital data and in medical records were discrepant. The additional estimated cost for non-salaried physicians delivering diagnostic services was $28,387.50. It was feasible to use secondary financial data to retrieve the cost of key diagnostic tests in a breast cancer dap and to compare the reliability of the costs obtained by that estimation method with hospital-reported costs. We identified the strengths and challenges of each approach. Lessons learned from this study have to be taken into consideration in future cost-effectiveness studies.

Differing levels of clinical evidence: exploring communication challenges in shared decision making. Introduction.

PubMed

Smith, Quentin W; Street, Richard L; Volk, Robert J; Fordis, Michael

2013-02-01

The near ubiquitous access to information is transforming the roles and relationships among clinical professionals, patients, and their care givers in nearly all aspects of healthcare. Informed patients engage their physicians in conversations about their conditions, options and the tradeoffs among diagnostic and therapeutic benefits and harms. The processes of care today increasingly and explicitly integrate exploration of patient values and preferences as patients and clinicians jointly engage in reaching decisions about care. The informed patient of today who can understand and use scientific information can participate as an equal partner with her clinician. Others with beliefs or educational, cultural, or literacy backgrounds that pose challenges to comprehending and applying evidence may face disenfranchisement. These barriers are significant enough, even in the face of certainty of evidence, that clinicians and investigators have given much thought to how best to engage all patients in decision making. However, barriers remain, as most decision making must occur in settings where uncertainty, if not considerable uncertainty, accompanies any statement of what we know. In September 2011, health care and health communication experts came together in Rockville, Maryland under the auspices of the Agency for Healthcare Research and Quality (AHRQ) John M. Eisenberg Center for Clinical Decisions and Communications Science Annual Meeting to explore the challenges of differing levels of evidence in promoting shared decisions and to propose strategies for going forward in addressing these challenges. Eight scholarly papers emerged, and with this introductory article, comprise this special issue of Medical Care Research and Review.

Development of Gold Nanoparticle towards Radioenhancement Therapy, Renal Clearance, siRNA Delivery and Light-Controlled Gene Silencing

NASA Astrophysics Data System (ADS)

Wang, Jianxin

Gold nanoparticles (GNPs) have been widely studied and used in research for diagnostic, prophylactic or therapeutic purposes. However, they still face many technical challenges before they can be used to effectively address unmet biomedical needs. The theme of this dissertation is focused on addressing challenges of GNPs in clinical translation, and to improve their potential for application in radioenhancement therapy and siRNA delivery. We demonstrate the facile self-assembly of micellar gold nanocapsules using zwitterionic surfactants, with hydrodynamic diameters below 10 nm, which holds promise for good renal clearance to promote the excretion of GNPs in human body. We also prepared PEI- and PEG-coated GNPs and demonstrated their uptake into HeLa cells with exposure to soft X-rays (120 kVp), based on the consideration that the proximity of GNPs to nuclear DNA may be beneficial for enhancing low-energy ionizing radiotherapy. GNP-mediated siRNA delivery may be challenged by nonspecific siRNA desorption during circulation, which can cause off-target effects and immunogenicity. The use of gold nanorods (GNRs) for siRNA delivery also faces challenges like reduced dispersion stability during siRNA functionalization. We developed an effective way to load siRNA onto GNRs at high density, using oleylsulfobetaine (OSB) as an intermediate surfactant and dithiocarbamates (DTCs) as desorption-resistant anchors for siRNA. The GNR?siRNA complexes provided excellent control for laser-triggered gene silencing.

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.

TOPICAL REVIEW: Biological and chemical sensors for cancer diagnosis

NASA Astrophysics Data System (ADS)

Simon, Elfriede

2010-11-01

The great challenge for sensor systems to be accepted as a relevant diagnostic and therapeutic tool for cancer detection is the ability to determine the presence of relevant biomarkers or biomarker patterns comparably to or even better than the traditional analytical systems. Biosensor and chemical sensor technologies are already used for several clinical applications such as blood glucose or blood gas measurements. However, up to now not many sensors have been developed for cancer-related tests because only a few of the biomarkers have shown clinical relevance and the performance of the sensor systems is not always satisfactory. New genomic and proteomic tools are used to detect new molecular signatures and identify which combinations of biomarkers may detect best the presence or risk of cancer or monitor cancer therapies. These molecular signatures include genetic and epigenetic signatures, changes in gene expressions, protein biomarker profiles and other metabolite profile changes. They provide new changes in using different sensor technologies for cancer detection especially when complex biomarker patterns have to be analyzed. To address requirements for this complex analysis, there have been recent efforts to develop sensor arrays and new solutions (e.g. lab on a chip) in which sampling, preparation, high-throughput analysis and reporting are integrated. The ability of parallelization, miniaturization and the degree of automation are the focus of new developments and will be supported by nanotechnology approaches. This review recaps some scientific considerations about cancer diagnosis and cancer-related biomarkers, relevant biosensor and chemical sensor technologies, their application as cancer sensors and consideration about future challenges.

Diagnostic imaging of child abuse

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

Kleinman, P.K.

1987-01-01

This book provides a description for all the known radiological alterations occurring in child abuse. This allows for precise interpretation of findings by radiologists. It also helps eliminate the confusion among both clinicians and non-medical personnel involved in the diagnosis, management, and legal issues related to child abuse. CONTENTS: Introduction; Skeletal trauma: general considerations; Extremity trauma; Bony thoracic trauma; Spinal trauma; Dating fractures; Visceral trauma; Head trauma; Miscellaneous forms of abuse and neglect; The postmortem examination; Differential diagnosis of child abuse; Legal considerations; Psychosocial considerations; Technical considerations and dosimetry.

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.

Economic Considerations for Moving beyond the Kato-Katz Technique for Diagnosing Intestinal Parasites As We Move Towards Elimination.

PubMed

Turner, Hugo C; Bettis, Alison A; Dunn, Julia C; Whitton, Jane M; Hollingsworth, T Déirdre; Fleming, Fiona M; Anderson, Roy M

2017-06-01

While the need for more sensitive diagnostics for intestinal helminths is well known, the cost of developing and implementing new tests is considered relatively high compared to the Kato-Katz technique. Here, we review the reported costs of performing the Kato-Katz technique. We also outline several economic arguments we believe highlight the need for further investment in alternative diagnostics, and considerations that should be made when comparing their costs. In our opinion, we highlight that, without new diagnostic methods, it will be difficult for policy makers to make the most cost-effective decisions and that the potentially higher unit costs of new methods can be outweighed by the long-term programmatic benefits they have (such as the ability to detect the interruption of transmission). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Considerations Underlying the Use of Mixed Group Validation

ERIC Educational Resources Information Center

Jewsbury, Paul A.; Bowden, Stephen C.

2013-01-01

Mixed Group Validation (MGV) is an approach for estimating the diagnostic accuracy of tests. MGV is a promising alternative to the more commonly used Known Groups Validation (KGV) approach for estimating diagnostic accuracy. The advantage of MGV lies in the fact that the approach does not require a perfect external validity criterion or gold…

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.

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

Quantitative polymerase chain reaction (PCR) for detection of aquatic animal pathogens in a diagnostic laboratory setting

USGS Publications Warehouse

Purcell, Maureen K.; Getchell, Rodman G.; McClure, Carol A.; Weber, S.E.; Garver, Kyle A.

2011-01-01

Real-time, or quantitative, polymerase chain reaction (qPCR) is quickly supplanting other molecular methods for detecting the nucleic acids of human and other animal pathogens owing to the speed and robustness of the technology. As the aquatic animal health community moves toward implementing national diagnostic testing schemes, it will need to evaluate how qPCR technology should be employed. This review outlines the basic principles of qPCR technology, considerations for assay development, standards and controls, assay performance, diagnostic validation, implementation in the diagnostic laboratory, and quality assurance and control measures. These factors are fundamental for ensuring the validity of qPCR assay results obtained in the diagnostic laboratory setting.

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.

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.

Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.

PubMed

Coccaro, Emil F

2011-01-01

This study was designed to develop a revised diagnostic criteria set for intermittent explosive disorder (IED) for consideration for inclusion in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). This revised criteria set was developed by integrating previous research criteria with elements from the current DSM-IV set of diagnostic criteria. Evidence supporting the reliability and validity of IED-IR ("IED Integrated Criteria") in a new and well-characterized group of subjects with personality disorder is presented. Clinical, phenomenologic, and diagnostic data from 201 individuals with personality disorder were reviewed. All IED diagnoses were assigned using a best-estimate process (eg, kappa for IED-IR >0.85). In addition, subjects meeting IED-IR criteria had higher scores on dimensional measures of aggression and had lower global functioning scores than non-IED-IR subjects, even when related variables were controlled. The IED-IR criteria were more sensitive than the DSM-IV criteria only in identifying subjects with significant impulsive-aggressive behavior by a factor of 16. We conclude that the IED-IR criteria can be reliably applied and have sufficient validity to warrant consideration as DSM-V criteria for IED. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Debris and shrapnel assessments for National Ignition Facility targets and diagnostics

NASA Astrophysics Data System (ADS)

Masters, N. D.; Fisher, A.; Kalantar, D.; Stölken, J.; Smith, C.; Vignes, R.; Burns, S.; Doeppner, T.; Kritcher, A.; Park, H.-S.

2016-05-01

High-energy laser experiments at the National Ignition Facility (NIF) can create debris and shrapnel capable of damaging laser optics and diagnostic instruments. The size, composition and location of target components and sacrificial shielding (e.g., disposable debris shields, or diagnostic filters) and the protection they provide is constrained by many factors, including: chamber and diagnostic geometries, experimental goals and material considerations. An assessment of the generation, nature and velocity of shrapnel and debris and their potential threats is necessary prior to fielding targets or diagnostics. These assessments may influence target and shielding design, filter configurations and diagnostic selection. This paper will outline the approach used to manage the debris and shrapnel risk associated with NIF targets and diagnostics and present some aspects of two such cases: the Material Strength Rayleigh- Taylor campaign and the Mono Angle Crystal Spectrometer (MACS).

Potential Impact and Study Considerations of Metabolomics in Cardiovascular Health and Disease: A Scientific Statement From the American Heart Association.

PubMed

Cheng, Susan; Shah, Svati H; Corwin, Elizabeth J; Fiehn, Oliver; Fitzgerald, Robert L; Gerszten, Robert E; Illig, Thomas; Rhee, Eugene P; Srinivas, Pothur R; Wang, Thomas J; Jain, Mohit

2017-04-01

Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine- N -oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine. © 2017 American Heart Association, Inc.

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

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.

Thiamine Deficiency in Tropical Pediatrics: New Insights into a Neglected but Vital Metabolic Challenge

PubMed Central

Hiffler, Laurent; Rakotoambinina, Benjamin; Lafferty, Nadia; Martinez Garcia, Daniel

2016-01-01

In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children. PMID:27379239

Advancing the field of 3D biomaterial printing.

PubMed

Jakus, Adam E; Rutz, Alexandra L; Shah, Ramille N

2016-01-11

3D biomaterial printing has emerged as a potentially revolutionary technology, promising to transform both research and medical therapeutics. Although there has been recent progress in the field, on-demand fabrication of functional and transplantable tissues and organs is still a distant reality. To advance to this point, there are two major technical challenges that must be overcome. The first is expanding upon the limited variety of available 3D printable biomaterials (biomaterial inks), which currently do not adequately represent the physical, chemical, and biological complexity and diversity of tissues and organs within the human body. Newly developed biomaterial inks and the resulting 3D printed constructs must meet numerous interdependent requirements, including those that lead to optimal printing, structural, and biological outcomes. The second challenge is developing and implementing comprehensive biomaterial ink and printed structure characterization combined with in vitro and in vivo tissue- and organ-specific evaluation. This perspective outlines considerations for addressing these technical hurdles that, once overcome, will facilitate rapid advancement of 3D biomaterial printing as an indispensable tool for both investigating complex tissue and organ morphogenesis and for developing functional devices for a variety of diagnostic and regenerative medicine applications.

In-vitro nanodiagnostic platform through nanoparticles and DNA-RNA nanotechnology.

PubMed

Chan, Ki; Ng, Tzi Bun

2015-04-01

Nanocomposites containing nanoparticles or nanostructured domains exhibit an even higher degree of material complexity that leads to an extremely high variability of nanostructured materials. This review introduces analytical concepts and techniques for nanomaterials and derives recommendations for a qualified selection of characterization techniques for specific types of samples, and focuses the characterization of nanoparticles and their agglomerates or aggregates. In addition, DNA nanotechnology and the more recent newcomer RNA nanotechnology have achieved almost an advanced status among nanotechnology researchers¸ therefore, the core features, potential, and significant challenges of DNA nanotechnology are also highlighted as a new discipline. Moreover, nanobiochips made by nanomaterials are rapidly emerging as a new paradigm in the area of large-scale biochemical analysis. The use of nanoscale components enables higher precision in diagnostics while considerably reducing the cost of the platform that leads this review to explore the use of nanoparticles, nanomaterials, and other bionanotechnologies for its application to nanodiagnostics in-vitro.

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

The common cold: potential for future prevention or cure.

PubMed

Passioti, Maria; Maggina, Paraskevi; Megremis, Spyridon; Papadopoulos, Nikolaos G

2014-02-01

The common cold is the most frequent, although generally mild, human disease. Human Rhinoviruses are the prevalent causative agents, but other viruses are also implicated. Being so common, viral colds, have significant implications on public health and quality of life, but may also be life-threatening for vulnerable groups of patients. Specific diagnosis and treatment of the common cold still remain unmet needs. Molecular diagnostic techniques allow specific detection of known pathogens as well as the identification of newly emerging viruses. Although a number of medications or natural treatments have been shown to have some effect, either on the number or on the severity of common colds, no single agent is considerably effective. Virus-specific management remains in most cases a challenging potential as many factors have to be taken into account, including the diversity of the viral genomes, the heterogeneity of affected individuals, as well as the complexity of this long standing host-virus relationship.

MR imaging of the pelvis: a guide to incidental musculoskeletal findings for abdominal radiologists.

PubMed

Gaetke-Udager, Kara; Girish, Gandikota; Kaza, Ravi K; Jacobson, Jon; Fessell, David; Morag, Yoav; Jamadar, David

2014-08-01

Occasionally patients who undergo magnetic resonance imaging for presumed pelvic disease demonstrate unexpected musculoskeletal imaging findings in the imaged field. Such incidental findings can be challenging to the abdominal radiologist, who may not be familiar with their appearance or know the appropriate diagnostic considerations. Findings can include both normal and abnormal bone marrow, osseous abnormalities such as Paget's disease, avascular necrosis, osteomyelitis, stress and insufficiency fractures, and athletic pubalgia, benign neoplasms such as enchondroma and bone island, malignant processes such as metastasis and chondrosarcoma, soft tissue processes such as abscess, nerve-related tumors, and chordoma, joint- and bursal-related processes such as sacroiliitis, iliopsoas bursitis, greater trochanteric pain syndrome, and labral tears, and iatrogenic processes such as bone graft or bone biopsy. Though not all-encompassing, this essay will help abdominal radiologists to identify and describe this variety of pelvic musculoskeletal conditions, understand key radiologic findings, and synthesize a differential diagnosis when appropriate.

Expert opinion: diagnosis and treatment of proximal hamstring tendinopathy.

PubMed

Lempainen, Lasse; Johansson, Kristian; Banke, Ingo J; Ranne, Juha; Mäkelä, Keijo; Sarimo, Janne; Niemi, Pekka; Orava, Sakari

2015-01-01

proximal hamstring tendinopathy (PHT) is a disabilitating disease often causing underperformance in the athletically demanding patients. The main symptom of PHT is lower gluteal pain especially during running or while prolonged sitting. Mainly affecting athletically active individuals, PHT is a considerable challenge for treating health care professionals. this paper aims to concisely present the literature on PHT to guide health care professionals treating these patients and doing research on the subject. we reviewed the literature on PHT through literature search of scientific journal databases. as a tendinopathic pathology, it is a rather recently discovered exertion injury. As with other chronic tendon overuse injuries, current treatment strategies are unspecific with uncertain outcomes due to the unknown etiology of the tendon degeneration. Diagnostic features as well as both operative and non-operative treatments are evaluated from a clinical perspective, providing up to date information for clinicians and sports medicine therapists dealing with hamstring problems. V.

Epigenetics Advancing Personalized Nanomedicine in Cancer Therapy

PubMed Central

Liu, Shujun

2012-01-01

Personalized medicine aims to deliver the right drug to a right patient at the right time. It offers unique opportunities to integrate new technologies and concepts to disease prognosis, diagnosis and therapeutics. While selective personalized therapies are conceptually impressive, the majority of cancer therapies have dismal outcome. Such therapeutic failure could result from no response, drug resistance, disease relapse or severe side effect from improper drug delivery. Nanomedicine, the application of nanotechnology in medicine, has a potential to advance the identification of diagnostic and prognostic biomarkers and the delivery of right drug to disease sites. Epigenetic aberrations dynamically contribute to cancer pathogenesis. Given the individualized traits of epigenetic biomarkers, epigenetic considerations would significantly refine personalized nanomedicine. This review aims to dissect the interface of personalized medicine with nanomedicine and epigenetics. I will outline the progress and highlight challenges and areas that can be further explored perfecting the personalized health care. PMID:22921595

Antifungal stewardship considerations for adults and pediatrics.

PubMed

Hamdy, Rana F; Zaoutis, Theoklis E; Seo, Susan K

2017-08-18

Antifungal stewardship refers to coordinated interventions to monitor and direct the appropriate use of antifungal agents in order to achieve the best clinical outcomes and minimize selective pressure and adverse events. Antifungal utilization has steadily risen over time in concert with the increase in number of immunocompromised adults and children at risk for invasive fungal infections (IFI). Challenges in diagnosing IFI often lead to delays in treatment and poorer outcomes. There are also emerging data linking prior antifungal exposure and suboptimal dosing to the emergence of antifungal resistance, particularly for Candida. Antimicrobial stewardship programs can take a multi-pronged bundle approach to ensure suitable prescribing of antifungals via post-prescription review and feedback and/or prior authorization. Institutional guidelines can also be developed to guide diagnostic testing in at-risk populations; appropriate choice, dose, and duration of antifungal agent; therapeutic drug monitoring; and opportunities for de-escalation and intravenous-to-oral conversion.

Neurosurgical Issues in Pregnancy.

PubMed

Can, Anil; Du, Rose

2017-12-01

Although rare, intracranial hemorrhage due to rupture of cerebral vascular malformations or intracranial aneurysms during pregnancy is a potentially devastating and life-threatening disorder, posing a diagnostic and therapeutic challenge to a multidisciplinary team of neurosurgeons, neurologists, obstetricians, and anesthesiologists. Despite the significant risk of morbidity and mortality affecting both the mother and the unborn child, knowledge of the natural history, epidemiology, and appropriate management of cerebral vascular malformations and intracranial aneurysms in pregnant women is limited. Although emergent neurosurgical concerns usually outweigh obstetric considerations, and treatment of these disorders is generally similar in pregnant and nonpregnant women, any necessary and feasible modifications to protect the unborn child should be made. This article reviews the management of ruptured intracranial aneurysms and cerebral vascular malformations, including arteriovenous malformations, cavernous malformations, and moyamoya disease, in women during pregnancy, partus, and puerperium. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Using an Informative Missing Data Model to Predict the Ability to Assess Recovery of Balance Control after Spaceflight

NASA Technical Reports Server (NTRS)

Feiveson, Alan H.; Wood, Scott J.; Jain, Varsha

2008-01-01

Astronauts show degraded balance control immediately after spaceflight. To assess this change, astronauts' ability to maintain a fixed stance under several challenging stimuli on a movable platform is quantified by "equilibrium" scores (EQs) on a scale of 0 to 100, where 100 represents perfect control (sway angle of 0) and 0 represents data loss where no sway angle is observed because the subject has to be restrained from falling. By comparing post- to pre-flight EQs for actual astronauts vs. controls, we built a classifier for deciding when an astronaut has recovered. Future diagnostic performance depends both on the sampling distribution of the classifier as well as the distribution of its input data. Taking this into consideration, we constructed a predictive ROC by simulation after modeling P(EQ = 0) in terms of a latent EQ-like beta-distributed random variable with random effects.

Getting Personal: Head and Neck Cancer Management in the Era of Genomic Medicine

PubMed Central

Birkeland, Andrew C.; Uhlmann, Wendy R.; Brenner, J. Chad; Shuman, Andrew G.

2015-01-01

Background Genetic testing is rapidly becoming an important tool in the management of patients with head and neck cancer. As we enter the era of genomics and personalized medicine, providers should be aware of testing options, counseling resources, and the benefits, limitations and future of personalized therapy. Methods This manuscript offers a primer to assist clinicians treating patients in anticipating and managing the inherent practical and ethical challenges of cancer care in the genomic era. Results Clinical applications of genomics for head and neck cancer are emerging. We discuss the indications for genetic testing, types of testing available, implications for care, privacy/disclosure concerns and ethical considerations. Hereditary genetic syndromes associated with head and neck neoplasms are reviewed, and online genetics resources are provided. Conclusions This article summarizes and contextualizes the evolving diagnostic and therapeutic options that impact the care of patients with head and neck cancer in the genomic era. PMID:25995036

Pharmacogenomics: a new clinical or regulatory paradigm? European experiences of pharmacogenomics in drug regulation and regulatory initiatives.

PubMed

Prasad, Krishna; Breckenridge, Alasdair

2011-10-01

Are regulatory agencies and processes up to speed? This is an often asked question. Recent advances in science and the improved knowledge of the human genome have a considerable influence on drug development and their impact on the regulatory aspect is also significant for several reasons, including changing stakeholder expectations and treatment paradigms. One of the challenges faced by the regulators is the need to adapt regulatory processes to accommodate the newer methodologies and techniques while ensuring that the biomarkers, tests and/or diagnostics, and the clinical trials are appropriate and fit for purpose. The change in emphasis in pharmacological treatment from a phenotype-based approach to newer methods is attractive but is it ready for universal adoption? This paper details some of the regulatory responses to the developments in this area. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Clinical guidelines for management of thyroid nodule and cancer during pregnancy.

PubMed

Galofré, Juan Carlos; Riesco-Eizaguirre, Garcilaso; Alvarez-Escolá, Cristina

2014-03-01

Special considerations are warranted in management of thyroid nodule and thyroid cancer during pregnancy. The diagnostic and therapeutic approach of thyroid nodules follows the standard practice in non-pregnant women. On the other hand, differentiated thyroid cancer management during pregnancy poses a number of challenges for the mother and fetus. The available data show that pregnancy is not a risk factor for thyroid cancer development or recurrence, although flare-ups cannot be completely ruled out in women with active disease. If surgery is needed, it should be performed during the second term or, preferably, after delivery. A majority of pregnant patients with low-risk disease only need adjustment in levothyroxine therapy. However, women with increased serum thyroglobulin levels before pregnancy or structural disease require regular thyroglobulin measurements and neck ultrasound throughout pregnancy. Pregnancy is an absolute contraindication for radioactive iodine administration. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Case Report: Disseminated Talaromyces (Penicillium) marneffei and Mycobacterium tuberculosis Coinfection in a Japanese Patient with Acquired Immunodeficiency Syndrome.

PubMed

Hatakeyama, Shuji; Yamashita, Takeshi; Sakai, Toshiyasu; Kamei, Katsuhiko

2017-07-01

Talaromyces marneffei is a dimorphic fungus endemic mainly in southeast and south Asia. It causes severe mycosis, usually in immunocompromised individuals, such as those with human immunodeficiency virus (HIV) infection. Concomitant infection with T. marneffei and other opportunistic pathogens is plausible because the majority of T. marneffei infections occur in patients with advanced HIV infection. Nonetheless, coinfection in the same site has rarely been reported, and poses a considerable diagnostic and therapeutic challenge. We report the case of an HIV-infected Japanese patient who had lived in Thailand for 6 years. The patient developed T. marneffei and Mycobacterium tuberculosis coinfection, and both pathogens were isolated from the same sites: a blood specimen and a lymph node aspirate. Clinicians should be aware of concomitant infection with T. marneffei and other pathogens in patients with advanced HIV disease who are living in or who have visited endemic areas.

Medicine and technology. Remarks on the notion of responsibility in the technology-assisted health care.

PubMed

Kwiatkowski, Waldemar

2018-06-01

The introduction of the modern diagnostic and therapeutic procedures to the medical practice provided a new challenge for the medicine. The art of medicine, with its default purpose of acting for the benefit of health, is therefore required to derive from technological progress effectively and rationally. As a result, the medical ethics has been engaged with the rules of economy and management of deficit medical procedures as well as their rational and fair distribution. The above suggests, that medics, given these recourses, should approach each patient with a consideration to their therapeutic rights. However, the physicians cannot just concentrate on the good of one particular patient, but must take into account joint responsibility for the good of a potential patient. This makes medical ethical dilemmas similar to the ethical issues of business. The notion of responsibility is the key for discriminating these two kinds of ethics.

Applying Research Domain Criteria (RDoC) to the study of fear and anxiety: A critical comment.

PubMed

Zoellner, Lori A; Foa, Edna B

2016-03-01

The goal of the Research Domain Criteria (RDoC) is to develop an interdisciplinary science of psychopathology, forming a template for research and disconnecting conceptual and empirical questions from traditional diagnostic entities. In this article, we review some of the challenges in the implementation of this framework within the field of pathological fear and anxiety, specifically commenting on the article by Hamm and colleagues (2016). The study of pathological fear and anxiety has had considerable, yet stalled, success in its understanding of underlying mechanisms, prevention, and treatment. With a shift toward RDoC, it is unclear what to do with the existing diagnostic labels, and the importance of defining and measuring phenotypes becomes paramount. Additional concerns include the role of psychological constructs and mechanisms, the use of self-report measures, the examination of replication and clinical utility, and the measurement of the role of the environment. Though a laudable and potentially necessary shift in focus, it remains to be seen whether new overall insights into psychopathology will emerge from focusing on small units of analyses and piecing them together and whether these insights will directly translate into the prevention of psychopathology, more efficacious treatments, and improved lives of patients. © 2016 Society for Psychophysiological Research.

Diagnostic challenges in celiac disease.

PubMed

Kowalski, Karol; Mulak, Agata; Jasińska, Maria; Paradowski, Leszek

2017-07-01

Diagnosis of celiac disease in adults is currently based on serologic tests in combination with histopathological assessment of small intestinal biopsy specimens. High titers of celiac-specific antibodies in immunocompetent patients with villous atrophy in a good quality biopsy sample allow us to state a confident diagnosis. The relief of symptoms and histological improvement after embarking on a gluten free diet further support the initial diagnosis. However, in some cases, these conditions are not fulfilled, which requires a critical evaluation of laboratory and histopathology results and a consideration of other potential causes for the observed pathologies. To avoid diagnostic uncertainty, both biopsy and laboratory testing should be performed on a diet containing gluten. Immune deficiency, cross reaction of antibodies and possibilities of seronegative or latent celiac disease should be considered while evaluating serology results. Uneven distribution and variable intensity of histopathological changes in the small intestine along with multiple disorders presenting a similar specimen image may lead to invalid biopsy results. Additional laboratory testing and careful examination of a patient's history may deliver important data for a differential diagnosis and a more specific biopsy evaluation. Persistence or recurrence of symptoms, despite the ongoing treatment, requires a revision of the initial diagnosis, an evaluation of the gluten free diet and a search for concurrent disorders or complications.

