The Inextricable Axis Of Targeted Diagnostic Imaging And Therapy: An Immunological Natural History Approach

PubMed Central

Cope, FO; Abbruzzese, B; Sanders, J; Metz, W; Sturms, K; Ralph, D; Blue, M; Zhang, J; Bracci, P; Bshara, W; Behr, S; Maurer, T; Beverly, A; Blay, B; Damughatla, A; Larsen, M; Mountain, C; Neylon, E; Parcel, K; Raghuraman, K; Ricks, K; Rose, L; Sivakumar, A; Streck, N; Wang, B; Wasco, C; Williams, A; McGrath, M

2016-01-01

Summary In considering the challenges of approaches to clinical imaging, we are faced with choices that sometimes are impacted by rather dogmatic notions about what is a better or worse technology to achieve the most useful diagnostic image for the patient. For example, is PET or SPECT most useful in imaging any particular disease dissemination? The dictatorial approach would be to choose PET, all other matters being equal. But is such a totalitarian attitude toward imaging selection still valid? In the face of new receptor targeted SPECT agents one must consider the remarkable specificity and sensitivity of these agents. 99mTc-Tilmanocept is one of the newest of these agents, now approved for guiding sentinel node biopsy (SLNB) in several solid tumors. Tilmanocept has a Kd of 3×10−11 M, and it specificity for the CD206 receptor is unlike any other agent to date. This coupled with a number of facts, that specific disease-associated macrophages express this receptor (100 to 150 thousand receptors), the receptor has multiple binding sites for tilmanocept (>2 sites per receptor) and that these receptors are recycled every 15 minutes to bind more tilmanocept (acting as intracellular “drug compilers” of tilmanocept into non-degraded vesicles), give serious pause as to how we select our approaches to diagnostic imaging. Clinically, the size of SLNs varies greatly, some, anatomically, below the machine resolution of SPECT. Yet, with tilmanocept targeting, the SLNs are highly visible with macrophages stably accruing adequate 99mTc-tilmanocept counting statistics, as high target-to-background ratios can compensate for spatial resolution blurring. Importantly, it may be targeted imaging agents per se, again such as tilmanocept, which may significantly shrink any perceived chasm between the imaging technologies and anchor the diagnostic considerations in the targeting and specificity of the agent rather than any lingering dogma about the hardware as the basis for

The inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach.

PubMed

Cope, Frederick O; Abbruzzese, Bonnie; Sanders, James; Metz, Wendy; Sturms, Kristyn; Ralph, David; Blue, Michael; Zhang, Jane; Bracci, Paige; Bshara, Wiam; Behr, Spencer; Maurer, Toby; Williams, Kenneth; Walker, Joshua; Beverly, Allison; Blay, Brooke; Damughatla, Anirudh; Larsen, Mark; Mountain, Courtney; Neylon, Erin; Parcel, Kaeli; Raghuraman, Kapil; Ricks, Kevin; Rose, Lucas; Sivakumar, Akhilesh; Streck, Nicholas; Wang, Bryan; Wasco, Christopher; Williams, Amifred; McGrath, Michael

2016-03-01

In considering the challenges of approaches to clinical imaging, we are faced with choices that sometimes are impacted by rather dogmatic notions about what is a better or worse technology to achieve the most useful diagnostic image for the patient. For example, is PET or SPECT most useful in imaging any particular disease dissemination? The dictatorial approach would be to choose PET, all other matters being equal. But is such a totalitarian attitude toward imaging selection still valid? In the face of new receptor targeted SPECT agents one must consider the remarkable specificity and sensitivity of these agents. (99m)Tc-Tilmanocept is one of the newest of these agents, now approved for guiding sentinel node biopsy (SLNB) in several solid tumors. Tilmanocept has a Kd of 3×10(-11)M, and it specificity for the CD206 receptor is unlike any other agent to date. This coupled with a number of facts, that specific disease-associated macrophages express this receptor (100 to 150 thousand receptors), that the receptor has multiple binding sites for tilmanocept (>2 sites per receptor) and that these receptors are recycled every 15 min to bind more tilmanocept (acting as intracellular "drug compilers" of tilmanocept into non-degraded vesicles), gives serious pause as to how we select our approaches to diagnostic imaging. Clinically, the size of SLNs varies greatly, some, anatomically, below the machine resolution of SPECT. Yet, with tilmanocept targeting, the SLNs are highly visible with macrophages stably accruing adequate (99m)Tc-tilmanocept counting statistics, as high target-to-background ratios can compensate for spatial resolution blurring. Importantly, it may be targeted imaging agents per se, again such as tilmanocept, which may significantly shrink any perceived chasm between the imaging technologies and anchor the diagnostic considerations in the targeting and specificity of the agent rather than any lingering dogma about the hardware as the basis for imaging

Matrix metalloproteinases in cancer: their value as diagnostic and prognostic markers and therapeutic targets.

PubMed

Hadler-Olsen, Elin; Winberg, Jan-Olof; Uhlin-Hansen, Lars

2013-08-01

Biomarkers are used as tools in cancer diagnostics and in treatment stratification. In most cancers, there are increased levels of one or several members of the matrix metalloproteinases (MMPs). This is a family of proteolytic enzymes that are involved in many phases of cancer progression, including angiogenesis, invasiveness, and metastasis. It has therefore been expected that MMPs could serve as both diagnostic and prognostic markers in cancer patients, but despite a huge number of studies, it has been difficult to establish MMPs as cancer biomarkers. In the present paper, we assess some of the challenges associated with MMP research as well as putative reasons for the conflicting data on the value of these enzymes as diagnostic and prognostic markers in cancer patients. We also review the prognostic value of a number of MMPs in patients with lung, colorectal, breast, and prostate cancers. The review also discusses MMPs as potential target molecules for therapeutic agents and new strategies for development of such drugs.

Nouveaux supraconducteurs à haute température critique à base de mercure

NASA Astrophysics Data System (ADS)

Michel, C.; Hervieu, M.; Martin, C.; Maignan, A.; Pelloquin, D.; Goutenoire, F.; Huvé, M.; Raveau, B.

1994-11-01

Structural and superconducting properties of new cations substituted mercury based oxides are described. They are mainly characterized by [ Hg{1-x}MxOδ] infty monolayers, however a compound with doubled [ Hg{1-x}MxOδ] infty layer is described for the first time. Critical temperatures vary in a large range 0leqslant T_cleqslant 130 K, but they are lower than those of related to pure mercury oxides. The influence of annealings in various atmospheres upon T_c is discussed. Les caractéristiques structurales et supraconductrices de nouveaux oxydes à base de mercure, dans lesquels le mercure est partiellement remplacé par un autre cation, sont décrites. Dans la majorité des cas, ces oxydes sont caractérisés par une monocouche [ Hg{1-x}MxOδ] infty ; cependant, pour la première fois un composé contenant une double couche majoritaire en mercure est isolé. Les températures critiques varient dans un large domaine (0-130 K) mais restent inférieures à celles des oxydes parents ll tout mercure gg. L'influence des recuits sous des atmosphères diverses est discutée.

[Prostate cancer diagnostic by saturation randomized biopsy versus rigid targeted biopsy].

PubMed

Defontaines, J; Salomon, L; Champy, C; Cholley, I; Chiaradia, M; de la Taille, A

2017-12-01

Optimal diagram teaming up randomized biopsy (BR) to targeted biopsy (BC) is still missing for the diagnostic of prostate cancer (CP). This study compares diagram of 6, 12 or 18 BR with or without BC rigid. Between January 2014 and May 2016, 120 patients had prostate biopsy BR and BC. Each patient had 18 BR and BC. Results compared sextant (6 BR), standard (12 BR) and saturation (18 BR) protocol with or without the adding of BC for the detection of CP. Rectal examination was normal, mean PSA at 8.99ng/mL and mean volume at 54cm 3 . It was first round for 48% of patients. Forty-four cancers were found by the group 18 BR+BC (control). The detection rate was respectively, for 6, 12 and 18 BR of 61%, 82% and 91%. The add of BC increased this detection of +27% for 6 BR+BC, +13% for 12 BR+BC and +9% for 18 BR+BC. BC found 70% of all CP. Nine percent of CP were missed by BR only. Significant CP (Gleason≥7) diagnostic was the same for 12 BR+BC and 18 BR+BC. The add of BC to BR increase the detection of CP by 10%. Twelve BR+BC is the optimal diagram for the diagnostic of CP finding 95% of CP and 97% of significant CP. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

panelcn.MOPS: Copy-number detection in targeted NGS panel data for clinical diagnostics.

PubMed

Povysil, Gundula; Tzika, Antigoni; Vogt, Julia; Haunschmid, Verena; Messiaen, Ludwine; Zschocke, Johannes; Klambauer, Günter; Hochreiter, Sepp; Wimmer, Katharina

2017-07-01

Targeted next-generation-sequencing (NGS) panels have largely replaced Sanger sequencing in clinical diagnostics. They allow for the detection of copy-number variations (CNVs) in addition to single-nucleotide variants and small insertions/deletions. However, existing computational CNV detection methods have shortcomings regarding accuracy, quality control (QC), incidental findings, and user-friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS with five state-of-the-art methods. With panelcn.MOPS leading the field, most methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs ranging in size from part of a region of interest (ROI), to whole genes, which may comprise all ROIs investigated in a given sample. The latter is enabled by analyzing reads from all ROIs of the panel, but presenting results exclusively for user-selected genes, thus avoiding incidental findings. Additionally, panelcn.MOPS offers QC criteria not only for samples, but also for individual ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS is freely available both as R package and standalone software with graphical user interface that is easy to use for clinical geneticists without any programming experience. panelcn.MOPS combines high sensitivity and specificity with user-friendliness rendering it highly suitable for routine clinical diagnostics. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

panelcn.MOPS: Copy‐number detection in targeted NGS panel data for clinical diagnostics

PubMed Central

Povysil, Gundula; Tzika, Antigoni; Vogt, Julia; Haunschmid, Verena; Messiaen, Ludwine; Zschocke, Johannes; Klambauer, Günter; Wimmer, Katharina

2017-01-01

Abstract Targeted next‐generation‐sequencing (NGS) panels have largely replaced Sanger sequencing in clinical diagnostics. They allow for the detection of copy‐number variations (CNVs) in addition to single‐nucleotide variants and small insertions/deletions. However, existing computational CNV detection methods have shortcomings regarding accuracy, quality control (QC), incidental findings, and user‐friendliness. We developed panelcn.MOPS, a novel pipeline for detecting CNVs in targeted NGS panel data. Using data from 180 samples, we compared panelcn.MOPS with five state‐of‐the‐art methods. With panelcn.MOPS leading the field, most methods achieved comparably high accuracy. panelcn.MOPS reliably detected CNVs ranging in size from part of a region of interest (ROI), to whole genes, which may comprise all ROIs investigated in a given sample. The latter is enabled by analyzing reads from all ROIs of the panel, but presenting results exclusively for user‐selected genes, thus avoiding incidental findings. Additionally, panelcn.MOPS offers QC criteria not only for samples, but also for individual ROIs within a sample, which increases the confidence in called CNVs. panelcn.MOPS is freely available both as R package and standalone software with graphical user interface that is easy to use for clinical geneticists without any programming experience. panelcn.MOPS combines high sensitivity and specificity with user‐friendliness rendering it highly suitable for routine clinical diagnostics. PMID:28449315

Development of companion diagnostics

DOE PAGES

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.; ...

2015-12-12

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods asmore » companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. Lastly, the review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic.« less

Development of companion diagnostics

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

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods asmore » companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. Lastly, the review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic.« less

Development of Companion Diagnostics

PubMed Central

Mankoff, David A.; Edmonds, Christine E.; Farwell, Michael D.; Pryma, Daniel A.

2016-01-01

The goal of individualized and targeted treatment and precision medicine requires the assessment of potential therapeutic targets to direct treatment selection. The biomarkers used to direct precision medicine, often termed companion diagnostics, for highly targeted drugs have thus far been almost entirely based on in vitro assay of biopsy material. Molecular imaging companion diagnostics offer a number of features complementary to those from in vitro assay, including the ability to measure the heterogeneity of each patient’s cancer across the entire disease burden and to measure early changes in response to treatment. We discuss the use of molecular imaging methods as companion diagnostics for cancer therapy with the goal of predicting response to targeted therapy and measuring early (pharmacodynamic) response as an indication of whether the treatment has “hit” the target. We also discuss considerations for probe development for molecular imaging companion diagnostics, including both small-molecule probes and larger molecules such as labeled antibodies and related constructs. We then describe two examples where both predictive and pharmacodynamic molecular imaging markers have been tested in humans: endocrine therapy for breast cancer and human epidermal growth factor receptor type 2–targeted therapy. The review closes with a summary of the items needed to move molecular imaging companion diagnostics from early studies into multicenter trials and into the clinic. PMID:26687857

Nanomedicine: nanoparticles, molecular biosensors, and targeted gene/drug delivery for combined single-cell diagnostics and therapeutics

NASA Astrophysics Data System (ADS)

Prow, Tarl W.; Salazar, Jose H.; Rose, William A.; Smith, Jacob N.; Reece, Lisa; Fontenot, Andrea A.; Wang, Nan A.; Lloyd, R. Stephen; Leary, James F.

2004-07-01

Next generation nanomedicine technologies are being developed to provide for continuous and linked molecular diagnostics and therapeutics. Research is being performed to develop "sentinel nanoparticles" which will seek out diseased (e.g. cancerous) cells, enter those living cells, and either perform repairs or induce those cells to die through apoptosis. These nanoparticles are envisioned as multifunctional "smart drug delivery systems". The nanosystems are being developed as multilayered nanoparticles (nanocrystals, nanocapsules) containing cell targeting molecules, intracellular re-targeting molecules, molecular biosensor molecules, and drugs/enzymes/gene therapy. These "nanomedicine systems" are being constructed to be autonomous, much like present-day vaccines, but will have sophisticated targeting, sensing, and feedback control systems-much more sophisticated than conventional antibody-based therapies. The fundamental concept of nanomedicine is to not to just kill all aberrant cells by surgery, radiation therapy, or chemotherapy. Rather it is to fix cells, when appropriate, one cell-at-a-time, to preserve and re-build organ systems. When cells should not be fixed, such as in cases where an improperly repaired cell might give rise to cancer cells, the nanomedical therapy would be to induce apoptosis in those cells to eliminate them without the damagin bystander effects of the inflammatory immune response system reacting to necrotic cells or those which have died from trauma or injury. The ultimate aim of nanomedicine is to combine diagnostics and therapeutics into "real-time medicine", using where possible in-vivo cytometry techniques for diagnostics and therapeutics. A number of individual components of these multi-component nanoparticles are already working in in-vitro and ex-vivo cell and tissue systems. Work has begun on construction of integrated nanomedical systems.

Development of a Targeted Next-Generation Sequencing Assay to Detect Diagnostically Relevant Mutations of JAK2, CALR, and MPL in Myeloproliferative Neoplasms.

PubMed

Frawley, Thomas; O'Brien, Cathal P; Conneally, Eibhlin; Vandenberghe, Elisabeth; Percy, Melanie; Langabeer, Stephen E; Haslam, Karl

2018-02-01

The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of mutations in these genes has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for mutations in these genes in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms. Polymerase chain reaction (PCR) primers were designed to target mutation hotspots in JAK2 exon 14, JAK2 exon 12, MPL exon 10, and CALR exon 9. Multiplexed PCR conditions were optimized by using qualitative PCR followed by NGS. Diagnostic genomic DNA from 35 MPN patients, known to harbor driver mutations in one of the target genes, was used to validate the assay. One hundred percent concordance was observed between the previously-identified mutations and those detected by NGS, with no false positives, nor any known mutations missed (specificity = 100%, CI = 0.96, sensitivity = 100%, CI = 0.89). Improved resolution of mutation sequences was also revealed by NGS analysis. Detection of diagnostically relevant driver mutations of MPN is enhanced by employing a targeted multiplex NGS approach. This assay presents a robust solution to classical MPN mutation screening, providing an alternative to time-consuming sequential analyses.

Modeling companion diagnostics in economic evaluations of targeted oncology therapies: systematic review and methodological checklist.

PubMed

Doble, Brett; Tan, Marcus; Harris, Anthony; Lorgelly, Paula

2015-02-01

The successful use of a targeted therapy is intrinsically linked to the ability of a companion diagnostic to correctly identify patients most likely to benefit from treatment. The aim of this study was to review the characteristics of companion diagnostics that are of importance for inclusion in an economic evaluation. Approaches for including these characteristics in model-based economic evaluations are compared with the intent to describe best practice methods. Five databases and government agency websites were searched to identify model-based economic evaluations comparing a companion diagnostic and subsequent treatment strategy to another alternative treatment strategy with model parameters for the sensitivity and specificity of the companion diagnostic (primary synthesis). Economic evaluations that limited model parameters for the companion diagnostic to only its cost were also identified (secondary synthesis). Quality was assessed using the Quality of Health Economic Studies instrument. 30 studies were included in the review (primary synthesis n = 12; secondary synthesis n = 18). Incremental cost-effectiveness ratios may be lower when the only parameter for the companion diagnostic included in a model is the cost of testing. Incorporating the test's accuracy in addition to its cost may be a more appropriate methodological approach. Altering the prevalence of the genetic biomarker, specific population tested, type of test, test accuracy and timing/sequence of multiple tests can all impact overall model results. The impact of altering a test's threshold for positivity is unknown as it was not addressed in any of the included studies. Additional quality criteria as outlined in our methodological checklist should be considered due to the shortcomings of standard quality assessment tools in differentiating studies that incorporate important test-related characteristics and those that do not. There is a need to refine methods for incorporating the characteristics

Optical diagnostics of mercury jet for an intense proton target.

PubMed

Park, H; Tsang, T; Kirk, H G; Ladeinde, F; Graves, V B; Spampinato, P T; Carroll, A J; Titus, P H; McDonald, K T

2008-04-01

An optical diagnostic system is designed and constructed for imaging a free mercury jet interacting with a high intensity proton beam in a pulsed high-field solenoid magnet. The optical imaging system employs a backilluminated, laser shadow photography technique. Object illumination and image capture are transmitted through radiation-hard multimode optical fibers and flexible coherent imaging fibers. A retroreflected illumination design allows the entire passive imaging system to fit inside the bore of the solenoid magnet. A sequence of synchronized short laser light pulses are used to freeze the transient events, and the images are recorded by several high speed charge coupled devices. Quantitative and qualitative data analysis using image processing based on probability approach is described. The characteristics of free mercury jet as a high power target for beam-jet interaction at various levels of the magnetic induction field is reported in this paper.

Effects of target heating on experiments using Kα and Kβ diagnostics.

PubMed

Palmeri, P; Boutoux, G; Batani, D; Quinet, P

2015-09-01

We describe the impact of heating and ionization on emission from the target of Kα and Kβ radiation induced by the propagation of hot electrons generated by laser-matter interaction. We consider copper as a test case and, starting from basic principles, we calculate the changes in emission wavelength, ionization cross section, and fluorescence yield as Cu is progressively ionized. We have finally considered the more realistic case when hot electrons have a distribution of energies with average energies of 50 and 500 keV (representative respectively of "shock ignition" and of "fast ignition" experiments) and in which the ions are distributed according to ionization equilibrium. In addition, by confronting our theoretical calculations with existing data, we demonstrate that this study offers a generic theoretical background for temperature diagnostics in laser-plasma interactions.

Using Targeted Active-Learning Exercises and Diagnostic Question Clusters to Improve Students' Understanding of Carbon Cycling in Ecosystems

ERIC Educational Resources Information Center

Maskiewicz, April Cordero; Griscom, Heather Peckham; Welch, Nicole Turrill

2012-01-01

In this study, we used targeted active-learning activities to help students improve their ways of reasoning about carbon flow in ecosystems. The results of a validated ecology conceptual inventory (diagnostic question clusters [DQCs]) provided us with information about students' understanding of and reasoning about transformation of inorganic and…

Neutral Beam Source and Target Plasma for Development of a Local Electric Field Fluctuation Diagnostic

NASA Astrophysics Data System (ADS)

Bakken, M. R.; Burke, M. G.; Fonck, R. J.; Lewicki, B. T.; Rhodes, A. T.; Winz, G. R.