Thermodynamic framework to assess low abundance DNA mutation detection by hybridization

PubMed Central

Willems, Hanny; Jacobs, An; Hadiwikarta, Wahyu Wijaya; Venken, Tom; Valkenborg, Dirk; Van Roy, Nadine; Vandesompele, Jo; Hooyberghs, Jef

2017-01-01

The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics in its broadest sense. Although many methods and sensors to detect or quantify these variations are available or under development, the number of underlying physico-chemical detection principles is limited. One of these principles is the hybridization of sample target DNA versus nucleic acid probes. We introduce a novel thermodynamics approach and develop a framework to exploit the specific detection capabilities of nucleic acid hybridization, using generic principles applicable to any platform. As a case study, we detect point mutations in the KRAS oncogene on a microarray platform. For the given platform and hybridization conditions, we demonstrate the multiplex detection capability of hybridization and assess the detection limit using thermodynamic considerations; DNA containing point mutations in a background of wild type sequences can be identified down to at least 1% relative concentration. In order to show the clinical relevance, the detection capabilities are confirmed on challenging formalin-fixed paraffin-embedded clinical tumor samples. This enzyme-free detection framework contains the accuracy and efficiency to screen for hundreds of mutations in a single run with many potential applications in molecular diagnostics and the field of personalised medicine. PMID:28542229

Using Language Sampling in Clinical Assessments with Bilingual Children: Challenges and Future Directions

PubMed Central

Gutiérrez-Clellen, Vera F.; Simon-Cereijido, Gabriela

2012-01-01

Current language tests designed to assess Spanish-English-speaking children have limited clinical accuracy and do not provide sufficient information to plan language intervention. In contrast, spontaneous language samples obtained in the two languages can help identify language impairment with higher accuracy. In this article, we describe several diagnostic indicators that can be used in language assessments based on spontaneous language samples. First, based on previous research with monolingual and bilingual English speakers, we show that a verb morphology composite measure in combination with a measure of mean length of utterance (MLU) can provide valuable diagnostic information for English development in bilingual children. Dialectal considerations are discussed. Second, we discuss the available research with bilingual Spanish speakers and show a series of procedures to be used for the analysis of Spanish samples: (a) limited MLU and proportional use of ungrammatical utterances; (b) limited grammatical accuracy on articles, verbs, and clitic pronouns; and (c) limited MLU, omission of theme arguments, and limited use of ditransitive verbs. Third, we illustrate the analysis of verb argument structure using a rubric as an assessment tool. Estimated scores on morphological and syntactic measures are expected to increase the sensitivity of clinical assessments with young bilingual children. Further research using other measures of language will be needed for older school-age children. PMID:19851951

An algorithmic approach to the brain biopsy--part I.

PubMed

Kleinschmidt-DeMasters, B K; Prayson, Richard A

2006-11-01

The formulation of appropriate differential diagnoses for a slide is essential to the practice of surgical pathology but can be particularly challenging for residents and fellows. Algorithmic flow charts can help the less experienced pathologist to systematically consider all possible choices and eliminate incorrect diagnoses. They can assist pathologists-in-training in developing orderly, sequential, and logical thinking skills when confronting difficult cases. To present an algorithmic flow chart as an approach to formulating differential diagnoses for lesions seen in surgical neuropathology. An algorithmic flow chart to be used in teaching residents. Algorithms are not intended to be final diagnostic answers on any given case. Algorithms do not substitute for training received from experienced mentors nor do they substitute for comprehensive reading by trainees of reference textbooks. Algorithmic flow diagrams can, however, direct the viewer to the correct spot in reference texts for further in-depth reading once they hone down their diagnostic choices to a smaller number of entities. The best feature of algorithms is that they remind the user to consider all possibilities on each case, even if they can be quickly eliminated from further consideration. In Part I, we assist the resident in learning how to handle brain biopsies in general and how to distinguish nonneoplastic lesions that mimic tumors from true neoplasms.

An algorithmic approach to the brain biopsy--part II.

PubMed

Prayson, Richard A; Kleinschmidt-DeMasters, B K

2006-11-01

The formulation of appropriate differential diagnoses for a slide is essential to the practice of surgical pathology but can be particularly challenging for residents and fellows. Algorithmic flow charts can help the less experienced pathologist to systematically consider all possible choices and eliminate incorrect diagnoses. They can assist pathologists-in-training in developing orderly, sequential, and logical thinking skills when confronting difficult cases. To present an algorithmic flow chart as an approach to formulating differential diagnoses for lesions seen in surgical neuropathology. An algorithmic flow chart to be used in teaching residents. Algorithms are not intended to be final diagnostic answers on any given case. Algorithms do not substitute for training received from experienced mentors nor do they substitute for comprehensive reading by trainees of reference textbooks. Algorithmic flow diagrams can, however, direct the viewer to the correct spot in reference texts for further in-depth reading once they hone down their diagnostic choices to a smaller number of entities. The best feature of algorithms is that they remind the user to consider all possibilities on each case, even if they can be quickly eliminated from further consideration. In Part II, we assist the resident in arriving at the correct diagnosis for neuropathologic lesions containing granulomatous inflammation, macrophages, or abnormal blood vessels.

The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2013-04-01

Prediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients. A total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups. Median of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently. PCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intelligent artifact classification for ambulatory physiological signals.

PubMed

Sweeney, Kevin T; Leamy, Darren J; Ward, Tomas E; McLoone, Sean

2010-01-01

Connected health represents an increasingly important model for health-care delivery. The concept is heavily reliant on technology and in particular remote physiological monitoring. One of the principal challenges is the maintenance of high quality data streams which must be collected with minimally intrusive, inexpensive sensor systems operating in difficult conditions. Ambulatory monitoring represents one of the most challenging signal acquisition challenges of all in that data is collected as the patient engages in normal activities of everyday living. Data thus collected suffers from considerable corruption as a result of artifact, much of it induced by motion and this has a bearing on its utility for diagnostic purposes. We propose a model for ambulatory signal recording in which the data collected is accompanied by labeling indicating the quality of the collected signal. As motion is such an important source of artifact we demonstrate the concept in this case with a quality of signal measure derived from motion sensing technology viz. accelerometers. We further demonstrate how different types of artifact might be tagged to inform artifact reduction signal processing elements during subsequent signal analysis. This is demonstrated through the use of multiple accelerometers which allow the algorithm to distinguish between disturbance of the sensor relative to the underlying tissue and movement of this tissue. A brain monitoring experiment utilizing EEG and fNIRS is used to illustrate the concept.

Risk stratification, genomic data and the law.

PubMed

Hall, Alison; Finnegan, Thomas; Chowdhury, Susmita; Dent, Tom; Kroese, Mark; Burton, Hilary

2018-02-22

Risk prediction models have a key role in stratified disease prevention, and the incorporation of genomic data into these models promises more effective personalisation. Although the clinical utility of incorporating genomic data into risk prediction tools is increasingly compelling, at least for some applications and disease types, the legal and regulatory implications have not been examined and have been overshadowed by discussions about clinical and scientific utility and feasibility. We held a workshop to explore relevant legal and regulatory perspectives from four EU Member States: France, Germany, the Netherlands and the UK. While we found no absolute prohibition on the use of such data in those tools, there are considerable challenges. Currently, these are modest and result from genomic data being classified as sensitive data under existing Data Protection regulation. However, these challenges will increase in the future following the implementation of EU Regulations on data protection which take effect in 2018, and reforms to the governance of the manufacture, development and use of in vitro diagnostic devices to be implemented in 2022. Collectively these will increase the regulatory burden placed on these products as risk stratification tools will be brought within the scope of these new Regulations. The failure to respond to the challenges posed by the use of genomic data in disease risk stratification tools could therefore prove costly to those developing and using such tools.

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.

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.

Chasing helminths and their economic impact on farmed ruminants.

PubMed

Charlier, Johannes; van der Voort, Mariska; Kenyon, Fiona; Skuce, Philip; Vercruysse, Jozef

2014-07-01

Global agriculture will be required to intensify production from a shrinking natural resource base. Helminth infections of ruminants are a major constraint on efficient livestock production. The current challenge is to develop diagnostic methods that detect the production impact of helminth infections on farms in order to target control measures and contribute to the global challenge of preserving food security. We review here our understanding of the effects of helminth infections and control practices on productivity and the diagnostic tools that can inform on this. By combining advances in helminth laboratory diagnostics and animal health economics, sustainable management of helminth infections can be integrated into the whole-farm economic context. Copyright © 2014 Elsevier Ltd. All rights reserved.

Imaging in primary hyperparathyroidism: focus on the evidence-based diagnostic performance of different methods.

PubMed

Treglia, Giorgio; Trimboli, Pierpaolo; Huellner, Martin; Giovanella, Luca

2018-06-01

Primary hyperparathyroidism (PHPT) is a common endocrine disorder usually due to hyperfunctioning parathyroid glands (HP). Surgical removal of HP is the main treatment in PHPT, particularly in symptomatic patients. The correct detection and localization of HP is challenging and crucial as it may guide surgical treatment in patients with PHPT. To date, different imaging methods have been used to detect and localize HP in patients with PHPT including radiology, nuclear medicine and hybrid techniques. This review was focused to describe the diagnostic performance of several imaging methods used in detecting HP in patients with PHPT. We have summarized the diagnostic performance of different imaging methods used in detecting HP in patients with PHPT taking into account recent evidence-based articles published in the literature. To this regard, findings of recently published meta-analyses on the diagnostic accuracy of imaging methods in PHPT were reported. Furthermore, a suggested imaging strategy taking into account the diagnostic performance and further consideration has been described. Cervical ultrasound (US) and parathyroid scintigraphy using 99mTc-MIBI are the most commonly employed first-line investigations in patients with PHPT, with many institutions using both methods in combination. The diagnostic performance of US and planar 99mTc-MIBI scintigraphy seems to be similar. The use of tomographic imaging (SPECT and SPECT/CT) increases the detection rate of HP compared to planar 99mTc-MIBI scintigraphy. Whereas traditional computed tomography (CT) has limited usefulness in PHPT, four dimensional CT (4D-CT) has similar diagnostic performance compared to tomographic parathyroid scintigraphy but a higher radiation dose. Although initial encouraging results, to date there is insufficient evidence to recommend the routine use of MRI or positron emission tomography (PET) with several radiopharmaceuticals in patients with PHPT. However, they could be useful alternatives in cases with negative or discordant findings at first-line imaging methods. Patients with PHPT who are candidates for parathyroidectomy should be referred to an expert clinician to decide which imaging studies to perform based on regional imaging capabilities. The imaging techniques with higher diagnostic performance in detecting and localizing HP seems to be 99mTc-MIBI SPECT/CT and 4D-CT. Taking into account several data beyond the diagnostic performance, the combination of cervical US performed by an experienced parathyroid sonographer and 99mTc-MIBI SPECT or SPECT//CT seems to be an optimal first-line strategy in the preoperative planning of patients with PHPT.

Investing in the use of a checklist during differential diagnoses consideration: what's the trade-off?

PubMed

Chew, Keng Sheng; van Merrienboer, Jeroen J G; Durning, Steven J

2017-11-29

A key challenge clinicians face when considering differential diagnoses is whether the patient data have been adequately collected. Insufficient data may inadvertently lead to premature closure of the diagnostic process. This study aimed to test the hypothesis that the application of a mnemonic checklist helps to stimulate more patient data collection, thus leading to better diagnostic consideration. A total of 88 final year medical students were assigned to either an educational intervention group or a control group in a non-equivalent group post-test only design. Participants in the intervention group received a tutorial on the use of a mnemonic checklist aimed to minimize cognitive errors in clinical decision-making. Two weeks later, the participants in both groups were given a script concordance test consisting of 10 cases, with 3 items per case, to assess their clinical decisions when additional data are given in the case scenarios. The Mann-Whitney U-test performed on the total scores from both groups showed no statistical significance (U = 792, z = -1.408, p = 0.159). When comparisons were made for the first half and the second half of the SCT, it was found that participants in the intervention group performed significantly better than participants in the control group in the first half of the test, with median scores of 9.15 (IQR 8.00-10.28) vs. 8.18 (IQR 7.16-9.24) respectively, U = 642.5, z = -2.661, p = 0.008. No significant difference was found in the second half of the test, with the median score of 9.58 (IQR 8.90-10.56) vs. 9.81 (IQR 8.83-11.12) for the intervention group and control group respectively (U = 897.5, z = -0.524, p = 0.60). Checklist use in differential diagnoses consideration did show some benefit. However, this benefit seems to have been traded off by the time and effort in using it. More research is needed to determine whether this benefit could be translated into clinical practice after repetitive use.

Posterior, Lateral, and Anterior Hip Pain Due to Musculoskeletal Origin: A Narrative Literature Review of History, Physical Examination, and Diagnostic Imaging.

PubMed

Battaglia, Patrick J; D'Angelo, Kevin; Kettner, Norman W

2016-12-01

The purpose of this study was to present a narrative review of the literature of musculoskeletal causes of adult hip pain, with special attention to history, physical examination, and diagnostic imaging. A narrative review of the English medical literature was performed by using the search terms "hip pain" AND "anterior," "lateral," and "posterior." Additionally, specific entities of hip pain or pain referral sources to the hip were searched for. We used the PubMed search engine through January 15, 2016. Musculoskeletal sources of adult hip pain can be divided into posterior, lateral, and anterior categories. For posterior hip pain, select considerations include lumbar spine and femoroacetabular joint referral, sacroiliac joint pathology, piriformis syndrome, and proximal hamstring tendinopathy. Gluteal tendinopathy and iliotibial band thickening are the most common causes of lateral hip pain. Anterior hip pain is further divided into causes that are intra-articular (ie, labral tear, osteoarthritis, osteonecrosis) and extra-articular (ie, snapping hip and inguinal disruption [athletic pubalgia]). Entrapment neuropathies and myofascial pain should also be considered in each compartment. A limited number of historical features and physical examination tests for evaluation of adult hip pain are supported by the literature and are discussed in this article. Depending on the clinical differential, the gamut of diagnostic imaging modalities recommended for accurate diagnosis include plain film radiography, computed tomography, magnetic resonance imaging, skeletal scintigraphy, and ultrasonography. The evaluation of adult hip pain is challenging. Clinicians should consider posterior, lateral, and anterior sources of pain while keeping in mind that these may overlap.

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.

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

Decision making about healthcare-related tests and diagnostic test strategies. Paper 2: a review of methodological and practical challenges.

PubMed

Mustafa, Reem A; Wiercioch, Wojtek; Cheung, Adrienne; Prediger, Barbara; Brozek, Jan; Bossuyt, Patrick; Garg, Amit X; Lelgemann, Monika; Büehler, Diedrich; Schünemann, Holger J

2017-12-01

In this first of a series of five articles, we provide an overview of how and why healthcare-related tests and diagnostic strategies are currently applied. We also describe how our findings can be integrated with existing frameworks for making decisions that guide the use of healthcare-related tests and diagnostic strategies. We searched MEDLINE, references of identified articles, chapters in relevant textbooks, and identified articles citing classic literature on this topic. We provide updated frameworks for the potential roles and applications of tests with suggested definitions and practical examples. We also discuss study designs that are commonly used to assess tests' performance and the effects of tests on people's health. These designs include diagnostic randomized controlled trials and retrospective validation. We describe the utility of these and other currently suggested designs, which questions they can answer and which ones they cannot. In addition, we summarize the challenges unique to decision-making resulting from the use of tests. This overview highlights current challenges in the application of tests in decision-making in healthcare, provides clarifications, and informs the proposed solutions. Copyright © 2017 Elsevier Inc. All rights reserved.

Navigating the challenges of digital health innovation: considerations and solutions in developing online and smartphone-application-based interventions for mental health disorders.

PubMed

Hill, Claire; Martin, Jennifer L; Thomson, Simon; Scott-Ram, Nick; Penfold, Hugh; Creswell, Cathy

2017-08-01

This article presents an analysis of challenges and considerations when developing digital mental health innovations. Recommendations include collaborative working between clinicians, researchers, industry and service users in order to successfully navigate challenges and to ensure e-therapies are engaging, acceptable, evidence based, scalable and sustainable. © The Royal College of Psychiatrists 2017.

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.

Novel Treponema pallidum Recombinant Antigens for Syphilis Diagnostics: Current Status and Future Prospects

PubMed Central

Kubanov, Aleksey; Runina, Anastassia

2017-01-01

The recombinant protein technology considerably promoted the development of rapid and accurate treponema-specific laboratory diagnostics of syphilis infection. For the last ten years, the immunodominant recombinant inner membrane lipoproteins are proved to be sensitive and specific antigens for syphilis screening. However, the development of an enlarged T. pallidum antigen panel for diagnostics of early and late syphilis and differentiation of syphilis stages or cured syphilis remains as actual goal of multidisciplinary expertise. Current review revealed novel recombinant antigens: surface-exposed proteins, adhesins, and periplasmic and flagellar proteins, which are promising candidates for the improved syphilis serological diagnostics. The opportunities and limitations of diagnostic usage of these antigens are discussed and the criteria for selection of optimal antigens panel summarized. PMID:28523273

The AMCP Format for Formulary Submissions: Welcome to Version 4.0.

PubMed

2016-05-01

Managed care pharmacists are increasingly presented with complex considerations related to prescription drug formulary management. As prescription drug spending soars, and new effective, but expensive drugs rush to the market, pharmacists and other health care decision makers must evaluate a myriad of important clinical and economic considerations in determining the relative value and, subsequently, the appropriate placement of a product within a formulary. The AMCP Format for Formulary Submissions, Version 4.0, is the next iteration of the Format, which was first released in 2000. Version 4.0, developed by pharmacists from health plan, manufacturer, and academic perspectives, provides updated recommendations on acquiring and evaluating clinical and economic evidence to inform formulary and medical policy decisions. It also includes new guidance related to emerging special topic considerations such as biosimilars, specialty pharmacy products, and companion diagnostic tests. Version 4.0 has been modified to improve the usability of the Format, with clarifying guidance related to logistical considerations such as a recommended time frame for implementation of Version 4.0, as well as dossier updates and ongoing communication between manufacturers and health care decision makers. The Format should be used as a framework for ongoing evidence-based dialogue between manufacturers and payers. The evolving health care landscape will require new levels of collaboration and communication among key stakeholders to successfully navigate the challenges of this new environment. The Format provides a framework to support these critical interactions related to product value by facilitating an evidence-based, transparent approach. This document was prepared by Jeff Lee, PharmD, FCCP, on behalf of the AMCP Format Executive Committee. Committee members reviewed and provided feedback on the final draft. No conflicts of interest, financial or otherwise, were reported.

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…

Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of Patients with Autism Spectrum Disorders from a Highly Consanguineous Population

ERIC Educational Resources Information Center

Al-Mamari, Watfa; Al-Saegh, Abeer; Al-Kindy, Adila; Bruwer, Zandre; Al-Murshedi, Fathiya; Al-Thihli, Khalid

2015-01-01

Autism Spectrum Disorders are a complicated group of disorders characterized with heterogeneous genetic etiologies. The genetic investigations for this group of disorders have expanded considerably over the past decade. In our study we designed a tired approach and studied the diagnostic yield of chromosomal microarray analysis on patients…

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 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.

Better Tests, Better Care: Improved Diagnostics for Infectious Diseases

PubMed Central

Caliendo, Angela M.; Gilbert, David N.; Ginocchio, Christine C.; Hanson, Kimberly E.; May, Larissa; Quinn, Thomas C.; Tenover, Fred C.; Alland, David; Blaschke, Anne J.; Bonomo, Robert A.; Carroll, Karen C.; Ferraro, Mary Jane; Hirschhorn, Lisa R.; Joseph, W. Patrick; Karchmer, Tobi; MacIntyre, Ann T.; Reller, L. Barth; Jackson, Audrey F.

2013-01-01

In this IDSA policy paper, we review the current diagnostic landscape, including unmet needs and emerging technologies, and assess the challenges to the development and clinical integration of improved tests. To fulfill the promise of emerging diagnostics, IDSA presents recommendations that address a host of identified barriers. Achieving these goals will require the engagement and coordination of a number of stakeholders, including Congress, funding and regulatory bodies, public health agencies, the diagnostics industry, healthcare systems, professional societies, and individual clinicians. PMID:24200831

Improvements in High Resolution Laryngeal Magnetic Resonance Imaging for Preoperative Transoral Laser Microsurgery and Radiotherapy Considerations in Early Lesions

PubMed Central

Ruytenberg, Thomas; Verbist, Berit M.; Vonk-Van Oosten, Jordi; Astreinidou, Eleftheria; Sjögren, Elisabeth V.; Webb, Andrew G.

2018-01-01

As the benefits, limitations, and contraindications of transoral laser microsurgery (TLM) in glottic carcinoma treatments become better defined, pretreatment imaging has become more important to assess the case-specific suitability of TLM and to predict functional outcomes both for treatment consideration and patient counseling. Magnetic resonance imaging (MRI) is the preferred modality to image such laryngeal tumors, even though imaging the larynx using MRI can be difficult. The first challenge is that there are no commercial radiofrequency (RF) coils that are specifically designed for imaging the larynx, and performance in terms of coverage and signal-to-noise ratio is compromised using general-purpose RF coils. Second, motion in the neck region induced by breathing, swallowing, and vessel pulsation can induce severe image artifacts, sometimes rendering the images unusable. In this paper, we design a dedicated RF coil array, which allows high quality high-resolution imaging of the larynx. In addition, we show that introducing respiratory-triggered acquisition improves the diagnostic quality of the images by minimizing breathing and swallowing artifacts. Together, these developments enable robust, essentially artifact-free images of the full larynx with an isotropic resolution of 1 mm to be acquired within a few minutes. PMID:29928638

PIM-1 kinase expression in adipocytic neoplasms: diagnostic and biological implications

PubMed Central

Nga, Min En; Swe, Nu Nu Ma; Chen, Kang Ting; Shen, Liang; Lilly, Michael B; Chan, Siew Pang; Salto-Tellez, Manuel; Das, Kakoli

2010-01-01

The differential diagnosis of soft tissue tumours poses a considerable challenge for pathologists, especially adipocytic tumours, as these may show considerable overlap in clinical presentation and morphological features with many other mesenchymal neoplasms. Hence, a specific and reliable marker that identifies adipocytic differentiation is much sought. We investigated the immunohistochemical expression of PIM-1 kinase in 35 samples of soft tissue tumours using tissue microarray technology and 49 full sections of adipocytic (n = 26) and non-adipocytic tumours (n = 23). Benign and malignant adipocytic tumours showed strong expression of PIM-1 while the non-adipocytic tumours were either negative or showed only weak staining for the protein. In myxoid liposarcomas, PIM-1 showed a distinct, unique vacuolar staining pattern, clearly outlining fine cytoplasmic lipid vacuoles. By contrast, non-adipocytic myxoid tumours (myxoma, chordoma and myxoid chondrosarcoma) did not show this vacuolar pattern of PIM-1 staining, although vacuolated cells were present on H&E. This differential expression was confirmed at a gene expression level in selected cases. Our results indicate that the expression of PIM-1 in adipose tissue may be a useful marker of adipocytic differentiation, in particular if the staining is both of high intensity and present in a unique, vacuolar pattern. PMID:19878356

Diagnostic reliability of MMPI-2 computer-based test interpretations.

PubMed

Pant, Hina; McCabe, Brian J; Deskovitz, Mark A; Weed, Nathan C; Williams, John E

2014-09-01

Reflecting the common use of the MMPI-2 to provide diagnostic considerations, computer-based test interpretations (CBTIs) also typically offer diagnostic suggestions. However, these diagnostic suggestions can sometimes be shown to vary widely across different CBTI programs even for identical MMPI-2 profiles. The present study evaluated the diagnostic reliability of 6 commercially available CBTIs using a 20-item Q-sort task developed for this study. Four raters each sorted diagnostic classifications based on these 6 CBTI reports for 20 MMPI-2 profiles. Two questions were addressed. First, do users of CBTIs understand the diagnostic information contained within the reports similarly? Overall, diagnostic sorts of the CBTIs showed moderate inter-interpreter diagnostic reliability (mean r = .56), with sorts for the 1/2/3 profile showing the highest inter-interpreter diagnostic reliability (mean r = .67). Second, do different CBTIs programs vary with respect to diagnostic suggestions? It was found that diagnostic sorts of the CBTIs had a mean inter-CBTI diagnostic reliability of r = .56, indicating moderate but not strong agreement across CBTIs in terms of diagnostic suggestions. The strongest inter-CBTI diagnostic agreement was found for sorts of the 1/2/3 profile CBTIs (mean r = .71). Limitations and future directions are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Theoretical Borderlands: Using Multiple Theoretical Perspectives to Challenge Inequitable Power Structures in Student Development Theory

ERIC Educational Resources Information Center

Abes, Elisa S.

2009-01-01

This article is an exploration of possibilities and methodological considerations for using multiple theoretical perspectives in research that challenges inequitable power structures in student development theory. Specifically, I explore methodological considerations when partnering queer theory and constructivism in research on lesbian identity…

Evaluation of a rapid diagnostic field test kit for identification of Phytophthora ramorum, P. kernoviae and other Phytophthora species at the point of inspection

Treesearch

C.R. Lane; E. Hobden; L. Laurenson; V.C. Barton; K.J.D. Hughes; H. Swan; N. Boonham; A.J. Inman

2008-01-01

Plant health regulations to prevent the introduction and spread of Phytophthora ramorum and P. kernoviae require rapid, cost effective diagnostic methods for screening large numbers of plant samples at the time of inspection. Current on-site techniques require expensive equipment, considerable expertise and are not suited for plant...

[Leiomyosarcoma of the mesentery. A case report and clinico-diagnostic considerations].

PubMed

Ferranti, F; Mancini, G; Rossi, M D; D'Aristotile, A; Ippoliti, A; De Ascentis, G; Monteferrante, E; Rotolo, A; Gaspari, A L

1996-12-01

Leiomyosarcoma of the mesentery is a rare neoplasm. The clinical manifestation is non-specific and preoperative diagnosis is often late. Mitotic activity shows no significant correlation with the biological behavior of neoplasm. The surgical excision is the therapy of choice but local recurrence is high. The authors report a case of leiomyosarcoma which was treated by surgical removal and underline the diagnostic difficulties.

The Influence of Socio-Economic Status and Age on Diagnosis and Service Recommendations for Psycho-Educationally Handicapped Children.

ERIC Educational Resources Information Center

Kelsey, John W.

With the advent of the Education for All Handicapped Children Act, (P.L. 94-142), diagnostic evaluations and recommendations for service should proceed on a logical and unbiased basis. Studies from the past decade have suggested that there is considerable bias in diagnostic labeling due to socioeconomic status and age of the child. In turn this…

Management of Epistaxis in Children and Adolescents: Avoiding a Chaotic Approach.

PubMed

Svider, Peter; Arianpour, Khashayar; Mutchnick, Sean

2018-06-01

This article provides an organized foundation that facilitates the management of acute epistaxis and an understanding of features that merit further diagnostic workup. Prompt management, including measures such as holding pressure and using nasal packing, takes precedence over comprehensive diagnostic workup. Severe, recurrent, and posteriorly based bleeds should prompt consideration of alternate interventions and expert consultation. Copyright © 2018 Elsevier Inc. All rights reserved.

Diagnostic standards for dopaminergic augmentation of restless legs syndrome: report from a World Association of Sleep Medicine-International Restless Legs Syndrome Study Group consensus conference at the Max Planck Institute.

PubMed

García-Borreguero, Diego; Allen, Richard P; Kohnen, Ralf; Högl, Birgit; Trenkwalder, Claudia; Oertel, Wolfgang; Hening, Wayne A; Paulus, Walter; Rye, David; Walters, Arthur; Winkelmann, Juliane; Earley, Christopher J

2007-08-01

Augmentation of symptom severity is the main complication of dopaminergic treatment of restless legs syndrome (RLS). The current article reports on the considerations of augmentation that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored Consensus Conference in April 2006 at the Max Planck Institute (MPI) in Munich, Germany, the conclusions of which were endorsed by the International RLS Study Group (IRLSSG) and the World Association of Sleep Medicine (WASM). The Consensus Conference sought to develop a better understanding of augmentation and generate a better operational definition for its clinical identification. Current concepts of the pathophysiology, clinical features, and therapy of RLS augmentation were evaluated by subgroups who presented a summary of their findings for general consideration and discussion. Recent data indicating sensitivity and specificity of augmentation features for identification of augmentation were also evaluated. The diagnostic criteria of augmentation developed at the National Institutes of Health (NIH) conference in 2002 were reviewed in light of current data and theoretical understanding of augmentation. The diagnostic value and criteria for each of the accepted features of augmentation were considered by the group. A consensus was then developed for a revised statement of the diagnostic criteria for augmentation. Five major diagnostic features of augmentation were identified: usual time of RLS symptom onset each day, number of body parts with RLS symptoms, latency to symptoms at rest, severity of the symptoms when they occur, and effects of dopaminergic medication on symptoms. The quantitative data available relating the time of RLS onset and the presence of other features indicated optimal augmentation criteria of either a 4-h advance in usual starting time for RLS symptoms or a combination of the occurrence of other features. A paradoxical response to changes in medication dose also indicates augmentation. Clinical significance of augmentation is defined. The Consensus Conference agreed upon new operational criteria for the clinical diagnosis of RLS augmentation: the MPI diagnostic criteria for augmentation. Areas needing further consideration for validating these criteria and for understanding the underlying biology of RLS augmentation are indicated.

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...

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.

Primary focal hyperhidrosis: diagnosis and management. .

PubMed

Wang, Rena; Solish, Nowell; Murray, Christian A

2008-12-01

Primary focal hyperhidrosis is a common and serious medical condition that causes considerable psychosocial morbidity. Diagnostic and effective management strategies can improve patients' quality of living dramatically.

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.

DSM-V from the perspective of the DSM-IV experience.

PubMed

Walsh, B Timothy

2007-11-01

This article provides a brief overview of the development of the diagnostic criteria for eating disorders in DSM-IV. The process by which DSM-IV was developed is reviewed, including perspectives on what constitutes diagnostic validity and clinical utility, and their importance in assessing proposed changes in diagnostic criteria. The question of whether alterations in diagnostic criteria would clearly improve clinical utility was a major consideration in the DSM-IV process. Because of concerns that changes in diagnostic criteria would be disruptive and might entail loss of established knowledge, the DSM-IV Task Force assumed a generally conservative stance vis-à-vis change. The process of developing DSM-V is just beginning, and it is far from clear what alterations in diagnostic criteria for eating disorders will occur. However, the evolution of DSM-IV may provide a useful perspective on the development of DSM-V. (c) 2007 by Wiley Periodicals, Inc.

Etiological analysis and predictive diagnostic model building of community-acquired pneumonia in adult outpatients in Beijing, China.

PubMed

Liu, Ya-Fen; Gao, Yan; Chen, Mei-Fang; Cao, Bin; Yang, Xiao-Hua; Wei, Lai

2013-07-09

Etiological epidemiology and diagnosis are important issues in adult community-acquired pneumonia (CAP), and identifying pathogens based on patient clinical features is especially a challenge. CAP-associated main pathogens in adults include viruses as well as bacteria. However, large-scale epidemiological investigations of adult viral CAP in China are still lacking. In this study, we analyzed the etiology of adult CAP in Beijing, China and constructed diagnostic models based on combinations of patient clinical factors. A multicenter cohort was established with 500 adult CAP outpatients enrolled in Beijing between November 2010 to October 2011. Multiplex and quantitative real-time fluorescence PCR were used to detect 15 respiratory viruses and mycoplasma pneumoniae, respectively. Bacteria were detected with culture and enzyme immunoassay of the Streptococcus pneumoniae urinary antigen. Univariate analysis, multivariate analysis, discriminatory analysis and Receiver Operating Characteristic (ROC) curves were used to build predictive models for etiological diagnosis of adult CAP. Pathogens were detected in 54.2% (271/500) of study patients. Viruses accounted for 36.4% (182/500), mycoplasma pneumoniae for 18.0% (90/500) and bacteria for 14.4% (72/500) of the cases. In 182 of the patients with viruses, 219 virus strains were detected, including 166 single and 53 mixed viral infections. Influenza A virus represented the greatest proportion with 42.0% (92/219) and 9.1% (20/219) in single and mixed viral infections, respectively. Factors selected for the predictive etiological diagnostic model of viral CAP included cough, dyspnea, absence of chest pain and white blood cell count (4.0-10.0) × 10(9)/L, and those of mycoplasma pneumoniae CAP were being younger than 45 years old and the absence of a coexisting disease. However, these models showed low accuracy levels for etiological diagnosis (areas under ROC curve for virus and mycoplasma pneumoniae were both 0.61, P < 0.05). Greater consideration should be given to viral and mycoplasma pneumoniae infections in adult CAP outpatients. While predictive etiological diagnostic models of viral and mycoplasma pneumoniae based on combinations of demographic and clinical factors may provide indications of etiology, diagnostic confirmation of CAP remains dependent on laboratory pathogen test results.

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.

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 ...

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.

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.

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.

Language Teacher Identities in the Southern United States: Transforming Rural Schools

ERIC Educational Resources Information Center

Fogle, Lyn Wright; Moser, Kelly

2017-01-01

Foreign language (FL) and English as a Second Language (ESL) teaching present considerable challenges in the rural U.S. South. Local language ideologies, budgetary considerations, and challenges in other curricular areas (e.g., math and science) lead to marginalizing both FL and ESL in schools. This article examines the personal and professional…

Overcoming the glass ceiling: views from the cellar and the roof.

PubMed

McCrady, Barbara S

2012-12-01

Women's experiences as professionals and behavior therapists have changed considerably in the past 40 years. The author describes early challenges and experiences of discrimination as a young female professional. Although women's opportunities have improved considerably, women still experience unique career challenges and choices. The author provides some suggestions for women's career development.

A 'difficult' insect allergy patient: reliable history of a sting, but all testing negative.

PubMed

Tracy, James M; Olsen, Jonathan A; Carlson, John

2015-08-01

Few conditions are as treatable as allergy to stinging insects, with venom immunotherapy (VIT) providing up to 98% protection to subsequent stings. The challenge with VIT is not in the treatment, but in the diagnosis. To offer VIT, one must determine a history of a systemic reaction to a stinging insect in conjunction with the presence venom-specific IgE. Current diagnostic methods, although sensitive and specific, are imperfect, and some newer testing options are not widely available. A conundrum occasionally faced is the patient with a reliable and compelling history of a systemic allergic reaction yet negative venom-specific testing. This diagnostic dilemma presents an opportunity to consider possible causes for this diagnostic challenge. Our evolving understanding of the role of occult mast cell disease may begin to help us understand this situation and develop appropriate management strategies. Venom-specific skin testing has long been the cornerstone of the evaluation of venom sensitivity and is often combined with in-vitro assays to add clarity, but even these occasionally may fall short. Exploring novel venom diagnostic testing methods may help to fill in some of the diagnostic gaps. Do currently available venom vaccines contain all the key venom species? Are there enough differences between insect species that we may simply be missing the relevant allergens? What is the significance of the antigenicity of carbohydrate moieties in venoms? What is the role of recombinant venom extracts? VIT is the definitive treatment for insect allergic individuals. To utilize VIT, identification of the relevant Hymenoptera is necessary. Unfortunately, this cannot always be accomplished. This deficiency can have several causes: a potential comorbid condition such as occult mast cell disease, limitations of currently available diagnostic resources, or testing vaccines with an insufficient coverage of relevant venom allergens. Exploring these potential causes may help to provide important insight into this important diagnostic conundrum. The use of a case report may help clarify this challenge.

[Diagnostic imaging of urolithiais. Current recommendations and new developments].

PubMed

Thalgott, M; Kurtz, F; Gschwend, J E; Straub, M

2015-07-01

Prevalence of urolithiasis is increasing in industrialized countries--in both adults and children, representing a unique diagnostic and therapeutic challenge. Risk-adapted diagnostic imaging currently means assessment with maximized sensitivity and specificity together with minimal radiation exposure. In clinical routine, imaging is performed by sonography, unenhanced computed tomography (NCCT) or intravenous urography (IVU) as well as plain kidney-ureter-bladder (KUB) radiographs. The aim of the present review is a critical guideline-based and therapy-aligned presentation of diagnostic imaging procedures for optimized treatment of urolithiasis considering the specifics in children and pregnant women.

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

Value of lower respiratory tract surveillance cultures to predict bacterial pathogens in ventilator-associated pneumonia: systematic review and diagnostic test accuracy meta-analysis.

PubMed

Brusselaers, Nele; Labeau, Sonia; Vogelaers, Dirk; Blot, Stijn

2013-03-01

In ventilator-associated pneumonia (VAP), early appropriate antimicrobial therapy may be hampered by involvement of multidrug-resistant (MDR) pathogens. A systematic review and diagnostic test accuracy meta-analysis were performed to analyse whether lower respiratory tract surveillance cultures accurately predict the causative pathogens of subsequent VAP in adult patients. Selection and assessment of eligibility were performed by three investigators by mutual consideration. Of the 525 studies retrieved, 14 were eligible for inclusion (all in English; published since 1994), accounting for 791 VAP episodes. The following data were collected: study and population characteristics; in- and exclusion criteria; diagnostic criteria for VAP; microbiological workup of surveillance and diagnostic VAP cultures. Sub-analyses were conducted for VAP caused by Staphylococcus aureus, Pseudomonas spp., and Acinetobacter spp., MDR microorganisms, frequency of sampling, and consideration of all versus the most recent surveillance cultures. The meta-analysis showed a high accuracy of surveillance cultures, with pooled sensitivities up to 0.75 and specificities up to 0.92 in culture-positive VAP. The area under the curve (AUC) of the hierarchical summary receiver-operating characteristic curve demonstrates moderate accuracy (AUC: 0.90) in predicting multidrug resistance. A sampling frequency of >2/week (sensitivity 0.79; specificity 0.96) and consideration of only the most recent surveillance culture (sensitivity 0.78; specificity 0.96) are associated with a higher accuracy of prediction. This study provides evidence for the benefit of surveillance cultures in predicting MDR bacterial pathogens in VAP. However, clinical and statistical heterogeneity, limited samples sizes, and bias remain important limitations of this meta-analysis.

Dependence on Tobacco and Nicotine Products: A Case for Product-Specific Assessment

PubMed Central

Eissenberg, Thomas

2012-01-01

The International Classification of Diseases and the Diagnostic and Statistical Manual for diagnosing tobacco/nicotine dependence emphasize the dependence-producing drug nicotine. These diagnostic tools have been challenged on grounds of poor predictive validity, and they do not differentiate across various forms of nicotine-containing products. In fact, nicotine-containing products (e.g., tobacco cigarettes, smokeless tobacco [ST], waterpipe, electronic cigarettes [ECIGs], and nicotine replacement [NR] products) have very different characteristics both in terms of sensory and behavioral involvement and also in pharmacokinetic and pharmacodynamic effects. For example, a cigarette and a nicotine patch are very different on almost every one of these dimensions. When ability to stop using a nicotine/tobacco product is used as a criterion for dependence, success rates vary considerably across products: Tobacco cigarette cessation is more difficult than ST cessation that in turn is more difficult than NR product cessation. Based on these results, we hypothesize that there is a continuum of dependence as much as there is a continuum of harm, with tobacco cigarettes and NR products on opposite ends of both continua and other products (waterpipe and ECIGs) somewhere in between. In order to capture more precisely the dependence produced by both nicotine and its administration forms, product-specific instruments may be required. The pros and cons of this approach are discussed. PMID:22459798

Human taeniasis: current insights into prevention and management strategies in endemic countries

PubMed Central

Okello, Anna L; Thomas, Lian Francesca

2017-01-01

Human taeniasis is a zoonotic condition resulting from infection with the adult stages of Taenia saginata (“beef tapeworm”), Taenia solium (“pork tapeworm”) or Taenia asiatica (“Asian tapeworm”). Although these parasites have a worldwide distribution, the overwhelming burden is felt by communities in low- and middle-income countries. This is particularly true for T. solium, whereby infection of the central nervous system with the larval stage of the parasite (neurocysticercosis) is a major cause of acquired epilepsy in low-resource settings. With a focus on endemic countries, this review provides an insight into the prevention and management of human taeniasis, concluding with some recent case studies describing their implementation. Discussion of the opportunities and challenges regarding current fecal and serological diagnostic assays for detecting Taenia spp. highlights the importance of accurate and accessible diagnostic options for the field situation. The lack of long-term impact on the parasites’ lifecycle from human anthelmintic treatment, coupled with the propensity for adverse reactions, highlights the importance of a “two-pronged” approach that considers the relevant animal hosts, particularly in the case of T. solium. Aside from the therapeutic options, this review reiterates the importance of adequate assessment and consideration of the associated behavioral and policy aspects around sanitation, hygiene and meat inspection that have been shown to support parasite control, and potential elimination, in endemic regions. PMID:28615981

Towards a new conceptualization of depression in older adult cancer patients: a review of the literature

PubMed Central

Saracino, Rebecca M.; Rosenfeld, Barry; Nelson, Christian J.

2016-01-01

Objectives Identifying depression in older adults with cancer presents a set of unique challenges, as it combines the confounding influences of cancer and its treatment with the developmental changes associated with aging. This paper reviews the phenomenology of depression in older adults, and individuals diagnosed with cancer. Method PsychInfo, PubMed, Web of Science, and Google Scholar databases were searched for English-language studies addressing the phenomenology, symptoms, or assessment of depression in older adults and those with cancer. Results The Diagnostic and Statistical Manual for Mental Disorders (DSM) criteria that appear to be relevant to both older adults and cancer patients are anhedonia, concentration difficulties, sleep disturbances, psychomotor retardation/agitation, and loss of energy. Possible alternative criteria that may be important considerations included constructs such as loss of purpose, loneliness, and irritability in older adults. Among cancer patients, tearfulness, social withdrawal, and not participating in treatment despite ability to do so were identified as potentially important symptoms. Conclusions Current DSM criteria may not adequately assess depression in older cancer patients and alternative criteria may be important to inform the understanding and identification of depression in this population. Enhancing diagnostic accuracy of depression is important as both the over-diagnosis and under-diagnosis is accompanied with significant costs. Thus, continued research exploring the phenomenology and identifying effective indicators of depression in older cancer patients is needed. PMID:26312455

Non-LTE modeling for the National Ignition Facility (and beyond)

NASA Astrophysics Data System (ADS)

Scott, H. A.; Hammel, B. A.; Hansen, S. B.

2012-05-01

Considerable progress has been made in the last year in the study of laser-driven inertial confinement fusion at the National Ignition Facility (NIF). Experiments have demonstrated symmetric capsule implosions with plasma conditions approaching those required for ignition. Improvements in computational models - in large part due to advances in non-LTE modeling - have resulted in simulations that match experimental results quite well for the X-ray drive, implosion symmetry and total wall emission [1]. Non-LTE modeling is a key part of the NIF simulation effort, affecting several aspects of experimental design and diagnostics. The X-rays that drive the capsule arise from high-Z material ablated off the hohlraum wall. Current capsule designs avoid excessive preheat from high-energy X-rays by shielding the fuel with a mid-Z dopant, which affects the capsule dynamics. The dopant also mixes into the hot spot through hydrodynamic instabilities, providing diagnostic possibilities but potentially impacting the energy balance of the capsule [2]. Looking beyond the NIF, a proposed design for a fusion reactor chamber depends on lowdensity high-Z gas absorbing X-rays and particles to protect the first wall [3]. These situations encompass a large range of temperatures, densities and spatial scales. They each emphasize different aspects of atomic physics and present a variety of challenges for non-LTE modeling. We discuss the relevant issues and summarize the current state of the modeling effort for these applications.

Current oncologic concepts and emerging techniques for imaging of head and neck squamous cell cancer

PubMed Central

Sadick, Maliha; Schoenberg, Stefan O.; Hoermann, Karl; Sadick, Haneen

2012-01-01

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and currently they account for 5% of all malignancies worldwide. Inspite of ongoing developments in diagnostic imaging and new therapeutic options, HNSCC still represents a multidisciplinary challenge. One of the most important prognostic factors in HNSCC is the presence of lymph node metastases. Patients with confirmed nodal involvement have a considerable reduction of their 5-year overall survival rate. In the era of individually optimised surgery, chemotherapy and intensity modulated radiotherapy, the main role of pre- and posttherapeutic imaging remains cancer detection at an early stage and accurate follow-up. The combined effort of early diagnosis and close patient monitoring after surgery and/or radio-chemotherapy influences disease progression and outcome predicition in patients with HNSCC. This review article focuses on currrent oncologic concepts and emerging tools in imaging of head and neck squamous cell cancer. Besides the diagnostic spectrum of the individual imaging modalities, their limitations are also discussed. One main part of this article is dedicated to PET-CT which combines functional and morphological imaging. Furthermore latest developments in MRI are presented with regard to lymph node staging and response prediction. Last but not least, a clinical contribution in this review explains, which information the head and neck surgeon requires from the multimodality imaging and its impact on operation planning. PMID:23320060

Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

PubMed Central

Fogel, Brent L.; Lee, Hane; Deignan, Joshua L.; Strom, Samuel P.; Kantarci, Sibel; Wang, Xizhe; Quintero-Rivera, Fabiola; Vilain, Eric; Grody, Wayne W.; Perlman, Susan; Geschwind, Daniel H.; Nelson, Stanley F.

2015-01-01

IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established. OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult- and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTS We examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURES Next-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTS We identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELEVANCE This study demonstrated that clinical exome sequencing in patients with adult-onset and sporadic presentations of ataxia is a high-yield test, providing a definitive diagnosis in more than one-fifth of patients and suggesting a potential diagnosis in more than one-third to guide additional phenotyping and diagnostic evaluation. Therefore, clinical exome sequencing is an appropriate consideration in the routine genetic evaluation of all patients presenting with chronic progressive cerebellar ataxia. PMID:25133958

Electroencephalography as a tool for evidence-based diagnosis and improved outcomes in children with epilepsy in a resource-poor setting.

PubMed

Lagunju, Ike Oluwa Abiola; Oyinlade, Alexander Opebiyi; Atalabi, Omolola Mojisola; Ogbole, Godwin; Tedimola, Olushola; Famosaya, Abimbola; Ogunniyi, Adesola; Ogunseyinde, Ayotunde Oluremi; Ragin, Ann

2015-01-01

Electroencephalography (EEG) remains the most important investigative modality in the diagnostic evaluation of individuals with epilepsy. Children living with epilepsy in the developing world are faced with challenges of lack of access to appropriate diagnostic evaluation and a high risk of misdiagnosis and inappropriate therapy. We appraised EEG studies in a cohort of Nigerian children with epilepsy seen in a tertiary center in order to evaluate access to and the impact of EEG in the diagnostic evaluation of the cases. Inter-ictal EEG was requested in all cases of pediatric epilepsy seen at the pediatric neurology clinic of the University College Hospital, Ibadan, Nigeria over a period of 18 months. Clinical diagnosis without EEG evaluation was compared with the final diagnosis post- EEG evaluation. A total of 329 EEGs were recorded in 329 children, aged 3 months to 16 years, median 61.0 months. Clinical evaluation pre-EEG classified 69.3% of the epilepsies as generalized. The a posteriori EEG evaluations showed a considerably higher proportion of localization-related epilepsies (33.6%). The final evaluation post EEG showed a 21% reduction in the proportion of cases labeled as generalized epilepsy and a 55% increase in cases of localization-related epilepsy(p<0.001). Here we show that there is a high risk of misdiagnosis and therefore the use of inappropriate therapies in children with epilepsy in the absence of EEG evaluation. The implications of our findings in the resource-poor country scenario are key for reducing the burden of care and cost of epilepsy treatment on both the caregivers and the already overloaded tertiary care services.

A Proposal for a Dimensional Classification System Based on the Shared Features of the "DSM-IV" Anxiety and Mood Disorders: Implications for Assessment and Treatment

ERIC Educational Resources Information Center

Brown, Timothy A.; Barlow, David H.

2009-01-01

A wealth of evidence attests to the extensive current and lifetime diagnostic comorbidity of the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., "DSM-IV") anxiety and mood disorders. Research has shown that the considerable cross-sectional covariation of "DSM-IV" emotional disorders is accounted for by common higher order…

Enrichment of target sequences for next-generation sequencing applications in research and diagnostics.

PubMed

Altmüller, Janine; Budde, Birgit S; Nürnberg, Peter

2014-02-01

Abstract Targeted re-sequencing such as gene panel sequencing (GPS) has become very popular in medical genetics, both for research projects and in diagnostic settings. The technical principles of the different enrichment methods have been reviewed several times before; however, new enrichment products are constantly entering the market, and researchers are often puzzled about the requirement to take decisions about long-term commitments, both for the enrichment product and the sequencing technology. This review summarizes important considerations for the experimental design and provides helpful recommendations in choosing the best sequencing strategy for various research projects and diagnostic applications.

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…

Short-wavelength free-electron laser sources and science: a review

NASA Astrophysics Data System (ADS)

Seddon, E. A.; Clarke, J. A.; Dunning, D. J.; Masciovecchio, C.; Milne, C. J.; Parmigiani, F.; Rugg, D.; Spence, J. C. H.; Thompson, N. R.; Ueda, K.; Vinko, S. M.; Wark, J. S.; Wurth, W.

2017-11-01

This review is focused on free-electron lasers (FELs) in the hard to soft x-ray regime. The aim is to provide newcomers to the area with insights into: the basic physics of FELs, the qualities of the radiation they produce, the challenges of transmitting that radiation to end users and the diversity of current scientific applications. Initial consideration is given to FEL theory in order to provide the foundation for discussion of FEL output properties and the technical challenges of short-wavelength FELs. This is followed by an overview of existing x-ray FEL facilities, future facilities and FEL frontiers. To provide a context for information in the above sections, a detailed comparison of the photon pulse characteristics of FEL sources with those of other sources of high brightness x-rays is made. A brief summary of FEL beamline design and photon diagnostics then precedes an overview of FEL scientific applications. Recent highlights are covered in sections on structural biology, atomic and molecular physics, photochemistry, non-linear spectroscopy, shock physics, solid density plasmas. A short industrial perspective is also included to emphasise potential in this area. Dedicated to John M J Madey (1943-2016) and Rodolfo Bonifacio (1940-2016) whose perception, drive and perseverance paved the way for the realisation and development of short-wavelength free-electron lasers.

Microfluidic system for high throughput characterisation of echogenic particles.

PubMed

Rademeyer, Paul; Carugo, Dario; Lee, Jeong Yu; Stride, Eleanor

2015-01-21

Echogenic particles, such as microbubbles and volatile liquid micro/nano droplets, have shown considerable potential in a variety of clinical diagnostic and therapeutic applications. The accurate prediction of their response to ultrasound excitation is however extremely challenging, and this has hindered the optimisation of techniques such as quantitative ultrasound imaging and targeted drug delivery. Existing characterisation techniques, such as ultra-high speed microscopy provide important insights, but suffer from a number of limitations; most significantly difficulty in obtaining large data sets suitable for statistical analysis and the need to physically constrain the particles, thereby altering their dynamics. Here a microfluidic system is presented that overcomes these challenges to enable the measurement of single echogenic particle response to ultrasound excitation. A co-axial flow focusing device is used to direct a continuous stream of unconstrained particles through the combined focal region of an ultrasound transducer and a laser. Both the optical and acoustic scatter from individual particles are then simultaneously recorded. Calibration of the device and example results for different types of echogenic particle are presented, demonstrating a high throughput of up to 20 particles per second and the ability to resolve changes in particle radius down to 0.1 μm with an uncertainty of less than 3%.

[Adrenal tumors. Principles of diagnostics and operative treatment].

PubMed

Gonsior, A; Pfeiffer, H; Führer, D; Liatsikos, E; Schwalenberg, T; Stolzenburg, J-U

2010-05-01

Adrenal masses are very heterogeneous and comprise benign or malignant tumors, unilateral or bilateral masses and variable endocrine activity. Because of these attributes adrenal gland masses are a clinical challenge. This article gives a summary of diagnostic steps and indications for adrenal surgery including perioperative management.

The clinical benefits, ethics, and economics of stratified medicine and companion diagnostics.

PubMed

Trusheim, Mark R; Berndt, Ernst R

2015-12-01

The stratified medicine companion diagnostic (CDx) cut-off decision integrates scientific, clinical, ethical, and commercial considerations, and determines its value to developers, providers, payers, and patients. Competition already sharpens these issues in oncology, and might soon do the same for emerging stratified medicines in autoimmune, cardiovascular, neurodegenerative, respiratory, and other conditions. Of 53 oncology targets with a launched therapeutic, 44 have competing therapeutics. Only 12 of 141 Phase III candidates addressing new targets face no competition. CDx choices might alter competitive positions and reimbursement. Under current diagnostic incentives, payers see novel stratified medicines that improve public health and increase costs, but do not observe companion diagnostics for legacy treatments that would reduce costs. It would be in the interests of payers to rediscover their heritage of direct investment in diagnostic development. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

NASA Space Flight Vehicle Fault Isolation Challenges

NASA Technical Reports Server (NTRS)

Neeley, James R.; Jones, James V.; Bramon, Christopher J.; Inman, Sharon K.; Tuttle, Loraine

2016-01-01

The Space Launch System (SLS) is the new NASA heavy lift launch vehicle in development and is scheduled for its first mission in 2018.SLS has many of the same logistics challenges as any other large scale program. However, SLS also faces unique challenges related to testability. This presentation will address the SLS challenges for diagnostics and fault isolation, along with the analyses and decisions to mitigate risk..

Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

PubMed

Lim, Wei Yin; Goh, Boon Tong; Khor, Sook Mei

2017-08-15

Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (μPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. μPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. μPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

The path to exploring physics in advanced devices with a heavy ion beam probe

NASA Astrophysics Data System (ADS)

Demers, D. R.; Fimognari, P. J.