2016-10-01

A new diagnostic measuring local E-> (r , t) fluctuations is being developed for plasma turbulence studies in tokamaks. This is accomplished by measuring fluctuations in the separation of the π components in the Hα motional Stark spectrum. Fluctuations in this separation are expected to be Ẽ / ẼEMSE 10-3EMSE 10-3 . In addition to a high throughput, high speed spectrometer, the project requires a low divergence (Ω 0 .5°) , 80 keV, 2.5 A H0 beam and a target plasma test stand. The beam employs a washer-stack arc ion source to achieve a high species fraction at full energy. Laboratory tests of the ion source demonstrate repeatable plasmas with Te 10 eV and ne 1.6 ×1017 m-3, sufficient for the beam ion optics requirements. Te and ne scalings of the ion source plasma are presented with respect to operational parameters. A novel three-phase resonant converter power supply will provide 6 mA/cm2 of 80 keV H0 at the focal plane for pulse lengths up to 15 ms, with low ripple δV / 80 keV 0.05 % at 280 kHz. Diagnostic development and validation tests will be performed on a magnetized plasma test stand with 0.5 T field. The test chamber will utilize a washer-stack arc source to produce a target plasma comparable to edge tokamak plasmas. A bias-plate with programmable power supply will be used to impose Ẽ within the target plasma. Work supported by US DOE Grant DE-FG02-89ER53296.

A distributed computational search strategy for the identification of diagnostics targets: application to finding aptamer targets for methicillin-resistant staphylococci.

PubMed

Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

2014-06-30

The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

A distributed computational search strategy for the identification of diagnostics targets: Application to finding aptamer targets for methicillin-resistant staphylococci.

PubMed

Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

2014-06-01

The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

Etudes optiques de nouveaux materiaux laser: Des orthosilicates dopes a l'ytterbium: Le yttrium (lutetium,scandium) pentoxide de silicium

NASA Astrophysics Data System (ADS)

Denoyer, Aurelie

La decouverte et l'elaboration de nouveaux materiaux laser solides suscitent beaucoup d'interet parmi la communaute scientifique. En particulier les lasers dans la gamme de frequence du micron debouchent sur beaucoup d'applications, en telecommunication, en medecine, dans le domaine militaire, pour la, decoupe des metaux (lasers de puissance), en optique non lineaire (doublage de frequence, bistabilite optique). Le plus couramment utilise actuellement est le Nd:YAG dans cette famille de laser, mais des remplacants plus performants sont toujours recherches. Les lasers a base d'Yb3+ possedent beaucoup d'avantages compares aux lasers Nd3+ du fait de leur structure electronique simple et de leur deterioration moins rapide. Parmi les matrices cristallines pouvant accueillir l'ytterbium, les orthosilicates Yb:Y 2SiO5, Yb:Lu2SiO5 et Yb:Sc2SiO 5 se positionnent tres bien, du fait de leur bonne conductivite thermique et du fort eclatement de leur champ cristallin necessaire a l'elaboration de lasers quasi-3 niveaux. De plus l'etude fine et systematique des proprietes microscopiques de nouveaux materiaux s'avere toujours tres interessante du point de vue de la recherche fondamentale, c'est ainsi que de nouveaux modeles sont concus (par exemple pour le champ cristallin) ou que de nouvelles proprietes inhabituelles sont decouvertes, menant a de nouvelles applications. Ainsi d'autres materiaux dopes a l'ytterbium sont connus pour leurs proprietes de couplage electron-phonon, de couplage magnetique, d'emission cooperative ou encore de bistabilite optique, mais ces proprietes n'ont encore jamais ete mises en evidence dans Yb:Y 2SiO5, Yb:Lu2SiO5 et Yb:Sc2SiO 5. Ainsi, cette these a pour but l'etude des proprietes optiques et des interactions microscopiques dans Yb:Y2SiO 5, Yb:Lu2SiO5 et Yb:Sc2SiO5. Nous utilisons principalement les techniques d'absorption IR et de spectroscopie Raman pour determiner les excitations du champ cristallin et les modes de vibration dans le materiau

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease.

PubMed

Ren, Hong-Gang; Adom, Djamilatou; Paczesny, Sophie

2018-05-01

Chronic graft-versus-host disease (cGVHD) continues to be the leading cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an increasingly applied curative method for both benign and malignant hematologic disorders. Biomarker identification is crucial for the development of noninvasive and cost-effective cGVHD diagnostic, prognostic, and predictive test for use in clinic. Furthermore, biomarkers may help to gain a better insight on ongoing pathophysiological processes. The recent widespread application of omics technologies including genomics, transcriptomics, proteomics and cytomics provided opportunities to discover novel biomarkers. Areas covered: This review focuses on biomarkers identified through omics that play a critical role in target identification for drug development, and that were verified in at least two independent cohorts. It also summarizes the current status on omics tools used to identify these useful cGVHD targets. We briefly list the biomarkers identified and verified so far. We further address challenges associated to their exploitation and application in the management of cGVHD patients. Finally, insights on biomarkers that are drug targetable and represent potential therapeutic targets are discussed. Expert commentary: We focus on biomarkers that play an essential role in target identification.

Diagnostic power of diffuse reflectance spectroscopy for targeted detection of breast lesions with microcalcifications

PubMed Central

Soares, Jaqueline S.; Barman, Ishan; Dingari, Narahara Chari; Volynskaya, Zoya; Liu, Wendy; Klein, Nina; Plecha, Donna; Dasari, Ramachandra R.; Fitzmaurice, Maryann

2013-01-01

Microcalcifications geographically target the location of abnormalities within the breast and are of critical importance in breast cancer diagnosis. However, despite stereotactic guidance, core needle biopsy fails to retrieve microcalcifications in up to 15% of patients. Here, we introduce an approach based on diffuse reflectance spectroscopy for detection of microcalcifications that focuses on variations in optical absorption stemming from the calcified clusters and the associated cross-linking molecules. In this study, diffuse reflectance spectra are acquired ex vivo from 203 sites in fresh biopsy tissue cores from 23 patients undergoing stereotactic breast needle biopsies. By correlating the spectra with the corresponding radiographic and histologic assessment, we have developed a support vector machine-derived decision algorithm, which shows high diagnostic power (positive predictive value and negative predictive value of 97% and 88%, respectively) for diagnosis of lesions with microcalcifications. We further show that these results are robust and not due to any spurious correlations. We attribute our findings to the presence of proteins (such as elastin), and desmosine and isodesmosine cross-linkers in the microcalcifications. It is important to note that the performance of the diffuse reflectance decision algorithm is comparable to one derived from the corresponding Raman spectra, and the considerably higher intensity of the reflectance signal enables the detection of the targeted lesions in a fraction of the spectral acquisition time. Our findings create a unique landscape for spectroscopic validation of breast core needle biopsy for detection of microcalcifications that can substantially improve the likelihood of an adequate, diagnostic biopsy in the first attempt. PMID:23267090

Target diagnostics for commissioning the AWE HELEN Laser Facility 100 TW chirped pulse amplification beam

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

Eagleton, R. T.; Clark, E. L.; Davies, H. M.

2006-10-15

The capability of the HELEN laser at the Atomic Weapons Establishment Aldermaston has been enhanced by the addition of a short-pulse laser beam to augment the twin opposing nanosecond time scale beams. The short-pulse beam utilizes the chirped pulse amplification (CPA) technique and is capable of delivering up to 60 J on target in a 500 fs pulse, around 100 TW, at the fundamental laser wavelength of 1.054 {mu}m. During the commissioning phase a number of diagnostic systems have been fielded, these include: x-ray pinhole imaging of the laser heated spot, charged particle time of flight, thermoluminescent dosimeter array, calibratedmore » radiochromic film, and CR39 nuclear track detector. These diagnostic systems have been used to verify the performance of the CPA beam to achieve a focused intensity of around 10{sup 19} W cm{sup -2} and to underwrite the facility radiological safety system.« less

Tumor Microenvironment Modulation via Gold Nanoparticles Targeting Malicious Exosomes: Implications for Cancer Diagnostics and Therapy

PubMed Central

Roma-Rodrigues, Catarina; Raposo, Luís R.; Cabral, Rita; Paradinha, Fabiana; Baptista, Pedro V.; Fernandes, Alexandra R.

2017-01-01

Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes’ release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs’ properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs’ role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression. PMID:28098821

Tumor Microenvironment Modulation via Gold Nanoparticles Targeting Malicious Exosomes: Implications for Cancer Diagnostics and Therapy.

PubMed

Roma-Rodrigues, Catarina; Raposo, Luís R; Cabral, Rita; Paradinha, Fabiana; Baptista, Pedro V; Fernandes, Alexandra R

2017-01-14

Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs' properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs' role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.

In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2–based Diagnostic Performance for Detection of Prostate Cancer

PubMed Central

Tan, Nelly; Lin, Wei-Chan; Khoshnoodi, Pooria; Asvadi, Nazanin H.; Yoshida, Jeffrey; Margolis, Daniel J. A.; Lu, David S. K.; Wu, Holden; Lu, David Y.; Huang, Jaioti

2017-01-01

Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging–guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10−6 mm2/sec vs 1111 × 10−6 mm2/sec, respectively; P < .01), smaller prostate volume (47.2 cm3 vs 75.4 cm3, respectively; P < .01), higher PSA density (0.16 vs 0.10, respectively; P < .01), and higher proportion of PI-RADS version 2 category 3–5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR

Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.

PubMed

Ellingford, Jamie M; Barton, Stephanie; Bhaskar, Sanjeev; Williams, Simon G; Sergouniotis, Panagiotis I; O'Sullivan, James; Lamb, Janine A; Perveen, Rahat; Hall, Georgina; Newman, William G; Bishop, Paul N; Roberts, Stephen A; Leach, Rick; Tearle, Rick; Bayliss, Stuart; Ramsden, Simon C; Nemeth, Andrea H; Black, Graeme C M

2016-05-01

To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). Case series. A total of 562 patients diagnosed with IRD. We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. Diagnostic yield of genomic testing. Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Using targeted active-learning exercises and diagnostic question clusters to improve students' understanding of carbon cycling in ecosystems.

PubMed

Maskiewicz, April Cordero; Griscom, Heather Peckham; Welch, Nicole Turrill

2012-01-01

In this study, we used targeted active-learning activities to help students improve their ways of reasoning about carbon flow in ecosystems. The results of a validated ecology conceptual inventory (diagnostic question clusters [DQCs]) provided us with information about students' understanding of and reasoning about transformation of inorganic and organic carbon-containing compounds in biological systems. These results helped us identify specific active-learning exercises that would be responsive to students' existing knowledge. The effects of the active-learning interventions were then examined through analysis of students' pre- and postinstruction responses on the DQCs. The biology and non-biology majors participating in this study attended a range of institutions and the instructors varied in their use of active learning; one lecture-only comparison class was included. Changes in pre- to postinstruction scores on the DQCs showed that an instructor's teaching method had a highly significant effect on student reasoning following course instruction, especially for questions pertaining to cellular-level, carbon-transforming processes. We conclude that using targeted in-class activities had a beneficial effect on student learning regardless of major or class size, and argue that using diagnostic questions to identify effective learning activities is a valuable strategy for promoting learning, as gains from lecture-only classes were minimal.

Using Targeted Active-Learning Exercises and Diagnostic Question Clusters to Improve Students' Understanding of Carbon Cycling in Ecosystems

PubMed Central

Maskiewicz, April Cordero; Griscom, Heather Peckham; Welch, Nicole Turrill

2012-01-01

In this study, we used targeted active-learning activities to help students improve their ways of reasoning about carbon flow in ecosystems. The results of a validated ecology conceptual inventory (diagnostic question clusters [DQCs]) provided us with information about students' understanding of and reasoning about transformation of inorganic and organic carbon-containing compounds in biological systems. These results helped us identify specific active-learning exercises that would be responsive to students' existing knowledge. The effects of the active-learning interventions were then examined through analysis of students' pre- and postinstruction responses on the DQCs. The biology and non–biology majors participating in this study attended a range of institutions and the instructors varied in their use of active learning; one lecture-only comparison class was included. Changes in pre- to postinstruction scores on the DQCs showed that an instructor's teaching method had a highly significant effect on student reasoning following course instruction, especially for questions pertaining to cellular-level, carbon-transforming processes. We conclude that using targeted in-class activities had a beneficial effect on student learning regardless of major or class size, and argue that using diagnostic questions to identify effective learning activities is a valuable strategy for promoting learning, as gains from lecture-only classes were minimal. PMID:22383618

Sequencing Needs for Viral Diagnostics

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

Gardner, S N; Lam, M; Mulakken, N J

2004-01-26

We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''nearmore » neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.« less

Conservation of Mannan Synthesis in Fungi of the Zygomycota and Ascomycota Reveals a Broad Diagnostic Target.

PubMed

Burnham-Marusich, Amanda R; Hubbard, Breeana; Kvam, Alexander J; Gates-Hollingsworth, Marcellene; Green, Heather R; Soukup, Eric; Limper, Andrew H; Kozel, Thomas R

2018-01-01

Ascomycetes and zygomycetes account for the majority of (i) fungi responsible for cutaneous, subcutaneous, and invasive human fungal infections, (ii) plant fungal pathogens, (iii) fungi that threaten global biodiversity, (iv) fungal agents of agricultural spoilage, and (v) fungi in water-damaged buildings. Rapid recognition of fungal infection (or contamination) enables early treatment (or remediation). A bioinformatics search found homologues of Saccharomyces cerevisiae Mnn9p present in members of the Zygomycota and Ascomycota phyla and absent in members of the Chytridiomycota and Basidiomycota. Mnn9p is a component of the yeast mannan polymerization complex and is necessary for α-1,6 mannan production. A monoclonal antibody (2DA6) was produced that was reactive with purified mannans of Mucor , Rhizopus , Aspergillus , Fusarium , and Candida species. Experimentation using a 2DA6 antigen capture enzyme-linked immunosorbent assay (ELISA) and extracts of fungi from the four phyla found agreement between the presence or absence of Mnn9p homologues and production or lack of production of mannan reactive with 2DA6. Studies of cell extracts from yeast mannan mutants identified α-1,6 mannan as the epitope recognized by 2DA6. To translate this finding into a point-of-use diagnostic, a 2DA6 lateral flow immunoassay was constructed that detected mannan in (i) extracts of dermatophytes and fungi that produce trauma-related infection and (ii) tissue from plants infected with Grosmannia clavigera or Sclerotium cepivorum These studies (i) revealed that the conservation of α-1,6-linked mannan in fungi of the Zygomycota and Ascomycota can be exploited as a broad diagnostic target and (ii) have provided a means to detect that target in an immunoassay platform that is well suited for clinic or field use. IMPORTANCE A key question asked when faced with an infection, an infestation, or environmental damage is whether it is a fungus. Identification of fungi as the cause of the

Conservation of Mannan Synthesis in Fungi of the Zygomycota and Ascomycota Reveals a Broad Diagnostic Target

PubMed Central

Hubbard, Breeana; Kvam, Alexander J.; Gates-Hollingsworth, Marcellene; Green, Heather R.; Soukup, Eric; Limper, Andrew H.; Kozel, Thomas R.

2018-01-01

ABSTRACT Ascomycetes and zygomycetes account for the majority of (i) fungi responsible for cutaneous, subcutaneous, and invasive human fungal infections, (ii) plant fungal pathogens, (iii) fungi that threaten global biodiversity, (iv) fungal agents of agricultural spoilage, and (v) fungi in water-damaged buildings. Rapid recognition of fungal infection (or contamination) enables early treatment (or remediation). A bioinformatics search found homologues of Saccharomyces cerevisiae Mnn9p present in members of the Zygomycota and Ascomycota phyla and absent in members of the Chytridiomycota and Basidiomycota. Mnn9p is a component of the yeast mannan polymerization complex and is necessary for α-1,6 mannan production. A monoclonal antibody (2DA6) was produced that was reactive with purified mannans of Mucor, Rhizopus, Aspergillus, Fusarium, and Candida species. Experimentation using a 2DA6 antigen capture enzyme-linked immunosorbent assay (ELISA) and extracts of fungi from the four phyla found agreement between the presence or absence of Mnn9p homologues and production or lack of production of mannan reactive with 2DA6. Studies of cell extracts from yeast mannan mutants identified α-1,6 mannan as the epitope recognized by 2DA6. To translate this finding into a point-of-use diagnostic, a 2DA6 lateral flow immunoassay was constructed that detected mannan in (i) extracts of dermatophytes and fungi that produce trauma-related infection and (ii) tissue from plants infected with Grosmannia clavigera or Sclerotium cepivorum. These studies (i) revealed that the conservation of α-1,6-linked mannan in fungi of the Zygomycota and Ascomycota can be exploited as a broad diagnostic target and (ii) have provided a means to detect that target in an immunoassay platform that is well suited for clinic or field use. IMPORTANCE A key question asked when faced with an infection, an infestation, or environmental damage is whether it is a fungus. Identification of fungi as the cause of the

Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma—A Review

PubMed Central

Siriwardena, Samadarani B. S. M.; Tsunematsu, Takaaki; Qi, Guangying; Ishimaru, Naozumi; Kudo, Yasusei

2018-01-01

It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)—the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC. PMID:29758011

Cognitive Function as a Trans-Diagnostic Treatment Target in Stimulant Use Disorders

PubMed Central

Sofuoglu, Mehmet; DeVito, Elise E.; Waters, Andrew J.; Carroll, Kathleen M.

2016-01-01

Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration (FDA) for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder, and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% - 73%, with the most common being mood disorders (13% - 64%) and anxiety disorders (21% - 50%), as well as non-substance induced psychotic disorders (under 10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder, and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible trans-diagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive

Tumeur de Frantz: deux nouveaux cas

PubMed Central

Bellarbi, Salma; Sina, Mohamed; Jahid, Ahmed; Zouaidia, Fouad; Bernoussi, Zakia; Mahassini, Najat

2013-01-01

A travers cet article, nous détaillons les caractéristiques clinico-pathologiques et discutons l'histogenèse de la tumeur de Frantz. Deux patients opérés pour tumeur de Frantz. Ils ont eu un traitement chirurgical seul. L'étude morphologique était couplée à un examen immuno-histochimique (IHC) utilisant les anticorps anti CD10, anti- vimentine, anti-énolase neuronale spécifique (NSE), anti-synaptophysine, anti-chromogranine A et anti-cytokératine. Un immuno-marquage à l'anti-oestrogène et l'anti-progestérone a été réalisé dans un cas. Il s'agissait d'une femme âgée de 45ans et d'un garçon de 12 ans. Les aspects échographiques et scannographiques étaient non spécifiques. Une exérèse chirurgicale complète a été réalisée dans les deux cas. L'analyse histologique évoquait une tumeur de Frantz. Le diagnostic a été retenu après étude immuno-histohimique. L'évolution était favorable sans récidive avec respectivement un recul de 18 et 16 mois. La tumeur de Frantz est une entité rare. Son diagnostic repose sur l'examen anatomopathologique complété par l'étude immuno-histochimique. Son pronostic est excellent après résection chirurgicale. PMID:23503717

Nike Facility Diagnostics and Data Acquisition System

NASA Astrophysics Data System (ADS)

Chan, Yung; Aglitskiy, Yefim; Karasik, Max; Kehne, David; Obenschain, Steve; Oh, Jaechul; Serlin, Victor; Weaver, Jim

2013-10-01

The Nike laser-target facility is a 56-beam krypton fluoride system that can deliver 2 to 3 kJ of laser energy at 248 nm onto targets inside a two meter diameter vacuum chamber. Nike is used to study physics and technology issues related to laser direct-drive ICF fusion, including hydrodynamic and laser-plasma instabilities, material behavior at extreme pressures, and optical and x-ray diagnostics for laser-heated targets. A suite of laser and target diagnostics are fielded on the Nike facility, including high-speed, high-resolution x-ray and visible imaging cameras, spectrometers and photo-detectors. A centrally-controlled, distributed computerized data acquisition system provides robust data management and near real-time analysis feedback capability during target shots. Work supported by DOE/NNSA.

Cancer diagnostics: The journey from histomorphology to molecular profiling.

PubMed

Ahmed, Atif A; Abedalthagafi, Malak

2016-09-06

Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management.

New targeted therapies and diagnostic methods for iron overload diseases.