2012-10-01

The scientific progression of alternative or advanced devices must be met with comparable diagnostic technologies. Heavy ion beam probe innovations from ongoing diagnostic development are meeting this challenge. The diagnostic is uniquely capable of measuring the radial electric field, critically important in stellarators, simultaneously with fluctuations of electron density and electric potential. HIBP measurements can also improve the understanding of edge physics in tokamaks and spherical tori. It can target issues associated with the pedestal region, including the mechanisms underlying the L-H transition, the onset and evolution of ELMs, and the evolution of the electron current density. Beam attenuation (and resulting low signal to noise levels), a challenge to operation on devices with large plasma cross-sections and high ne and Te, can be mitigated with greater beam energies and currents. Other application challenges, such as measurements of plasma fluctuations and profile variations with elevated temporal and spatial resolutions, can be achieved with innovative detectors. The scientific studies motivating the implementation of an HIBP on HSX, ASDEX-U, and W7-X will be presented along with preliminary scoping studies.

Comparison of computer systems and ranking criteria for automatic melanoma detection in dermoscopic images.

PubMed

Møllersen, Kajsa; Zortea, Maciel; Schopf, Thomas R; Kirchesch, Herbert; Godtliebsen, Fred

2017-01-01

Melanoma is the deadliest form of skin cancer, and early detection is crucial for patient survival. Computer systems can assist in melanoma detection, but are not widespread in clinical practice. In 2016, an open challenge in classification of dermoscopic images of skin lesions was announced. A training set of 900 images with corresponding class labels and semi-automatic/manual segmentation masks was released for the challenge. An independent test set of 379 images, of which 75 were of melanomas, was used to rank the participants. This article demonstrates the impact of ranking criteria, segmentation method and classifier, and highlights the clinical perspective. We compare five different measures for diagnostic accuracy by analysing the resulting ranking of the computer systems in the challenge. Choice of performance measure had great impact on the ranking. Systems that were ranked among the top three for one measure, dropped to the bottom half when changing performance measure. Nevus Doctor, a computer system previously developed by the authors, was used to participate in the challenge, and investigate the impact of segmentation and classifier. The diagnostic accuracy when using an automatic versus the semi-automatic/manual segmentation is investigated. The unexpected small impact of segmentation method suggests that improvements of the automatic segmentation method w.r.t. resemblance to semi-automatic/manual segmentation will not improve diagnostic accuracy substantially. A small set of similar classification algorithms are used to investigate the impact of classifier on the diagnostic accuracy. The variability in diagnostic accuracy for different classifier algorithms was larger than the variability for segmentation methods, and suggests a focus for future investigations. From a clinical perspective, the misclassification of a melanoma as benign has far greater cost than the misclassification of a benign lesion. For computer systems to have clinical impact, their performance should be ranked by a high-sensitivity measure.

Mathematics Diagnostic Testing in Engineering: An International Comparison between Ireland and Portugal

ERIC Educational Resources Information Center

Carr, M.; Fidalgo, C.; Bigotte de Almeida, M. E.; Branco, J. R.; Santos, V.; Murphy, E.; Ní Fhloinn, E.

2015-01-01

Concern has been expressed throughout Europe about the significant deficiencies in the basic mathematical skills of many engineering undergraduates. Mathematics diagnostic tests in the UK, Ireland and Portugal have shown these shortcomings, which provide a challenge to those striving to introduce more innovative educational practices into…

[A modern look at benign stenosing lesions. Etiology and pathogenesis of diagnostic capabilities. A systematic review].

PubMed

Pakhabova, E Iu; Belova, G V

2012-01-01

The problem of nonneoplastic stenosis of major duodenal papilla is on joint of gastroenterology and surgery and present a challenge for physicians. This article reviews what is known about the pathogenesis, epidemiology and diagnostics of papillostenosis and sphincter of Oddi dysfunction.

The effect of threat of litigation on forensic pathologist diagnostic decision making.

PubMed

Oliver, William Russell

2011-12-01

Recent litigation involving medical examiners has caused concern over certifying deaths. We administered a survey of 716 medical examiners regarding the effects of the threat of litigation. Two hundred twenty-two medical examiners responded (31%). Of those who responded, approximately 13.5% admitted to having modified their diagnostic findings due to threat of litigation, and approximately 32.5% stated these considerations would affect their decisions in the future. Physicians who indicated they had or would modify their diagnoses expressed more concern over the possibility of litigation. Chiefs of services were less likely than staff members to indicate changing diagnoses. Practitioners whose jurisdictions included rural areas were significantly more likely to indicate that litigation considerations would affect their diagnoses in the future, although this was not true with those who had already modified their diagnoses. No correlation was found with elected versus appointed positions, accreditation status, sex, race, geographic location, or board certification. Although very few medical examiners have actually been sued because of their diagnoses, a demonstrated threat of litigation has a substantial effect on diagnostic decision making.

Tuberculous otitis media: a significant diagnostic challenge.

PubMed

Vaamonde, Pedro; Castro, Crisanto; García-Soto, Nicolas; Labella, Torcuato; Lozano, Ascensión

2004-06-01

This study was undertaken to revise the diagnostic characteristics of tuberculous otitis media (TOM), a disorder that is often diagnosed late, leading to delay in specific treatment. Retrospective study of a longitudinal series of 10 TOM patients over a 7-year period at an institutional referral center. Most patients showed intractable otorrhea, moderately severe hearing loss, and necrotic eardrums with granulation tissue and single perforations. Multiple perforations, facial palsy, and cervical adenopathies were rare (<10% of patients). CT generally showed soft tissue involvement of the middle ear without bone erosion. The most effective laboratory test microbiological culture of exudate (diagnostic efficacy 71%). Specific antibiotic treatment was effective in all cases. The diagnosis of TOM remains a significant challenge for otorhinolaryngologists. If there are strong clinical grounds for suspicion, standard laboratory tests for tuberculosis should be repeated even if initially negative.

Perspectives on diagnostic strategies for hyperglycemia in pregnancy - dealing with the barriers and challenges in China.

PubMed

Wei, Yumei; Yang, Huixia

2018-04-18

Hyperglycemia is one of the most common medical conditions women encounter during pregnancy. Hyperglycemia in pregnancy (HIP) is an issue of increasing concern to both obstetricians and administrators and it brings health issues for both mothers and offspring, not only early complications, but also long-term effects. HIP may either have been pre-gestational diabetes mellitus (pGDM), or gestational diabetes mellitus (GDM). After two-child policy fully carried out in China, the incidence of HIP would be increased further. There are many important issues such as the high prevalence of DM misdiagnosis, the diagnostic criteria of GDM, the strategies of GDM management in China need to deal with. We would focus on the barriers and challenges of diagnostic strategies for hyperglycemia in pregnancy in China. Copyright © 2018. Published by Elsevier B.V.

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

PubMed

Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

2018-02-19

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Compounding diagnostic delays: a qualitative study of point-of-care testing in South Africa.

PubMed

Engel, Nora; Davids, Malika; Blankvoort, Nadine; Pai, Nitika Pant; Dheda, Keertan; Pai, Madhukar

2015-04-01

Successful point-of-care (POC) testing (completion of test-and-treat cycle in one patient encounter) has immense potential to reduce diagnostic and treatment delays, and improve patient and public health outcomes. We explored what tests are done and how in public/private, rural/urban hospitals and clinics in South Africa and whether they can ensure successful POC testing. This qualitative research study examined POC testing across major diseases in Cape Town, Durban and Eastern Cape. We conducted 101 semi-structured interviews and seven focus group discussions with doctors, nurses, community health workers, patients, laboratory technicians, policymakers, hospital managers and diagnostic manufacturers. In South Africa, diagnostics are characterised by a centralised system. Most tests conducted on the spot can be made to work successfully as POC tests. The majority of public/private clinics and smaller hospitals send samples via couriers to centralised laboratories and retrieve results the same way, via internet, fax or phone. The main challenge to POC testing lies in transporting samples and results, while delays risk patient loss from diagnostic/treatment pathways. Strategies to deal with associated delays create new problems, such as artificially prolonged turnaround times, strains on human resources and quality of testing, compounding additional diagnostic and treatment delays. For POC testing to succeed, particular characteristics of diagnostic ecosystems and adaptations of professional practices to overcome associated challenges must be taken into account. © 2014 John Wiley & Sons Ltd.

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.

Diagnosis of Food Allergy.

PubMed

Gupta, Malika; Cox, Amanda; Nowak-Węgrzyn, Anna; Wang, Julie

2018-02-01

Food allergy diagnosis remains challenging. Most standard methods are unable to differentiate sensitization from clinical allergy. Recognizing food allergy is of utmost importance to prevent life-threatening reactions. On the other hand, faulty interpretation of tests leads to overdiagnosis and unnecessary food avoidances. Highly predictive models have been established for major food allergens based on skin prick testing and food-specific immunoglobulin E but are lacking for most other foods. Although many newer diagnostic techniques are improving the accuracy of food allergy diagnostics, an oral food challenge remains the only definitive method of confirming a food allergy. Copyright © 2017 Elsevier Inc. All rights reserved.

microRNA Expression Profiling: Technologies, Insights, and Prospects.

PubMed

Roden, Christine; Mastriano, Stephen; Wang, Nayi; Lu, Jun

2015-01-01

Since the early days of microRNA (miRNA) research, miRNA expression profiling technologies have provided important tools toward both better understanding of the biological functions of miRNAs and using miRNA expression as potential diagnostics. Multiple technologies, such as microarrays, next-generation sequencing, bead-based detection system, single-molecule measurements, and quantitative RT-PCR, have enabled accurate quantification of miRNAs and the subsequent derivation of key insights into diverse biological processes. As a class of ~22 nt long small noncoding RNAs, miRNAs present unique challenges in expression profiling that require careful experimental design and data analyses. We will particularly discuss how normalization and the presence of miRNA isoforms can impact data interpretation. We will present one example in which the consideration in data normalization has provided insights that helped to establish the global miRNA expression as a tumor suppressor. Finally, we discuss two future prospects of using miRNA profiling technologies to understand single cell variability and derive new rules for the functions of miRNA isoforms.

[Listeriosis in pregnancy--case report].

PubMed

Barlik, Magdalena; Seremak-Mrozikiewicz, Agnieszka; Drews, Krzysztof

2014-04-01

Listeriosis is a rather rare infectious disease but its incidence in pregnancy is over 20 times higher than in the general population. Pregnant women with listeriosis comprise one-third of all listeriosis cases. Listeriosis is a foodborne disease. Sporadic as well as epidemic cases of listeriosis are usually related to contaminated processed food, especially meat dishes served in fast-food restaurants and dairy products. Pregnant women are at an increased risk for listeriosis infection. Unfortunately the symptoms are not specific and the diagnosis presents a considerable challenge. Although the literature offers some case reports on a complicated course of listeriosis during pregnancy the infection usually runs a mild course in pregnant women. Regardless, fetal or neonatal infection is related to very high risk of lethal complications in the newborn, among others: sepsis, meningitis or pneumonia. In this paper we present a case of a 28-year-old gravida with listeriosis. We described the course of the infection, diagnostic process and treatment in both, the mother and the newborn.

Expert opinion: diagnosis and treatment of proximal hamstring tendinopathy

PubMed Central

Lempainen, Lasse; Johansson, Kristian; Banke, Ingo J.; Ranne, Juha; Mäkelä, Keijo; Sarimo, Janne; Niemi, Pekka; Orava, Sakari

2015-01-01

Summary Background: proximal hamstring tendinopathy (PHT) is a disabilitating disease often causing underperformance in the athletically demanding patients. The main symptom of PHT is lower gluteal pain especially during running or while prolonged sitting. Mainly affecting athletically active individuals, PHT is a considerable challenge for treating health care professionals. Purpose: this paper aims to concisely present the literature on PHT to guide health care professionals treating these patients and doing research on the subject. Methods: we reviewed the literature on PHT through literature search of scientific journal databases. Conclusions: as a tendinopathic pathology, it is a rather recently discovered exertion injury. As with other chronic tendon overuse injuries, current treatment strategies are unspecific with uncertain outcomes due to the unknown etiology of the tendon degeneration. Diagnostic features as well as both operative and non-operative treatments are evaluated from a clinical perspective, providing up to date information for clinicians and sports medicine therapists dealing with hamstring problems. Level of evidence: V. PMID:25878983

[Current aspects of therapy conversion for multiple sclerosis].

PubMed

Kolber, P; Luessi, F; Meuth, S G; Klotz, L; Korn, T; Trebst, C; Tackenberg, B; Kieseier, B; Kümpfel, T; Fleischer, V; Tumani, H; Wildemann, B; Lang, M; Flachenecker, P; Meier, U; Brück, W; Limmroth, V; Haghikia, A; Hartung, H-P; Stangel, M; Hohlfeld, R; Hemmer, B; Gold, R; Wiendl, H; Zipp, F

2015-10-01

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

Degenerative Mitral Stenosis: Unmet Need for Percutaneous Interventions.

PubMed

Sud, Karan; Agarwal, Shikhar; Parashar, Akhil; Raza, Mohammad Q; Patel, Kunal; Min, David; Rodriguez, Leonardo L; Krishnaswamy, Amar; Mick, Stephanie L; Gillinov, A Marc; Tuzcu, E Murat; Kapadia, Samir R

2016-04-19

Degenerative mitral stenosis (DMS) is an important cause of mitral stenosis, developing secondary to severe mitral annular calcification. With the increase in life expectancy and improved access to health care, more patients with DMS are likely to be encountered in developed nations. These patients are generally elderly with multiple comorbidities and often are high-risk candidates for surgery. The mainstay of therapy in DMS patients is medical management with heart rate control and diuretic therapy. Surgical intervention might be delayed until symptoms are severely limiting and cannot be managed by medical therapy. Mitral valve surgery is also challenging in these patients because of the presence of extensive calcification. Hence, there is a need to develop an alternative percutaneous treatment approach for patients with DMS who are otherwise inoperable or at high risk for surgery. In this review, we summarize the available data on the epidemiology of DMS and diagnostic considerations and current treatment strategies for these patients. © 2016 American Heart Association, Inc.

Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus.

PubMed

Rosário, Pedro Weslley; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa Maria Z; Maia, Ana Luiza; Vaisman, Mário

2013-06-01

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

Epidemiology, Diagnosis, and Management of Clostridium difficile Infection in Patients with Inflammatory Bowel Disease

PubMed Central

Rao, Krishna; Higgins, Peter D. R.

2016-01-01

Clostridium difficile infection (CDI) is a major source of morbidity and mortality for the US healthcare system, and frequently complicates the course of inflammatory bowel disease (IBD). Patients with IBD are more likely to be colonized with C. difficile and develop active infection than the general population. They are also more likely to have severe CDI and develop subsequent complications such as IBD flare, colectomy, or death. Even after successful initial treatment and recovery, recurrent CDI is common. Management of CDI in IBD is fraught with diagnostic and therapeutic challenges, since the clinical presentations of CDI and IBD flare have considerable overlap. Fecal microbiota transplantation can be successful in curing recurrent CDI when other treatments have failed, but may also trigger IBD flare and this warrants caution. New, experimental treatments including vaccines, monoclonal antibodies, and non-toxigenic strains of C. difficile offer promise but are not yet available for clinicians. A better understanding of the complex relationship between the gut microbiota, CDI, and IBD is needed. PMID:27120571

Breakthrough Invasive Mold Infections in the Hematology Patient: Current Concepts and Future Directions.

PubMed

Lionakis, Michail S; Lewis, Russell E; Kontoyiannis, Dimitrios P

2018-05-31

Although the widespread use of mold-active agents (especially the new-generation of triazoles) has resulted in reductions of documented invasive mold infections (IMIs) in patients with hematological malignancies and allogeneic hematopoietic stem cell transplantation (HSCT), a subset of such patients still develop breakthrough IMIs (bIMIs). There are no data from prospective randomized clinical trials to guide therapeutic decisions in the different scenarios of bIMIs. In this viewpoint, we present the current status of our understanding of the clinical, diagnostic and treatment challenges of bIMIs in high-risk adult patients with hematological cancer and/or HSCT receiving mold-active antifungals and outline common clinical scenarios. As a rule, managing bIMIs demands an individualized treatment plan that takes into account the host, including co-morbidities, certainty of diagnosis and site of bIMIs, local epidemiology, considerations for fungal resistance, and antifungal pharmacological properties. Finally, we highlight areas that require future investigation in this complex area of clinical mycology.

Differential diagnosis of the scalp hair folliculitis.

PubMed

Lugović-Mihić, Liborija; Barisić, Freja; Bulat, Vedrana; Buljan, Marija; Situm, Mirna; Bradić, Lada; Mihić, Josip

2011-09-01

Scalp hair folliculitis is a relatively common condition in dermatological practice and a major diagnostic and therapeutic challenge due to the lack of exact guidelines. Generally, inflammatory diseases of the pilosebaceous follicle of the scalp most often manifest as folliculitis. There are numerous infective agents that may cause folliculitis, including bacteria, viruses and fungi, as well as many noninfective causes. Several noninfectious diseases may present as scalp hair folliculitis, such as folliculitis decalvans capillitii, perifolliculitis capitis abscendens et suffodiens, erosive pustular dermatitis, lichen planopilaris, eosinophilic pustular folliculitis, etc. The classification of folliculitis is both confusing and controversial. There are many different forms of folliculitis and several classifications. According to the considerable variability of histologic findings, there are three groups of folliculitis: infectious folliculitis, noninfectious folliculitis and perifolliculitis. The diagnosis of folliculitis occasionally requires histologic confirmation and cannot be based solely on clinical appearance of scalp lesions. This article summarizes prominent variants of inflammatory diseases of the scalp hair follicle with differential diagnosis and appertaining histological features.

The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies.

PubMed

Li, Alvin W; Yin, Emily S; Stahl, Maximilian; Kim, Tae Kon; Panse, Gauri; Zeidan, Amer M; Leventhal, Jonathan S

2017-11-01

Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. In addition, infections with cutaneous involvement are common in immunocompromised patients with myeloid disease. Given the varying presentations, dermatologic findings associated with myeloid malignancies can pose diagnostic challenges for hematologists and dermatologists. In this clinical review intended for the practicing hematologist/oncologist, we discuss the presentation, diagnosis, treatment, and prognostic value of the most common cutaneous manifestations associated with myeloid malignancies using illustrative macro- and microscopic figures and with a special emphasis on practical considerations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent advances in metamaterial split-ring-resonator circuits as biosensors and therapeutic agents.

PubMed

RoyChoudhury, Sohini; Rawat, Vaishali; Jalal, Ahmed Hasnain; Kale, S N; Bhansali, Shekhar

2016-12-15

Potential applications of thin film metamaterials are diverse and their realization to offer miniaturized waveguides, antennas and shielding patterns are on anvil. These artificially engineered structures can produce astonishing electromagnetic responses because of their constituents being engineered at much smaller dimensions than the wavelength of the incident electromagnetic wave, hence behaving as artificial materials. Such micro-nano dimensions of thin film metamaterial structures can be customized for various applications due to their exclusive responses to not only electromagnetic, but also to acoustic and thermal waves that surpass the natural materials' properties. In this paper, the recent major advancements in the emerging fields of diagnostics (sensors) and therapeutics involving thin film metamaterials have been reviewed and underlined; discussing their edge over conventional counterpart techniques; concentrating on their design considerations and feasible ways of achieving them. Challenges faced in sensitivity, precision, accuracy and factors that interfere with the degree of performance of the sensors are also dealt with, herein. Copyright © 2016 Elsevier B.V. All rights reserved.

Automated fluorescent miscroscopic image analysis of PTBP1 expression in glioma

PubMed Central

Becker, Aline; Elder, Brad; Puduvalli, Vinay; Winter, Jessica; Gurcan, Metin

2017-01-01

Multiplexed immunofluorescent testing has not entered into diagnostic neuropathology due to the presence of several technical barriers, amongst which includes autofluorescence. This study presents the implementation of a methodology capable of overcoming the visual challenges of fluorescent microscopy for diagnostic neuropathology by using automated digital image analysis, with long term goal of providing unbiased quantitative analyses of multiplexed biomarkers for solid tissue neuropathology. In this study, we validated PTBP1, a putative biomarker for glioma, and tested the extent to which immunofluorescent microscopy combined with automated and unbiased image analysis would permit the utility of PTBP1 as a biomarker to distinguish diagnostically challenging surgical biopsies. As a paradigm, we utilized second resections from patients diagnosed either with reactive brain changes (pseudoprogression) and recurrent glioblastoma (true progression). Our image analysis workflow was capable of removing background autofluorescence and permitted quantification of DAPI-PTBP1 positive cells. PTBP1-positive nuclei, and the mean intensity value of PTBP1 signal in cells. Traditional pathological interpretation was unable to distinguish between groups due to unacceptably high discordance rates amongst expert neuropathologists. Our data demonstrated that recurrent glioblastoma showed more DAPI-PTBP1 positive cells and a higher mean intensity value of PTBP1 signal compared to resections from second surgeries that showed only reactive gliosis. Our work demonstrates the potential of utilizing automated image analysis to overcome the challenges of implementing fluorescent microscopy in diagnostic neuropathology. PMID:28282372

Nuclear imaging and radiation therapy in canine and feline thyroid disease.

PubMed

Feeney, Daniel A; Anderson, Kari L

2007-07-01

The indications, techniques, and expectations for radionuclide diagnostic studies on canine and feline thyroid glands are presented. In addition, the considerations surrounding radioiodine or external beam radiotherapy for benign and malignant thyroid disease are reviewed. The intent of this article is to familiarize primary care veterinarians with the utility of and outcome of the ionizing radiation-based diagnostic and therapeutic techniques for assessing and treating canine and feline thyroid disease.

State of the industry for drug-diagnostic development: challenge and change on the path to precision medicine.

PubMed

Milne, Christopher-Paul; Cohen, Joshua; Chakravarthy, Ranjana; Awatin, Josephine

2016-07-01

Four challenges to the adoption of personalized medicine were identified in the mid-2000s - adherence to the blockbuster model, the lack of a supportive regulatory environment, the dysfunctional payment system and physician barriers. In this article, we report on our study findings based on interviews with 24 senior executives from leading drug and diagnostics companies to assess progress made in addressing those challenges over the last decade. Overall, we found that even with payer pushback and adjusting to new business models, the majority of developers expected their business to increase over the next 5 years. Several factors that unexpectedly helped to shape the personalized medicine landscape, such as the growth of support in genomic medicine from the public sector, are also discussed.

Advancing Diagnostics to Address Antibacterial Resistance: The Diagnostics and Devices Committee of the Antibacterial Resistance Leadership Group

PubMed Central

Tsalik, Ephraim L.; Petzold, Elizabeth; Kreiswirth, Barry N.; Bonomo, Robert A.; Banerjee, Ritu; Lautenbach, Ebbing; Evans, Scott R.; Hanson, Kimberly E.; Klausner, Jeffrey D.

2017-01-01

Abstract Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics. PMID:28350903

A Framework to Debug Diagnostic Matrices

NASA Technical Reports Server (NTRS)

Kodal, Anuradha; Robinson, Peter; Patterson-Hine, Ann

2013-01-01

Diagnostics is an important concept in system health and monitoring of space operations. Many of the existing diagnostic algorithms utilize system knowledge in the form of diagnostic matrix (D-matrix, also popularly known as diagnostic dictionary, fault signature matrix or reachability matrix) gleaned from physical models. But, sometimes, this may not be coherent to obtain high diagnostic performance. In such a case, it is important to modify this D-matrix based on knowledge obtained from other sources such as time-series data stream (simulated or maintenance data) within the context of a framework that includes the diagnostic/inference algorithm. A systematic and sequential update procedure, diagnostic modeling evaluator (DME) is proposed to modify D-matrix and wrapper logic considering least expensive solution first. This iterative procedure includes conditions ranging from modifying 0s and 1s in the matrix, or adding/removing the rows (failure sources) columns (tests). We will experiment this framework on datasets from DX challenge 2009.

Dealing with low-incidence serious diseases in general practice

PubMed Central

Buntinx, Frank; Mant, David; Van den Bruel, Ann; Donner-Banzhof, Norbert; Dinant, Geert-Jan

2011-01-01

Cost-effective health care depends on high-quality triage. The most challenging aspect of triage, which GPs confront on a regular basis, is diagnosing rare but serious disease. Failure to shoulder any risk in this situation overloads the health system and subjects patients to unnecessary investigation. Adopting too high a risk threshold leads to missed cases, late diagnosis, and sometimes avoidable death. It also undermines the credibility of primary care practitioners. Quantification of diagnostic risk suggests there is a potential risk gap between the maximum certainty with which GPs can assess the risk of serious disease at presentation and the minimum certainty required by many health systems for further investigation or hospital referral. Physician gut-feeling and diagnostic safety netting are often employed to fill the gap. Neither strategy is well defined or well supported by evidence. It should be possible to reduce the diagnostic risk gap cost-effectively by adopting more explicit diagnostic algorithms and providing better GP access to new diagnostic technologies. It is also essential, given the decreasing experience of triage clinicians employed in a number of countries, that a teachable evidence base is constructed for gut feeling and diagnostic safety netting. However, this construction of an evidence base requires very large-scale studies, and the global primary care research community remains small. The challenge therefore needs to be met by urgent and effective international collaboration. PMID:21401991

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.

Assessment and mitigation of diagnostic-generated electromagnetic interference at the National Ignition Facilitya)

NASA Astrophysics Data System (ADS)

Brown, C. G.; Ayers, J.; Felker, B.; Ferguson, W.; Holder, J. P.; Nagel, S. R.; Piston, K. W.; Simanovskaia, N.; Throop, A. L.; Chung, M.; Hilsabeck, T.

2012-10-01

Electromagnetic interference (EMI) is an ever-present challenge at laser facilities such as the National Ignition Facility (NIF). The major source of EMI at such facilities is laser-target interaction that can generate intense electromagnetic fields within, and outside of, the laser target chamber. In addition, the diagnostics themselves can be a source of EMI, even interfering with themselves. In this paper we describe EMI generated by ARIANE and DIXI, present measurements, and discuss effects of the diagnostic-generated EMI on ARIANE's CCD and on a PMT nearby DIXI. Finally we present some of the efforts we have made to mitigate the effects of diagnostic-generated EMI on NIF diagnostics.

Diagnostic and Therapeutic Management of a First Unprovoked Seizure in Children and Adolescents With a Focus on the Revised Diagnostic Criteria for Epilepsy.

PubMed

Sansevere, Arnold J; Avalone, Jennifer; Strauss, Lauren Doyle; Patel, Archana A; Pinto, Anna; Ramachandran, Maya; Fernandez, Ivan Sanchez; Bergin, Ann M; Kimia, Amir; Pearl, Phillip L; Loddenkemper, Tobias

2017-07-01

By definition, unprovoked seizures are not precipitated by an identifiable factor, such as fever or trauma. A thorough history and physical examination are essential to caring for pediatric patients with a potential first unprovoked seizure. Differential diagnosis, EEG, neuroimaging, laboratory tests, and initiation of treatment will be reviewed. Treatment is typically initiated after 2 unprovoked seizures, or after 1 seizure in select patients with distinct epilepsy syndromes. Recent expansion of the definition of epilepsy by the ILAE allows for the diagnosis of epilepsy to be made after the first seizure if the clinical presentation and supporting diagnostic studies suggest a greater than 60% chance of a second seizure. This review summarizes the current literature on the diagnostic and therapeutic management of first unprovoked seizure in children and adolescents while taking into consideration the revised diagnostic criteria of epilepsy.

Diagnosis and Management of Hyperthyroidism in Pregnancy: A Review.

PubMed

King, Jennifer Renae; Lachica, Ruben; Lee, Richard H; Montoro, Martin; Mestman, Jorge

2016-11-01

Hyperthyroidism has important implications for pregnancy, affecting both mother and fetus. Appropriate maternal and fetal management iscritical to avoiding adverse pregnancy outcomes and requires a multidisciplinary approach. To describe maternal diagnosis and management of hyperthyroidism, across all stages of pregnancy. In addition, to review clinical signs of fetal thyroid dysfunction due to maternal Graves disease and discuss management considerations. Review of published articles on PubMed and guidelines by recognized governing organizations regarding the diagnostic and management considerations for hyperthyroidism in pregnancy, from preconception to the postpartum period. Diagnosis of maternal hyperthyroidism involves both clinical symptoms and laboratory findings. Antithyroid medications are the mainstay of therapy, with trimester-specific pregnancy goals. Hyperthyroidism due to Graves disease has important diagnostic and management considerations for the fetus and neonate. Hyperthyroidism in pregnancy affects mother, fetus, and neonate. Interpretation of thyroid tests and understanding the appropriate use of antithyroid drugs are fundamental. Proper education of physicians providing care to women with hyperthyroidism is essential and starts before pregnancy. Postpartum follow-up is an essential part of the care. A systematic approach to management will ensure optimal pregnancy outcomes.

Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

PubMed

Hanning, Sara M; Orlu Gul, Mine; Winslade, Jackie; Baarslag, Manuel A; Neubert, Antje; Tuleu, Catherine

2016-09-25

A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project. Copyright © 2016 Elsevier B.V. All rights reserved.

Challenges in Social Communication in Asperger Syndrome and High-Functioning Autism

ERIC Educational Resources Information Center

Rubin, Emily; Lennon, Laurie

2004-01-01

Despite the inclusion of Asperger syndrome in the Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV) American Psychiatric Association [APA], 1994) 10 years ago, there is ongoing debate regarding its validity as a diagnostic construct, particularly relative to the diagnosis of autistic disorder when it is not accompanied…

Sharing the Diagnostic Process in the Clinical Teaching Environment: A Case Study

ERIC Educational Resources Information Center

Cuello-Garcia; Carlos

2005-01-01

Revealing or visualizing the thinking involved in making clinical decisions is a challenge. A case study is presented with a visual implement for sharing the diagnostic process. This technique adapts the Bayesian approach to the case presentation. Pretest probabilities and likelihood ratios are gathered to obtain post-test probabilities of every…

Diagnostic Competence of Primary School Mathematics Teachers during Classroom Situations

ERIC Educational Resources Information Center

Hoth, Jessica; Döhrmann, Martina; Kaiser, Gabriele; Busse, Andreas; König, Johannes; Blömeke, Sigrid

2016-01-01

One of the main challenges for teachers during teaching in class is the diagnosis of students' learning and thinking processes. For this purpose, teachers must perceive relevant information, they need to interpret this information and finally, they need to respond and select suitable opportunities to learn. In this paper, diagnostic processes in…

Addressing Barriers to the Development and Adoption of Rapid Diagnostic Tests in Global Health.

PubMed

Miller, Eric; Sikes, Hadley D

Immunochromatographic rapid diagnostic tests (RDTs) have demonstrated significant potential for use as point-of-care diagnostic tests in resource-limited settings. Most notably, RDTs for malaria have reached an unparalleled level of technological maturity and market penetration, and are now considered an important complement to standard microscopic methods of malaria diagnosis. However, the technical development of RDTs for other infectious diseases, and their uptake within the global health community as a core diagnostic modality, has been hindered by a number of extant challenges. These range from technical and biological issues, such as the need for better affinity agents and biomarkers of disease, to social, infrastructural, regulatory and economic barriers, which have all served to slow their adoption and diminish their impact. In order for the immunochromatographic RDT format to be successfully adapted to other disease targets, to see widespread distribution, and to improve clinical outcomes for patients on a global scale, these challenges must be identified and addressed, and the global health community must be engaged in championing the broader use of RDTs.

Addressing Barriers to the Development and Adoption of Rapid Diagnostic Tests in Global Health

PubMed Central

Miller, Eric; Sikes, Hadley D.

2015-01-01

Immunochromatographic rapid diagnostic tests (RDTs) have demonstrated significant potential for use as point-of-care diagnostic tests in resource-limited settings. Most notably, RDTs for malaria have reached an unparalleled level of technological maturity and market penetration, and are now considered an important complement to standard microscopic methods of malaria diagnosis. However, the technical development of RDTs for other infectious diseases, and their uptake within the global health community as a core diagnostic modality, has been hindered by a number of extant challenges. These range from technical and biological issues, such as the need for better affinity agents and biomarkers of disease, to social, infrastructural, regulatory and economic barriers, which have all served to slow their adoption and diminish their impact. In order for the immunochromatographic RDT format to be successfully adapted to other disease targets, to see widespread distribution, and to improve clinical outcomes for patients on a global scale, these challenges must be identified and addressed, and the global health community must be engaged in championing the broader use of RDTs. PMID:26594252

Electrochemistry-based Approaches to Low Cost, High Sensitivity, Automated, Multiplexed Protein Immunoassays for Cancer Diagnostics

PubMed Central

Dixit, Chandra K.; Kadimisetty, Karteek; Otieno, Brunah A.; Tang, Chi; Malla, Spundana; Krause, Colleen E.; Rusling, James F.

2015-01-01

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. Simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that doesn’t require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for highly sensitive detection of the panel of cancer-specific biomarkers with high specificity and at the same time have the potential to be translated into a POC. PMID:26525998

Electrochemistry-based approaches to low cost, high sensitivity, automated, multiplexed protein immunoassays for cancer diagnostics.

PubMed

Dixit, Chandra K; Kadimisetty, Karteek; Otieno, Brunah A; Tang, Chi; Malla, Spundana; Krause, Colleen E; Rusling, James F

2016-01-21

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. The simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that does not require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for the highly sensitive detection of a panel of cancer-specific biomarkers with high specificity which at the same time has the potential to be translated into POC applications.

Idiom of distress or delusional state? Cultural clash as the cause of misdiagnosis: a case report.

PubMed

Ulman, Anne-Marie; Bar, Faina

2011-01-01

The Beta Israel (House of Israel) represent a total number of more than 100,000 individuals. Ethiopian Jewish culture is based on a tribal cultural model. With their arrival in Israel, many difficulties surfaced. Ethiopian Jews had to deal with cultural choices that challenged their traditions. It has been suggested that the trauma of their journey coupled to the difficulties of the adaptation process to Israeli society, ( the culture shock), was directly responsible for psychopathology found among this population. It also appeared that culture plays a central role in the construction of the clinical picture, blurring at times the boundary between expressions of distress and pathology. It became increasingly difficult to draw the line between culturally normative behavior and psychopathology. The following case report underlines the importance of socio cultural considerations in both staff and patients, and illustrates the dangers of misdiagnosis due to patient therapeutic team cultural clash. A 41 year old woman of Ethiopian origin was hospitalized for suspected schizophrenia. Because of the striking contrast between the patients behavior, responses and so called psychotic content, possible misunderstanding based on cultural differences was considered by the clinical management team. This case underlines the dangers of the psychiatric diagnostic process, emphasizes the important role of sociocultural backgrounds of both staff and patients in patient management and encourages the consideration of cultural factors in all patient evaluations.

Radiological Diagnoses in the Context of Emigration: Infectious diseases.

PubMed

Stojkovic, Marija; Müller, Jan; Junghanss, Thomas; Weber, Tim Frederik

2018-02-01

 Globalization and emigration impact on the spectrum of diseases challenging health care systems. Medical practitioners have to particularly prepare for infectious diseases.  The database of a health care center specialized on tropical medicine was screened for patients with history of migration and one of the following diagnoses: Cystic echinococcosis, tuberculosis, schistosomiasis, visceral leishmaniosis, and neurocysticercosis. Representative casuistics were prepared from select case histories. Radiological pertinent knowledge was compiled based on literature search.  A small selection of frequently imported infectious diseases covers a considerable fraction of health care problems associated with migration. For cystic echinococcosis, schistosomiasis, and neurocysticercosis imaging is the most relevant diagnostic procedure defining also disease stages. Tuberculosis and visceral leishmaniosis are important differentials for malignant diseases.  Imaging plays a meaningful role in diagnosis, treatment stratification, and follow-up of imported infectious diseases. Radiological skills concerning these diseases are important for providing health care for patients in context of migration.   · Imaging plays a meaningful role in multidisciplinary care for imported infectious diseases.. · A small selection covers a considerable fraction of infectious diseases expected in context of migration.. · Stojkovic M, Müller J, Junghanss T et al. Radiological Diagnoses in the Context of Emigration: Infectious diseases. Fortschr Röntgenstr 2018; 190: 121 - 133. © Georg Thieme Verlag KG Stuttgart · New York.

Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders

PubMed Central

Levman, Jacob; Takahashi, Emi

2015-01-01

Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us. PMID:26640765

Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders.

PubMed

Levman, Jacob; Takahashi, Emi

2015-01-01

Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us.

Stress echocardiography in contemporary clinical cardiology: practical considerations and accreditation

PubMed Central

Shah, Benoy N; MacNab, Anita; Lynch, Jane; Hampson, Reinette; Senior, Roxy; Steeds, Richard P

2018-01-01

Stress echocardiography is a widely utilised test in patients with known or suspected coronary artery disease (CAD), valvular heart disease and cardiomyopathies. Its advantages include the ubiquitous availability of echocardiography, lack of ionising radiation, choice of physiological or pharmacological stressors, good diagnostic accuracy and robust supporting evidence base. SE has evolved significantly as a technique over the past three decades and has benefitted considerably from improvements in overall image quality (superior resolution), machine technology (e.g. digital cine-loop acquisition and side-by-side image display) and development of second-generation ultrasound contrast agents that have improved reader confidence and diagnostic accuracy. The purpose of this article is to review the breadth of SE in contemporary clinical cardiology and discuss the recently launched British Society of Echocardiography (BSE) Stress Echocardiography accreditation scheme. PMID:29358185

Acute and emergency care for thyrotoxicosis and thyroid storm.

PubMed

Idrose, Alzamani Mohammad

2015-07-01

Thyroid hormones affect all organ systems and, in excess, can cause increased metabolic rate, heart rate, ventricle contractility, and gastrointestinal motility as well as muscle and central nervous system excitability. Thyroid storm is the extreme manifestation of thyrotoxicosis with an estimated incidence of 0.20 per 100,000 per year among hospitalized patients in Japan. The mortality of thyroid storm without treatment ranges from 80% to 100%; but with treatment, the mortality rate is between 10% and 50%. The diagnostic strategy for thyroid storm may take into consideration Burch-Wartofsky scoring or Akamizu's diagnostic criteria. Multiple treatment aims need to be addressed in managing thyroid storm effectively. This paper puts together all aspects to be considered for the management of hyperthyroidism and thyroid storm during the acute and emergency phase as well as consideration of special populations.

Acute and emergency care for thyrotoxicosis and thyroid storm

PubMed Central

2015-01-01

Thyroid hormones affect all organ systems and, in excess, can cause increased metabolic rate, heart rate, ventricle contractility, and gastrointestinal motility as well as muscle and central nervous system excitability. Thyroid storm is the extreme manifestation of thyrotoxicosis with an estimated incidence of 0.20 per 100,000 per year among hospitalized patients in Japan. The mortality of thyroid storm without treatment ranges from 80% to 100%; but with treatment, the mortality rate is between 10% and 50%. The diagnostic strategy for thyroid storm may take into consideration Burch–Wartofsky scoring or Akamizu's diagnostic criteria. Multiple treatment aims need to be addressed in managing thyroid storm effectively. This paper puts together all aspects to be considered for the management of hyperthyroidism and thyroid storm during the acute and emergency phase as well as consideration of special populations. PMID:29123713

Childhood Enuresis: Current Diagnostic Formulations, Salient Findings, and Effective Treatment Modalities.

PubMed

Thurber, Steven

2017-06-01

Enuresis constitutes a frequently encountered problem area for children that may adversely affect social and emotional adjustment. This type of incontinence has been of concern to the human family for centuries. A brief history of enuresis is presented followed by current conceptualizations, diagnostic criteria, prevalence rates and psychiatric comorbidities. Historic notions of causation together with ineffective, sometimes barbaric treatments are then discussed, ending with a presentation of evidence-based treatment modalities, with the urine alarm being an essential element of effective treatment. An intervention termed dry bed training combines the urine alarm with a series of procedures designed in part to reduce relapse potential and should be a primary consideration for implementation by treatment professionals. Finally, a brief case study is presented illustrating special etiological and treatment considerations with juvenile psychiatric patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation Of The Diagnostic Performance Of A Multimedia Medical Communications System.

NASA Astrophysics Data System (ADS)

Robertson, John G.; Coristine, Marjorie; Goldberg, Morris; Beeton, Carolyn; Belanger, Garry; Tombaugh, Jo W.; Hickey, Nancy M.; Millward, Steven F.; Davis, Michael; Whittingham, David

1989-05-01

The central concern of radiologists when evaluating Picture Archiving Communication System (PACS) is the diagnostic performance of digital images compared to the original analog versions of the same images. Considerable work has been done comparing the ROC curves of various types of digital systems to the corresponding analog systems for the detection of specific phantoms or diseases. Although the studies may notify the radiologists that for a specific lesion a digital system may perform as well as the analog system, it tells the radiologists very little about the impact on diagnostic performance of a digital system in the general practice of radiology. We describe in this paper an alternative method for evaluating the diagnostic performance of a digital system and a preliminary experiment we conducted to test the methodology.

Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics.

PubMed

Langabeer, Stephen E

2016-01-01

The majority of patients with classical myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia, and primary myelofibrosis harbor distinct disease-driving mutations within the JAK2 , CALR , or MPL genes. The term triple-negative has been recently applied to those MPN without evidence of these consistent mutations, prompting whole or targeted exome sequencing approaches to determine the driver mutational status of this subgroup. These strategies have identified numerous novel mutations that occur in alternative exons of both JAK2 and MPL , the majority of which result in functional activation. Current molecular diagnostic approaches may possess insufficient coverage to detect these alternative mutations, prompting further consideration of targeted exon sequencing into routine diagnostic practice. How to incorporate these illuminating findings into the expanding molecular diagnostic algorithm for MPN requires continual attention.

Making psychiatric semiology great again: A semiologic, not nosologic challenge.

PubMed

Micoulaud-Franchi, J-A; Quiles, C; Batail, J-M; Lancon, C; Masson, M; Dumas, G; Cermolacce, M

2018-06-06

This article analyzes whether psychiatric disorders can be considered different from non-psychiatric disorders on a nosologic or semiologic point of view. The supposed difference between psychiatric and non-psychiatric disorders relates to the fact that the individuation of psychiatric disorders seems more complex than for non-psychiatric disorders. This individuation process can be related to nosologic and semiologic considerations. The first part of the article analyzes whether the ways of constructing classifications of psychiatric disorders are different than for non-psychiatric disorders. The ways of establishing the boundaries between the normal and the pathologic, and of classifying the signs and symptoms in different categories of disorder, are analyzed. Rather than highlighting the specificity of psychiatric disorders, nosologic investigation reveals conceptual notions that apply to the entire field of medicine when we seek to establish the boundaries between the normal and the pathologic and between different disorders. Psychiatry is thus very important in medicine because it exemplifies the inherent problem of the construction of cognitive schemes imposed on clinical and scientific medical information to delineate a classification of disorders and increase its comprehensibility and utility. The second part of this article assesses whether the clinical manifestations of psychiatric disorders (semiology) are specific to the point that they are entities that are different from non-psychiatric disorders. The attribution of clinical manifestations in the different classifications (Research Diagnostic Criteria, Diagnostic Statistic Manual, Research Domain Criteria) is analyzed. Then the two principal models on signs and symptoms, i.e. the latent variable model and the causal network model, are assessed. Unlike nosologic investigation, semiologic analysis is able to reveal specific psychiatric features in a patient. The challenge, therefore, is to better define and classify signs and symptoms in psychiatry based on a dual and mutually interactive biological and psychological perspective, and to incorporate semiologic psychiatry into an integrative, multilevel and multisystem brain and cognitive approach. Copyright © 2018 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Useful marker of oscillatory lung function in methacholine challenge test-comparison of reactance and resistance with dose-response slope.

PubMed

Yoon, Jung Won; Shin, Youn Ho; Jee, Hye Mi; Chang, Sun Jung; Baek, Ji Hyeon; Choi, Sun Hee; Kim, Hyeong Yun; Han, Man Yong

2014-06-01

There are few studies focusing on the comparison of resistance (Rrs) and reactance (Xrs) in impulse oscillometry system (IOS) in the bronchial challenge test using dose-response slope (DRS), a quantitative index of bronchial hyperresponsiveness. We conducted a case-control study of 144 asthmatic and 218 non-asthmatic children to compare the diagnostic accuracy of two-point linear DRS for FEV1 , Rrs5 , and Xrs5 (DRS_FEV1 , DRS_Rrs5 , and DRS_Xrs5 ) and assessed various diagnostic cut-off points of provocation concentrations (PC) using receiver operating characteristic (ROC) curves. DRS_FEV1 had a stronger correlation with DRS_Xrs5 (r = 0.739, P < 0.001) than with DRS_Rrs5 (r = 0.652, P < 0.001) and the area under the ROC curves of DRS_Xrs5 (0.737) was similar to that of DRS_FEV1 (0.732) and higher than that of DRS_Rrs5 (0.668). The area under the ROC curves in order of greater value was as follows: absolute change of Xrs5 (Abs_Xrs5 ) (0.759) > percent change of FEV1 (Pch_FEV1 ) (0.735) > Pch_Xrs5 (0.727) > Abs_Rrs5 (0.690) > Pch_Rrs5 (0.630). PC78 _Xrs5 and PC0.17 _Xrs5 of IOS showed considerably good sensitivity and specificity comparable to those of PC20 _FEV1 by spirometry. Additional 18 (13%) children who showed normal spirometric measures were identified as asthmatics with the use of IOS. The utility of the DRS_Xrs5 to differentiate asthmatics from controls was comparable to that of the DRS_FEV1 and better than that of the DRS_Rrs5 . In addition, IOS could detect additional asthmatic patients who did not show positive responses in spirometry. © 2013 Wiley Periodicals, Inc.

Somatic symptom disorder, a new DSM-5 diagnosis of an old clinical challenge

PubMed Central

Rosic, Tea; Kalra, Sameer; Samaan, Zainab

2016-01-01

Somatic symptom disorder (SSD) is characterised by a dysfunctional preoccupation with one or more physical symptoms. Patients with SSD often pursue excessive and unnecessary investigations, hospitalisations and treatments that significantly affect quality of life and drain healthcare resources. Thus, appropriate diagnosis and careful management are required to mitigate the patient's distress and to reduce the burden to the healthcare system. SSD is a new disorder defined in the Diagnostic and Statistical Manual Fifth Edition (DSM-5), replacing somatoform and related disorders in the DSM-4-Text Revision with diagnostic criteria that are inclusive of a broad array of presentations. This report presents a detailed clinical case of an elderly man with a history of frequent hospital visits presenting with SSD. We discuss diagnostic challenges and evidence-based management in acute inpatient as well as in outpatient settings. We also review data on healthcare utilisation associated with SSD. PMID:26759438

[Primary malignant melanoma of the central nervous system: A diagnostic challenge].

PubMed

Quillo-Olvera, Javier; Uribe-Olalde, Juan Salvador; Alcántara-Gómez, Leopoldo Alberto; Rejón-Pérez, Jorge Dax; Palomera-Gómez, Héctor Guillermo

2015-01-01

The rare incidence of primary malignant melanoma of the central nervous system and its ability to mimic other melanocytic tumors on images makes it a diagnostic challenge for the neurosurgeon. A 51-year-old patient, with a tumor located in the right forniceal callosum area. Total surgical excision was performed. Histopathological result was consistent with the diagnosis of primary malignant melanoma of the central nervous system, after ruling out extra cranial and extra spinal melanocytic lesions. The primary malignant melanoma of the central nervous system is extremely rare. There are features in magnetic resonance imaging that increase the diagnostic suspicion; nevertheless there are other tumors with more prevalence that share some of these features through image. Since there is not an established therapeutic standard its prognosis is discouraging. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Sequencing-based diagnostics for pediatric genetic diseases: progress and potential

PubMed Central

Tayoun, Ahmad Abou; Krock, Bryan; Spinner, Nancy B.

2016-01-01

Introduction The last two decades have witnessed revolutionary changes in clinical diagnostics, fueled by the Human Genome Project and advances in high throughput, Next Generation Sequencing (NGS). We review the current state of sequencing-based pediatric diagnostics, associated challenges, and future prospects. Areas Covered We present an overview of genetic disease in children, review the technical aspects of Next Generation Sequencing and the strategies to make molecular diagnoses for children with genetic disease. We discuss the challenges of genomic sequencing including incomplete current knowledge of variants, lack of data about certain genomic regions, mosaicism, and the presence of regions with high homology. Expert Commentary NGS has been a transformative technology and the gap between the research and clinical communities has never been so narrow. Therapeutic interventions are emerging based on genomic findings and the applications of NGS are progressing to prenatal genetics, epigenomics and transcriptomics. PMID:27388938

Propulsion Controls and Diagnostics Research in Support of NASA Aeronautics and Exploration Mission Programs

NASA Technical Reports Server (NTRS)

Garg, Sanjay

2011-01-01

The Controls and Dynamics Branch (CDB) at National Aeronautics and Space Administration (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 propulsion controls and diagnostics technologies that will help meet the challenging goals of NASA programs under the Aeronautics Research and Exploration Systems Missions. This paper provides a brief overview of the various CDB tasks in support of the NASA programs. 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.

Mid-infrared Laser Absorption Diagnostics for Detonation Studies

NASA Astrophysics Data System (ADS)

Spearrin, R. M.; Goldenstein, C. S.; Jeffries, J. B.; Hanson, R. K.

Detonation-based engines represent a challenging application for diagnostics due to the wide range of thermodynamic conditions involved (T~500-3000 K, P~2-60 atm) and the short time scales of change (~10- 6 to 10- 4 sec) associated with such systems. Non-intrusive laser absorption diagnostics can provide high time-resolution and have been employed extensively in shock tube kinetics experiments (P~1-20 atm), offering high potential for application in detonation environments with modest utilization to date [1-4]. Limiting factors in designing effective tunable laser absorption sensors for detonation engines can be divided into two sets of challenges: high-pressure, high-temperature absorption spectroscopy and harsh thermo-mechanical environments. The present work, conducted in a high-pressure shock tube and operating detonation combustor, addresses both sets of difficulties, with the objective of developing time-resolved, in-situ temperature and concentration sensors for detonation studies.

Cost-effectiveness of various methods of diagnosing hypersensitivity to Alternaria.

PubMed

Escudero, A I; Sánchez-Guerrero, I M; Mora, A M; Soriano, V; López, J D; García, F J; Negro, J M; Hernández, J; Pagán, J A

1993-01-01

This study was undertaken for two reasons: 1) It is more difficult to diagnose hypersensitivity to molds than to other allergens, so an evaluation of diagnostic tests was needed. 2) Alternaria is the principal cause of mold sensitization in our area. Sixty-six patients (20 +/- 4 years) were selected and divided into two groups. Group A was made up of patients with rhinitis and/or asthma due to Alternaria sensitization. Group B consisted of patients sensitized to other allergens and patients with nonrespiratory allergic disorders. Skin tests (prick and intradermal), challenge tests (conjunctival, nasal, and bronchial), and specific IgE determination were performed for all patients. A biologically standardized extract of Alternaria tenuis (Alergia e Inmunología Abelló, S. A., Madrid, Spain) obtained from a single batch was used for all tests. Our diagnostic criterion was a clinical history of rhinitis or asthma that coincided with the results of nasal/bronchial challenge. The diagnostic value of the other tests was compared to this criterion. In the group of rhinitic patients, skin tests and conjunctival challenge were more sensitive than specific IgE determination. In asthmatic patients, the most sensitive techniques were nasal and conjunctival challenges, followed by prick and intradermal skin tests, and, lastly, serum specific IgE determination. When rhinitis and asthma were considered jointly, the most sensitive test was conjunctival challenge, followed by skin-prick and intradermal tests. All tests had the same specificity, regardless of disorder. Nasal challenge was positive in all patients. Skin tests are easy to perform, cheap, non-traumatic for the patient, and sufficiently specific and sensitive for the diagnosis of Alternaria hypersensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic gap in Bovine viral diarrhea virus serology during the periparturient period in cattle.

PubMed

Bachofen, Claudia; Bollinger, Barbara; Peterhans, Ernst; Stalder, Hanspeter; Schweizer, Matthias

2013-09-01

Detection of antibodies against Bovine viral diarrhea virus (BVDV) in serum and milk by enzyme-linked immunosorbent assay (ELISA) is a crucial part of all ongoing national schemes to eradicate this important cattle pathogen. Serum and milk are regarded as equally suited for antibody measurement. However, when retesting a seropositive cow 1 day after calving, the serum was negative in 6 out of 9 different ELISAs. To further investigate this diagnostic gap around parturition, pre- and postcalving serum and milk samples of 5 cows were analyzed by BVDV antibody ELISA and serum neutralization test (SNT). By ELISA, 3 out of the 5 animals showed a diagnostic gap in the serum for up to 12 days around calving but all animals remained positive in SNT. In milk, the ELISA was strongly positive after birth but antibody levels decreased considerably within the next few days. Because of the immunoglobulin G (IgG)1-specific transport of serum antibodies into the mammary gland for colostrum production, the IgG subclass specificity of the total and the BVDV-specific antibodies were determined. Although all 5 animals showed a clear decrease in the total and BVDV-specific IgG1 antibody levels at parturition, the precalving IgG1-to-IgG2 ratios of the BVDV-specific antibodies were considerably lower in animals that showed the diagnostic gap. Results showed that BVDV seropositive cows may become "false" negative in several ELISAs in the periparturient period and suggest that the occurrence of this diagnostic gap is influenced by the BVDV-specific IgG subclass response of the individual animal.

[Toxocariasis].

PubMed

Stensvold, Christen Rune; Nielsen, Henrik Vedel; Petersen, Eskild

2011-01-17

The clinical presentation of toxocariasis, a zoonotic parasitosis transmitted from dogs and cats to humans, can be very diverse, which is one of the reasons why Toxocara-related disease may go unnoticed. This paper gives a brief summary of the various clinical presentations (covert/common toxocariasis, visceral larva migrans, ocular toxocariasis and neurotoxocariasis), diagnostic and differential-diagnostic considerations as well as treatment and prevention. In brief, the diagnosis of human toxocariasis relies mainly on patient data, anamnestic information, symptoms, eosinophil count and total-IgE levels.