PubMed

Kolnagou, Annita; Kontoghiorghe, Christina N; Kontoghiorghes, George John

2018-01-01

Millions of people worldwide suffer from iron overload toxicity diseases such as transfusional iron overload in thalassaemia and hereditary haemochromatosis. The accumulation and presence of toxic focal iron deposits causing tissue damage can also be identified in Friedreich's ataxia, Alzheimer's, Parkinson's, renal and other diseases. Different diagnostic criteria of toxicity and therapeutic interventions apply to each disease of excess or misplaced iron. Magnetic resonance imaging relaxation times T2 and T2* for monitoring iron deposits in organs and iron biomarkers such as serum ferritin and transferrin iron saturation have contributed in the elucidation of iron toxicity mechanisms and pathways, and also the evaluation of the efficacy and mode of action of chelating drugs in the treatment of diseases related to iron overload, toxicity and metabolism. Similarly, histopathological and electron microscopy diagnostic methods have revealed mechanisms of iron overload toxicity at cellular and sub-cellular levels. These new diagnostic criteria and chelator dose adjustments could apply in different or special patient categories e.g. thalassaemia patients with normal iron stores, where iron deficiency and over-chelation toxicity should be avoided.

Utilization of diagnostic ultrasound and intravenous lipid-encapsulated perfluorocarbons in non-invasive targeted cardiovascular therapeutics.

PubMed

Porter, Thomas R; Choudhury, Songita A; Xie, Feng

2016-01-01

Diagnostic ultrasound (DUS) pressures have the ability to induce inertial cavitation (IC) of systemically administered microbubbles; this bioeffect has many diagnostic and therapeutic implications in cardiovascular care. Diagnostically, commercially available lipid-encapsulated perfluorocarbons (LEP) can be utilized to improve endocardial and vascular border delineation as well as assess myocardial perfusion. Therapeutically, the liquid jets induced by IC can alter endothelial function and dissolve thrombi within the immediate vicinity of the cavitating microbubbles. The cavitating LEP can also result in the localized release of any bound therapeutic substance at the site of insonation. DUS-induced IC has been tested in pre-clinical studies to determine what effect it has on acute vascular and microvascular thrombosis as well as nitric oxide (NO) release. These pre-clinical studies have consistently shown that DUS-induced IC of LEP is effective in restoring coronary vascular and microvascular flow in acute ST segment elevation myocardial infarction (STEMI), with microvascular flow improving even if upstream large vessel flow has not been achieved. The initial clinical trials examining the efficacy of short pulse duration DUS high mechanical index impulses in patients with STEMI are underway, and preliminary studies have suggested that earlier epicardial vessel recanalization can be achieved prior to arriving in the cardiac catheterization laboratory. DUS high mechanical index impulses have also been effective in pre-clinical studies for targeting DNA delivery that has restored islet cell function in type I diabetes and restored vascular flow in the extremities downstream from a peripheral vascular occlusion. Improvements in this technique will come from three dimensional arrays for therapeutic applications, more automated delivery techniques that can be applied in the field, and use of submicron-sized acoustically activated LEP droplets that may better permeate the

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

PubMed

Stenzel, Werner; Schoser, Benedikt

2017-08-01

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

Plasmodium glyceraldehyde-3-phosphate dehydrogenase: A potential malaria diagnostic target.

PubMed

Krause, Robert G E; Hurdayal, Ramona; Choveaux, David; Przyborski, Jude M; Coetzer, Theresa H T; Goldring, J P Dean

2017-08-01

Malaria rapid diagnostic tests (RDTs) are immunochromatographic tests detecting Plasmodial histidine-rich protein 2 (HRP2), lactate dehydrogenase (LDH) and aldolase. HRP2 is only expressed by Plasmodium falciparum parasites and the protein is not expressed in several geographic isolates. LDH-based tests lack sensitivity compared to HRP2 tests. This study explored the potential of the Plasmodial glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), as a new malaria diagnostic biomarker. The P. falciparum and P. yoelii proteins were recombinantly expressed in BL21(DE3) Escherischia coli host cells and affinity purified. Two epitopes (CADGFLLIGEKKVSVFA and CAEKDPSQIPWGKCQV) specific to P. falciparum GAPDH and one common to all mammalian malaria species (CKDDTPIYVMGINH) were identified. Antibodies were raised in chickens against the two recombinant proteins and the three epitopes and affinity purified. The antibodies detected the native protein in parasite lysates as a 38 kDa protein and immunofluorescence verified a parasite cytosolic localization for the native protein. The antibodies suggested a 4-6 fold higher concentration of native PfGAPDH compared to PfLDH in immunoprecipitation and ELISA formats, consistent with published proteomic data. PfGAPDH shows interesting potential as a malaria diagnostic biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

Disposable blast shields for use on NIF imaging diagnostics

NASA Astrophysics Data System (ADS)

Smith, Cal A.; Wang, Karen M.; Masters, Nathan

2015-08-01

The NIFs 192 lasers can deliver 2 MJ of energy to Target Chamber Center (TCC) to produce environments not available in any other experimental laboratory. The NIFs ability to deliver such intense energy to a small volume causes harsh consequences to experimental equipment and supporting diagnostics such as holhraums, support packages, target positioners, diagnostic equipment, and laser optics. Of these, the hohlraum and support packages are typically quickly vaporized and transformed into an expanding shell of high-hypersonic gases referred to as debris wind. During an experimental event such as fusion implosion, the target diagnostic components used to measure key observables in the experiment are subjected to extreme pressures and impact shocks due to incident debris wind loading. As diagnostics are positioned closer to TCC, the diagnostic pinhole stacks and other components along the diagnostic structure become more likely to be at or above the yield strength of the materials commonly used. In particular, the pinhole stack components and data recording instruments behind the pinholes are the most costly to replace. Thus, a conceptual configuration for a pinhole shield is proposed, analyzed, and tested with the intent of mitigating damage to the pinhole stack and imaging equipment and allowing immediate re-use of this diagnostic equipment. This pinhole shield would be a replaceable window that can be replaced quickly by inserting and removing it before and after each experimental laser shot, which will allow NIF to benefit from significant material and labor costs.

Rapid molecular diagnostics of severe primary immunodeficiency determined by using targeted next-generation sequencing.

PubMed

Yu, Hui; Zhang, Victor Wei; Stray-Pedersen, Asbjørg; Hanson, Imelda Celine; Forbes, Lisa R; de la Morena, M Teresa; Chinn, Ivan K; Gorman, Elizabeth; Mendelsohn, Nancy J; Pozos, Tamara; Wiszniewski, Wojciech; Nicholas, Sarah K; Yates, Anne B; Moore, Lindsey E; Berge, Knut Erik; Sorte, Hanne; Bayer, Diana K; ALZahrani, Daifulah; Geha, Raif S; Feng, Yanming; Wang, Guoli; Orange, Jordan S; Lupski, James R; Wang, Jing; Wong, Lee-Jun

2016-10-01

Primary immunodeficiency diseases (PIDDs) are inherited disorders of the immune system. The most severe form, severe combined immunodeficiency (SCID), presents with profound deficiencies of T cells, B cells, or both at birth. If not treated promptly, affected patients usually do not live beyond infancy because of infections. Genetic heterogeneity of SCID frequently delays the diagnosis; a specific diagnosis is crucial for life-saving treatment and optimal management. We developed a next-generation sequencing (NGS)-based multigene-targeted panel for SCID and other severe PIDDs requiring rapid therapeutic actions in a clinical laboratory setting. The target gene capture/NGS assay provides an average read depth of approximately 1000×. The deep coverage facilitates simultaneous detection of single nucleotide variants and exonic copy number variants in one comprehensive assessment. Exons with insufficient coverage (<20× read depth) or high sequence homology (pseudogenes) are complemented by amplicon-based sequencing with specific primers to ensure 100% coverage of all targeted regions. Analysis of 20 patient samples with low T-cell receptor excision circle numbers on newborn screening or a positive family history or clinical suspicion of SCID or other severe PIDD identified deleterious mutations in 14 of them. Identified pathogenic variants included both single nucleotide variants and exonic copy number variants, such as hemizygous nonsense, frameshift, and missense changes in IL2RG; compound heterozygous changes in ATM, RAG1, and CIITA; homozygous changes in DCLRE1C and IL7R; and a heterozygous nonsense mutation in CHD7. High-throughput deep sequencing analysis with complete clinical validation greatly increases the diagnostic yield of severe primary immunodeficiency. Establishing a molecular diagnosis enables early immune reconstitution through prompt therapeutic intervention and guides management for improved long-term quality of life. Copyright © 2016 American

Targeting clinical outcomes: Endovascular simulation improves diagnostic coronary angiography skills.

PubMed

Schimmel, Daniel R; Sweis, Ranya; Cohen, Elaine R; Davidson, Charles; Wayne, Diane B

2016-02-15

The purpose of this study is to determine the effects of simulation-based medical education (SBME) on the skills required to perform coronary angiography in the cardiac catheterization laboratory. Cardiovascular fellows commonly learn invasive procedures on patients. Because this approach is not standardized, it can result in inconsistent skill acquisition through exclusion of concepts and skills. Also, the learning curve varies between trainees yielding variability in skill acquisition. Therefore, coronary angiography skills are an excellent target for SBME in an environment in which direct patient care is not jeopardized. From January 2013 to June 2013, 14 cardiovascular fellows entering the cardiac catheterization laboratory at a tertiary care teaching hospital were tested on an endovascular simulator to assess baseline skills. All fellows subsequently underwent didactic teaching and preceptor-lead training on the endovascular simulator. Topics included basic catheterization skills and a review of catheterization laboratory systems. Following training, all fellows underwent a post-training assessment on the endovascular simulator. Paired t tests were used to compare items on the skills checklist and simulator defined variables. Cardiovascular fellows scored significantly higher on a diagnostic coronary angiography skills checklist following SBME using an endovascular simulator. The mean pretest score was 66.6% (SD = 9.7%) compared to 86.0% (SD = 6.3%) following simulator training (P < 0.001). Additional findings include significant reduction in procedure time and use of cine-fluoroscopy at posttest. SBME significantly improved cardiovascular fellows' performance of simulated coronary angiography skills. Standardized simulation-based education is a valuable adjunct to traditional clinical education for cardiovascular fellows. © 2015 Wiley Periodicals, Inc.

False Positivity of Non-Targeted Infections in Malaria Rapid Diagnostic Tests: The Case of Human African Trypanosomiasis

PubMed Central

Gillet, Philippe; Mumba Ngoyi, Dieudonné; Lukuka, Albert; Kande, Viktor; Atua, Benjamin; van Griensven, Johan; Muyembe, Jean-Jacques; Jacobs, Jan; Lejon, Veerle

2013-01-01

Background In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense. Methodology/Principal Findings Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients. Conclusions/Significance Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests. PMID:23638201

Development of PETAL diagnostics: PETAPhys project

NASA Astrophysics Data System (ADS)

Raffestin, D.; Boutoux, G.; Baggio, J.; Batani, D.; Blanchot, N.; Bretheau, D.; Hulin, S.; D'Humieres, E.; Granet, F.; Longhi, Th.; Meyer, Ch.; Moreno, Q.; Nuter, R.; Rault, J.; Tikhonchuk, V.; Universite de Bordeaux/Celia Team; CEA. DAM/Cesta Team

2017-10-01

Beginning of autumn 2017, PETAL, a Petawatt laser beam, will be operated for experiments on the LMJ facility at the CEA/ Cesta research center. The PETAPhys project provides a support to the qualification phase of the PETAL laser operation. Within the PETAPhys project, we are developing two simple and robust diagnostics permitting both to characterize the focal spot of the PETAL beam and to measure the hard X-ray spectrum at each shot. The first diagnostic consists in optical imaging of the PETAL beam focal spot in the spectral range of the second and third harmonic radiation emitted from the target. The second diagnostic is a hard X-ray dosimeter consisting in a stack of imaging plates (IP) and filters, either placed inside a re-entrant tube or inserted close to target. Numerical simulations as well as experiments on small scale facilities have been performed to design these diagnostics. If available, preliminary results from PETAL experiments will be discussed. We acknowledge the financial support from the French National Research Agency (ANR) in the framework of ``the investments for the future'' Programme IdEx Bordeaux-LAPHIA (ANR-10-IDEX-03-02).

A Research Agenda for Malaria Eradication: Diagnoses and Diagnostics

PubMed Central

2011-01-01

Many of malaria's signs and symptoms are indistinguishable from those of other febrile diseases. Detection of the presence of Plasmodium parasites is essential, therefore, to guide case management. Improved diagnostic tools are required to enable targeted treatment of infected individuals. In addition, field-ready diagnostic tools for mass screening and surveillance that can detect asymptomatic infections of very low parasite densities are needed to monitor transmission reduction and ensure elimination. Antibody-based tests for infection and novel methods based on biomarkers need further development and validation, as do methods for the detection and treatment of Plasmodium vivax. Current rapid diagnostic tests targeting P. vivax are generally less effective than those targeting Plasmodium falciparum. Moreover, because current drugs for radical cure may cause serious side effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, more information is needed on the distribution of G6PD-deficiency variants as well as tests to identify at-risk individuals. Finally, in an environment of very low or absent malaria transmission, sustaining interest in elimination and maintaining resources will become increasingly important. Thus, research is required into the context in which malaria diagnostic tests are used, into diagnostics for other febrile diseases, and into the integration of these tests into health systems. PMID:21311583

Diagnostic Performance of Multiparametric Magnetic Resonance Imaging and Fusion Targeted Biopsy to Detect Significant Prostate Cancer.

PubMed

Hoffmann, Manuela A; Taymoorian, Kasra; Ruf, Christian; Gerhards, Arnd; Leyendecker, Karlheinz; Stein, Thomas; Jakobs, Frank M; Schreckenberger, Mathias

2017-12-01

Multiparametric magnetic resonance imaging combined with ultrasound-fusion-targeted biopsy of the prostate intends to increase diagnostic precision, which has to be clarified. We performed multiparametric magnetic resonance imaging followed by ultrasound-fusion-guided perineal biopsy in 99 male patients with elevated prostate-specific-antigen and previous negative standard biopsy-procedures. In 33/99 patients (33%) no malignancy could be confirmed by histopathology. Low-grade carcinomas (Gleason-Score 6+7a) were found in 42/66 (64%) and high-grade carcinomas (Gleason-Score ≥7b) in 24/66 (36%) men. A high-grade carcinoma corresponded to PI-RADS 4 or 5 (suspected malignancy) in 21/24 cases, which accounted for a sensitivity of 88% and negative-predictive-value of 85% (p=0.002). Differentiation between high-/low-grade carcinomas (Gleason-Score ≤7a vs. ≥7b) by means of PI-RADS related to a sensitivity of 88% and a negative-predictive-value of 70% (p=0.74). The results support the view that multiparametric magnetic resonance imaging/ultrasound-fusion-guided biopsy promotes considerably higher detection rates of clinically relevant prostate malignancies than do conventional diagnostic procedures. With regard to differentiation between high- and low-grade carcinomas, no significant difference was demonstrated. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The National Ignition Facility Diagnostic Set at the Completion of the National Ignition Campaign, September 2012

DOE PAGES

Kilkenny, J. D.; Bell, P. M.; Bradley, D. K.; ...

2016-01-06

At the completion of the National Ignition Campaign (NIC), the National Ignition Facility (NIF) had about 36 different types of diagnostics. These were based on several decades of development on Nova and OMEGA and involved the whole U.S. inertial confinement fusion community. In 1994, the Joint Central Diagnostic Team documented a plan for a limited set of NIF diagnostics in the NIF Conceptual Design Report. Two decades later, these diagnostics, and many others, were installed workhorse tools for all users of NIF. We give a short description of each of the 36 different types of NIC diagnostics grouped by themore » function of the diagnostics, namely, target drive, target response and target assembly, stagnation, and burn. A comparison of NIF diagnostics with the Nova diagnostics shows that the NIF diagnostic capability is broadly equivalent to that of Nova in 1999. Although NIF diagnostics have a much greater degree of automation and rigor than Nova’s, new diagnostics are limited such as the higher-speed X-ray imager. Lastly, recommendations for future diagnostics on the NIF are discussed.« less

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.

Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

DTIC Science & Technology

2014-07-01

Huflejt ME. Processing and analysis of serum antibody binding signals from Printed Glycan Arrays for diagnostic and prognostic applications. Int J...rats 542 LeCLex1-6’(LeC1-3’)Lac-sp4 543 Lex1-6’(LeB1-3’)Lac-sp4 641 E.coli oligosaccharide -2 (1208) 642 E.coli oligosaccharide -3 (1210) 254 More

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test

PubMed Central

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-01-01

Purpose Genetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use. Methods We prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing. Results WGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24% P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A. Conclusion WGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort. PMID:28771251

Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.

PubMed

Lionel, Anath C; Costain, Gregory; Monfared, Nasim; Walker, Susan; Reuter, Miriam S; Hosseini, S Mohsen; Thiruvahindrapuram, Bhooma; Merico, Daniele; Jobling, Rebekah; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Sung, Wilson W L; Wang, Zhuozhi; Bikangaga, Peter; Boelman, Cyrus; Carter, Melissa T; Cordeiro, Dawn; Cytrynbaum, Cheryl; Dell, Sharon D; Dhir, Priya; Dowling, James J; Heon, Elise; Hewson, Stacy; Hiraki, Linda; Inbar-Feigenberg, Michal; Klatt, Regan; Kronick, Jonathan; Laxer, Ronald M; Licht, Christoph; MacDonald, Heather; Mercimek-Andrews, Saadet; Mendoza-Londono, Roberto; Piscione, Tino; Schneider, Rayfel; Schulze, Andreas; Silverman, Earl; Siriwardena, Komudi; Snead, O Carter; Sondheimer, Neal; Sutherland, Joanne; Vincent, Ajoy; Wasserman, Jonathan D; Weksberg, Rosanna; Shuman, Cheryl; Carew, Chris; Szego, Michael J; Hayeems, Robin Z; Basran, Raveen; Stavropoulos, Dimitri J; Ray, Peter N; Bowdin, Sarah; Meyn, M Stephen; Cohn, Ronald D; Scherer, Stephen W; Marshall, Christian R

2018-04-01

PurposeGenetic testing is an integral diagnostic component of pediatric medicine. Standard of care is often a time-consuming stepwise approach involving chromosomal microarray analysis and targeted gene sequencing panels, which can be costly and inconclusive. Whole-genome sequencing (WGS) provides a comprehensive testing platform that has the potential to streamline genetic assessments, but there are limited comparative data to guide its clinical use.MethodsWe prospectively recruited 103 patients from pediatric non-genetic subspecialty clinics, each with a clinical phenotype suggestive of an underlying genetic disorder, and compared the diagnostic yield and coverage of WGS with those of conventional genetic testing.ResultsWGS identified diagnostic variants in 41% of individuals, representing a significant increase over conventional testing results (24%; P = 0.01). Genes clinically sequenced in the cohort (n = 1,226) were well covered by WGS, with a median exonic coverage of 40 × ±8 × (mean ±SD). All the molecular diagnoses made by conventional methods were captured by WGS. The 18 new diagnoses made with WGS included structural and non-exonic sequence variants not detectable with whole-exome sequencing, and confirmed recent disease associations with the genes PIGG, RNU4ATAC, TRIO, and UNC13A.ConclusionWGS as a primary clinical test provided a higher diagnostic yield than conventional genetic testing in a clinically heterogeneous cohort.

Gold-manganese nanoparticles for targeted diagnostic and imaging

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

Murph, Simona Hunyadi

Imagine the possibility of non-invasive, non-radiation based Magnetic resonance imaging (MRI) in combating cardiac disease. Researchers at the Savannah River National Laboratory (SRNL) are developing a process that would use nanotechnology in a novel, targeted approach that would allow MRIs to be more descriptive and brighter, and to target specific organs. Researchers at SRNL have discovered a way to use multifunctional metallic gold-manganese nanoparticles to create a unique, targeted positive contrast agent. SRNL Senior Scientist Dr. Simona Hunyadi Murph says she first thought of using the nanoparticles for cardiac disease applications after learning that people who survive an infarct exhibitmore » up to 15 times higher rate of developing chronic heart failure, arrhythmias and/or sudden death compared to the general population. Without question, nanotechnology will revolutionize the future of technology. The development of functional nanomaterials with multi-detection modalities opens up new avenues for creating multi-purpose technologies for biomedical applications.« less

Heavy Ion Fusion Science Virtual National Laboratory 4th Quarter 2009 Milestone Report: Measure and simulate target temperature and dynamic response in optimized NDCX-I configurations with initial diagnostics suite

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

Bieniosek, F.M.; Barnard, J.J.; Henestroza, E.

2009-09-30

This milestone has been met. The effort contains two main components: (1) Experimental results of warm dense matter target experiments on optimized NDCX-I configurations that include measurements of target temperature and transient target behavior. (2) A theoretical model of the target response to beam heating that includes an equilibrium heating model of the target foil and a model for droplet formation in the target for comparison with experimental results. The experiments on ion-beam target heating use a 300-350-keV K{sup +} pulsed beam from the Neutralized Compression Drift Experiment (NDCX-I) accelerator at LBNL. The NDCX-I accelerator delivers an uncompressed pulse beammore » of several microseconds with a typical power density of >100 kW/cm{sup 2} over a final focus spot size of about 1 mm. An induction bunching module the NDCX-I compresses a portion of the beam pulse to reach a much higher power density over 2 nanoseconds. Under these conditions the free-standing foil targets are rapidly heated to temperatures to over 4000 K. We model the target thermal dynamics using the equation of heat conduction for the temperature T(x,t) as a function of time (t) and spatial dimension along the beam direction (x). The competing cooling processes release energy from the surface of the foil due to evaporation, radiation, and thermionic (Richardson) emission. A description of the experimental configuration of the target chamber and results from initial beam-target experiments are reported in our FY08 4th Quarter and FY09 2nd Quarter Milestone Reports. The WDM target diagnostics include a high-speed multichannel optical pyrometer, optical streak camera, VISAR, and high-speed gated cameras. The fast optical pyrometer is a unique and significant new diagnostic which provides valuable information on the temperature evolution of the heated target.« less

THE ROLE OF TARGET ORGAN DIAGNOSTIC APPROACH IN SEASONAL ALLERGIC RHINITIS: NASAL SMEAR EOSINOPHILS.

PubMed

Nurkic, Jasmina; Ahmad, Mona Al; Arifhodzic, Nermina; Jusufovic, Edin

2016-04-01

negative SPT during the highest peak of season, in contrast to control group. NES showed moderate sensitivity, relatively high specificity and importance as screening test in SPT negative patients. Evaluation of AR demand wide and improved diagnostic approach due to significant number of SPT negative patients with positive NSE based on natural allergen stimulation. Our results emphasize locale allergic response of nasal mucosa and importance of target organ diagnostic approach.

Identification of Optimal Epitopes for Plasmodium falciparum Rapid Diagnostic Tests That Target Histidine-Rich Proteins 2 and 3

PubMed Central

Lee, Nelson; Gatton, Michelle L.; Pelecanos, Anita; Bubb, Martin; Gonzalez, Iveth; Bell, David; Cheng, Qin

2012-01-01

Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs. PMID:22259210

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

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

Tuberculosis Diagnostics in 2015: Landscape, Priorities, Needs, and Prospects

PubMed Central

Pai, Madhukar; Schito, Marco

2015-01-01

In 2015, tuberculosis remains a major global health problem, and drug-resistant tuberculosis is a growing threat. Although tuberculosis diagnosis in many countries is still reliant on older tools, new diagnostics are changing the landscape. Stimulated, in part, by the success and roll out of Xpert MTB/RIF, there is now considerable interest in new technologies. The landscape looks promising, with a robust pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and development of shorter-duration tuberculosis drug regimens. Another concern is the relative absence of non–sputum-based diagnostics in the pipeline for children and of biomarker tests for triage, cure, and progression of latent Mycobacterium tuberculosis infection. Several initiatives, described in this supplement, have been launched to further stimulate product development and policy, including assessment of needs and priorities, development of target product profiles, compilation of data on resistance-associated mutations, and assessment of market size and potential for new diagnostics. Advocacy is needed to increase funding for tuberculosis research and development, and governments in high-burden countries must invest more in tuberculosis control to meet post-2015 targets for care, control, and prevention. PMID:25765103

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses.

PubMed

Ramkumar, Hema L; Gudiseva, Harini V; Kishaba, Kameron T; Suk, John J; Verma, Rohan; Tadimeti, Keerti; Thorson, John A; Ayyagari, Radha

2017-02-01

To test the utility of targeted sequencing as a method of clinical molecular testing in patients diagnosed with inherited retinal degeneration (IRD). After genetic counseling, peripheral blood was drawn from 188 probands and 36 carriers of IRD. Single gene testing was performed on each patient in a Clinical Laboratory Improvement Amendment (CLIA) certified laboratory. DNA was isolated, and all exons in the gene of interest were analyzed along with 20 base pairs of flanking intronic sequence. Genetic testing was most often performed on ABCA4, CTRP5, ELOV4, BEST1, CRB1, and PRPH2. Pathogenicity of novel sequence changes was predicted by PolyPhen2 and sorting intolerant from tolerant (SIFT). Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Analysis confirmed 12 (34%) of individuals as carriers of familial mutations associated with IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3 (1). Targeted analysis of clinically suspected genes in 225 subjects resulted in a positive molecular diagnosis in 26% of patients with dominant IRD and 59% of patients with recessive IRD. Novel damaging mutations were identified in four genes. Single gene screening is not an ideal method for diagnostic testing given the phenotypic and genetic heterogeneity among IRD cases. High-throughput sequencing of all genes associated with retinal degeneration may be more efficient for molecular diagnosis.

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.

Radiochromic film diagnostics for laser-driven ion beams

NASA Astrophysics Data System (ADS)

Kaufman, J.; Margarone, Daniele; Candiano, Giacomo; Kim, I. Jong; Jeong, Tae Moon; Pšikal, Jan; Romano, F.; Cirrone, P.; Scuderi, V.; Korn, Georg

2015-05-01

Radiochromic film (RCF) based multichannel diagnostics utilizes the concept of a stack detector comprised of alternating layers of RCFs and shielding aluminium layers. An algorithm based on SRIM simulations is used to correct the accumulated dose. Among the standard information that can be obtained is the maximum ion energy and to some extend the beam energy spectrum. The main area where this detector shines though is the geometrical characterization of the beam. Whereas other detectors such as Thomson parabola spectrometer or Faraday cups detect only a fraction of the outburst cone, the RCF stack placed right behind the target absorbs the whole beam. A complete 2D and to some extend 3D imprint of the ion beam allows us to determine parameters such as divergence or beam center shift with respect to the target normal. The obvious drawback of such diagnostics is its invasive character. But considering that only a few successful shots (2-3) are needed per one kind of target to perform the analysis, the drawbacks are acceptable. In this work, we present results obtained with the RCF diagnostics using both conventional accelerators and laser-driven ion beams during 2 experimental campaigns.

Custom oligonucleotide array-based CGH: a reliable diagnostic tool for detection of exonic copy-number changes in multiple targeted genes

PubMed Central

Vasson, Aurélie; Leroux, Céline; Orhant, Lucie; Boimard, Mathieu; Toussaint, Aurélie; Leroy, Chrystel; Commere, Virginie; Ghiotti, Tiffany; Deburgrave, Nathalie; Saillour, Yoann; Atlan, Isabelle; Fouveaut, Corinne; Beldjord, Cherif; Valleix, Sophie; Leturcq, France; Dodé, Catherine; Bienvenu, Thierry; Chelly, Jamel; Cossée, Mireille

2013-01-01

The frequency of disease-related large rearrangements (referred to as copy-number mutations, CNMs) varies among genes, and search for these mutations has an important place in diagnostic strategies. In recent years, CGH method using custom-designed high-density oligonucleotide-based arrays allowed the development of a powerful tool for detection of alterations at the level of exons and made it possible to provide flexibility through the possibility of modeling chips. The aim of our study was to test custom-designed oligonucleotide CGH array in a diagnostic laboratory setting that analyses several genes involved in various genetic diseases, and to compare it with conventional strategies. To this end, we designed a 12-plex CGH array (135k; 135 000 probes/subarray) (Roche Nimblegen) with exonic and intronic oligonucleotide probes covering 26 genes routinely analyzed in the laboratory. We tested control samples with known CNMs and patients for whom genetic causes underlying their disorders were unknown. The contribution of this technique is undeniable. Indeed, it appeared reproducible, reliable and sensitive enough to detect heterozygous single-exon deletions or duplications, complex rearrangements and somatic mosaicism. In addition, it improves reliability of CNM detection and allows determination of boundaries precisely enough to direct targeted sequencing of breakpoints. All of these points, associated with the possibility of a simultaneous analysis of several genes and scalability ‘homemade' make it a valuable tool as a new diagnostic approach of CNMs. PMID:23340513

Targeted treatment of mutated EGFR-expressing non-small-cell lung cancer: focus on erlotinib with companion diagnostics

PubMed Central

Karachaliou, Niki; Rosell, Rafael

2014-01-01

Deeper understanding of the pathobiology of non-small-cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in the progression to metastatic disease. The discovery of epidermal growth factor receptor (EGFR) mutations in 15%–20% of lung adenocarcinomas and the associated response to EGFR tyrosine kinase inhibitors have provided a successful avenue of attack in late-stage adenocarcinomas. Use of the EGFR tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib is limited to patients who have adenocarcinomas with known activating EGFR mutations. However, the EGFR mutation testing landscape is varied and includes many screening and targeted methods, each with its own benefits and limitations. These tests can simplify the drug discovery process, make clinical trials more efficient and informative, and individualize cancer therapy. In practice, the choice of method should be determined by the nature of the sample to be tested, the testing laboratory’s expertise and access to equipment, and whether the detection of only known activating EGFR mutations, or of all possible mutations, is required. Development of companion diagnostic tests for this identification is advancing; nevertheless, the use of such tests merits greater attention. PMID:28210145

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.

PubMed

Bhaskar, Sonu; Tian, Furong; Stoeger, Tobias; Kreyling, Wolfgang; de la Fuente, Jesús M; Grazú, Valeria; Borm, Paul; Estrada, Giovani; Ntziachristos, Vasilis; Razansky, Daniel

2010-03-03

fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.

Definitions and outlook targeting x-ray exposure of patients in diagnostic imaging

NASA Astrophysics Data System (ADS)

Regulla, Dieter F.

2011-03-01

Computer tomography (CT) is vital and currently irreplaceable in diagnostic radiology. But CT operates with ionizing radiation which may cause cancer or non-cancer diseases in humans. The degree of radiation impact depends on the dose administered by an investigation. And this is the core issue: Even CT exams executed lege artis, administer doses to patients which by magnitude are far beyond the level of hitherto known doses of conventional film-screen techniques. Patients undergoing one or multiple CT examinations, digital angiographies or interventions will be exposed to effective doses between roughly several mSv and several 100 mSv depending on type and frequency of the diagnostic investigations. From the radiation protection point of view, there is therefore the worldwide problem of formulating firm rules for the control of these high-dose investigations, as dose limits can not be established for reasons of the medical benefit. This makes the difference compared with radiation protection for occupationally exposed persons. What remains is "software", namely "justification" and "optimization". Justification requires balancing the interests between the health benefit and the potential harm of an exam which has to be responsibly executed by the physician himself; therefore the radiologists' associations are in the duty to prepare practicable rules for justification. Optimization again needs a cooperative solution, and that is the establishment of reference doses for diagnostic examinations, to be checked by the technical service of the producers' companies. Experts and authorities have been aware of the high-dose dilemma in diagnostic imaging since long. It is time for the reflection of active solutions and their implementation into practice.

Dementia diagnosis and post-diagnostic support in Scottish rural communities: experiences of people with dementia and their families.

PubMed

Innes, Anthea; Szymczynska, Paulina; Stark, Cameron

2014-03-01

This paper explores the reported difficulties and satisfactions with diagnostic processes and post-diagnostic support offered to people with dementia and their families living in the largest remote and rural region in Scotland. A consultation with 18 participants, six people with dementia and 12 family members, was held using semi-structured interviews between September and November 2010. Three points in the diagnostic process were explored: events and experiences pre-diagnosis; the experience of the diagnostic process; and post-diagnostic support. Experiences of people with dementia and their carers varied at all three points in the diagnostic process. Participant experiences in this study suggest greater efforts are required to meet Government diagnosis targets and that post-diagnostic support needs to be developed and monitored to ensure that once a diagnosis is given people are well-supported. Without post-diagnostic provision Government targets for diagnosis are just that, quota targets, rather than a means to improve service experiences.

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

The evolving potential of companion diagnostics.

PubMed

Khoury, Joseph D

2016-01-01

The scope of companion diagnostics in cancer has undergone significant shifts in the past few years, with increased development of targeted therapies and novel testing platforms. This has provided new opportunities to effect unprecedented paradigm shifts in the application of personalized medicine principles for patients with cancer. These shifts involve assay platforms, analytes, regulations, and therapeutic approaches. As opportunities involving each of these facets of companion diagnostics expand, close collaborations between key stakeholders should be enhanced to ensure optimal performance characteristics and patient outcomes.

X-ray diffraction diagnostic design for the National Ignition Facility

NASA Astrophysics Data System (ADS)

Ahmed, Maryum F.; House, Allen; Smith, R. F.; Ayers, Jay; Lamb, Zachary S.; Swift, David W.

2013-09-01

This paper describes the design considerations for Target Diffraction In-Situ (TARDIS), an x-ray diffraction diagnostic at the National Ignition Facility. A crystal sample is ramp-compressed to peak pressures between 10 and 30 Mbar and, during a pressure hold period, is probed with quasi-monochromatic x-rays emanating from a backlighter source foil. The crystal spectrography diffraction lines are recorded onto image plates. The crystal sample, filter, and image plates are packaged into one assembly, allowing for accurate and repeatable target to image plate registration. Unconverted laser light impinges upon the device, generating debris, the effects of which have been mitigated. Dimpled blast shields, high strength steel alloy, and high-z tungsten are used to shield and protect the image plates. A tapered opening was designed to provide adequate thickness of shielding materials without blocking the drive beams or x-ray source from reaching the crystal target. The high strength steel unit serves as a mount for the crystal target and x-ray source foil. A tungsten body contains the imaging components. Inside this sub-assembly, there are three image plates: a 160 degree field of view curved plate directly opposite the target opening and two flat plates for the top and bottom. A polycarbonate frame, coated with the appropriate filter material and embedded with registration features for image plate location, is inserted into the diagnostic body. The target assembly is metrologized and then the diagnostic assembly is attached.

He Did What?: The role of diagnosticity in revising implicit evaluations

PubMed Central

Cone, Jeremy; Ferguson, Melissa J.

2015-01-01

Research suggests that implicit evaluations are relatively insensitive to single instances of new, countervailing information that contradicts prior learning. In six experiments, however, we identify the critical role of the perceived diagnosticity of that new information: counter-attitudinal information that is deemed highly diagnostic of the target's true nature leads to a complete reversal of the previous implicit evaluation. Experiments 1a and 1b establish this effect by showing that newly-formed implicit evaluations are reversed minutes later with exposure to a single piece of highly diagnostic information. Experiment 2 demonstrates a valence asymmetry in participants’ likelihood of exhibiting rapid reversals of newly formed positive versus negative implicit evaluations. Experiment 3 provides evidence that a target must be personally responsible for the counter-attitudinal behavior and not merely incidentally associated with a negative act. Experiment 4 shows that participants exhibit revision only when they judge the target's counter-attitudinal behavior as offensive and thus diagnostic of his character. Experiment 5 demonstrates the behavioral implications of newly-revised implicit evaluations. These studies show that newly-formed implicit evaluations can be completely overturned through deliberative considerations about a single piece of counter-attitudinal information. PMID:25365037

Diagnostics for invasive Salmonella infections: current challenges and future directions

PubMed Central

Andrews, Jason R.; Ryan, Edward T.

2015-01-01

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

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

PubMed

Andrews, Jason R; Ryan, Edward T

2015-06-19

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

Embedding CLIPS in a database-oriented diagnostic system

NASA Technical Reports Server (NTRS)

Conway, Tim

1990-01-01

This paper describes the integration of C Language Production Systems (CLIPS) into a powerful portable maintenance aid (PMA) system used for flightline diagnostics. The current diagnostic target of the system is the Garrett GTCP85-180L, a gas turbine engine used as an Auxiliary Power Unit (APU) on some C-130 military transport aircraft. This project is a database oriented approach to a generic diagnostic system. CLIPS is used for 'many-to-many' pattern matching within the diagnostics process. Patterns are stored in database format, and CLIPS code is generated by a 'compilation' process on the database. Multiple CLIPS rule sets and working memories (in sequence) are supported and communication between the rule sets is achieved via the export and import commands. Work is continuing on using CLIPS in other portions of the diagnostic system and in re-implementing the diagnostic system in the Ada language.

Sampling and RNA quality for successful diagnostics using quantitative PCR

USDA-ARS?s Scientific Manuscript database

Diagnostic analyses of RNA targets are widely used in honey bee pathology. These diagnostics can be compromised by the actions of endogenous RNA-degrading enzymes activated upon bee death. RNA degradation can be minimized by storage at ultra-cold temperatures or by immersion in high-salt buffers. H...

MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects.

PubMed

Miao, Jinglei; Wu, Song; Peng, Zhi; Tania, Mousumi; Zhang, Chaoyue

2013-08-01

MicroRNAs (miRNAs) are small RNA molecules, which can interfere with the expression of several genes and act as gene regulator. miRNAs have been proved as a successful diagnostic and therapeutic tool in several cancers. In this review, the differential expression of miRNAs in osteosarcoma and their possibility to be used as diagnostic and therapeutic tools have been discussed. Osteosarcoma is the most common primary bone tumor that mainly affects children and adolescents. The current treatment of osteosarcoma remains difficult, and osteosarcoma causes many deaths because of its complex pathogenesis and resistance to conventional treatments. Several studies demonstrated that the differential expression patterns of miRNAs are a promising tool for the diagnosis and treatment of osteosarcoma. Although some aspect of the mechanism of action of miRNAs in controlling osteosarcoma has been identified (e.g., targeting the Notch signaling pathway), it is far beyond to the clear understanding of miRNA targets in osteosarcoma. Identification of the specific target of miRNAs may aid molecular targets for drug development and future relief of osteosarcoma.

Point-of-care oral-based diagnostics

PubMed Central

Hart, RW; Mauk, MG; Liu, C; Qiu, X; Thompson, JA; Chen, D; Malamud, D; Abrams, WR; Bau, HH

2014-01-01

Many of the target molecules that reside in blood are also present in oral fluids, albeit at lower concentrations. Oral fluids are, however, relatively easy and safe to collect without the need for specialized equipment and training. Thus, oral fluids provide convenient samples for medical diagnostics. Recent advances in lab-on-a-chip technologies have made minute, fully integrated diagnostic systems practical for an assortment of point-of-care tests. Such systems can perform either immunoassays or molecular diagnostics outside centralized laboratories within time periods ranging from minutes to an hour. The article briefly reviews recent advances in devices for point-of-care testing with a focus on work that has been carried out by the authors as part of a NIH program. PMID:21521419

Molecular diagnostics for human leptospirosis.

PubMed

Waggoner, Jesse J; Pinsky, Benjamin A

2016-10-01

The definitive diagnosis of leptospirosis, which results from infection with spirochetes of the genus Leptospira, currently relies on the use of culture, serological testing (microscopic agglutination testing), and molecular detection. The purpose of this review is to describe new molecular diagnostics for Leptospira and discuss advancements in the use of available methods. Efforts have been focused on improving the clinical sensitivity of Leptospira detection using molecular methods. In this review, we describe a reoptimized pathogenic species-specific real-time PCR (targeting lipL32) that has demonstrated improved sensitivity, findings by two groups that real-time reverse-transcription PCR assays targeting the 16S rrs gene can improve detection, and two new loop-mediated amplification techniques. Quantitation of leptospiremia, detection in different specimen types, and the complementary roles played by molecular detection and microscopic agglutination testing will be discussed. Finally, a protocol for Leptospira strain subtyping using variable number tandem repeat targets and high-resolution melting will be described. Molecular diagnostics have an established role for the diagnosis of leptospirosis and provide an actionable diagnosis in the acute setting. The use of real-time reverse-transcription PCR for testing serum/plasma and cerebrospinal fluid, when available, may improve the detection of Leptospira without decreasing clinical specificity.

Resilient actions in the diagnostic process and system performance.