Clinical and diagnostic features of East Coast fever (Theileria parva) infection of cattle.

PubMed

Irvin, A D; Mwamachi, D M

1983-08-27

East Coast fever is a tick-borne protozoal disease affecting cattle in a large part of East and Central Africa. Since the vector occurs over an even wider range there is considerable potential for the disease to spread to countries which are currently disease free. This article, describing the clinical and diagnostic features of East Coast fever, may remind authorities in these countries of the potential hazards posed by the disease.

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

Cost Implications of Value-Based Pricing for Companion Diagnostic Tests in Precision Medicine.

PubMed

Zaric, Gregory S

2016-07-01

Many interpretations of personalized medicine, also referred to as precision medicine, include discussions of companion diagnostic tests that allow drugs to be targeted to those individuals who are most likely to benefit or that allow treatment to be designed in a way such that individuals who are unlikely to benefit do not receive treatment. Many authors have commented on the clinical and competitive implications of companion diagnostics, but there has been relatively little formal analysis of the cost implications of companion diagnostics, although cost reduction is often cited as a significant benefit of precision medicine. We investigate the potential impact on costs of precision medicine implemented through the use of companion diagnostics. We develop a framework in which the costs of companion diagnostic tests are determined by considerations of profit maximization and cost effectiveness. We analyze four scenarios that are defined by the incremental cost-effectiveness ratio of the new drug in the absence of a companion diagnostic test. We find that, in most scenarios, precision medicine strategies based on companion diagnostics should be expected to lead to increases in costs in the short term and that costs would fall only in a limited number of situations.

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/.

Thyrotropinoma and multinodular goiter: A diagnostic challenge for hyperthyroidism.

PubMed

Aksoy, Duygu Yazgan; Gedik, Arzu; Cinar, Nese; Soylemezoglu, Figen; Berker, Mustafa; Gurlek, Omer Alper

2013-11-01

Thyroid disorders are frequently encountered. The diagnosis is straightforward unless clinical or laboratory findings are inconclusive and/or perplexing. Hyperthyroidism due to a thyrotropin-secreting pituitary adenoma rarely occurs and symptoms due to thyroid hormone excess are subtle. The presentation of the disease becomes unusual when co-secretion of other hormones with thyrotropin or concomitant thyroid parenchymal pathology exist. We present the case of a 63-year-old female patient with thyrotropinoma co-secreting growth hormone and multinodular goiter. She developed hyperthyroidism first due to thyrotropinoma and later due to a toxic nodule. Herein, we discuss the diagnostic and therapeutic challenges of hyperthyroidism with atypical presentation.

Laser-optical methods for earlier diagnostics of plant and seed diseases in various habitant media taking into consideration anthropogenic and biological pollution

NASA Astrophysics Data System (ADS)

Lisker, Joseph S.; Dmitriev, Andrey P.

1999-12-01

By the method of the computer laser-optical photometry the investigation of the cereal stability for the various diseases taken into consideration the stability of tomato seeds to their interaction with the phytopathogenes and the phytotoxicity of microscopic fungi on the wheat seedlings was carried out. Original result for the investigation of optical-physiological characteristics of plants and seeds are shown.

Symptoms, Diagnosis, and Treatment of Cow's Milk Allergy.

PubMed

Vandenplas, Yvan; Marchand, Johan; Meyns, Lien

2015-01-01

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate because there are no specific symptoms and reliable diagnostic tests. Literature was searched using databases to find original papers and reviews on this topic. A "challenge test" is still recommended as the most specific and sensitive diagnostic test, although a positive challenge test does not proof the involvement of the immune system. Only in the rare case of anaphylaxis, the challenge tests is not recommended. The Cow's Milk Symptom Score (CoMiSS) is an awareness tool for health care professionals to better recognize symptoms caused by the ingestion of cow's milk, but still needs validation. Today, the recommended diagnostic approach consists of an elimination diet with an extensive cow's milk based hydrolysate, followed by a challenge test. Amino acid based formula is reserved for the severe cases. Rice hydrolysates are gaining popularity, because they have been shown to be effective, have a better acceptability, and to be cheaper than the extensive cow's milk based hydrolysates. Soy infant formula may offer an additional alternative option as reviews concluded that about 10-15% of infants allergic to cow's milk will also react to soy. Gastro-intestinal microbiota manipulation may be of additional benefit in the treatment of CMA. The development of rice hydrolysates challenge the use of Today, extensive cow's milk based extensive hydrolysates remain the first option for the majority of patients and amino acid formula for the most severe cases. Rice hydrolysates and soy infant formula are considered as second choice options.

Assessment and Mitigation of Diagnostic-Generated Electromagnetic Interference at the National Ignition Facility

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

Brown, C G; Ayers, M J; Felker, B

2012-04-20

Electromagnetic interference (EMI) is an ever-present challenge at laser facilities such as the National Ignition Facility (NIF). The major source of EMI at such facilities is laser-target interaction that can generate intense electromagnetic fields within, and outside of, the laser target chamber. In addition, the diagnostics themselves can be a source of EMI, even interfering with themselves. In this paper we describe EMI generated by ARIANE and DIXI, present measurements, and discuss effects of the diagnostic-generated EMI on ARIANE's CCD and on a PMT nearby DIXI. Finally we present some of the efforts we have made to mitigate the effectsmore » of diagnostic-generated EMI on NIF diagnostics.« less

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…

Molecular detection of Plasmodium knowlesi in a Dutch traveler by real-time PCR.

PubMed

Link, Lonneke; Bart, Aldert; Verhaar, Nienke; van Gool, Tom; Pronk, Marjolijn; Scharnhorst, Volkher

2012-07-01

Plasmodium knowlesi infection with low parasitemia presents a diagnostic challenge, as rapid diagnostic tests are often negative and identification to the species level by microscopy is difficult. P. knowlesi malaria in a traveler is described, and real-time PCR is demonstrated to support fast and reliable diagnosis and identification to the species level.

Effects of Concept Map Extraction and a Test-Based Diagnostic Environment on Learning Achievement and Learners' Perceptions

ERIC Educational Resources Information Center

Lin, Yu-Shih; Chang, Yi-Chun; Liew, Keng-Hou; Chu, Chih-Ping

2016-01-01

Computerised testing and diagnostics are critical challenges within an e-learning environment, where the learners can assess their learning performance through tests. However, a test result based on only a single score is insufficient information to provide a full picture of learning performance. In addition, because test results implicitly…

Polyuria and polydipsia in horses.

PubMed

McKenzie, Erica C

2007-12-01

Polyuria and polydipsia provide a diagnostic challenge for the equine clinician. This article describes the various known causes of polyuria and polydipsia in horses and provides a description of a systematic diagnostic approach for assessing horses with polyuria and polydipsia to delineate the underlying cause. Treatment and management strategies for addressing polyuria and polydipsia in horses are also described.

Autism Spectrum Disorder in Down Syndrome: Cluster Analysis of Aberrant Behaviour Checklist Data Supports Diagnosis

ERIC Educational Resources Information Center

Ji, N. Y.; Capone, G. T.; Kaufmann, W. E.

2011-01-01

Background: The diagnostic validity of autism spectrum disorder (ASD) based on Diagnostic and Statistical Manual of Mental Disorders (DSM) has been challenged in Down syndrome (DS), because of the high prevalence of cognitive impairments in this population. Therefore, we attempted to validate DSM-based diagnoses via an unbiased categorisation of…

MACRA, MIPS, and the New Medicare Quality Payment Program: An Update for Radiologists.

PubMed

Rosenkrantz, Andrew B; Nicola, Gregory N; Allen, Bibb; Hughes, Danny R; Hirsch, Joshua A

2017-03-01

The Medicare Access and CHIP Reauthorization Act (MACRA) of 2015 advances the goal of tying Medicare payments to quality and value. In April 2016, CMS published an initial proposed rule for MACRA, renaming it the Quality Payment Program (QPP). Under QPP, clinicians receive payments through either advanced alternative payment models or the Merit-Based Incentive Payment System (MIPS), a consolidation of existing federal performance programs that applies positive or negative adjustments to fee-for-service payments. Most physicians will participate in MIPS. This review highlights implications of the QPP and MIPS for radiologists. Although MIPS incorporates radiology-specific quality measures, radiologists will also be required to participate in other practice improvement activities, including patient engagement. Recognizing physicians' unique practice patterns, MIPS will provide special considerations in performance evaluation for physicians with limited face-to-face patient interaction. Although such considerations will affect radiologists' likelihood of success under QPP, many practitioners will be ineligible for the considerations under currently proposed criteria. Reporting using qualified clinical data registries will benefit radiologists' performance by allowing expanded arrays of MIPS and non-MIPS specialty-specific measures. A group practice reporting option will substantially reduce administrative burden but introduce new challenges by requiring uniform determination of patient-facing status and performance measurement for all of the group's physicians (diagnostic radiologists, interventional radiologists, and nonradiologists) under the same taxpayer identification number. Given that the initial MIPS performance period begins in 2017, radiologists must begin preparing for QPP and taking actions to ensure their future success under this new quality-based payment system. Copyright © 2016 American College of Radiology. 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

Bringing diagnostics to developing countries: an interview with Rosanna Peeling.

PubMed

Peeling, Rosanna

2015-01-01

Interview with Professor Rosanna Peeling, PhD by Claire Raison (Commissioning Editor) Professor Rosanna Peeling is Chair of Diagnostic Research at the London School of Hygiene and Tropical Medicine (London, UK) and founded the International Diagnostics Centre at the institution. Professor Peeling previously worked for the WHO in Geneva, Switzerland, and continues to work on innovations for molecular diagnostics for point-of-care use in developing countries, addressing challenges posed by lack of funding and resources, regulatory issues and under-developed healthcare systems in these locations. Here, she discusses her career, recent progress in the field and how connectivity will affect global healthcare.

AC-DC electropenetrography: a new diagnostic technology for study of feeding behavior of piercing-sucking insects

USDA-ARS?s Scientific Manuscript database

Studying feeding, plant damage, and transmission of plant pathogens by hemipteran insect pests is challenging. Hemipteran piercing-sucking mouthparts, the stylets, are probed into opaque plant tissues precluding direct observation. This challenge was overcome by the invention of electropenetrography...

Educational agenda for diagnostic error reduction

PubMed Central

Trowbridge, Robert L; Dhaliwal, Gurpreet; Cosby, Karen S

2013-01-01

Diagnostic errors are a major patient safety concern. Although the majority of diagnostic errors are partially attributable to cognitive mistakes, the most effective means of improving clinician cognition in order to achieve gains in diagnostic reliability are unclear. We propose a tripartite educational agenda for improving diagnostic performance among students, residents and practising physicians. This agenda includes strengthening the metacognitive abilities of clinicians, fostering intuitive reasoning and increasing awareness of the role of systems in the diagnostic process. The evidence supporting initiatives in each of these realms is reviewed and a course of future implementation and study is proposed. The barriers to designing and implementing this agenda are substantial and include limited evidence supporting these initiatives and the challenges of changing the practice patterns of practising physicians. Implementation will need to be accompanied by rigorous evaluation. PMID:23764435

Small business development for molecular diagnostics.

PubMed

Anagostou, Anthanasia; Liotta, Lance A

2012-01-01

Molecular profiling, which is the application of molecular diagnostics technology to tissue and blood -specimens, is an integral element in the new era of molecular medicine and individualized therapy. Molecular diagnostics is a fertile ground for small business development because it can generate products that meet immediate demands in the health-care sector: (a) Detection of disease risk, or early-stage disease, with a higher specificity and sensitivity compared to previous testing methods, and (b) "Companion diagnostics" for stratifying patients to receive a treatment choice optimized to their individual disease. This chapter reviews the promise and challenges of business development in this field. Guidelines are provided for the creation of a business model and the generation of a marketing plan around a candidate molecular diagnostic product. Steps to commercialization are outlined using existing molecular diagnostics companies as learning examples.

The "Diagnostic Guideline for Anxiety and Challenging Behaviour" for Persons with Intellectual Disabilities: Preliminary Outcomes on Internalizing Problems, Challenging Behaviours, Quality of Life and Clients' Satisfaction

ERIC Educational Resources Information Center

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

2017-01-01

Background: People with intellectual disabilities are vulnerable to develop psychopathology (in particular anxiety) and related challenging behaviour. Method: A comparative multiple case study with an experimental and a control condition. Results: The application of the guideline showed a trend of decreases of internalizing problems (P = 0.07) and…

Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

PubMed Central

van de Stolpe, Anja; den Toonder, Jaap M. J.

2014-01-01

Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics. PMID:24879438

Review of Current Applications of Immunohistochemistry in Pediatric Nonneoplastic Gastrointestinal, Hepatobiliary, and Pancreatic Lesions

PubMed Central

de Nanassy, Joseph; El Demellawy, Dina

2017-01-01

Immunohistochemical (IHC) stains are widely used by pathologists for a variety of considerations in the diagnostic workup of pediatric nonneoplastic lesions in gastrointestinal (GI), hepatic, biliary, and pancreatic lesions. The pathologic changes cover a wide range and types of presentations, including inflammatory (bacterial and viral), metaplastic, posttransplant lymphoproliferative, autoimmune, metabolic, degenerative, developmental, and genetic conditions, among others. The everyday practical value of IHC stains covers primary identification, confirmation, differential, and/or exclusionary roles in the hands and eyes and minds of the practitioners. This article is intended to review and discuss the currently available IHC stains for a variety of pediatric GI, hepatobiliary, and pancreatic lesions as encountered in the day-to-day practice of pathologists and clinicians. It reflects the most recent methods and types of IHC stains with the stated aim of helping to provide a quick reference for diagnostic considerations and thereby facilitate the workup of a broad range of GI and related conditions in a pediatric population. The tables provide a handy reference on a wide range of IHC stains for commonly encountered lesions covering a variety of pediatric GI, hepatobiliary, and pancreatic conditions that are amenable to light microscopic diagnostic interpretation. PMID:28469406

Advancing Diagnostics to Address Antibacterial Resistance: The Diagnostics and Devices Committee of the Antibacterial Resistance Leadership Group.

PubMed

Tsalik, Ephraim L; Petzold, Elizabeth; Kreiswirth, Barry N; Bonomo, Robert A; Banerjee, Ritu; Lautenbach, Ebbing; Evans, Scott R; Hanson, Kimberly E; Klausner, Jeffrey D; Patel, Robin

2017-03-15

Diagnostics are a cornerstone of the practice of infectious diseases. However, various limitations frequently lead to unmet clinical needs. In most other domains, diagnostics focus on narrowly defined questions, provide readily interpretable answers, and use true gold standards for development. In contrast, infectious diseases diagnostics must contend with scores of potential pathogens, dozens of clinical syndromes, emerging pathogens, rapid evolution of existing pathogens and their associated resistance mechanisms, and the absence of gold standards in many situations. In spite of these challenges, the importance and value of diagnostics cannot be underestimated. Therefore, the Antibacterial Resistance Leadership Group has identified diagnostics as 1 of 4 major areas of emphasis. Herein, we provide an overview of that development, highlighting several examples where innovation in study design, content, and execution is advancing the field of infectious diseases diagnostics. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Statistical analysis of Turbine Engine Diagnostic (TED) field test data

NASA Astrophysics Data System (ADS)

Taylor, Malcolm S.; Monyak, John T.

1994-11-01

During the summer of 1993, a field test of turbine engine diagnostic (TED) software, developed jointly by U.S. Army Research Laboratory and the U.S. Army Ordnance Center and School, was conducted at Fort Stuart, GA. The data were collected in conformance with a cross-over design, some of whose considerations are detailed. The initial analysis of the field test data was exploratory, followed by a more formal investigation. Technical aspects of the data analysis insights that were elicited are reported.

Diagnostic problems in thyroid FNAs.

PubMed

Galera-Davidson, H

1997-12-01

The use of FNA cytology to diagnose pathologic conditions of the thyroid has increased considerably in recent years, particularly since it has reduced by half the number of patients undergoing surgery. On the one hand, this diagnostic technique has attracted a certain amount of well justified criticism, but on the other, recent cytohistologic correlations and new scientific knowledge are continually improving its application. We shall discuss the latter aspect in more detail and deal with some simple but informative points which the pathologist may find useful in daily practice.

Stennis Space Center's approach to liquid rocket engine health monitoring using exhaust plume diagnostics

NASA Technical Reports Server (NTRS)

Gardner, D. G.; Tejwani, G. D.; Bircher, F. E.; Loboda, J. A.; Van Dyke, D. B.; Chenevert, D. J.

1991-01-01

Details are presented of the approach used in a comprehensive program to utilize exhaust plume diagnostics for rocket engine health-and-condition monitoring and assessing SSME component wear and degradation. This approach incorporates both spectral and video monitoring of the exhaust plume. Video monitoring provides qualitative data for certain types of component wear while spectral monitoring allows both quantitative and qualitative information. Consideration is given to spectral identification of SSME materials and baseline plume emissions.

Plasmonic enhancement of cyanine dyes for near-infrared light-triggered photodynamic/photothermal therapy and fluorescent imaging

NASA Astrophysics Data System (ADS)

Lu, Mindan; Kang, Ning; Chen, Chuan; Yang, Liuqing; Li, Yang; Hong, Minghui; Luo, Xiangang; Ren, Lei; Wang, Xiumin

2017-11-01

Near-infrared (NIR) triggered cyanine dyes have attracted considerable attention in multimodal tumor theranostics. However, NIR cyanine dyes used in tumor treatment often suffer from low fluorescence intensity and weak singlet oxygen generation efficiency, resulting in inadequate diagnostic and therapy efficacy for tumors. It is still a great challenge to improve both the photodynamic therapy (PDT) and fluorescent imaging (FLI) efficacy of cyanine dyes in tumor applications. Herein, a novel multifunctional nanoagent AuNRs@SiO2-IR795 was developed to realize the integrated photothermal/photodynamic therapy (PTT/PDT) and FLI at a very low dosage of IR795 (0.4 μM) based on metal-enhanced fluorescence (MEF) effects. In our design, both the fluorescence intensity and reactive oxygen species of AuNRs@SiO2-IR795 nanocomposites were significantly enhanced up to 51.7 and 6.3 folds compared with free IR795, owing to the localized surface plasmon resonance band of AuNRs overlapping with the absorption or fluorescence emission band of the IR795 dye. Under NIR laser irradiation, the cancer cell inhibition efficiency in vitro with synergetic PDT/PTT was up to 82.3%, compared with 10.3% for free IR795. Moreover, the enhanced fluorescence intensity of our designed nanocomposites was helpful to track their behavior in tumor cells. Therefore, our designed nanoagents highlight the applications of multimodal diagnostics and therapy in tumors based on MEF.

A complicated case of amyand's hernia involving a perforated appendix and its management using minimally invasive laparoscopic surgery: A case report.

PubMed

Al-Ramli, Wisam; Khodear, Yahya; Aremu, Muyiwa; El-Sayed, Abdel Basset

2016-01-01

Amyand's hernia is a rare condition of inguinal hernia in which the appendix is incarcerated within the hernia sac through the internal ring. Complications include acute appendicitis and perforated appendicitis, which are rare in incidence, accounting for about 0.1% of cases. 1 These complications prove a diagnostic challenge due to their vague clinical presentation and atypical laboratory and radiological findings. Until recently, open appendectomy was the mainstay of treatment. Laparoscopic surgery offers a less invasive approach to confirming a diagnosis and serving as a therapeutic tool in equivocal cases. We report a case of a previously healthy 20-year-old male presenting with atypical signs and symptoms, as well as blood investigation results, and radiological findings of a perforated appendix within an Amyand's hernia. The patient was successfully managed using a minimally invasive laparoscopic appendectomy approach. Until recently, open appendectomy was considered the mainstay in the management of complicated Amyand's hernia. Laparoscopic surgery provides a new avenue for dealing with diagnostic uncertainty with advantages including faster recovery time, reduced hospital stay, and better quality of life. This case report highlights the concealing effects of an Amyand's hernia on a perforated appendix, the considerations required when an equivocal diagnosis present and the safe use of the minimally invasive laparoscopic surgery in the treatment of this rare condition. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma.

PubMed

Yao, Mingjie; Zhao, Jingmin; Lu, Fengmin

2016-01-26

Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia.

Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges.

PubMed

Dua, Shelley; Dowey, James; Foley, Loraine; Islam, Sabita; King, Yvonne; Ewan, Pamela; Clark, Andrew T

2018-02-27

Serum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown. The objective of this study was to determine whether tryptase rises in food allergic reactions, optimal sampling time points, and a diagnostic cutoff for confirming a clinical reaction. Characterized peanut allergic patients were recruited and underwent up to 4 peanut challenges and 1 placebo challenge each. Tryptase was measured serially on challenge days both before (baseline) and during the challenge. The peak percentage tryptase rise (peak/baseline) was related to reaction severity. Receiver operating characteristic (ROC) curves were generated establishing an optimal diagnostic cutoff. Tryptase was analyzed in 160 reactive (9% anaphylaxis) and 45 nonreactive (placebo) challenges in 50 adults aged 18 to 39 years. Tryptase rose above the normal range (11.4 ng/mL) in 4 of 160 reactions. When compared with baseline levels, a rise was observed in 100 of 160 (62.5%) reactions and 0 of 45 placebo challenges. The median rise (95% confidence interval [CI]) for all reactions was 25% (13.3% to 33.3%) and 70.8% (33.3% to 300%) during anaphylaxis. Peak levels occurred at 2 hours and correlated with severity (P < .05). Moderate-to-severe respiratory symptoms, generalized erythema, dizziness, and hypotension were correlated with a higher peak/baseline tryptase (P < .05). ROC curve analysis demonstrated the optimal cutoff to identify a reaction as a 30% rise (sensitivity 0.53; specificity 0.85), area under the curve 0.72 (95% CI, 0.67-0.78). Serum tryptase measurement is valuable in food allergic reactions, and correlates with symptom severity. Comparing peak reaction levels at 2 hours with baseline is essential. A rise in tryptase of 30% is associated with food allergic reactions. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Coagulation disorders and their cutaneous presentations: Diagnostic work-up and treatment.

PubMed

Dabiri, Ganary; Damstetter, Elizabeth; Chang, Yunyoung; Baiyee Ebot, Emily; Powers, Jennifer Gloeckner; Phillips, Tania

2016-05-01

Both inherited and acquired hypercoagulable states can present with nonspecific clinical manifestations, such as petechiae, purpura, livedo reticularis, and ulcerations. A good history and physical examination are crucial to diagnoses of these conditions. Inherited conditions tend to present either in neonatal period or later in life, while acquired conditions typically occur later in life. Diagnostic studies are performed to identify the coagulation cascade deficiency or defect. Treatment primarily hinges on anticoagulation and wound care. In this article, we provide an in-depth analysis of the clinical manifestations, diagnostic considerations, and management options of patients in hypercoagulable states. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Status of holographic interferometry at Wright Patterson Air Force Base

NASA Technical Reports Server (NTRS)

Seibert, George

1987-01-01

At Wright Patterson AFB, holographic interferometry has been used for nearly 15 years in a variety of supersonic and hypersonic wind tunnels. Specifically, holographic interferometry was used to study boundary layers, shock boundary layer interaction, and general flow diagnostics. Although a considerable amount of quantitative work was done, the difficulty of reducing data severely restricted this. In the future, it is of interest to use holographic interferometry in conjunction with laser Doppler velocimetry to do more complete diagnostics. Also, there is an interest to do particle field diagnostics in the combustion research facility. Finally, there are efforts in nondestructive testing where automated fringe readout and analysis would be extremely helpful.

Gambling Disorder and Other Behavioral Addictions: Recognition and Treatment

PubMed Central

Yau, Yvonne H. C.; Potenza, Marc N.

2015-01-01

Addiction professionals and the public are recognizing that certain nonsubstance behaviors—such as gambling, Internet use, video-game playing, sex, eating, and shopping—bear resemblance to alcohol and drug dependence. Growing evidence suggests that these behaviors warrant consideration as nonsubstance or “behavioral” addictions and has led to the newly introduced diagnostic category “Substance-Related and Addictive Disorders” in DSM-5. At present, only gambling disorder has been placed in this category, with insufficient data for other proposed behavioral addictions to justify their inclusion. This review summarizes recent advances in our understanding of behavioral addictions, describes treatment considerations, and addresses future directions. Current evidence points to overlaps between behavioral and substance-related addictions in phenomenology, epidemiology, comorbidity, neurobiological mechanisms, genetic contributions, responses to treatments, and prevention efforts. Differences also exist. Recognizing behavioral addictions and developing appropriate diagnostic criteria are important in order to increase awareness of these disorders and to further prevention and treatment strategies. PMID:25747926

A diagnostic and statistical manual of mental disorders history of premenstrual dysphoric disorder.

PubMed

Zachar, Peter; Kendler, Kenneth S

2014-04-01

The proposals to include a menstruation-related mood disorder in the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R), and DSM-IV led to intense public and behind-the-scenes controversy. Although the controversies surrounding the DSM-5 revision were greater in number than the controversies of the earlier revisions, the DSM-5 proposal to include a menstruation-related mood disorder was not among them. Premenstrual dysphoric disorder was made an official disorder in the DSM-5 with no significant protest. To understand the factors that led to this change, we interviewed those psychiatrists and psychologists who were most involved in the DSM-IV revision. On the basis of these interviews, we offer a list of empirical and nonempirical considerations that led to the DSM-IV compromise and explore how key alterations in these considerations led to a different outcome for the DSM-5.

A comparison of DSM-IV-TR and DSM-5 definitions for sexual dysfunctions: critiques and challenges.

PubMed

Sungur, Mehmet Z; Gündüz, Anil

2014-02-01

The diagnostic criteria of sexual dysfunctions (SDs) are paramount for the development of sexual medicine as reliable diagnoses are essential to guide treatment plans. Prior Diagnostic and Statistical Manual of Mental Disorders (DSM) classifications based definitions of SD mostly on expert opinions and included imprecise terms. The validity of diagnoses of SD has only recently been challenged, and efforts are made to make more operational definitions. This paper aims to compare and contrast the recently released Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) diagnostic criteria of SD with that of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition Text Revision (DSM-IV-TR) and explains the rationale for making changes in the new DSM-5. It also aims to address some issues to be considered further for the future. Online proposed American Psychiatric Association website DSM-5, the new released DSM-5, and DSM-IV-TR diagnostic criteria for SD were thoroughly inspected, and an extensive literature search was performed for comparative reasons. Changes in diagnostic criteria of DSM-5 were detected, and DSM-IV-TR and DSM-5 diagnostic criteria for SD were compared and contrasted. Diagnostic criteria were more operationalized, and explicit duration and frequency criteria were set up in DSM-5 for purposes of good clinical research. Classifications based on simple linear sexual response were abandoned, and diagnostic classifications were separately made for males and females. Desire and arousal disorders in women were merged. Drifting apart from linear sexual response cycle may be an advancement in establishing specific diagnostic criteria for different genders. However, it is still a question of debate whether there is enough evidence to lump sexual interest and arousal disorders in females. Making more precise definitions is important to differentiate disorders from other transient conditions. However, there is still room to improve our definitions and find a way to include gay and lesbian individuals. Further discussions and debates are expected to be continued in the future. © 2013 International Society for Sexual Medicine.