PubMed

Smith, Michael W; Davis Giardina, Traber; Murphy, Daniel R; Laxmisan, Archana; Singh, Hardeep

2013-12-01

Systemic issues can adversely affect the diagnostic process. Many system-related barriers can be masked by 'resilient' actions of frontline providers (ie, actions supporting the safe delivery of care in the presence of pressures that the system cannot readily adapt to). We explored system barriers and resilient actions of primary care providers (PCPs) in the diagnostic evaluation of cancer. We conducted a secondary data analysis of interviews of PCPs involved in diagnostic evaluation of 29 lung and colorectal cancer cases. Cases covered a range of diagnostic timeliness and were analysed to identify barriers for rapid diagnostic evaluation, and PCPs' actions involving elements of resilience addressing those barriers. We rated these actions according to whether they were usual or extraordinary for typical PCP work. Resilient actions and associated barriers were found in 59% of the cases, in all ranges of timeliness, with 40% involving actions rated as beyond typical. Most of the barriers were related to access to specialty services and coordination with patients. Many of the resilient actions involved using additional communication channels to solicit cooperation from other participants in the diagnostic process. Diagnostic evaluation of cancer involves several resilient actions by PCPs targeted at system deficiencies. PCPs' actions can sometimes mitigate system barriers to diagnosis, and thereby impact the sensitivity of 'downstream' measures (eg, delays) in detecting barriers. While resilient actions might enable providers to mitigate system deficiencies in the short run, they can be resource intensive and potentially unsustainable. They complement, rather than substitute for, structural remedies to improve system performance. Measures to detect and fix system performance issues targeted by these resilient actions could facilitate diagnostic safety.

Resilient Actions in the Diagnostic Process and System Performance

PubMed Central

Smith, Michael W.; Giardina, Traber Davis; Murphy, Daniel R.; Laxmisan, Archana; Singh, Hardeep

2013-01-01

Objectives Systemic issues can adversely affect the diagnostic process. Many system-related barriers can be masked by ‘resilient’ actions of frontline providers (ie, actions supporting the safe delivery of care in the presence of pressures that the system cannot readily adapt to). We explored system barriers and resilient actions of primary care providers (PCPs) in the diagnostic evaluation of cancer. Methods We conducted a secondary data analysis of interviews of PCPs involved in diagnostic evaluation of 29 lung and colorectal cancer cases. Cases covered a range of diagnostic timeliness and were analyzed to identify barriers for rapid diagnostic evaluation, and PCPs’ actions involving elements of resilience addressing those barriers. We rated these actions according to whether they were usual or extraordinary for typical PCP work. Results Resilient actions and associated barriers were found in 59% of the cases, in all ranges of timeliness, with 40% involving actions rated as beyond typical. Most of the barriers were related to access to specialty services and coordination with patients. Many of the resilient actions involved using additional communication channels to solicit cooperation from other participants in the diagnostic process. Discussion Diagnostic evaluation of cancer involves several resilient actions by PCPs targeted at system deficiencies. PCPs’ actions can sometimes mitigate system barriers to diagnosis, and thereby impact the sensitivity of ‘downstream’ measures (eg, delays) in detecting barriers. While resilient actions might enable providers to mitigate system deficiencies in the short run, they can be resource intensive and potentially unsustainable. They complement, rather than substitute for, structural remedies to improve system performance. Measures to detect and fix system performance issues targeted by these resilient actions could facilitate diagnostic safety. PMID:23813210

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.

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

Plasmon-Based Colorimetric Nanosensors for Ultrasensitive Molecular Diagnostics.

PubMed

Tang, Longhua; Li, Jinghong

2017-07-28

Colorimetric detection of target analytes with high specificity and sensitivity is of fundamental importance to clinical and personalized point-of-care diagnostics. Because of their extraordinary optical properties, plasmonic nanomaterials have been introduced into colorimetric sensing systems, which provide significantly improved sensitivity in various biosensing applications. Here we review the recent progress on these plasmonic nanoparticles-based colorimetric nanosensors for ultrasensitive molecular diagnostics. According to their different colorimetric signal generation mechanisms, these plasmonic nanosensors are classified into two categories: (1) interparticle distance-dependent colorimetric assay based on target-induced forming cross-linking assembly/aggregate of plasmonic nanoparticles; and (2) size/morphology-dependent colorimetric assay by target-controlled growth/etching of the plasmonic nanoparticles. The sensing fundamentals and cutting-edge applications will be provided for each of them, particularly focusing on signal generation and/or amplification mechanisms that realize ultrasensitive molecular detection. Finally, we also discuss the challenge and give our future perspective in this emerging field.

Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1.

PubMed

Fanfone, Deborah; Despretz, Nadège; Stanicki, Dimitri; Rubio-Magnieto, Jenifer; Fossépré, Mathieu; Surin, Mathieu; Rorive, Sandrine; Salmon, Isabelle; Vander Elst, Luce; Laurent, Sophie; Muller, Robert N; Saussez, Sven; Burtea, Carmen

2017-10-06

The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.

Debris characterization diagnostic for the NIF

NASA Astrophysics Data System (ADS)

Miller, M. C.; Celeste, J. R.; Stoyer, M. A.; Suter, L. J.; Tobin, M. T.; Grun, J.; Davis, J. F.; Barnes, C. W.; Wilson, D. C.

2001-01-01

Generation of debris from targets and by x-ray ablation of surrounding materials will be a matter of concern for experimenters and National Ignition Facility (NIF) operations. Target chamber and final optics protection, for example debris shield damage, drive the interest for NIF operations. Experimenters are primarily concerned with diagnostic survivability, separation of mechanical versus radiation induced test object response in the case of effects tests, and radiation transport through the debris field when the net radiation output is used to benchmark computer codes. In addition, radiochemical analysis of activated capsule debris during ignition shots can provide a measure of the ablator <ρr>. Conceptual design of the Debris Monitor and Rad-Chem Station, one of the NIF core diagnostics, is presented. Methods of debris collection, particle size and mass analysis, impulse measurement, and radiochemical analysis are given. A description of recent experiments involving debris collection and impulse measurement on the OMEGA and Pharos lasers is also provided.

Molecular diagnostics of periodontitis.

PubMed

Korona-Głowniak, Izabela; Siwiec, Radosław; Berger, Marcin; Malm, Anna; Szymańska, Jolanta

2017-01-28

The microorganisms that form dental plaque are the main cause of periodontitis. Their identification and the understanding of the complex relationships and interactions that involve these microorganisms, environmental factors and the host's health status enable improvement in diagnostics and targeted therapy in patients with periodontitis. To this end, molecular diagnostics techniques (both techniques based on the polymerase chain reaction and those involving nucleic acid analysis via hybridization) come increasingly into use. On the basis of a literature review, the following methods are presented: polymerase chain reaction (PCR), real-time polymerase chain reaction (real-time PCR), 16S rRNA-encoding gene sequencing, checkerboard and reverse-capture checkerboard hybridization, microarrays, denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE), as well as terminal restriction fragment length polymorphism (TRFLP) and next generation sequencing (NGS). The advantages and drawbacks of each method in the examination of periopathogens are indicated. The techniques listed above allow fast detection of even small quantities of pathogen present in diagnostic material and prove particularly useful to detect microorganisms that are difficult or impossible to grow in a laboratory.

Experimental investigation of adiabatic compression and heating using collision of an MHD-driven jet with a gas target cloud for magnetized target fusion

NASA Astrophysics Data System (ADS)

Seo, Byonghoon; Li, Hui; Bellan, Paul

2017-10-01

We are studying magnetized target fusion using an experimental method where an imploding liner compressing a plasma is simulated by a high-speed MHD-driven plasma jet colliding with a gas target cloud. This has the advantage of being non-destructive so orders of magnitude more shots are possible. Since the actual density and temperature are much more modest than fusion-relevant values, the goal is to determine the scaling of the increase in density and temperature when an actual experimental plasma is adiabatically compressed. Two new-developed diagnostics are operating and providing data. The first new diagnostic is a fiber-coupled interferometer which measures line-integrated electron density not only as a function of time, but also as a function of position along the jet. The second new diagnostic is laser Thomson scattering which measures electron density and temperature at the location where the jet collides with the cloud. These diagnostics show that when the jet collides with a target cloud the jet slows down substantially and both the electron density and temperature increase. The experimental measurements are being compared with 3D MHD and hybrid kinetic numerical simulations that model the actual experimental geometry.

Diagnosing ion-beam targets, data acquisition, reactor conditions

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

Mendel, Jr., C. W.

1982-01-01

The final lecture will discuss diagnostics of the target. These are very difficult because of the short times, small spatial extent, and extreme values of temperature and pressure. Diagnostics for temperature, density profile, and neutron production will be discussed. A few minutes will be devoted to data acquisition needs. The lecture will end with a discussion of current areas where improvements are needed and future diagnostics that will be required for reactor conditions.

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.

Impact of antepartum diagnostic amnioinfusion on targeted ultrasound imaging of pregnancies presenting with severe oligo- and anhydramnios: An analysis of 61 cases.

PubMed

Vikraman, Seneesh Kumar; Chandra, Vipin; Balakrishnan, Bijoy; Batra, Meenu; Sethumadhavan, Sreeja; Patil, Swapneel Neelkanth; Nair, Sabila; Kannoly, Gopinathan

2017-05-01

The primary objective our study was to assess the role of diagnostic antepartum amnioinfusion on the yield from targeted ultrasounds performed in pregnancies with severe oligo- and anhydramnios. This was a retrospective and descriptive study, conducted in the fetal medicine units of two private tertiary care referral centers in south India. The details of all the cases of diagnostic amnioinfusion performed at these two centers from January 2009 to June 2016 were collected and analyzed. Inclusion criteria were pregnancies between 17 and 26 weeks of gestational age with severe oligo- or anhydramnios. Pregnancies with obvious preterm premature rupture of membranes (PPROM) were excluded. The primary outcome measure was the improvement in diagnostic information pertaining to cause of severe oligo- and anhydramnios, and the nature of such anomalies. A total of 61 cases of were identified. The median gestational age at performance of the procedure was 22 weeks [IQR, 19.5-23]. The mean volume of normal saline infused was 314±54ml. A significant increase in the single vertical pocket (SVP) was observed following the procedure (pre-procedure SVP=0.6±0.9cm, post procedure SVP=3.4±1.7; paired t test, p<0.001). In 37 cases (37/61, 60.7%), there were no pre-procedure ultrasound findings. There was significant overall detection of abnormalities post procedure (mean pre-procedure findings=0.39±0.49, mean post procedure findings=1.59±1.24; paired t test, p<0.001). The most frequent group of anomalies/abnormalities were renal (36/61, 59%), followed by PPROM (13/61, 21.3%) and finally fetal growth restriction (11/61, 18%). Antepartum amnioinfusion is a valuable ancillary technique in prenatal diagnosis as it increases the diagnostic yield from pregnancies presenting with severe oligo- and anhydramnios. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances in sarcoma diagnostics and treatment

PubMed Central

Dancsok, Amanda R; Asleh-Aburaya, Karama; Nielsen, Torsten O

2017-01-01

The heterogeneity of sarcomas with regard to molecular genesis, histology, clinical characteristics, and response to treatment makes management of these rare yet diverse neoplasms particularly challenging. This review encompasses recent developments in sarcoma diagnostics and treatment, including cytotoxic, targeted, epigenetic, and immune therapy agents. In the past year, groups internationally explored the impact of adding mandatory molecular testing to histological diagnosis, reporting some changes in diagnosis and/or management; however, the impact on outcomes could not be adequately assessed. Transcriptome sequencing techniques have brought forward new diagnostic tools for identifying fusions and/or characterizing unclassified entities. Next-generation sequencing and advanced molecular techniques were also applied to identify potential targets for directed and epigenetic therapy, where preclinical studies reported results for agents active within the receptor tyrosine kinase, mTOR, Notch, Wnt, Hedgehog, Hsp90, and MDM2 signaling networks. At the level of clinical practice, modest developments were seen for some sarcoma subtypes in conventional chemotherapy and in therapies targeting the pathways activated by various receptor tyrosine kinases. In the burgeoning field of immune therapy, sarcoma work is in its infancy; however, elaborate protocols for immune stimulation are being explored, and checkpoint blockade agents advance from preclinical models to clinical studies. PMID:27732970

Simulated performance of the optical Thomson scattering diagnostic designed for the National Ignition Facility

DOE PAGES

Ross, J. S.; Datte, P.; Divol, L.; ...

2016-07-28

An optical Thomson scattering diagnostic has been designed for the National Ignition Facility to characterize under-dense plasmas. Here, we report on the design of the system and the expected performance for different target configurations. The diagnostic is designed to spatially and temporally resolve the Thomson scattered light from laser driven targets. The diagnostic will collect scattered light from a 50 × 50 × 200 μm volume. The optical design allows operation with different probe laser wavelengths. A deep-UV probe beam (λ 0 = 210 nm) will be used to Thomson scatter from electron plasma densities of ~5 × 10 20more » cm -3 while a 3ω probe will be used for plasma densities of ~1 × 10 19 cm -3. The diagnostic package contains two spectrometers: the first to resolve Thomson scattering from ion acoustic wave fluctuations and the second to resolve scattering from electron plasma wave fluctuations. Expected signal levels relative to background will be presented for typical target configurations (hohlraums and a planar foil).« less

Simulated performance of the optical Thomson scattering diagnostic designed for the National Ignition Facility.

PubMed

Ross, J S; Datte, P; Divol, L; Galbraith, J; Froula, D H; Glenzer, S H; Hatch, B; Katz, J; Kilkenny, J; Landen, O; Manuel, A M; Molander, W; Montgomery, D S; Moody, J D; Swadling, G; Weaver, J

2016-11-01

An optical Thomson scattering diagnostic has been designed for the National Ignition Facility to characterize under-dense plasmas. We report on the design of the system and the expected performance for different target configurations. The diagnostic is designed to spatially and temporally resolve the Thomson scattered light from laser driven targets. The diagnostic will collect scattered light from a 50 × 50 × 200 μm volume. The optical design allows operation with different probe laser wavelengths. A deep-UV probe beam (λ 0 = 210 nm) will be used to Thomson scatter from electron plasma densities of ∼5 × 10 20 cm -3 while a 3ω probe will be used for plasma densities of ∼1 × 10 19 cm -3 . The diagnostic package contains two spectrometers: the first to resolve Thomson scattering from ion acoustic wave fluctuations and the second to resolve scattering from electron plasma wave fluctuations. Expected signal levels relative to background will be presented for typical target configurations (hohlraums and a planar foil).

Simulated performance of the optical Thomson scattering diagnostic designed for the National Ignition Facility

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

Ross, J. S., E-mail: ross36@llnl.gov; Datte, P.; Divol, L.

2016-11-15

An optical Thomson scattering diagnostic has been designed for the National Ignition Facility to characterize under-dense plasmas. We report on the design of the system and the expected performance for different target configurations. The diagnostic is designed to spatially and temporally resolve the Thomson scattered light from laser driven targets. The diagnostic will collect scattered light from a 50 × 50 × 200 μm volume. The optical design allows operation with different probe laser wavelengths. A deep-UV probe beam (λ{sub 0} = 210 nm) will be used to Thomson scatter from electron plasma densities of ∼5 × 10{sup 20} cm{supmore » −3} while a 3ω probe will be used for plasma densities of ∼1 × 10{sup 19} cm{sup −3}. The diagnostic package contains two spectrometers: the first to resolve Thomson scattering from ion acoustic wave fluctuations and the second to resolve scattering from electron plasma wave fluctuations. Expected signal levels relative to background will be presented for typical target configurations (hohlraums and a planar foil).« less

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging and Fusion Guided Targeted Biopsy Evaluated by Transperineal Template Saturation Prostate Biopsy for the Detection and Characterization of Prostate Cancer.

PubMed

Mortezavi, Ashkan; Märzendorfer, Olivia; Donati, Olivio F; Rizzi, Gianluca; Rupp, Niels J; Wettstein, Marian S; Gross, Oliver; Sulser, Tullio; Hermanns, Thomas; Eberli, Daniel

2018-02-21

We evaluated the diagnostic accuracy of multiparametric magnetic resonance imaging and multiparametric magnetic resonance imaging/transrectal ultrasound fusion guided targeted biopsy against that of transperineal template saturation prostate biopsy to detect prostate cancer. We retrospectively analyzed the records of 415 men who consecutively presented for prostate biopsy between November 2014 and September 2016 at our tertiary care center. Multiparametric magnetic resonance imaging was performed using a 3 Tesla device without an endorectal coil, followed by transperineal template saturation prostate biopsy with the BiopSee® fusion system. Additional fusion guided targeted biopsy was done in men with a suspicious lesion on multiparametric magnetic resonance imaging, defined as Likert score 3 to 5. Any Gleason pattern 4 or greater was defined as clinically significant prostate cancer. The detection rates of multiparametric magnetic resonance imaging and fusion guided targeted biopsy were compared with the detection rate of transperineal template saturation prostate biopsy using the McNemar test. We obtained a median of 40 (range 30 to 55) and 3 (range 2 to 4) transperineal template saturation prostate biopsy and fusion guided targeted biopsy cores, respectively. Of the 124 patients (29.9%) without a suspicious lesion on multiparametric magnetic resonance imaging 32 (25.8%) were found to have clinically significant prostate cancer on transperineal template saturation prostate biopsy. Of the 291 patients (70.1%) with a Likert score of 3 to 5 clinically significant prostate cancer was detected in 129 (44.3%) by multiparametric magnetic resonance imaging fusion guided targeted biopsy, in 176 (60.5%) by transperineal template saturation prostate biopsy and in 187 (64.3%) by the combined approach. Overall 58 cases (19.9%) of clinically significant prostate cancer would have been missed if fusion guided targeted biopsy had been performed exclusively. The sensitivity of

WE-AB-206-01: Diagnostic Ultrasound Imaging Quality Assurance

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

Zagzebski, J.

The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. The goal of this ultrasound hands-on workshop is to demonstrate quality control (QC) testing in diagnostic ultrasound and to provide updates in ACR ultrasound accreditation requirements. The first half of this workshop will include two presentations reviewing diagnostic ultrasound QA/QC and ACR ultrasound accreditation requirements. The second half of the workshop will include live demonstrations of basic QC tests. An array of ultrasound testing phantoms and ultrasound scanners will be available for attendees to learn diagnostic ultrasound QC in a hands-on environmentmore » with live demonstrations and on-site instructors. The targeted attendees are medical physicists in diagnostic imaging. Learning Objectives: Gain familiarity with common elements of a QA/QC program for diagnostic ultrasound imaging dentify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools Learn ACR ultrasound accreditation requirements Jennifer Walter is an employee of American College of Radiology on Ultrasound Accreditation.« less

Impact and cost-effectiveness of current and future tuberculosis diagnostics: the contribution of modelling

PubMed Central

Houben, R.; Cohen, T.; Pai, M.; Cobelens, F.; Vassall, A.; Menzies, N. A.; Gomez, G. B.; Langley, I.; Squire, S. B.; White, R.

2014-01-01

SUMMARY The landscape of diagnostic testing for tuberculosis (TB) is changing rapidly, and stakeholders need urgent guidance on how to develop, deploy and optimize TB diagnostics in a way that maximizes impact and makes best use of available resources. When decisions must be made with only incomplete or preliminary data available, modelling is a useful tool for providing such guidance. Following a meeting of modelers and other key stakeholders organized by the TB Modelling and Analysis Consortium, we propose a conceptual framework for positioning models of TB diagnostics. We use that framework to describe modelling priorities in four key areas: Xpert® MTB/RIF scale-up, target product profiles for novel assays, drug susceptibility testing to support new drug regimens, and the improvement of future TB diagnostic models. If we are to maximize the impact and cost-effectiveness of TB diagnostics, these modelling priorities should figure prominently as targets for future research. PMID:25189546

Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases.

PubMed

Punetha, Jaya; Kesari, Akanchha; Uapinyoying, Prech; Giri, Mamta; Clarke, Nigel F; Waddell, Leigh B; North, Kathryn N; Ghaoui, Roula; O'Grady, Gina L; Oates, Emily C; Sandaradura, Sarah A; Bönnemann, Carsten G; Donkervoort, Sandra; Plotz, Paul H; Smith, Edward C; Tesi-Rocha, Carolina; Bertorini, Tulio E; Tarnopolsky, Mark A; Reitter, Bernd; Hausmanowa-Petrusewicz, Irena; Hoffman, Eric P

2016-05-27

Molecular diagnostics in the genetic myopathies often requires testing of the largest and most complex transcript units in the human genome (DMD, TTN, NEB). Iteratively targeting single genes for sequencing has traditionally entailed high costs and long turnaround times. Exome sequencing has begun to supplant single targeted genes, but there are concerns regarding coverage and needed depth of the very large and complex genes that frequently cause myopathies. To evaluate efficiency of next-generation sequencing technologies to provide molecular diagnostics for patients with previously undiagnosed myopathies. We tested a targeted re-sequencing approach, using a 45 gene emulsion PCR myopathy panel, with subsequent sequencing on the Illumina platform in 94 undiagnosed patients. We compared the targeted re-sequencing approach to exome sequencing for 10 of these patients studied. We detected likely pathogenic mutations in 33 out of 94 patients with a molecular diagnostic rate of approximately 35%. The remaining patients showed variants of unknown significance (35/94 patients) or no mutations detected in the 45 genes tested (26/94 patients). Mutation detection rates for targeted re-sequencing vs. whole exome were similar in both methods; however exome sequencing showed better distribution of reads and fewer exon dropouts. Given that costs of highly parallel re-sequencing and whole exome sequencing are similar, and that exome sequencing now takes considerably less laboratory processing time than targeted re-sequencing, we recommend exome sequencing as the standard approach for molecular diagnostics of myopathies.

New diagnostic methods for pneumonia in the ICU.

PubMed

Douglas, Ivor S

2016-04-01

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

Use of the 2.8 French Progreat microcatheter in diagnostic cerebral angiography.

PubMed

Griauzde, Julius; Gemmete, Joseph J; Shastri, Ravi; Pandey, Aditya S; Chaudhary, Neeraj

2017-01-01

Tortuous vascular anatomy poses a significant challenge to performing diagnostic cerebral angiography. To report a new cerebral angiography technique for overcoming tortuous aortic and supra-aortic anatomy using a 2.8 French (F) Progreat microcatheter (0.028 inch (internal diameter) (Terumo; Somerset, New Jersey, USA) to obtain a diagnostic cerebral angiogram. A retrospective analysis of consecutive cases undergoing diagnostic cerebral angiography at our institution between 1 January 2013 and 30 November 2015 in which a 2.8F Progreat microcatheter was used. Clinical and operative notes were reviewed and correlated with imaging. Radiologic imaging, including CT, MRI, and digital subtraction angiography, was reviewed. Neurologic, systemic, and local complications were recorded on the basis of clinical follow-up results after each angiographic examination. Events that occurred within 24 h of the angiography were considered to be complications of the procedure. Initial attempts at catheterization of the target vessel with various 4F and 5F catheters were unsuccessful owing to tortuosity, atherosclerotic disease, or occlusion of the catheter in the target vessel. Microcatheterization of the target vessel was successful in 59/62 (95%) target vessels. A diagnostic cerebral angiogram with a power injection was obtained in 59 (100%) of the successfully catheterized vessels. In one case, angiography proceeded to aneurysm coiling after over-the-wire exchange. In two cases, angiography proceeded to mechanical thrombectomy after over-the-wire exchange. No procedural complications were seen. The 2.8F Progreat microcatheter can be used to obtain a diagnostic cerebral angiogram in patients with anatomic challenges limiting catheterization by standard techniques. 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/.

Antibodies Targeting EMT

DTIC Science & Technology

2015-10-01

breast cancer does not have specific antibody drugs like Herceptin, and there is considerable need for targeted therapeutics and diagnostic...mesenchymal transition” or EMT. This process is important in several cancers , but is particularly associated with “triple-negative” breast cancer ...pathways in cancer cells and make a major impact on breast cancer . 15. SUBJECT TERMS Monoclonal Antibody, Epithelial to Mesenchymal Transition, Antibody

Interceptive Beam Diagnostics - Signal Creation and Materials Interactions

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

Plum, Michael; Spallation Neutron Source, Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, TN

2004-11-10

The focus of this tutorial will be on interceptive beam diagnostics such as wire scanners, screens, and harps. We will start with an overview of the various ways beams interact with materials to create signals useful for beam diagnostics systems. We will then discuss the errors in a harp or wire scanner profile measurement caused by errors in wire position, number of samples, and signal errors. Finally we will apply our results to two design examples-the SNS wire scanner system and the SNS target harp.

Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

PubMed

van den Bosch, Sven; Vogel, Wouter V; Raaijmakers, Cornelis P; Dijkema, Tim; Terhaard, Chris H J; Al-Mamgani, Abrahim; Kaanders, Johannes H A M

2018-05-03

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Targeted proteins for diagnostic imaging: does chemistry make a difference?

PubMed

Fritzberg, A R; Beaumier, P L

1992-03-01

The Oyen et al. study is valuable in that it systematically evaluates several of the factors involved in radiolabeled protein uptake and retention in infectious foci. The role of particular proteins and their receptor specific interactions seems to be inconsequential in agreement with the findings of other. However, the role of the radiolabel was shown to be important and significant differences were delineated from comparisons of the radionuclides and their associated chemistries. The conclusion implicating radionuclide chemistry and associated linkages underscores the need to optimize the attachment and labeling chemical modifications of protein carriers. Evaluation criteria should include serum stability, determination and assessment of the effect of molar substitution ratio, and potential for improving blood clearance without reducing the target-to-non-target ratio. Important areas for future study include characterization of radioactive metabolites and the design and synthesis of new ligands which direct the disposition of metabolites reducing retention in normal organs or accelerating renal excretion. Additionally, intracellular processing of radiolabel, compartmental distribution and strategies for augmenting internalization and retention within the target cell merit detailed exploration. For each radionuclide of interest, 111In, radioiodines, 99mTc and others, improved chemical moieties exist for controlling radiolabel fate. When carrying out mechanistic and evaluative studies, clear-cut conclusions will only be reached when defined and controlled chemistry is used. Having established a "gold standard," simplifications in radiolabeling and other chemical refinements can then be pursued with a quantitative understanding of the trade-offs in targeting agent performance versus other considerations such as cost reduction, simplicity, and convenience.

Antibodies Targeting EMT

DTIC Science & Technology

2015-10-01

of breast cancer does not have specific antibody drugs like Herceptin, and there is considerable need for targeted therapeutics and diagnostic...epithelial to mesenchymal transition” or EMT. This process is important in several cancers , but is particularly associated with “triple-negative” breast ...pathways in cancer cells and make a major impact on breast cancer . 15. SUBJECT TERMS Monoclonal Antibody, Epithelial to Mesenchymal Transition

Targeted Therapies in NSCLC: Emerging oncogene targets following the success of EGFR

PubMed Central

Berge, Eamon M; Doebele, Robert C

2014-01-01

The diagnostic testing, treatment and prognosis of non-small cell lung cancer (NSCLC) has undergone a paradigm shift since the discovery of sensitizing mutations in the epidermal growth factor receptor (EGFR) gene in a subset of NSCLC patients. Several additional oncogenic mutations, including gene fusions and amplifications have since been discovered, with a number of drugs that target each specific oncogene. This review focuses on oncogenes in NSCLC other than EGFR and their companion ‘targeted therapies’. Particular emphasis is placed on the role of ALK, ROS1, RET, MET, BRAF, and HER2 in NSCLC. PMID:24565585

WE-AB-206-00: Diagnostic QA/QC Hands-On Workshop

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

NONE

The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. The goal of this ultrasound hands-on workshop is to demonstrate quality control (QC) testing in diagnostic ultrasound and to provide updates in ACR ultrasound accreditation requirements. The first half of this workshop will include two presentations reviewing diagnostic ultrasound QA/QC and ACR ultrasound accreditation requirements. The second half of the workshop will include live demonstrations of basic QC tests. An array of ultrasound testing phantoms and ultrasound scanners will be available for attendees to learn diagnostic ultrasound QC in a hands-on environmentmore » with live demonstrations and on-site instructors. The targeted attendees are medical physicists in diagnostic imaging. Learning Objectives: Gain familiarity with common elements of a QA/QC program for diagnostic ultrasound imaging dentify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools Learn ACR ultrasound accreditation requirements Jennifer Walter is an employee of American College of Radiology on Ultrasound Accreditation.« less

Nuclear Diagnostics at the National Ignition Facility, 2013-2015

NASA Astrophysics Data System (ADS)

Yeamans, C. B.; Cassata, W. S.; Church, J. A.; Fittinghoff, D. N.; Gatu Johnson, M.; Gharibyan, N.; Határik, R.; Sayre, D. B.; Sio, H. W.; Bionta, R. M.; Bleuel, D. L.; Caggiano, J. A.; Cerjan, C. J.; Cooper, G. W.; Eckart, M. J.; Edwards, E. R.; Faye, S. A.; Forrest, C. J.; Frenje, J. A.; Glebov, V. Yu; Grant, P. M.; Grim, G. P.; Hartouni, E. P.; Herrmann, H. W.; Kilkenny, J. D.; Knauer, J. P.; Mackinnon, A. J.; Merrill, F. E.; Moody, K. J.; Moran, M. J.; Petrasso, R. D.; Phillips, T. W.; Rinderknecht, H. G.; Schneider, D. H. G.; Sepke, S. M.; Shaughnessy, D. A.; Stoeffl, W.; Velsko, C. A.; Volegov, P.

2016-05-01

The National Ignition Facility (NIF) relies on a suite of nuclear diagnostics to measure the neutronic output of experiments. Neutron time-of-flight (NTOF) and neutron activation diagnostics (NAD) provide performance metrics of absolute neutron yield and neutron spectral content: spectral width and non-thermal content, from which implosion physical quantities of temperature and scattering mass are inferred. Spatially-distributed flange- mounted NADs (FNAD) measure, with nearly identical systematic uncertainties, primary DT neutron emission to infer a whole-sky neutron field. An automated FNAD system is being developed. A magnetic recoil spectrometer (MRS) shares few systematics with comparable NTOF and NAD devices, and as such is deployed for independent measurement of the primary neutronic quantities. The gas-Cherenkov Gamma Reaction History (GRH) instrument records four energy channels of time-resolved gamma emission to measure nuclear bang time and burn width, as well as to infer carbon areal density in experiments utilizing plastic or diamond capsules. A neutron imaging system (NIS) takes two images of the neutron source, typically gated to create coregistered 13-15 MeV primary and 6-12 MeV downscattered images. The radiochemical analysis of gaseous samples (RAGS) instrument pumps target chamber gas to a chemical reaction and fractionation system configured with gamma counters, allowing measurement of radionuclides with half-lives as short as 8 seconds. Solid radiochemistry collectors (SRC) with backing NAD foils collect target debris, where activated materials from the target assembly are used as indicators of neutron spectrum content, and also serve as the primary diagnostic for nuclear forensic science experiments. Particle time-of-flight (PTOF) measures compression-bang time using DT- or DD-neutrons, as well as shock bang-time using D3He-protons for implosions with lower x-ray background. In concert, these diagnostics serve to measure the basic and advanced

Diagnostic imaging advances in murine models of colitis.

PubMed

Brückner, Markus; Lenz, Philipp; Mücke, Marcus M; Gohar, Faekah; Willeke, Peter; Domagk, Dirk; Bettenworth, Dominik

2016-01-21

Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.

The future of targeted peptidomics.

PubMed

Findeisen, Peter

2013-12-01

Targeted MS is becoming increasingly important for sensitive and specific quantitative detection of proteins and respective PTMs. In this article, Ceglarek et al. [Proteomics Clin. Appl. 2013, 7, 794-801] present an LC-MS-based method for simultaneous quantitation of seven apolipoproteins in serum specimens. The assay fulfills many necessities of routine diagnostic applications, namely, low cost, high throughput, and good reproducibility. We anticipate that validation of new biomarkers will speed up with this technology and the palette of laboratory-based diagnostic tools will hopefully be augmented significantly in the near future. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diagnostic reasoning strategies and diagnostic success.

PubMed

Coderre, S; Mandin, H; Harasym, P H; Fick, G H

2003-08-01

Cognitive psychology research supports the notion that experts use mental frameworks or "schemes", both to organize knowledge in memory and to solve clinical problems. The central purpose of this study was to determine the relationship between problem-solving strategies and the likelihood of diagnostic success. Think-aloud protocols were collected to determine the diagnostic reasoning used by experts and non-experts when attempting to diagnose clinical presentations in gastroenterology. Using logistic regression analysis, the study found that there is a relationship between diagnostic reasoning strategy and the likelihood of diagnostic success. Compared to hypothetico-deductive reasoning, the odds of diagnostic success were significantly greater when subjects used the diagnostic strategies of pattern recognition and scheme-inductive reasoning. Two other factors emerged as independent determinants of diagnostic success: expertise and clinical presentation. Not surprisingly, experts outperformed novices, while the content area of the clinical cases in each of the four clinical presentations demonstrated varying degrees of difficulty and thus diagnostic success. These findings have significant implications for medical educators. It supports the introduction of "schemes" as a means of enhancing memory organization and improving diagnostic success.

Future of diagnostic microbiology.

PubMed

Khardori, N

2014-01-01

Diagnostic Microbiology is the tool that makes it possible to identify the exact etiology of infectious diseases and the most optimal therapy at the level of individual patients as well as communities. Conventional methods require time to grow the microbes in vitro under specific conditions and not all microbes are easily cultivable. This is followed by biochemical methods for identification which also require hours and sometimes days. Transport of the specimens under less than ideal conditions, prior use of antibiotics and small number of organisms are among the factors that render culture-based methods less reliable. Newer methods depend on amplification of nucleic acids followed by use of probes for identification. This mitigates the need for higher microbial load, presence of metabolically active viable organisms and shortens the time to reporting. These methods can be used to detect antibiotic resistance genes directly from the specimen and help direct targeted therapy. Since these methods will not fulfill all the diagnostic needs, a second approach is being used to shorten the time to identification after the organism has already grown. Mass spectrometry and bioinformatics are the tools making this possible. This review gives a historical perspective on diagnostic microbiology, discusses the pitfalls of current methodology and provides an overview of newer and future methods.

Diagnostic Peptide Discovery: Prioritization of Pathogen Diagnostic Markers Using Multiple Features

PubMed Central

Carmona, Santiago J.; Sartor, Paula A.; Leguizamón, María S.; Campetella, Oscar E.; Agüero, Fernán

2012-01-01

The availability of complete pathogen genomes has renewed interest in the development of diagnostics for infectious diseases. Synthetic peptide microarrays provide a rapid, high-throughput platform for immunological testing of potential B-cell epitopes. However, their current capacity prevent the experimental screening of complete “peptidomes”. Therefore, computational approaches for prediction and/or prioritization of diagnostically relevant peptides are required. In this work we describe a computational method to assess a defined set of molecular properties for each potential diagnostic target in a reference genome. Properties such as sub-cellular localization or expression level were evaluated for the whole protein. At a higher resolution (short peptides), we assessed a set of local properties, such as repetitive motifs, disorder (structured vs natively unstructured regions), trans-membrane spans, genetic polymorphisms (conserved vs. divergent regions), predicted B-cell epitopes, and sequence similarity against human proteins and other potential cross-reacting species (e.g. other pathogens endemic in overlapping geographical locations). A scoring function based on these different features was developed, and used to rank all peptides from a large eukaryotic pathogen proteome. We applied this method to the identification of candidate diagnostic peptides in the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We measured the performance of the method by analyzing the enrichment of validated antigens in the high-scoring top of the ranking. Based on this measure, our integrative method outperformed alternative prioritizations based on individual properties (such as B-cell epitope predictors alone). Using this method we ranked 10 million 12-mer overlapping peptides derived from the complete T. cruzi proteome. Experimental screening of 190 high-scoring peptides allowed the identification of 37 novel epitopes with diagnostic potential, while none

Real-time interferometric diagnostics of rubidium plasma

NASA Astrophysics Data System (ADS)

Djotyan, G. P.; Bakos, J. S.; Kedves, M. Á.; Ráczkevi, B.; Dzsotjan, D.; Varga-Umbrich, K.; Sörlei, Zs.; Szigeti, J.; Ignácz, P.; Lévai, P.; Czitrovszky, A.; Nagy, A.; Dombi, P.; Rácz, P.

2018-03-01

A method of interferometric real-time diagnostics is developed and applied to rubidium plasma created by strong laser pulses in the femtosecond duration range at different initial rubidium vapor densities using a Michelson-type interferometer. A cosine fit with an exponentially decaying relative phase is applied to the obtained time-dependent interferometry signals to measure the density-length product of the created plasma and its recombination time constant. The presented technique may be applicable for real-time measurements of rubidium plasma dynamics in the AWAKE experiment at CERN, as well as for real-time diagnostics of plasmas created in different gaseous media and on surfaces of solid targets.

Engineered Hybrid Nanoparticles for On-Demand Diagnostics and Therapeutics.

PubMed

Nguyen, Kim Truc; Zhao, Yanli

2015-12-15

Together with the simultaneous development of nanomaterials and molecular biology, the bionano interface brings about various applications of hybrid nanoparticles in nanomedicine. The hybrid nanoparticles not only present properties of the individual components but also show synergistic effects for specialized applications. Thus, the development of advanced hybrid nanoparticles for targeted and on-demand diagnostics and therapeutics of diseases has rapidly become a hot research topic in nanomedicine. The research focus is to fabricate novel classes of programmable hybrid nanoparticles that are precisely engineered to maximize drug concentrations in diseased cells, leading to enhanced efficacy and reduced side effects of chemotherapy for the disease treatment. In particular, the hybrid nanoparticle platforms can simultaneously target diseased cells, enable the location to be imaged by optical methods, and release therapeutic drugs to the diseased cells by command. This Account specially discusses the rational fabrication of integrated hybrid nanoparticles and their applications in diagnostics and therapeutics. For diagnostics applications, hybrid nanoparticles can be utilized as imaging agents that enable detailed visualization at the molecular level. By the use of suitable targeting ligands incorporated on the nanoparticles, targeted optical imaging may be feasible with improved performance. Novel imaging techniques such as multiphoton excitation and photoacoustic imaging using near-infrared light have been developed using the intrinsic properties of particular nanoparticles. The use of longer-wavelength excitation sources allows deeper penetration into the human body for disease diagnostics and at the same time reduces the adverse effects on normal tissues. Furthermore, multimodal imaging techniques have been achieved by combining several types of components in nanoparticles, offering higher accuracy and better spatial views, with the aim of detecting life

Method and apparatus for producing cryogenic targets

DOEpatents

Murphy, James T.; Miller, John R.

1984-01-01

An improved method and apparatus are given for producing cryogenic inertially driven fusion targets in the fast isothermal freezing (FIF) method. Improved coupling efficiency and greater availability of volume near the target for diagnostic purposes and for fusion driver beam propagation result. Other embodiments include a new electrical switch and a new explosive detonator, all embodiments making use of a purposeful heating by means of optical fibers.

Creation of a diagnostic wait times measurement framework based on evidence and consensus.

PubMed

Gilbert, Julie E; Dobrow, Mark J; Kaan, Melissa; Dobranowski, Julian; Srigley, John R; Jusko Friedman, Audrey; Irish, Jonathan C

2014-09-01

Public reporting of wait times worldwide has to date focused largely on treatment wait times and is limited in its ability to capture earlier parts of the patient journey. The interval between suspicion and diagnosis or ruling out of cancer is a complex phase of the cancer journey. Diagnostic delays and inefficient use of diagnostic imaging procedures can result in poor patient outcomes, both physical and psychosocial. This study was designed to develop a framework that could be adopted for multiple disease sites across different jurisdictions to enable the measurement of diagnostic wait times and diagnostic delay. Diagnostic benchmarks and targets in cancer systems were explored through a targeted literature review and jurisdictional scan. Cancer system leaders and clinicians were interviewed to validate the information found in the jurisdictional scan. An expert panel was assembled to review and, through a modified Delphi consensus process, provide feedback on a diagnostic wait times framework. The consensus process resulted in agreement on a measurement framework that identified suspicion, referral, diagnosis, and treatment as the main time points for measuring this critical phase of the patient journey. This work will help guide initiatives designed to improve patient access to health services by developing an evidence-based approach to standardization of the various waypoints during the diagnostic pathway. The diagnostic wait times measurement framework provides a yardstick to measure the performance of programs that are designed to manage and expedite care processes between referral and diagnosis or ruling out of cancer. Copyright © 2014 by American Society of Clinical Oncology.

Brain: The Potential Diagnostic and Therapeutic Target for Glaucoma.