Spacelab

NASA Image and Video Library

1985-07-01

This STS-51F mission onboard Photograph shows some of the Spacelab-2 instruments in the cargo bay of the Orbiter Challenger. The Plasma Diagnostics Package (PDP). shown at the end of the Remote Manipulator System (RMS), used instruments on a subsatellite to study natural plasma processes, orbiter-induced plasma processes, and beam plasma physics. Fourteen instruments were mounted on the PDP for measurements of various plasma characteristics. The X-ray Telescope (XRT), is at the front. The goal of this investigation was to image and examine the X-ray emissions from clusters of galaxies in order to study the mechanisms that cause high-temperature emissions and to determine the weight of galactic clusters. The Small Helium-Cooled Infrared Telescope (IRT) is at the right behind the XRT. The objective of this investigation was to measure and map diffused and discrete infrared astronomical sources while evaluating the Space Shuttle as a platform for infrared astronomy. At the same time, a new large superfluid helium dewar system for cooling the telescope was evaluated. The egg-shaped Cosmic Ray Nuclei experiment (CRNE) is shown at the rear. This investigation was to study the composition of high-energy cosmic rays by using a large instrument exposed to space for a considerable period of time. Spacelab-2 (STS-51F, 19th Shuttle mission) was launched aboard the Space Shuttle Orbiter Challenger on July 29, 1985.

Giant Colonic Diverticulum: a Rare Diagnostic and Therapeutic Challenge of Diverticular Disease.

PubMed

Macht, Ryan; Sheldon, Holly K; Fisichella, P Marco

2015-08-01

A giant colonic diverticulum is a diverticulum of the colon greater than 4 cm in diameter that can present, albeit rarely, as a complication of diverticular disease. We discuss the three different histologic subtypes that have been described and the challenges in the diagnosis and treatment.

Computational Approach for Securing Radiology-Diagnostic Data in Connected Health Network using High-Performance GPU-Accelerated AES.

PubMed

Adeshina, A M; Hashim, R

2017-03-01

Diagnostic radiology is a core and integral part of modern medicine, paving ways for the primary care physicians in the disease diagnoses, treatments and therapy managements. Obviously, all recent standard healthcare procedures have immensely benefitted from the contemporary information technology revolutions, apparently revolutionizing those approaches to acquiring, storing and sharing of diagnostic data for efficient and timely diagnosis of diseases. Connected health network was introduced as an alternative to the ageing traditional concept in healthcare system, improving hospital-physician connectivity and clinical collaborations. Undoubtedly, the modern medicinal approach has drastically improved healthcare but at the expense of high computational cost and possible breach of diagnosis privacy. Consequently, a number of cryptographical techniques are recently being applied to clinical applications, but the challenges of not being able to successfully encrypt both the image and the textual data persist. Furthermore, processing time of encryption-decryption of medical datasets, within a considerable lower computational cost without jeopardizing the required security strength of the encryption algorithm, still remains as an outstanding issue. This study proposes a secured radiology-diagnostic data framework for connected health network using high-performance GPU-accelerated Advanced Encryption Standard. The study was evaluated with radiology image datasets consisting of brain MR and CT datasets obtained from the department of Surgery, University of North Carolina, USA, and the Swedish National Infrastructure for Computing. Sample patients' notes from the University of North Carolina, School of medicine at Chapel Hill were also used to evaluate the framework for its strength in encrypting-decrypting textual data in the form of medical report. Significantly, the framework is not only able to accurately encrypt and decrypt medical image datasets, but it also successfully encrypts and decrypts textual data in Microsoft Word document, Microsoft Excel and Portable Document Formats which are the conventional format of documenting medical records. Interestingly, the entire encryption and decryption procedures were achieved at a lower computational cost using regular hardware and software resources without compromising neither the quality of the decrypted data nor the security level of the algorithms.

[Diagnostic approach to the mild head trauma of the adult in Emergency Medicine: between biomarkers and imaging].

PubMed

Lippi, Giuseppe; Cervellin, Gianfranco

2013-03-01

Head trauma is one of the most frequent disabling diseases, with annual incidence of approximately 250-600 patients per 100,000, and mortality of 17 cases per 100,000. The mild head injury is nearly 15 times more frequent than the moderate, and more than 20 times than the severe. Although there are still contradictions regarding the clinical significance of the term "head injury", it can not be considered synonymous with traumatic brain injury. The main challenge in the diagnosis lies in the fact that severe intracranial lesions are often associated with mild head injury, especially in the presence of specific risk factors. Despite the diagnostic gold standard is represented by computed tomography (CT), its systematic performance in all patients is unadvisable for limited prevalence of positivity, radiological risk, high cost and complexity. Several potential biomarkers have been proposed for the screening of patients, but protein S100B seems now the most promising for some clinical and analytical considerations. After performing a meta-analysis of clinical trials in patients with mild head injury, we calculated a cumulative area under the curve of 0.753 (95% CI, 0.752-0.754), a negative predictive value of 97.7% (95% CI, 97.5-97.8 %) and positive predictive value of 23.6% (95% CI, 23.2-24.0%) for brain injury. We therefore developed a diagnostic algorithm based on the preliminary assessment of the Glasgow Coma Scale (GCS). Patients with GCS ​​<14 are subjected to CT, those with values GCS​14-15 without risk factors are discharged, whereas protein S100B is assessed stat in those with GCS ​​14-15 and the presence of risk factors. According to the value of the marker, patients with a concentration below the diagnostic cut-offs are discharged, whereas CT is performed in those with higher concentrations. By combining the percentage of positive CT scans in patients with mild head trauma and the negative predictive value of protein S100B, this protocol would safely abate unnecessary CT by 30-50% and costs by 28%.

Understanding sexual, paraphilic, and gender dysphoria disorders in DSM-5.

PubMed

DeFeo, Jennifer

2015-01-01

With every Diagnostic and Statistical Manual of Mental Disorders that has been published, there has been controversy within controversy; however, what appears to be lacking is the importance of truly understanding what, why, and how the changes impact the community at large. Issues such as homosexuality, the five axial diagnostic system, and transitioning from a medical model to a biopsychosocial model have been hot topics that have led clinicians to challenge the reliability and validity of the manual throughout history. As clinicians and medical professionals, it is important to objectively look at the manual and become educated on how and why these changes exist. With that being said, this commentary aims to challenge the article " Problems with the Sexual Disorders Sections of DSM-5" by Colin A. Ross (2015). The structure of this commentary purposefully mirrors the structure of the commentary that it is challenging.

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.

Application of the Systematic Sensor Selection Strategy for Turbofan Engine Diagnostics

NASA Technical Reports Server (NTRS)

Sowers, T. Shane; Kopasakis, George; Simon, Donald L.

2008-01-01

The data acquired from available system sensors forms the foundation upon which any health management system is based, and the available sensor suite directly impacts the overall diagnostic performance that can be achieved. While additional sensors may provide improved fault diagnostic performance, there are other factors that also need to be considered such as instrumentation cost, weight, and reliability. A systematic sensor selection approach is desired to perform sensor selection from a holistic system-level perspective as opposed to performing decisions in an ad hoc or heuristic fashion. The Systematic Sensor Selection Strategy is a methodology that optimally selects a sensor suite from a pool of sensors based on the system fault diagnostic approach, with the ability of taking cost, weight, and reliability into consideration. This procedure was applied to a large commercial turbofan engine simulation. In this initial study, sensor suites tailored for improved diagnostic performance are constructed from a prescribed collection of candidate sensors. The diagnostic performance of the best performing sensor suites in terms of fault detection and identification are demonstrated, with a discussion of the results and implications for future research.

Application of the Systematic Sensor Selection Strategy for Turbofan Engine Diagnostics

NASA Technical Reports Server (NTRS)

Sowers, T. Shane; Kopasakis, George; Simon, Donald L.

2008-01-01

The data acquired from available system sensors forms the foundation upon which any health management system is based, and the available sensor suite directly impacts the overall diagnostic performance that can be achieved. While additional sensors may provide improved fault diagnostic performance there are other factors that also need to be considered such as instrumentation cost, weight, and reliability. A systematic sensor selection approach is desired to perform sensor selection from a holistic system-level perspective as opposed to performing decisions in an ad hoc or heuristic fashion. The Systematic Sensor Selection Strategy is a methodology that optimally selects a sensor suite from a pool of sensors based on the system fault diagnostic approach, with the ability of taking cost, weight and reliability into consideration. This procedure was applied to a large commercial turbofan engine simulation. In this initial study, sensor suites tailored for improved diagnostic performance are constructed from a prescribed collection of candidate sensors. The diagnostic performance of the best performing sensor suites in terms of fault detection and identification are demonstrated, with a discussion of the results and implications for future research.

Cheyletiella infestation in the dog: observations on diagnostic methods and clinical signs.

PubMed

Saevik, B K; Bredal, W; Ulstein, T L

2004-10-01

The aims of this study were to evaluate the ability of diagnostic methods to detect naturally occurring Cheyletiella infestation in dogs, and to quantify and relate the number of mites and eggs present to clinical signs. Privately owned dogs with skin problems were eligible for inclusion in the study. Four diagnostic tests were performed on each dog in the following order: tape impression, hair plucking, skin scraping and vacuum cleaning. Dogs with positive test results for Cheyletiella infestation in at least one of the tests under evaluation were included in the study (n=27). The severity of pruritus and scaling was graded on a four-point fixed scale. The diagnostic findings in vacuum cleaning samples provided a semiquantitative measure of the grade of infestation. The vacuum cleaning test gave a positive test result in all dogs and was significantly more efficient than the other tests evaluated (P<0.01). The number of diagnostic findings varied considerably among the different vacuum samples. No significant relationship between the number of diagnostic findings and severity of clinical signs was detected.

Sample size in studies on diagnostic accuracy in ophthalmology: a literature survey.

PubMed

Bochmann, Frank; Johnson, Zoe; Azuara-Blanco, Augusto

2007-07-01

To assess the sample sizes used in studies on diagnostic accuracy in ophthalmology. Design and sources: A survey literature published in 2005. The frequency of reporting calculations of sample sizes and the samples' sizes were extracted from the published literature. A manual search of five leading clinical journals in ophthalmology with the highest impact (Investigative Ophthalmology and Visual Science, Ophthalmology, Archives of Ophthalmology, American Journal of Ophthalmology and British Journal of Ophthalmology) was conducted by two independent investigators. A total of 1698 articles were identified, of which 40 studies were on diagnostic accuracy. One study reported that sample size was calculated before initiating the study. Another study reported consideration of sample size without calculation. The mean (SD) sample size of all diagnostic studies was 172.6 (218.9). The median prevalence of the target condition was 50.5%. Only a few studies consider sample size in their methods. Inadequate sample sizes in diagnostic accuracy studies may result in misleading estimates of test accuracy. An improvement over the current standards on the design and reporting of diagnostic studies is warranted.

Acquired pathology of the pediatric spine and spinal cord.

PubMed

Palasis, Susan; Hayes, Laura L

2015-09-01

Pediatric spine pathology poses a diagnostic challenge for radiologists. Acquired spine pathology often yields nonspecific signs and symptoms in children, especially in the younger age groups, and diagnostic delay can carry significant morbidity. This review is focused on some of the more common diagnostic dilemmas we face when attempting to evaluate and diagnose acquired pediatric spine anomalies in daily practice. An understanding of some of the key differentiating features of these disease processes in conjunction with pertinent history, physical exam, and advanced imaging techniques can indicate the correct diagnosis.

Drug sensitivity testing platforms for gastric cancer diagnostics.

PubMed

Lau, Vianne; Wong, Andrea Li-Ann; Ng, Christopher; Mok, Yingting; Lakshmanan, Manikandan; Yan, Benedict

2016-02-01

Gastric cancer diagnostics has traditionally been histomorphological and primarily the domain of surgical pathologists. Although there is an increasing usage of molecular and genomic techniques for clinical diagnostics, there is an emerging field of personalised drug sensitivity testing. In this review, we describe the various personalised drug sensitivity testing platforms and discuss the challenges facing clinical adoption of these assays for gastric cancer. 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/

Drug-device trials for infectious diseases: CDRH perspective.

PubMed

Meier, Kristen L; Gitterman, Steven

2011-05-01

Assessing the performance of new diagnostic tests for infectious diseases has traditionally focused on comparing the new assay against a reference standard such as culture. In this paper, we suggest that clinical trial designs with both a diagnostic and therapeutic component may be necessary to evaluate the safety and effectiveness of nonmicrobiologically based assays, with a specific emphasis on the test/marker-stratified design. General design challenges for trials of infectious diseases that simultaneously study both diagnostic and therapeutic components (eg, both devices and drugs) are also discussed.

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

MUROKH,A.; FRIGOLA,P.; ET AL

We describe a diagnostics system developed, to measure exponential gain properties and the electron beam dynamics inside the strong focusing 4-m long undulator for the VISA (Visible to Infrared SASE Amplifier) FEL. The technical challenges included working inside the small undulator gap, optimizing the electron beam diagnostics in the high background environment of the spontaneous undulator radiation, multiplexing and transporting the photon beam. Initial results are discussed.

Afterword: Considerations for Future Practice of Assessment and Accountability

ERIC Educational Resources Information Center

Bresciani, Marilee J.

2013-01-01

This afterword offers challenges and considerations as the assessment movement continues to develop. The author offers some simple considerations for readers to ponder as they advance their evidence-based decision making processes, and encourages others to use these methods within the context of recent neuroscientific evidence that learning and…

Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants.

PubMed

Schalock, Peter C; Thyssen, Jacob P

2013-01-01

Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated. Diagnostic criteria for hypersensitivity reactions after metallic device implantation are evaluated in this study by a multinational group of patch testers using Thyssen's previously published criteria. A total of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013 American Contact Dermatitis Society meetings answered a survey regarding their opinions on topics relating to metal hypersensitivity. Four major and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found the following criteria useful (major criteria): chronic dermatitis beginning weeks to months after metallic implantation, eruption overlying the metal implant, positive patch test to a metal component of the implant, and complete clearing after removal of the potentially allergenic implant. Minor criteria (<61% of respondents) were as follows: systemic allergic dermatitis reaction, therapy-resistant dermatitis, morphology consistent with dermatitis, histology consistent with allergic contact dermatitis, and a positive in vitro test to metals (eg, lymphocyte transformation test). In the challenging situation such as a symptomatic or failing orthopedic device, applying these 4 major criteria and the 5 supportive minor criteria may be useful for guiding decision making.

Use of Electromagnetic Navigational Transthoracic Needle Aspiration (E-TTNA) for Sampling of Lung Nodules.

PubMed

Arias, Sixto; Lee, Hans; Semaan, Roy; Frimpong, Bernice; Ortiz, Ricardo; Feller-Kopman, David; Oakjones-Burgess, Karen; Yarmus, Lonny

2015-05-23

Lung nodule evaluation represents a clinical challenge especially in patients with intermediate risk for malignancy. Multiple technologies are presently available to sample nodules for pathological diagnosis. Those technologies can be divided into bronchoscopic and non-bronchoscopic interventions. Electromagnetic navigational bronchoscopy is being extensively used for the endobronchial approach to peripheral lung nodules but has been hindered by anatomic challenges resulting in a 70% diagnostic yield. Electromagnetic navigational guided transthoracic needle lung biopsy is novel non-bronchoscopic method that uses a percutaneous electromagnetic tip tracked needle to obtain core biopsy specimens. Electromagnetic navigational transthoracic needle aspiration complements bronchoscopic techniques potentially allowing the provider to maximize the diagnostic yield during one single procedure. This article describes a novel integrated diagnostic approach to pulmonary lung nodules. We propose the use of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging; radial EBUS, navigational bronchoscopy and E-TTNA during one single procedure to maximize diagnostic yield and minimize the number of invasive procedures needed to obtain a diagnosis. This manuscript describes in detail how the navigation transthoracic procedure is performed. Additional clinical studies are needed to determine the clinical utility of this novel technology.

Emerging Pathogens: Challenges and Successes of Molecular Diagnostics

PubMed Central

Dong, Jianli; Olano, Juan P.; McBride, Jere W.; Walker, David H.

2008-01-01

More than 50 emerging and reemerging pathogens have been identified during the last 40 years. Until 1992 when the Institute of Medicine issued a report that defined emerging infectious diseases, medicine had been complacent about such infectious diseases despite the alarm bells of infections with human immunodeficiency virus. Molecular tools have proven useful in discovering and characterizing emerging viruses and bacteria such as Sin Nombre virus (hantaviral pulmonary syndrome), hepatitis C virus, Bartonella henselae (cat scratch disease, bacillary angiomatosis), and Anaplasma phagocytophilum (human granulocytotropic anaplasmosis). The feasibility of applying molecular diagnostics to dangerous, fastidious, and uncultivated agents for which conventional tests do not yield timely diagnoses has achieved proof of concept for many agents, but widespread use of cost-effective, validated commercial assays has yet to occur. This review presents representative emerging viral respiratory infections, hemorrhagic fevers, and hepatitides, as well as bacterial and parasitic zoonotic, gastrointestinal, and pulmonary infections. Agent characteristics, epidemiology, clinical manifestations, and diagnostic methods are tabulated for another 22 emerging viruses and five emerging bacteria. The ongoing challenge to the field of molecular diagnostics is to apply contemporary knowledge to facilitate agent diagnosis as well as to further discoveries of novel pathogens. PMID:18403608

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.

Clinical Assessment and Management of Toddlers With Suspected Autism Spectrum Disorder: Insights From Studies of High-Risk Infants

PubMed Central

Zwaigenbaum, Lonnie; Bryson, Susan; Lord, Catherine; Rogers, Sally; Carter, Alice; Carver, Leslie; Chawarska, Kasia; Constantino, John; Dawson, Geraldine; Dobkins, Karen; Fein, Deborah; Iverson, Jana; Klin, Ami; Landa, Rebecca; Messinger, Daniel; Ozonoff, Sally; Sigman, Marian; Stone, Wendy; Tager-Flusberg, Helen; Yirmiya, Nurit

2010-01-01

With increased public awareness of the early signs and recent American Academy of Pediatrics recommendations that all 18- and 24-month-olds be screened for autism spectrum disorders, there is an increasing need for diagnostic assessment of very young children. However, unique challenges exist in applying current diagnostic guidelines for autism spectrum disorders to children under the age of 2 years. In this article, we address challenges related to early detection, diagnosis, and treatment of autism spectrum disorders in this age group. We provide a comprehensive review of findings from recent studies on the early development of children with autism spectrum disorders, summarizing current knowledge on early signs of autism spectrum disorders, the screening properties of early detection tools, and current best practice for diagnostic assessment of autism spectrum disorders before 2 years of age. We also outline principles of effective intervention for children under the age of 2 with suspected/confirmed autism spectrum disorders. It is hoped that ongoing studies will provide an even stronger foundation for evidence-based diagnostic and intervention approaches for this critically important age group. PMID:19403506

Computational circular dichroism estimation for point-of-care diagnostics via vortex half-wave retarders

NASA Astrophysics Data System (ADS)

Haider, Shahid A.; Tran, Megan Y.; Wong, Alexander

2018-02-01

Observing the circular dichroism (CD) caused by organic molecules in biological fluids can provide powerful indicators of patient health and provide diagnostic clues for treatment. Methods for this kind of analysis involve tabletop devices that weigh tens of kilograms with costs on the order of tens of thousands of dollars, making them prohibitive in point-of-care diagnostic applications. In an e ort to reduce the size, cost, and complexity of CD estimation systems for point-of-care diagnostics, we propose a novel method for CD estimation that leverages a vortex half-wave retarder in between two linear polarizers and a two-dimensional photodetector array to provide an overall complexity reduction in the system. This enables the measurement of polarization variations across multiple polarizations after they interact with a biological sample, simultaneously, without the need for mechanical actuation. We further discuss design considerations of this methodology in the context of practical applications to point-of-care diagnostics.

Thyroid stunning: fact or fiction?

PubMed

McDougall, I Ross; Iagaru, Andrei

2011-03-01

Stunning of thyroid tissue by diagnostic activities of (131)I has been described by some investigators and refuted by others. The support both for and against stunning has at times been enthusiastic and vigorous. We present the data from both sides of the debate in an attempt to highlight the strengths and deficiencies in the investigations cited. Clinical, animal, and in vitro studies are included. There are considerable differences in clinical practice, such as the administered activity for diagnostic whole-body scan, delay between diagnostic scan and treatment, time between treatment and posttherapy scanning, and timing of follow-up studies, that have to be analyzed with care. Other factors that often cannot be judged, such as levels of thyroid-stimulating hormone and serum iodine at time of diagnostic testing versus treatment could have an influence on stunning. Larger diagnostic doses and longer delays to therapy appear to increase the likelihood of stunning. The stunning effect of early-absorbed radiation from the therapy should also be considered. Copyright © 2011 Elsevier Inc. All rights reserved.

Understanding the medical and nonmedical value of diagnostic testing.

PubMed

Lee, David W; Neumann, Peter J; Rizzo, John A

2010-01-01

To develop a framework for defining the potential value of diagnostic testing, and discuss its implications for the health-care delivery system. We reviewed the conceptual and empirical literature related to the valuing of diagnostic tests, and used this information to create a framework for characterizing their value. We then made inferences about the impact of this framework on health insurance coverage, health technology assessment, physician-patient relationships, and public health policy. Three dimensions can effectively classify the potential value created by diagnostic tests: 1) medical value (impact on treatment decisions); 2) planning value (affect on patients' ability to make better life decisions); and 3) psychic value (how test information affects patients' sense of self). This comprehensive framework for valuing diagnostics suggests that existing health technology assessments may systematically under- or overvalue diagnostics, leading to potentially incorrect conclusions about cost-effectiveness. Further, failure to account for all value dimensions may lead to distorted payments under a value-based health-care system. The potential value created by medical diagnostics incorporates medical value as well as value associated with well-being and planning. Consideration of all three dimensions has important implications for technology assessment and value-based payment.

An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

PubMed Central

Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

2016-01-01

As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

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.

Diagnostic accuracy of patch test in children with food allergy.

PubMed

Caglayan Sozmen, Sule; Povesi Dascola, Carlotta; Gioia, Edoardo; Mastrorilli, Carla; Rizzuti, Laura; Caffarelli, Carlo

2015-08-01

The gold standard test for confirming whether a child has clinical hypersensitivity reactions to foods is the oral food challenge. Therefore, there is increasing interest in simpler diagnostic markers of food allergy, especially in children, to avoid oral food challenge. The goal of this study was to assess the diagnostic accuracy of atopy patch test in comparison with oral food challenge. We investigated 243 children (mean age, 51 months) referred for evaluation of suspected egg or cow's milk allergy. Skin prick test and atopy patch test were carried out, and after a 2 weeks elimination diet, oral food challenge was performed. Two hundred and forty-three children underwent OFC to the suspected food. We found clinically relevant food allergies in 40 (65%) children to egg and in 22 (35%) to cow's milk. The sensitivity of skin prick test for both milk and egg was 92%, specificity 91%, positive predictive value 35%, and negative predictive value of 93%. Sensitivity, specificity, positive predictive value, and negative predictive value of atopy patch test for both milk and egg were 21%, 73%, 20%, and 74%, respectively. Our study suggests that there is insufficient evidence for the routine use of atopy patch test for the evaluation of egg and cow's milk allergy. OFC remains gold standard for the diagnosis of egg and milk allergy even in the presence of high costs in terms of both time and risks during application. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Obturator hernia: A diagnostic challenge.

PubMed

Kulkarni, Sanjeev R; Punamiya, Aditya R; Naniwadekar, Ramchandra G; Janugade, Hemant B; Chotai, Tejas D; Vimal Singh, T; Natchair, Arafath

2013-01-01

Obturator hernia is an extremely rare type of hernia with relatively high mortality and morbidity. Its early diagnosis is challenging since the signs and symptoms are non specific. Here in we present a case of 70 years old women who presented with complaints of intermittent colicky abdominal pain and vomiting. Plain radiograph of abdomen showed acute dilatation of stomach. Ultrasonography showed small bowel obstruction at the mid ileal level with evidence of coiled loops of ileum in pelvis. On exploration, Right Obstructed Obturator hernia was found. The obstructed Intestine was reduced and resected and the obturator foramen was closed with simple sutures. Postoperative period was uneventful. Obturator hernia is a rare pelvic hernia and poses a diagnostic challenge. Obturator hernia occurs when there is protrusion of intra-abdominal contents through the obturator foramen in the pelvis. The signs and symptoms are non specific and generally the diagnosis is made during exploration for the intestinal obstruction, one of the four cardinal features. Others are pain on the medial aspect of thigh called as Howship Rombergs sign, repeated attacks of Intestinal Obstruction and palpable mass on the medial aspect of thigh. Obturator hernia is a rare but significant cause of intestinal obstruction especially in emaciated elderly woman and a diagnostic challenge for the Doctors. CT scan is valuable to establish preoperative diagnosis. Surgery either open or laproscopic, is the only treatment. The need for the awareness is stressed and CT scan can be helpful. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Paving the road to personalized medicine: recommendations on regulatory, intellectual property and reimbursement challenges

PubMed Central

Knowles, Lori; Luth, Westerly; Bubela, Tania

2017-01-01

Abstract Personalized medicine (PM) aims to harness a wave of ‘omics’ discoveries to facilitate research and discovery of targeted diagnostics and therapies and increase the efficiency of healthcare systems by predicting and treating individual predispositions to diseases or conditions. Despite significant investment, limited progress has been made bringing PM to market. We describe the major perceived regulatory, intellectual property, and reimbursement challenges to the development, translation, adoption, and implementation of PM products into clinical care. We conducted a scoping review to identify (i) primary challenges for the development and implementation of PM identified in the academic literature; (ii) solutions proposed in the academic literature to address these challenges; and (iii) gaps that exist in that literature. We identified regulatory barriers to PM development and recommendations in 344 academic papers. Regulatory uncertainty was a cross-cutting theme that appeared in conjunction with other themes including: reimbursement; clinical trial regulation; regulation of co-development; unclear evidentiary requirements; insufficient incentives for research and development; incompatible information systems; and different regulation of different diagnostics. To fully realize the benefits of PM for healthcare systems and patients, regulatory, intellectual property, and reimbursement challenges need to be addressed in lock step with scientific advances. PMID:29868182

Information theoretic quantification of diagnostic uncertainty.

PubMed

Westover, M Brandon; Eiseman, Nathaniel A; Cash, Sydney S; Bianchi, Matt T

2012-01-01

Diagnostic test interpretation remains a challenge in clinical practice. Most physicians receive training in the use of Bayes' rule, which specifies how the sensitivity and specificity of a test for a given disease combine with the pre-test probability to quantify the change in disease probability incurred by a new test result. However, multiple studies demonstrate physicians' deficiencies in probabilistic reasoning, especially with unexpected test results. Information theory, a branch of probability theory dealing explicitly with the quantification of uncertainty, has been proposed as an alternative framework for diagnostic test interpretation, but is even less familiar to physicians. We have previously addressed one key challenge in the practical application of Bayes theorem: the handling of uncertainty in the critical first step of estimating the pre-test probability of disease. This essay aims to present the essential concepts of information theory to physicians in an accessible manner, and to extend previous work regarding uncertainty in pre-test probability estimation by placing this type of uncertainty within a principled information theoretic framework. We address several obstacles hindering physicians' application of information theoretic concepts to diagnostic test interpretation. These include issues of terminology (mathematical meanings of certain information theoretic terms differ from clinical or common parlance) as well as the underlying mathematical assumptions. Finally, we illustrate how, in information theoretic terms, one can understand the effect on diagnostic uncertainty of considering ranges instead of simple point estimates of pre-test probability.

Computer-aided dermoscopy for diagnosis of melanoma

PubMed Central

Barzegari, Masoomeh; Ghaninezhad, Haiedeh; Mansoori, Parisa; Taheri, Arash; Naraghi, Zahra S; Asgari, Masood

2005-01-01

Background Computer-aided dermoscopy using artificial neural networks has been reported to be an accurate tool for the evaluation of pigmented skin lesions. We set out to determine the sensitivity and specificity of a computer-aided dermoscopy system for diagnosis of melanoma in Iranian patients. Methods We studied 122 pigmented skin lesions which were referred for diagnostic evaluation or cosmetic reasons. Each lesion was examined by two clinicians with naked eyes and all of their clinical diagnostic considerations were recorded. The lesions were analyzed using a microDERM® dermoscopy unit. The output value of the software for each lesion was a score between 0 and 10. All of the lesions were excised and examined histologically. Results Histopathological examination revealed melanoma in six lesions. Considering only the most likely clinical diagnosis, sensitivity and specificity of clinical examination for diagnosis of melanoma were 83% and 96%, respectively. Considering all clinical diagnostic considerations, the sensitivity and specificity were 100% and 89%. Choosing a cut-off point of 7.88 for dermoscopy score, the sensitivity and specificity of the score for diagnosis of melanoma were 83% and 96%, respectively. Setting the cut-off point at 7.34, the sensitivity and specificity were 100% and 90%. Conclusion The diagnostic accuracy of the dermoscopy system was at the level of clinical examination by dermatologists with naked eyes. This system may represent a useful tool for screening of melanoma, particularly at centers not experienced in the field of pigmented skin lesions. PMID:16000171

Challenges Facing Teachers New to Working in Schools Overseas

ERIC Educational Resources Information Center

Halicioglu, Margaret L.

2015-01-01

This article considers the potential challenges facing teachers moving abroad for the first time, both professional challenges in their school and personal challenges in their private life. It suggests that such teachers embarking on a professional adventure overseas would benefit from careful consideration of the kind of school they will thrive…

Pandemic Influenza and Pregnancy: An Opportunity to Reassess Maternal Bioethics

PubMed Central

Beigi, Richard H.

2009-01-01

Large-scale infectious epidemics present the medical community with numerous medical and ethical challenges. Recent attention has focused on the likelihood of an impending influenza pandemic caused by the H5N1 virus. Pregnant women in particular present policymakers with great challenges to planning for such a public health emergency. By recognizing the specific considerations needed for this population, we can preemptively address the issues presented by infectious disease outbreaks. We reviewed the important ethical challenges presented by pregnant women and highlighted the considerations for all vulnerable groups when planning for a pandemic at both the local and the national level. PMID:19461111

Point-of-care diagnostics: extending the laboratory network to reach the last mile.

PubMed

Drain, Paul K; Rousseau, Christine

2017-03-01

More point-of-care (POC) diagnostic tests are becoming available for HIV diagnosis and treatment in resource-limited settings. These novel technologies have the potential to foster decentralized HIV care and treatment for the benefit of clinical laboratories, HIV clinics, and HIV-infected patients. There continue to be many business, technological, and operational challenges that limit product development and regulatory approval, which limits products available for the required operational and cost-effectiveness studies and delays policy adoption and implementation. Although the rapid HIV diagnostic test has been widely successful, the pathways for POC CD4 cell count and HIV viral load assay analyzers have been more challenging. We describe significant hurdles for product development, approval, and implementation, which include the business case, technical development, clinical impact, and integrating laboratory and clinical networks. The objective of this review is to highlight the obstacles for developing and implementing appropriate strategies for POC HIV testing assays to improve the clinical services for HIV-infected patients in resource-limited settings.

Brain collection, standardized neuropathologic assessment, and comorbidity in ADNI participants

PubMed Central

Franklin, Erin E.; Perrin, Richard J.; Vincent, Benjamin; Baxter, Michael; Morris, John C.; Cairns, Nigel J.

2015-01-01

Introduction The Alzheimer’s Disease Neuroimaging Initiative Neuropathology Core (ADNI-NPC) facilitates brain donation, ensures standardized neuropathologic assessments, and maintains a tissue resource for research. Methods The ADNI-NPC coordinates with performance sites to promote autopsy consent, facilitate tissue collection and autopsy administration, and arrange sample delivery to the NPC, for assessment using NIA-AA neuropathologic diagnostic criteria. Results The ADNI-NPC has obtained 45 participant specimens and neuropathologic assessments have been completed in 36 to date. Challenges in obtaining consent at some sites have limited the voluntary autopsy rate to 58%. Among assessed cases, clinical diagnostic accuracy for Alzheimer disease (AD) is 97%; however, 58% show neuropathologic comorbidities. Discussion Challenges facing autopsy consent and coordination are largely resource-related. The neuropathologic assessments indicate that ADNI’s clinical diagnostic accuracy for AD is high; however, many AD cases have comorbidities that may impact the clinical presentation, course, and imaging and biomarker results. These neuropathologic data permit multimodal and genetic studies of these comorbidities to improve diagnosis and provide etiologic insights. PMID:26194314

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.

Challenges to Laser-Based Imaging Techniques in Gas Turbine Combustor Systems for Aerospace Applications

NASA Technical Reports Server (NTRS)

Locke, Randy J.; Anderson, Robert C.; Zaller, Michelle M.; Hicks, Yolanda R.

1998-01-01

Increasingly severe constraints on emissions, noise and fuel efficiency must be met by the next generation of commercial aircraft powerplants. At NASA Lewis Research Center (LeRC) a cooperative research effort with industry is underway to design and test combustors that will meet these requirements. To accomplish these tasks, it is necessary to gain both a detailed understanding of the combustion processes and a precise knowledge of combustor and combustor sub-component performance at close to actual conditions. To that end, researchers at LeRC are engaged in a comprehensive diagnostic investigation of high pressure reacting flowfields that duplicate conditions expected within the actual engine combustors. Unique, optically accessible flame-tubes and sector rig combustors, designed especially for these tests. afford the opportunity to probe these flowfields with the most advanced, laser-based optical diagnostic techniques. However, these same techniques, tested and proven on comparatively simple bench-top gaseous flame burners, encounter numerous restrictions and challenges when applied in these facilities. These include high pressures and temperatures, large flow rates, liquid fuels, remote testing, and carbon or other material deposits on combustor windows. Results are shown that document the success and versatility of these nonintrusive optical diagnostics despite the challenges to their implementation in realistic systems.

Towards first principle medical diagnostics: on the importance of disease-disease and sign-sign interactions

NASA Astrophysics Data System (ADS)

Ramezanpour, Abolfazl; Mashaghi, Alireza

2017-07-01

A fundamental problem in medicine and biology is to assign states, e.g. healthy or diseased, to cells, organs or individuals. State assignment or making a diagnosis is often a nontrivial and challenging process and, with the advent of omics technologies, the diagnostic challenge is becoming more and more serious. The challenge lies not only in the increasing number of measured properties and dynamics of the system (e.g. cell or human body) but also in the co-evolution of multiple states and overlapping properties, and degeneracy of states. We develop, from first principles, a generic rational framework for state assignment in cell biology and medicine, and demonstrate its applicability with a few simple theoretical case studies from medical diagnostics. We show how disease-related statistical information can be used to build a comprehensive model that includes the relevant dependencies between clinical and laboratory findings (signs) and diseases. In particular, we include disease-disease and sign-sign interactions and study how one can infer the probability of a disease in a patient with given signs. We perform comparative analysis with simple benchmark models to check the performances of our models. We find that including interactions can significantly change the statistical importance of the signs and diseases. This first principles approach, as we show, facilitates the early diagnosis of disease by taking interactions into accounts, and enables the construction of consensus diagnostic flow charts. Additionally, we envision that our approach will find applications in systems biology, and in particular, in characterizing the phenome via the metabolome, the proteome, the transcriptome, and the genome.

Family Connections: Visual Supports for Promoting Social Skills in Young Children--A Family Perspective

ERIC Educational Resources Information Center

Moody, Amelia K.

2012-01-01

Family members of children with autism spectrum disorders (ASDs) often face social, emotional, and behavioral challenges in the home. Difficulty communicating with family members, forming relationships with friends, and responding appropriately to others can cause significant challenges in the home (Diagnostic and Statistical Manual of Mental…

Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

PubMed

Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

2017-10-01

Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

[Neurocognitive disorders in DSM-5: pervasive changes in the diagnostics of dementia].

PubMed

Maier, W; Barnikol, U B

2014-05-01

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) proposes an innovative chapter on neurocognitive disorders (NCD) as a substitute for the dementia, delirium and amnestic disorders chapter in DSM-IV. This NCD chapter promotes a most innovative change compared to DSM-IV. While the term delirium is preserved, the commonly used term dementia does not occur as a diagnostic entity. Neurocognitive disorders are more inclusive than dementias; they also cover early prodromal stages of dementias below the DSM-IV threshold. The diagnosis of NCDs requires essentially neuropsychological testing preferentially with standardized instruments. Special focus is given to etiological subtyping taking former diagnostic consensus processes by expert groups into consideration. The subsequent more extensive concept of NCD also allows the diagnosis of etiological-specific prodromal states of cognitive impairments. The changes from DSM-IV to DSM-5 are critically discussed.

Hybrid-modality high-resolution imaging: for diagnostic biomedical imaging and sensing for disease diagnosis

NASA Astrophysics Data System (ADS)

Murukeshan, Vadakke M.; Hoong Ta, Lim

2014-11-01

Medical diagnostics in the recent past has seen the challenging trend to come up with dual and multi-modality imaging for implementing better diagnostic procedures. The changes in tissues in the early disease stages are often subtle and can occur beneath the tissue surface. In most of these cases, conventional types of medical imaging using optics may not be able to detect these changes easily due to its penetration depth of the orders of 1 mm. Each imaging modality has its own advantages and limitations, and the use of a single modality is not suitable for every diagnostic applications. Therefore the need for multi or hybrid-modality imaging arises. Combining more than one imaging modalities overcomes the limitation of individual imaging method and integrates the respective advantages into a single setting. In this context, this paper will be focusing on the research and development of two multi-modality imaging platforms. The first platform combines ultrasound and photoacoustic imaging for diagnostic applications in the eye. The second platform consists of optical hyperspectral and photoacoustic imaging for diagnostic applications in the colon. Photoacoustic imaging is used as one of the modalities in both platforms as it can offer deeper penetration depth compared to optical imaging. The optical engineering and research challenges in developing the dual/multi-modality platforms will be discussed, followed by initial results validating the proposed scheme. The proposed schemes offer high spatial and spectral resolution imaging and sensing, and is expected to offer potential biomedical imaging solutions in the near future.

Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study.

PubMed

Allison, Kimberly H; Rendi, Mara H; Peacock, Sue; Morgan, Tom; Elmore, Joann G; Weaver, Donald L

2016-12-01

This study examined the case-specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast. Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histological features, which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists' perceptions of case difficulty, borderline features or whether they would obtain a second opinion were also examined for associations with agreement. Of the 2070 participant interpretations of the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (P < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (P < 0.001). Diagnostic agreement ranged from 10% to 89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytological monotony were associated with higher agreement. Lower agreement rates were associated with solid or micropapillary architecture, borderline cytological monotony, or cases without a diagnostic area that was obvious on low power. The results of this study suggest that pathologists frequently recognize the challenge of ADH cases, with some cases being more prone to diagnostic variability. In addition, there are specific histological features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. © 2016 John Wiley & Sons Ltd.

Histologic Features associated with Diagnostic Agreement in Atypical Ductal Hyperplasia of the Breast: Illustrative Cases from the B-Path Study

PubMed Central

Allison, Kimberly H.; Rendi, Mara H.; Peacock, Sue; Morgan, Tom; Elmore, Joann G.; Weaver, Donald L.

2016-01-01

Background Case specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast are poorly understood. Methods Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histologic features which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists’ perceptions of case difficulty, borderline features, or if they would obtain a second opinion were also examined for associations with agreement. Results Of the 2,070 participant interpretations on the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (p < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (p < 0.001). Diagnostic agreement ranged from 10–89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytologic monotony were associated with higher agreement. Lower agreement rates were associated with solid or micro-papillary architecture, borderline cytologic monotony or cases without a diagnostic area that was obvious on low power. Conclusions The results of this study suggest that pathologists frequently recognize the challenge of ADH cases with some cases more prone to diagnostic variability. In addition, there are specific histologic features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. PMID:27398812

Attention Deficit Disorder: Diagnosis, Etiology and Treatment.

ERIC Educational Resources Information Center

Barabasz, Marianne; Barabasz, Arreed

1996-01-01

Provides most recent information on attention deficit disorder including: (1) diagnostic considerations according to the latest behavioral criteria and breakthroughs using neurometric EEG assessment; (2) prevalence; (3) etiologies; (4) neurological basis; and (5) treatments. Evaluates alternatives to medication, behavior modification, cognitive…

Dosimetric considerations in dental applications

NASA Technical Reports Server (NTRS)

Goble, J. C.

1978-01-01

The integration of the Lixiscope into dental procedures was studied and compared with conventional dental radiographic techniques. It was found that through the use of intraoral sealed sources in conjunction with microchannel plate technology, the Lixiscope gives increased diagnostic information with decreased radiation dosage.

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

How Many People have Alcohol Use Disorders? Using the Harmful Dysfunction Analysis to Reconcile Prevalence Estimates in Two Community Surveys

PubMed Central

Wakefield, Jerome C.; Schmitz, Mark F.

2014-01-01

Community prevalence rates of alcohol use disorders (AUDs) provided by epidemiological studies using DSM-based diagnostic criteria pose several challenges: the rates appear implausibly high to many epidemiologists; they do not converge across similar studies; and, due to low service utilization by those diagnosed as disordered, they yield estimates of unmet need for services so high that credibility for planning purposes is jeopardized. For example, two early community studies using DSM diagnostic criteria, the Epidemiologic Catchment Area Study (ECA) and the National Comorbidity Survey (NCS), yielded lifetime AUD prevalence rates of 14 and 24%, respectively, with NCS unmet need for services 19% of the entire population. Attempts to address these challenges by adding clinical significance requirements to diagnostic criteria have proven unsuccessful. Hypothesizing that these challenges are due to high rates of false-positive diagnoses of problem drinking as AUDs, we test an alternative approach. We use the harmful dysfunction (HD) analysis of the concept of mental disorder as a guide to construct more valid criteria within the framework of the standard out-of-control model of AUD. The proposed HD criteria require harm and dysfunction, where harm can be any negative social, personal, or physical outcome, and dysfunction requires either withdrawal symptoms or inability to stop drinking. Using HD criteria, ECA and NCS lifetime prevalences converge to much-reduced rates of 6 and 6.8%, respectively. Due to higher service utilization rates, NCS lifetime unmet need is reduced to 3.4%. Service use and duration comparisons suggest that HD criteria possess increased diagnostic validity. Moreover, HD criteria eliminate 90% of transient teenage drinking from disorder status. The HD version of the out-of-control model thus potentially resolves the three classic prevalence challenges while offering a more rigorous approach to distinguishing AUDs from problematic drinking. PMID:24550847

INTRA-UNDULATOR MEASUREMENTS AT VISA FEL.

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

MUROKH,A.; FRIGOLA,P.; ET AL

2000-08-13

We describe a diagnostics system developed, to measure exponential gain properties and the electron beam dynamics inside the strong focusing 4-m long undulator for the VISA (Visible to Infrared SASE Amplifier) FEL. The technical challenges included working inside the small undulator gap, optimizing the electron beam diagnostics in the high background environment of the spontaneous undulator radiation, multiplexing and transporting the photon beam. Initial results are discussed.

Intra-undulator measurements at VISA FEL

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

Murokh, A; Frigola, P; Pellegrini, C

2000-08-10

We describe a diagnostics system developed, to measure exponential gain properties and the electron beam dynamics inside the strong focusing 4-m long undulator for the VISA (Visible to Infrared SASE Amplifier) FEL. The technical challenges included working inside the small undulator gap, optimizing the electron beam diagnostics in the high background environment of the spontaneous undulator radiation, multiplexing and transporting the photon beam. Initial results are discussed.

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

A crying baby: not simply infant colic.

PubMed

Onesimo, Roberta; Giorgio, Valentina; Monaco, Serena; Fundarò, Carlo

2012-08-21

Hypertrophic pyloric stenosis is a relatively common condition, but atypical presentations can present a diagnostic challenge. We describe the case of a 9-week-old Latin male infant who presented with a 2-day history of intermittent crying and poor feeding. He was suspected to have intussusception but was affected by and successfully treated for hypertrophic pyloric stenosis. Diagnostic tools of atypical HPS cases are discussed.

Reliability of criteria for borderline personality disorder: a comparison of DSM-III and the Diagnostic Interview for Borderline Patients.

PubMed

Frances, A; Clarkin, J F; Gilmore, M; Hurt, S W; Brown, R

1984-09-01

The authors compared the reliability of two methods of distinguishing borderline personality disorder--DSM-III and the Diagnostic Interview for Borderline Patients. The reference group, outpatients with other personality disorders and without major axis I pathology, was more difficult to distinguish from the patients with borderline personality disorder than such groups used in previous samples. The sensitivity and specificity of the Diagnostic Interview for Borderline Patients were calculated, with DSM-III used as a criterion. The findings confirm considerable overlap between borderline and schizotypal personality disorders, more impairment in functioning in borderline patients than in those with other personality disorders, and the high reliability with which borderline personality disorder can be diagnosed.

Dissecting aneurysms of posterior communicating artery itself: anatomical, diagnostic, clinical, and therapeutical considerations.

PubMed

Kocak, Burak; Tureci, Ercan; Kizilkilic, Osman; Islak, Civan; Kocer, Naci

2013-09-01

Posterior communicating artery (PCoA) itself is an unusual location for intracranial aneurysms in that isolated dissections or dissecting aneurysms are extremely rare. In the way of correct diagnosis of dissecting aneurysms of PCoA itself, a proper understanding of (1) the anatomy of the PCoA and its perforator branches, (2) some particular diagnostic features, and (3) related clinical aspects is of significant importance. Although there are no established treatment strategies for this particular type of aneurysms, the endovascular approach might be considered as a plausible one. In this paper, our scope was to report five cases with dissecting aneurysm of the PCoA itself and to discuss this rare vascular pathology from anatomical, diagnostic, clinical, and therapeutical perspectives.

Laser diagnostics for combustion temperature and species

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

Eckbreth, A.C.

1987-01-01

Laser approaches to combustion diagnostics are of considerable interest due to their remote, nonintrusive and in-situ character, unlimited temperature capability and potential for simultaneous temporal and spatial resolution, This book aims to make these powerful and important new tools in combustion research understandable. The focus of this text is on spectroscopically-based, spatially-precise laser techniques for temperature and chemical composition measurements in reacting and nonreacting flows. After introductory chapters providing a fundamental theoretical and experimental background, attention is directed to diagnostics based upon spontaneous Raman and Rayleigh scattering, coherent anti-Stokes Raman spectroscopy (CARS) and laser-induced fluorescence (LIFS). The book concludes withmore » a treatment of techniques which permit spatially-resolved measurements over an entire two-dimensional field simultaneously.« less

Loeffler 4.0: Diagnostic Metagenomics.

PubMed

Höper, Dirk; Wylezich, Claudia; Beer, Martin

2017-01-01

A new world of possibilities for "virus discovery" was opened up with high-throughput sequencing becoming available in the last decade. While scientifically metagenomic analysis was established before the start of the era of high-throughput sequencing, the availability of the first second-generation sequencers was the kick-off for diagnosticians to use sequencing for the detection of novel pathogens. Today, diagnostic metagenomics is becoming the standard procedure for the detection and genetic characterization of new viruses or novel virus variants. Here, we provide an overview about technical considerations of high-throughput sequencing-based diagnostic metagenomics together with selected examples of "virus discovery" for animal diseases or zoonoses and metagenomics for food safety or basic veterinary research. © 2017 Elsevier Inc. All rights reserved.

Diagnostic methods for atmospheric inversions of long-lived greenhouse gases

NASA Astrophysics Data System (ADS)

Michalak, Anna M.; Randazzo, Nina A.; Chevallier, Frédéric

2017-06-01

The ability to predict the trajectory of climate change requires a clear understanding of the emissions and uptake (i.e., surface fluxes) of long-lived greenhouse gases (GHGs). Furthermore, the development of climate policies is driving a need to constrain the budgets of anthropogenic GHG emissions. Inverse problems that couple atmospheric observations of GHG concentrations with an atmospheric chemistry and transport model have increasingly been used to gain insights into surface fluxes. Given the inherent technical challenges associated with their solution, it is imperative that objective approaches exist for the evaluation of such inverse problems. Because direct observation of fluxes at compatible spatiotemporal scales is rarely possible, diagnostics tools must rely on indirect measures. Here we review diagnostics that have been implemented in recent studies and discuss their use in informing adjustments to model setup. We group the diagnostics along a continuum starting with those that are most closely related to the scientific question being targeted, and ending with those most closely tied to the statistical and computational setup of the inversion. We thus begin with diagnostics based on assessments against independent information (e.g., unused atmospheric observations, large-scale scientific constraints), followed by statistical diagnostics of inversion results, diagnostics based on sensitivity tests, and analyses of robustness (e.g., tests focusing on the chemistry and transport model, the atmospheric observations, or the statistical and computational framework), and close with the use of synthetic data experiments (i.e., observing system simulation experiments, OSSEs). We find that existing diagnostics provide a crucial toolbox for evaluating and improving flux estimates but, not surprisingly, cannot overcome the fundamental challenges associated with limited atmospheric observations or the lack of direct flux measurements at compatible scales. As atmospheric inversions are increasingly expected to contribute to national reporting of GHG emissions, the need for developing and implementing robust and transparent evaluation approaches will only grow.

[Developmental abnormalities and nevi of the scalp].

PubMed

Behle, V; Hamm, H

2014-12-01

Unusual congenital or early-onset skin lesions on the scalp often pose a diagnostic challenge particularly as the clinical evaluation may be hampered by dense hair growth. Thus, this paper provides a concise review on developmental abnormalities and nevi with exclusive or predominant scalp localization. Aplasia cutis congenita occurs as an isolated finding, in association with genetic syndromes, nevi and anomalies or as a consequence of intrauterine trauma and teratogens. A hairless area with a narrow surrounding rim of hypertrichosis (hair collar sign) may point to occult cranial dysraphism, especially if accompanied by further suggestive signs as port-wine stains, large hemangiomas, dimples, congenital dermoid cysts, and sinuses. Many diverse entities may hide behind cutis verticis gyrata with the primary essential form being rare and representing a diagnosis of exclusion. In contrast to former belief, benign adnexal tumors arise in a nevus sebaceus considerably more often than basal cell carcinomas and other malignant epithelial tumors. Provided that tumor development is not suspected, excision of a nevus sebaceus nevus is indicated primarily for aesthetic-psychosocial reasons. However, surgical treatment is considerably easier in small children. Nevus sebaceus may be a cutaneous marker for several complex syndromes whereas nevus psiloliparus presents almost always in connection with encephalocraniocutaneous lipomatosis. Congenital melanocytic nevi of the scalp tend toward clinical regression, so that surgical intervention in large lesions should be carefully considered. In contrast, the threshold for excision of blue nevi and other conspicuous melanocytic nevi on the scalp should be low, especially since they are difficult to monitor.

The evolution of endometrial carcinoma classification through application of immunohistochemistry and molecular diagnostics: past, present and future.

PubMed

Goebel, Emily A; Vidal, August; Matias-Guiu, Xavier; Blake Gilks, C

2017-12-12

Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours. There followed studies of immunomarkers and then mutational studies of single genes, in attempts to improve subclassification. While these have revealed significant differences in protein expression and mutation profiles between endometrioid and serous carcinomas, there is also considerable overlap, so that there remain challenges in subclassification of endometrial carcinoma. Gene panel testing, using next-generation sequencing, was applied to endometrial cancers and highlighted that there are tumours that show genetic alterations intermediate between classic Type I/endometrioid and Type II/serous carcinomas. The Cancer Genome Atlas studies of endometrioid and serous carcinoma offered revolutionary insight into the subclassification of endometrial carcinoma, i.e. that there are four distinct categories of endometrial carcinoma, rather than two, based on genomic architecture. In this review, we provide an overview of immunohistochemical and molecular markers in endometrial carcinoma and comment on the important future directions in endometrial carcinoma subclassification arising from The Cancer Genome Atlas results.

The Challenge and Challenging of Childhood Studies? Learning from Disability Studies and Research with Disabled Children

ERIC Educational Resources Information Center

Tisdall, E. Kay M.

2012-01-01

Childhood studies have argued for the social construction of childhood, respecting children and childhood in the present, and recognising children's agency and rights. Such perspectives have parallels to, and challenges for, disability studies. This article considers such parallels and challenges, leading to a (re)consideration of research claims…

A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

PubMed

Smith, Cartney E; Shkumatov, Artem; Withers, Sarah G; Yang, Binxia; Glockner, James F; Misra, Sanjay; Roy, Edward J; Wong, Chun-Ho; Zimmerman, Steven C; Kong, Hyunjoon

2013-11-26

Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.

Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature

PubMed Central

Abrams, Daniel J; Rojas, Donald C; Arciniegas, David B

2008-01-01

Considerable debate surrounds the inclusion of schizoaffective disorder in psychiatric nosology. Schizoaffective disorder may be a variant of schizophrenia in which mood symptoms are unusually prominent but not unusual in type. This condition may instead reflect a severe form of either major depressive or bipolar disorder in which episode-related psychotic symptoms fail to remit completely between mood episodes. Alternatively, schizoaffective disorder may reflect the co-occurrence of two relatively common psychiatric illnesses, schizophrenia and a mood disorder (major depressive or bipolar disorder). Each of these formulations of schizoaffective disorder presents nosological challenges because the signs and symptoms of this condition cross conventional categorical diagnostic boundaries between psychotic disorders and mood disorders. The study, evaluation, and treatment of persons presently diagnosed with schizoaffective may be more usefully informed by a dimensional approach. It is in this context that this article reviews and contrasts the categorical and dimensional approaches to its description, neurobiology, and treatment. Based on this review, an argument for the study and treatment of this condition using a dimensional approach is offered. PMID:19337453