PubMed

Faiq, Muneeb A; Dada, Rima; Kumar, Ashutosh; Saluja, Daman; Dada, Tanuj

2016-01-01

Glaucoma is a form of multifactorial ocular neurodegeneration with immensely complex etiology, pathogenesis and pathology. Though the mainstream therapeutic management of glaucoma is lowering of intraocular pressure, there is, as of now, no cure for the disease. New evidences ardently suggest brain involvement in all aspects of this malady. This consequently advocates the opinion that brain should be the spotlight of glaucoma research and may form the impending and promising target for glaucoma diagnosis and treatment. The present analysis endeavors at understanding glaucoma vis-à-vis brain structural and/or functional derangement and central nervous system (CNS) degeneration. Commencing with the premise of developing some understanding about the brain-nature of ocular structures; we discuss the nature of the cellular and molecular moieties involved in glaucoma and Alzheimer's disease. Substantial deal of literature implies that glaucoma may well be a disease of the brain, nevertheless, manifesting as progressive loss of vision. If that is the case, then targeting brain will be far more imperative in glaucoma therapeutics than any other remedial regimen currently being endorsed.

Diagnostic decision-making and strategies to improve diagnosis.

PubMed

Thammasitboon, Satid; Cutrer, William B

2013-10-01

A significant portion of diagnostic errors arises through cognitive errors resulting from inadequate knowledge, faulty data gathering, and/or faulty verification. Experts estimate that 75% of diagnostic failures can be attributed to clinician diagnostic thinking failure. The cognitive processes that underlie diagnostic thinking of clinicians are complex and intriguing, and it is imperative that clinicians acquire explicit appreciation and application of different cognitive approaches to make decisions better. A dual-process model that unifies many theories of decision-making has emerged as a promising template for understanding how clinicians think and judge efficiently in a diagnostic reasoning process. The identification and implementation of strategies for decreasing or preventing such diagnostic errors has become a growing area of interest and research. Suggested strategies to decrease diagnostic error incidence include increasing clinician's clinical expertise and avoiding inherent cognitive errors to make decisions better. Implementing Interventions focused solely on avoiding errors may work effectively for patient safety issues such as medication errors. Addressing cognitive errors, however, requires equal effort on expanding the individual clinician's expertise. Providing cognitive support to clinicians for robust diagnostic decision-making serves as the final strategic target for decreasing diagnostic errors. Clinical guidelines and algorithms offer another method for streamlining decision-making and decreasing likelihood of cognitive diagnostic errors. Addressing cognitive processing errors is undeniably the most challenging task in reducing diagnostic errors. While many suggested approaches exist, they are mostly based on theories and sciences in cognitive psychology, decision-making, and education. The proposed interventions are primarily suggestions and very few of them have been tested in the actual practice settings. Collaborative research effort is

Recent Progress in Nanomedicine: Therapeutic, Diagnostic and Theranostic Applications

PubMed Central

Rizzo, Larissa Y.; Theek, Benjamin; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2013-01-01

In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-) physiological processes. In addition, ever more efforts have been undertaken to combine diagnostic and therapeutic properties within a single nanomedicine formulation. These so-called nanotheranostics are able to provide valuable information on drug delivery, drug release and drug efficacy, and they are considered to be highly useful for personalizing nanomedicine-based (chemo-) therapeutic interventions. PMID:23578464

Method and apparatus for producing cryogenic targets

DOEpatents

Murphy, J.T.; Miller, J.R.

1984-08-07

An improved method and apparatus are given for producing cryogenic inertially driven fusion targets in the fast isothermal freezing (FIF) method. Improved coupling efficiency and greater availability of volume near the target for diagnostic purposes and for fusion driver beam propagation result. Other embodiments include a new electrical switch and a new explosive detonator, all embodiments making use of a purposeful heating by means of optical fibers. 6 figs.

Circulating and disseminated tumor cells: diagnostic tools and therapeutic targets in motion

PubMed Central

Lin, Peter P.; Gires, Olivier

2017-01-01

Enumeration of circulating tumor cells (CTCs) in peripheral blood with the gold standard CellSearchTM has proven prognostic value for tumor recurrence and progression of metastatic disease. Therefore, the further molecular characterization of isolated CTCs might have clinical relevance as liquid biopsy for therapeutic decision-making and to monitor disease progression. The direct analysis of systemic cancer appears particularly important in view of the known disparity in expression of therapeutic targets as well as epithelial-to-mesenchymal transition (EMT)-based heterogeneity between primary and systemic tumor cells, which all substantially complicate monitoring and therapeutic targeting at present. Since CTCs are the potential precursor cells of metastasis, their in-depth molecular profiling should also provide a useful resource for target discovery. The present review will discuss the use of systemically spread cancer cells as liquid biopsy and focus on potential target antigens. PMID:27683128

[Molecular and immunohistochemical diagnostics in melanoma].

PubMed

Schilling, B; Griewank, K G

2016-07-01

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

Blood culture-negative endocarditis: Improving the diagnostic yield using new diagnostic tools.

PubMed

Fournier, Pierre-Edouard; Gouriet, Frédérique; Casalta, Jean-Paul; Lepidi, Hubert; Chaudet, Hervé; Thuny, Franck; Collart, Frédéric; Habib, Gilbert; Raoult, Didier

2017-11-01

Blood culture-negative endocarditis (BCNE) may represent up to 70% of all endocarditis cases, depending on series. From 2001 to 2009, we implemented in our laboratory a multimodal diagnostic strategy for BCNE that included systematized testing of blood, and when available, valvular biopsy specimens using serological, broad range molecular, and histopathological assays. A causative microorganism was identified in 62.7% of patients.In this study from January 2010 to December 2015, in an effort to increase the number of identified causative microorganisms, we prospectively added to our diagnostic protocol specific real-time (RT) polymerase chain reaction (PCR) assays targeting various endocarditis agents, and applied them to all patients with BCNE admitted to the 4 public hospitals in Marseille, France.A total of 283 patients with BCNE were included in the study. Of these, 177 were classified as having definite endocarditis. Using our new multimodal diagnostic strategy, we identified an etiology in 138 patients (78.0% of cases). Of these, 3 were not infective (2.2%) and 1 was diagnosed as having Mycobacterium bovis BCG endocarditis. By adding specific PCR assays from blood and valvular biopsies, which exhibited a significantly greater sensitivity (P < 10) than other methods, causative agents, mostly enterococci, streptococci, and zoonotic microorganisms, were identified in an additional 27 patients (14 from valves only, 11 from blood only, and 2 from both). Finally, in another 107 patients, a pathogen was detected using serology in 37, valve culture in 8, broad spectrum PCR from valvular biopsies and blood in 19 and 2, respectively, immunohistochemistry from valves in 3, and a combination of several assays in 38.By adding specific RT-PCR assays to our systematic PCR testing of patients with BCNE, we increased the diagnostic efficiency by 24.3%, mostly by detecting enterococci and streptococci that had not been detected by other diagnostic methods, but also agents

Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

PubMed

Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

2015-01-01

In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

Appropriate targeting of artemisinin-based combination therapy by community health workers using malaria rapid diagnostic tests: findings from randomized trials in two contrasting areas of high and low malaria transmission in south-western Uganda.

PubMed

Ndyomugyenyi, Richard; Magnussen, Pascal; Lal, Sham; Hansen, Kristian; Clarke, Siân E

2016-09-01

To compare the impact of malaria rapid diagnostic tests (mRDTs), used by community health workers (CHWs), on the proportion of children <5 years of age receiving appropriately targeted treatment with artemisinin-based combination therapy (ACT), vs. presumptive treatment. Cluster-randomized trials were conducted in two contrasting areas of moderate-to-high and low malaria transmission in rural Uganda. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches: (i) presumptive clinical diagnosis of malaria [control arm] and (ii) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [intervention arm], with village as the unit of randomisation. Treatment decisions by CHWs were validated by microscopy on a reference blood slide collected at the time of consultation, to compare the proportion of children <5 years receiving appropriately targeted ACT treatment, defined as patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving artemether-lumefantrine or rectal artesunate, and patients with no malaria parasites not given ACT. In the moderate-to-high transmission area, ACT treatment was appropriately targeted in 79.3% (520/656) of children seen by CHWs using mRDTs to diagnose malaria, vs. 30.8% (215/699) of children seen by CHWs using presumptive diagnosis (P < 0.001). In the low transmission area, 90.1% (363/403) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8% (64/817) seen by CHWs using presumptive diagnosis (P < 0.001). Low mRDT sensitivity in children with low-density parasitaemia (<200 parasites/μl) was identified as a potential concern. When equipped with mRDTs, ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites. mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within

Advances in point-of-care technologies for molecular diagnostics.

PubMed

Zarei, Mohammad

2017-12-15

Advances in miniaturization, nanotechnology, and microfluidics, along with developments in cloud-connected point-of-care (POC) diagnostics technologies are pushing the frontiers of POC devices toward low-cost, user-friendly, and enhanced sensitivity molecular-level diagnostics. The combination of various bio-sensing platforms within smartphone-integrated electronic readers provides accurate on-site and on-time diagnostics based on various types of chemical and biological targets. Further, 3D printing technology shows a huge potential toward fabrication and improving the performance of POC devices. Integration of skin-like flexible sensors with wireless communication technology creates a unique opportunity for continuous, real-time monitoring of patients for both preventative healthcare and during disease outbreaks. Here, we review recent developments and advances in POC technologies and describe how these advances enhance the performance of POC platforms. Also, this review describes challenges, directions, and future trends on application of emerging technologies in POC diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Epidermal Growth Factor Receptor (EGFR) Kinase Inhibitors and Non-Small Cell Lung Cancer (NSCLC) - Advances in Molecular Diagnostic Techniques to Facilitate Targeted Therapy.

PubMed

Ghafoor, Qamar; Baijal, Shobhit; Taniere, Phillipe; O'Sullivan, Brendan; Evans, Matthew; Middleton, Gary

2017-12-21

A subset of patients with non-small cell lung cancer (NSCLC) respond well to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), due to the presence of sensitising mutations in the gene encoding EGFR. Mutations associated with resistance to first generation EGFR TKIs have also been identified, which lead to therapeutic failure and the requirement for new drugs. Three generations of EGFR TKIs have been developed and either have been, or are being, evaluated as first and/or second line therapeutic agents. In this review, we consider the advances in molecular diagnostic techniques that are used, or are in development, to facilitate the targeted EGFR TKI therapy of patients with NSCLC. A literature search was conducted in May 2017 using PubMed, and spanning the period September 2005 (EU approval date of erlotinib) to May 2017. Search terms used were: EGFR TKI, NSCLC, clinical trial, erlotinib, gefitinib, afatinib, EGFR mutations, Exon 19 deletion, and Leu858Arg. The use of molecular data, in conjunction with other clinical and diagnostic information, will assist physicians to make the best therapeutic choice for each patient with advanced NSCLC. Personalized medicine and a rapidly developing therapy landscape will enable these patients to achieve optimal responses to EGFR TKIs.

The Effect of Molecular Diagnostics on the Treatment of Glioma.

PubMed

Bush, Nancy Ann Oberheim; Butowski, Nicholas

2017-04-01

This review summarizes the use of molecular diagnostics in glioma and its effect on the development of novel therapeutics and management decisions. Genomic and proteomic profiling of brain tumors has provided significant expansion of our understanding of oncogenesis, characterization, and prognostication of brain tumors. Molecular markers such as MGMT, EGFR, IDH, 1p19q, ATRX, TERT, FGFR-TACC, and BRAF are now being used to classify brain tumors as well as influence management decisions. Several of these markers are also being used as therapeutic targets. We review the use of several molecular diagnostics in gliomas and discuss their impact on drug development and clinical trial design. In the future, molecular characterization based on a specific genomic, proteomic as well as transcriptomes for bioformatics analysis will provide clinicians the ability to rationally select drugs with actionable targets for each patient.

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests

PubMed Central

2012-01-01

Background The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. Methods A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 h and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a non-febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. Results A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p = 0.01). Over-treatment with ACT of patients without

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2011-08-01

induced RSR breast cell model, in which cyclin E can be conditionally induced to trigger RSR in normal breast cells. Using this model, we demonstrated...which makes these defects effective targets for both breast cancer prevention and breast cancer treatment. This project is to use cutting-edge...defective RSR; identify drugs that target these defects; and develop RSR-defect-targeting nanoparticles for diagnostic imaging, prevention, and

The oral-systemic connection: role of salivary diagnostics

NASA Astrophysics Data System (ADS)

Malamud, Daniel

2013-05-01

Utilizing saliva instead of blood for diagnosis of both local and systemic health is a rapidly emerging field. Recognition of oral-systemic interrelationships for many diseases has fostered collaborations between medicine and dentistry, and many of these collaborations rely on salivary diagnostics. The oral cavity is easily accessed and contains most of the analytes present in blood. Saliva and mucosal transudate are generally utilized for oral diagnostics, but gingival crevicular fluid, buccal swabs, dental plaque and volatiles may also be useful depending on the analyte being studied. Examples of point-of-care devices capable of detecting HIV, TB, and Malaria targets are being developed and discussed in this overview.

Podocytes from the diagnostic and therapeutic point of view.

PubMed

Müller-Deile, Janina; Schiffer, Mario

2017-08-01

The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function. Incubation of cultured human podocyte cell lines with sera from patients with active glomerular diseases is currently also used to identify novel circulating factors with pathophysiological relevance for the glomerular filtration barrier. In addition, treatment of detached urinary podocytes from patients with substances that restore their cytoskeleton might serve as a novel personalized tool to estimate their potential for podocyte recovery ex vivo.

Targeted Magnetic Hyperthermia for Lung Cancer

DTIC Science & Technology

2012-09-01

Despite significant advances in diagnostic techniques an d the disco very of new molecularl y targeted therapies , lung cancer (specifically, non-small...vibrating sample magneto metry) and heating rates. The effect of MH on overall tumor cell kill was determined in A549 cells (NSCLCs) based on the amou nt of

Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases.

PubMed

Moral, Mario E G; Siahaan, Teruna J

2017-01-01

Overexpressed cell-surface receptors are hallmarks of many disease states and are often used as markers for targeting diseased cells over healthy counterparts. Cell adhesion peptides, which are often derived from interacting regions of these receptor-ligand proteins, mimic surfaces of intact proteins and, thus, have been studied as targeting agents for various payloads to certain cell targets for cancers and autoimmune diseases. Because many cytotoxic agents in the free form are often harmful to healthy cells, the use of cell adhesion peptides in targeting their delivery to diseased cells has been studied to potentially reduce required effective doses and associated harmful side-effects. In this review, multiple cell adhesion peptides from extracellular matrix and ICAM proteins were used to selectively direct drug payloads, signal-inhibitor peptides, and diagnostic molecules, to diseased cells over normal counterparts. RGD constructs have been used to improve the selectivity and efficacy of diagnostic and drug-peptide conjugates against cancer cells. From this precedent, novel conjugates of antigenic and cell adhesion peptides, called Bifunctional Peptide Inhibitors (BPIs), have been designed to selectively regulate immune cells and suppress harmful inflammatory responses in autoimmune diseases. Similar peptide conjugations with imaging agents have delivered promising diagnostic methods in animal models of rheumatoid arthritis. BPIs have also been shown to generate immune tolerance and suppress autoimmune diseases in animal models of type-1 diabetes, rheumatoid arthritis, and multiple sclerosis. Collectively, these studies show the potential of cell adhesion peptides in improving the delivery of drugs and diagnostic agents to diseased cells in clinical settings. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Approche à l’égard des nouveaux anticoagulants oraux en pratique familiale

PubMed Central

Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

2014-01-01

Résumé Objectif Traiter des différentes éventualités pouvant survenir durant le suivi clinique et la prise en charge prolongés des patients prenant de nouveaux anticoagulants oraux (NACO). Qualité des données Aux fins de cette révision narrative (non systématique), nous avons effectué une recherche dans la base de données PubMed afin de relever des études cliniques récentes (soit de janvier 2008 à la semaine 32 de 2013) portant sur l’emploi des NACO pour la prévention des AVC dans les cas de fibrillation auriculaire et le traitement de la thromboembolie veineuse aiguë. Nous avons utilisé cette base de données probantes pour répondre à nos questions prédéfinies ayant trait à l’emploi des NACO en pratique générale. Message principal Le dabigatran et le rivaroxaban doivent être pris avec les repas afin de limiter la dyspepsie et de favoriser l’absorption, respectivement. Aucun NACO n’est accompagné de restrictions alimentaires, à l’exception de la consommation modérée d’alcool, et le rivaroxaban et l’apixaban peuvent être écrasés, au besoin. Les antiacides ne semblent pas perturber l’efficacité des NACO. Comme c’est le cas avec la warfarine, les patients traités aux NACO doivent éviter l’emploi prolongé d’anti-inflammatoires non stéroïdiens et d’antiplaquettaires. Chez les patients devant subir une chirurgie, il faut interrompre la prise de NACO de 2 à 5 jours avant l’intervention, en fonction du risque de saignement, et le traitement par le NACO doit être habituellement repris au moins 24 heures après la chirurgie. Il n’est habituellement pas nécessaire d’effectuer un test préopératoire de coagulation. Chez les patients qui développent un saignement, un saignement mineur ne justifie habituellement pas un test de laboratoire ni l’interruption du traitement par le NACO; dans le cas des saignements majeurs, il faut se concentrer sur l’application de mesures localisées visant à endiguer le

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.

Nanotechnology-Based Surface Plasmon Resonance Affinity Biosensors for In Vitro Diagnostics

PubMed Central

Antiochia, Riccarda; Bollella, Paolo; Favero, Gabriele

2016-01-01

In the last decades, in vitro diagnostic devices (IVDDs) became a very important tool in medicine for an early and correct diagnosis, a proper screening of targeted population, and also assessing the efficiency of a specific therapy. In this review, the most recent developments regarding different configurations of surface plasmon resonance affinity biosensors modified by using several nanostructured materials for in vitro diagnostics are critically discussed. Both assembly and performances of the IVDDs tested in biological samples are reported and compared. PMID:27594884

Glyco-Immune Diagnostic Signatures and Therapeutic Targets of Mesothelioma

DTIC Science & Technology

2012-07-01

are those of the author (s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by...Therapeutic Targets of Mesothelioma 5b. GRANT NUMBER W81XWH-10-1-0399 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR (S) 5d. PROJECT NUMBER Harvey Pass... AUTHOR (S) W91ZSQ9305N632 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER New York University School of Medicine,550

Aptamer-modified nanoparticles and their use in cancer diagnostics and treatment.

PubMed

Reinemann, Christine; Strehlitz, Beate

2014-01-06

Aptamers are single-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) oligonucleotides, which are able to bind their target with high selectivity and affinity. Owing to their multiple talents, aptamers combined with nanoparticles are nanosystems well qualified for the development of new biomedical devices for analytical, imaging, drug delivery and many other medical applications. Because of their target affinity, aptamers can direct the transport of aptamer-nanoparticle conjugates. The binding of the aptamers to the target "anchors" the nanoparticle-aptamer conjugates at their site of action. In this way, nanoparticle-based bioimaging and smart drug delivery are enabled, especially by use of systematically developed aptamers for cancer-associated biomarkers. This review article gives a brief overview of recent relevant research into aptamers and trends in their use in cancer diagnostics and therapy. A concise description of aptamers, their development and functionalities relating to nanoparticle modification is given. The main part of the article is dedicated to current developments of aptamer-modified nanoparticles and their use in cancer diagnostics and treatment.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

PROcess Based Diagnostics PROBE

NASA Technical Reports Server (NTRS)

Clune, T.; Schmidt, G.; Kuo, K.; Bauer, M.; Oloso, H.

2013-01-01

Many of the aspects of the climate system that are of the greatest interest (e.g., the sensitivity of the system to external forcings) are emergent properties that arise via the complex interplay between disparate processes. This is also true for climate models most diagnostics are not a function of an isolated portion of source code, but rather are affected by multiple components and procedures. Thus any model-observation mismatch is hard to attribute to any specific piece of code or imperfection in a specific model assumption. An alternative approach is to identify diagnostics that are more closely tied to specific processes -- implying that if a mismatch is found, it should be much easier to identify and address specific algorithmic choices that will improve the simulation. However, this approach requires looking at model output and observational data in a more sophisticated way than the more traditional production of monthly or annual mean quantities. The data must instead be filtered in time and space for examples of the specific process being targeted.We are developing a data analysis environment called PROcess-Based Explorer (PROBE) that seeks to enable efficient and systematic computation of process-based diagnostics on very large sets of data. In this environment, investigators can define arbitrarily complex filters and then seamlessly perform computations in parallel on the filtered output from their model. The same analysis can be performed on additional related data sets (e.g., reanalyses) thereby enabling routine comparisons between model and observational data. PROBE also incorporates workflow technology to automatically update computed diagnostics for subsequent executions of a model. In this presentation, we will discuss the design and current status of PROBE as well as share results from some preliminary use cases.

Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus

PubMed Central

van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

2015-01-01

Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Conclusions: Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. (Hepatology 2015;61:1174–1182) PMID:25482139

Next generation diagnostic molecular pathology: critical appraisal of quality assurance in Europe.

PubMed

Dubbink, Hendrikus J; Deans, Zandra C; Tops, Bastiaan B J; van Kemenade, Folkert J; Koljenović, S; van Krieken, Han J M; Blokx, Willeke A M; Dinjens, Winand N M; Groenen, Patricia J T A

2014-06-01

Tumor evaluation in pathology is more and more based on a combination of traditional histopathology and molecular analysis. Due to the rapid development of new cancer treatments that specifically target aberrant proteins present in tumor cells, treatment decisions are increasingly based on the molecular features of the tumor. Not only the number of patients eligible for targeted precision medicine, but also the number of molecular targets per patient and tumor type is rising. Diagnostic molecular pathology, the discipline that determines the molecular aberrations present in tumors for diagnostic, prognostic or predictive purposes, is faced with true challenges. The laboratories have to meet the need of comprehensive molecular testing using only limited amount of tumor tissue, mostly fixed in formalin and embedded in paraffin (FFPE), in short turnaround time. Choices must be made for analytical methods that provide accurate, reliable and cost-effective results. Validation of the test procedures and results is essential. In addition, participation and good performance in internal (IQA) and external quality assurance (EQA) schemes is mandatory. In this review, we critically evaluate the validation procedure for comprehensive molecular tests as well as the organization of quality assurance and assessment of competence of diagnostic molecular pathology laboratories within Europe. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography.

PubMed

Harman, David J; Ryder, Stephen D; James, Martin W; Jelpke, Matthew; Ottey, Dominic S; Wilkes, Emilie A; Card, Timothy R; Aithal, Guruprasad P; Guha, Indra Neil

2015-05-03

To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting. Prospective cross-sectional study. Two primary care practices (adult patient population 10,479) in Nottingham, UK. Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology. A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE). Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis. We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population. A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis. The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is part of a continuing longitudinal cohort study. Published by the BMJ Publishing Group Limited. For permission to use (where

Defining a new diagnostic assessment parameter for wound care: Elevated protease activity, an indicator of nonhealing, for targeted protease-modulating treatment.

PubMed

Serena, Thomas E; Cullen, Breda M; Bayliff, Simon W; Gibson, Molly C; Carter, Marissa J; Chen, Lingyun; Yaakov, Raphael A; Samies, John; Sabo, Matthew; DeMarco, Daniel; Le, Namchi; Galbraith, James

2016-05-01

It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil-derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2-4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies. © 2016 by the Wound Healing Society.

Short-term and long-term attentional biases to frequently encountered target features.

PubMed

Sha, Li Z; Remington, Roger W; Jiang, Yuhong V

2017-07-01

It has long been known that frequently occurring targets are attended better than infrequent ones in visual search. But does this frequency-based attentional prioritization reflect momentary or durable changes in attention? Here we observed both short-term and long-term attentional biases for visual features as a function of different types of statistical associations between the targets, distractors, and features. Participants searched for a target, a line oriented horizontally or vertically among diagonal distractors, and reported its length. In one set of experiments we manipulated the target's color probability: Targets were more often in Color 1 than in Color 2. The distractors were in other colors. Participants found Color 1 targets more quickly than Color 2 targets, but this preference disappeared immediately when the target's color became random in the subsequent testing phase. In the other set of experiments, we manipulated the diagnostic values of the two colors: Color 1 was more often a target than a distractor; Color 2 was more often a distractor than a target. Participants found Color 1 targets more quickly than Color 2 targets. Importantly, and in contrast to the first set of experiments, the featural preference was sustained in the testing phase. These results suggest that short-term and long-term attentional biases are products of different statistical information. Finding a target momentarily activates its features, inducing short-term repetition priming. Long-term changes in attention, on the other hand, may rely on learning diagnostic features of the targets.

MO-AB-210-00: Diagnostic Ultrasound Imaging Quality Control and High Intensity Focused Ultrasound Therapy Hands-On Workshop

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

NONE

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant

Successful Combination of Nucleic Acid Amplification Test Diagnostics and Targeted Deferred Neisseria gonorrhoeae Culture

PubMed Central

Wind, Carolien M.; de Vries, Henry J. C.; Schim van der Loeff, Maarten F.; Unemo, Magnus

2015-01-01

Nucleic acid amplification tests (NAATs) are recommended for the diagnosis of N. gonorrhoeae infections because of their superior sensitivity. Increasing NAAT use causes a decline in crucial antimicrobial resistance (AMR) surveillance data, which rely on culture. We analyzed the suitability of the ESwab system for NAAT diagnostics and deferred targeted N. gonorrhoeae culture to allow selective and efficient culture based on NAAT results. We included patients visiting the STI Clinic Amsterdam, The Netherlands, in 2013. Patient characteristics and urogenital and rectal samples for direct N. gonorrhoeae culture, standard NAAT, and ESwab were collected. Standard NAAT and NAAT on ESwab samples were performed using the Aptima Combo 2 assay for N. gonorrhoeae and C. trachomatis. Two deferred N. gonorrhoeae cultures were performed on NAAT-positive ESwab samples after storage at 4°C for 1 to 3 days. We included 2,452 samples from 1,893 patients. In the standard NAAT, 107 samples were N. gonorrhoeae positive and 284 were C. trachomatis positive. The sensitivities of NAAT on ESwab samples were 83% (95% confidence interval [CI], 75 to 90%) and 87% (95% CI, 82 to 90%), respectively. ESwab samples were available for 98 of the gonorrhea-positive samples. Of these, 82% were positive in direct culture and 69% and 56% were positive in the 1st and 2nd deferred cultures, respectively (median storage times, 27 and 48 h, respectively). Deferred culture was more often successful in urogenital samples or when the patient had symptoms at the sampling site. Deferred N. gonorrhoeae culture of stored ESwab samples is feasible and enables AMR surveillance. To limit the loss in NAAT sensitivity, we recommend obtaining separate samples for NAAT and deferred culture. PMID:25832300

Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.

PubMed

Bachawal, Sunitha V; Jensen, Kristin C; Wilson, Katheryne E; Tian, Lu; Lutz, Amelie M; Willmann, Jürgen K

2015-06-15

Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. ©2015 American Association for Cancer Research.

Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus.

PubMed

van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

2015-04-01

Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. © 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

2012 HIV Diagnostics Conference: the molecular diagnostics perspective.

PubMed

Branson, Bernard M; Pandori, Mark

2013-04-01

2012 HIV Diagnostic Conference Atlanta, GA, USA, 12-14 December 2012. This report highlights the presentations and discussions from the 2012 National HIV Diagnostic Conference held in Atlanta (GA, USA), on 12-14 December 2012. Reflecting changes in the evolving field of HIV diagnostics, the conference provided a forum for evaluating developments in molecular diagnostics and their role in HIV diagnosis. In 2010, the HIV Diagnostics Conference concluded with the proposal of a new diagnostic algorithm which included nucleic acid testing to resolve discordant screening and supplemental antibody test results. The 2012 meeting, picking up where the 2010 meeting left off, focused on scientific presentations that assessed this new algorithm and the role played by RNA testing and new developments in molecular diagnostics, including detection of total and integrated HIV-1 DNA, detection and quantification of HIV-2 RNA, and rapid formats for detection of HIV-1 RNA.

Plaque autofluorescence as potential diagnostic targets for oral malodor

NASA Astrophysics Data System (ADS)

Lee, Eun-Song; Yim, Hyun-Kyung; Lee, Hyung-Suk; Choi, Jong-Hoon; Kwon, Ho-Keun; Kim, Baek-Il

2016-08-01

The aim of this study was to determine whether the degree of tongue and interdental plaque can be used to assess oral malodor by quantifying their fluorescence as detected using quantitative light-induced fluorescence (QLF) technology. Ninety-nine subjects who complained of oral malodor were included. The level of oral malodor was quantified using the organoleptic score (OLS) and the concentration of volatile sulfur compounds (VSCs). The fluorescence properties of tongue and interdental plaque were quantified as scores calculated by multiplying the intensity and area of fluorescence in QLF-digital images, and the combined plaque fluorescence (CPF) score was obtained by summing the scores for the two regions. The associations of the scores with malodor levels and the diagnostic accuracy of the CPF score were analyzed. The two plaque fluorescence scores and their combined score differed significantly with the level of oral malodor (p<0.001). The CPF score was moderately correlated with OLS (r=0.64) and VSC levels (r=0.54), and its area under the receiver operating characteristic curve was 0.77 for identifying subjects with definite oral malodor (OLS≥2). In conclusion, plaque fluorescence from tongue and interdental sites as detected using QLF technology can be used to assess the level of oral malodor.

Laser Irradiated Foam Targets: Absorption and Radiative Properties

NASA Astrophysics Data System (ADS)

Salvadori, Martina; Luigi Andreoli, Pier; Cipriani, Mattia; Consoli, Fabrizio; Cristofari, Giuseppe; De Angelis, Riccardo; di Giorgio, Giorgio; Giulietti, Danilo; Ingenito, Francesco; Gus'kov, Sergey Yu.; Rupasov, Alexander A.

2018-01-01

An experimental campaign to characterize the laser radiation absorption of foam targets and the subsequent emission of radiation from the produced plasma was carried out in the ABC facility of the ENEA Research Center in Frascati (Rome). Different targets have been used: plastic in solid or foam state and aluminum targets. The activated different diagnostics allowed to evaluate the plasma temperature, the density distribution, the fast particle spectrum and the yield of the X-Ray radiation emitted by the plasma for the different targets. These results confirm the foam homogenization action on laser-plasma interaction, mainly attributable to the volume absorption of the laser radiation propagating in such structured materials. These results were compared with simulation absorption models of the laser propagating into a foam target.

Current Status of Prostate-Specific Membrane Antigen Targeting in Nuclear Medicine: Clinical Translation of Chelator Containing Prostate-Specific Membrane Antigen Ligands Into Diagnostics and Therapy for Prostate Cancer.

PubMed

Kratochwil, Clemens; Afshar-Oromieh, Ali; Kopka, Klaus; Haberkorn, Uwe; Giesel, Frederik L

2016-09-01

The prostate-specific membrane antigen (PSMA) is expressed by approximately 90% of prostate carcinomas. The expression correlates with unfavorable prognostic factors, such as a high Gleason score, infiltrative growth, metastasis, and hormone-independence. The high specificity, especially in the undifferentiated stage, makes it an excellent target for diagnosis and therapy. Therefore, antibodies and small molecule inhibitors have been developed for imaging and therapy. In 2011 PSMA-11, a ligand that consists of the Glu-urea-motif and the chelator HBED-CC, which can be exclusively radiolabeled with (68)Ga for PET imaging, presented the clinical breakthrough for prostate cancer diagnostics. In two large diagnostic studies (n = 319 and n = 248) PET/CT with PSMA-11 successfully localized the recurrent tumor in approximately 90% of patients with biochemical relapse. Integrating PSMA-PET/CT into the planning phase of radiotherapy, the treatment concept is changed in 30%-50% of the patients. The combination of the Glu-urea-motif with DOTA, which can be labeled with several diagnostic and therapeutic radionuclides, opened new avenues for therapeutic usage of the small-molecule PSMA ligands. In the beginning of 2016, there are four confirmative reports (n = 19, n = 24, n = 30, and n = 56) from four different centers reporting a PSA response in approximately 70% of patients treated with (177)Lu-labeled PSMA ligands. In conclusion, the data available up to now indicate a widespread use of PSMA ligands for diagnostic applications with respect to staging, detection of recurrence, or metastases in patients with rising tumor markers and for therapy in case of failure of guideline-compliant treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigating inertial confinement fusion target fuel conditions through x-ray spectroscopya)

NASA Astrophysics Data System (ADS)

Hansen, Stephanie B.

2012-05-01

Inertial confinement fusion (ICF) targets are designed to produce hot, dense fuel in a neutron-producing core that is surrounded by a shell of compressing material. The x-rays emitted from ICF plasmas can be analyzed to reveal details of the temperatures, densities, gradients, velocities, and mix characteristics of ICF targets. Such diagnostics are critical to understand the target performance and to improve the predictive power of simulation codes.

System Related Interventions to Reduce Diagnostic Error: A Narrative Review

PubMed Central

Singh, Hardeep; Graber, Mark L.; Kissam, Stephanie M.; Sorensen, Asta V.; Lenfestey, Nancy F.; Tant, Elizabeth M.; Henriksen, Kerm; LaBresh, Kenneth A.

2013-01-01

Background Diagnostic errors (missed, delayed, or wrong diagnosis) have gained recent attention and are associated with significant preventable morbidity and mortality. We reviewed the recent literature to identify interventions that have been, or could be, implemented to address systems-related factors that contribute directly to diagnostic error. Methods We conducted a comprehensive search using multiple search strategies. We first identified candidate articles in English between 2000 and 2009 from a PubMed search that exclusively evaluated for articles related to diagnostic error or delay. We then sought additional papers from references in the initial dataset, searches of additional databases, and subject matter experts. Articles were included if they formally evaluated an intervention to prevent or reduce diagnostic error; however, we also included papers if interventions were suggested and not tested in order to inform the state-of-the science on the topic. We categorized interventions according to the step in the diagnostic process they targeted: patient-provider encounter, performance and interpretation of diagnostic tests, follow-up and tracking of diagnostic information, subspecialty and referral-related; and patient-specific. Results We identified 43 articles for full review, of which 6 reported tested interventions and 37 contained suggestions for possible interventions. Empirical studies, though somewhat positive, were non-experimental or quasi-experimental and included a small number of clinicians or health care sites. Outcome measures in general were underdeveloped and varied markedly between studies, depending on the setting or step in the diagnostic process involved. Conclusions Despite a number of suggested interventions in the literature, few empirical studies have tested interventions to reduce diagnostic error in the last decade. Advancing the science of diagnostic error prevention will require more robust study designs and rigorous definitions

Research Diagnostic Criteria for Temporomandibular Disorders: Validity of Axis I Diagnoses

PubMed Central

Truelove, Edmond; Pan, Wei; Look, John O.; Mancl, Lloyd A.; Ohrbach, Richard K.; Velly, Ana; Huggins, Kimberly; Lenton, Patricia; Schiffman, Eric L.

2011-01-01

AIMS To estimate the criterion validity of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I TMD diagnoses. METHODS A combined total of 614 TMD community and clinic cases and 91 controls were examined at 3 study sites. RDC/TMD Axis I diagnoses were algorithmically derived from an examination performed by calibrated dental hygienists. Reference standards (Gold Standards) were established by means of consensus diagnoses rendered by 2 TMD experts using all available clinical data, including imaging studies. Validity of the RDC/TMD Axis I TMD diagnoses was estimated relative to reference-standard diagnoses (gold standard diagnoses). Target sensitivity and specificity were set a priori at ≥ 0.70 and ≥ 0.95, respectively. RESULTS Target sensitivity and specificity were not observed for any of the 8 RDC/TMD diagnoses. The highest validity was achieved for Group Ia myofascial pain (sensitivity 0.65, specificity 0.92) and Group Ib myofascial pain with limited opening (sensitivity 0.79, specificity 0.92). Target sensitivity and specificity were observed only when both Group I diagnoses were combined (0.87 and 0.98, respectively). For Group II (disc displacements) and Group III (arthralgia, arthritis, arthrosis) diagnoses, all estimates for sensitivity were below target (0.03 to 0.53), and specificity ranged from below to on target (0.86 to 0.99). CONCLUSION The RDC/TMD Axis I TMD diagnoses did not reach the targets set at sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Target validity was obtained only for myofascial pain without differentiation between normal and limited opening. Revision of the current Axis I TMD diagnostic algorithms is warranted to improve their validity. PMID:20213030

Diagnostic Error in Stroke-Reasons and Proposed Solutions.

PubMed

Bakradze, Ekaterina; Liberman, Ava L

2018-02-13

We discuss the frequency of stroke misdiagnosis and identify subgroups of stroke at high risk for specific diagnostic errors. In addition, we review common reasons for misdiagnosis and propose solutions to decrease error. According to a recent report by the National Academy of Medicine, most people in the USA are likely to experience a diagnostic error during their lifetimes. Nearly half of such errors result in serious disability and death. Stroke misdiagnosis is a major health care concern, with initial misdiagnosis estimated to occur in 9% of all stroke patients in the emergency setting. Under- or missed diagnosis (false negative) of stroke can result in adverse patient outcomes due to the preclusion of acute treatments and failure to initiate secondary prevention strategies. On the other hand, the overdiagnosis of stroke can result in inappropriate treatment, delayed identification of actual underlying disease, and increased health care costs. Young patients, women, minorities, and patients presenting with non-specific, transient, or posterior circulation stroke symptoms are at increased risk of misdiagnosis. Strategies to decrease diagnostic error in stroke have largely focused on early stroke detection via bedside examination strategies and a clinical decision rules. Targeted interventions to improve the diagnostic accuracy of stroke diagnosis among high-risk groups as well as symptom-specific clinical decision supports are needed. There are a number of open questions in the study of stroke misdiagnosis. To improve patient outcomes, existing strategies to improve stroke diagnostic accuracy should be more broadly adopted and novel interventions devised and tested to reduce diagnostic errors.

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.

MicroRNAs and exosomes in depression: Potential diagnostic biomarkers.

PubMed

Tavakolizadeh, Jahanshir; Roshanaei, Kambiz; Salmaninejad, Arash; Yari, Reza; Nahand, Javid Sadri; Sarkarizi, Hoda Khoshdel; Mousavi, Seyed Mojtaba; Salarinia, Reza; Rahmati, Majid; Mousavi, Seyed Farshid; Mokhtari, Ryan; Mirzaei, Hamed

2018-05-01

Depression is known as one of important psychiatric disorders which could be associated with disability among various populations. Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV) and international statistical classification of diseases and related health problems (ICD-10) could be used as subjective diagnostic schemes for identification of mental disorders such as depression. Utilization of subjective diagnostic schemes are associated with limitations. Hence, it seems that employing of new diagnosis platforms is required. Multiple lines of evidence indicated that measurement of several biomarkers could be useful for detection patients with depression. Among of various types of biomarkers, microRNAs (miRNAs) have been emerged as powerful tools for diagnosis patients with depression. MiRNAs are small non-coding RNAs which act as epigenetic regulators. It has been showed that these molecules have critical roles in pathogenesis of many diseases such as depression. These molecules exert their effects via targeting a variety of cellular and molecular pathways involved in initiation and progression of depression. Hence, miRNAs could be used as diagnostic and therapeutic biomarkers in patients with depression. Besides miRNAs, exosomes as nano- carriers could have been emerged as diagnostic biomarkers in several diseases such as depression. These vesicles are able to carry several cargos such as DNAs, proteins, mRNAs, and miRNAs to recipient cells. Here, we summarized several miRNAs involved in pathogenesis and response to treatment of depression which could be used as diagnostic biomarkers. Moreover, we highlighted exosomes as new diagnostic biomarkers for patients with depression. © 2017 Wiley Periodicals, Inc.

[Diagnostic algorithm in chronic myeloproliferative diseases (CMPD)].

PubMed

Haferlach, Torsten; Bacher, Ulrike; Kern, Wolfgang; Schnittger, Susanne; Haferlach, Claudia

2007-09-15

The Philadelphia-negative chronic myeloproliferative diseases (CMPD) are very complex and heterogeneous disorders. They are represented by polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia (CNL), and chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) according to the WHO classification. Before, diagnostics were mainly focused on clinical and morphological aspects, but in recent years cytogenetics and fluorescence in situ hybridization (FISH) found entrance in routine schedules as chromosomal abnormalities are relevant for prognosis and classification. Recently, there is rapid progress in the field of molecular characterization: the JAK2V617F mutation which shows a high incidence in PV, CIMF, and ET already plays a central role and will probably soon be included in follow-up procedures. Due to the detection of mutations in exon 12 of the JAK2 gene or mutations in the MPL gene the variety of activating mutations in the CMPD is still increasing. In CEL/HES the detection of the FIP1L1-PDGFRA fusion gene and overexpression of PDGFRA and PDGFRB led to targeted therapy with tyrosine kinase inhibitors. Thus, diagnostics in the CMPD transform toward a multimodal diagnostic concept based on a combination of methods - cyto-/histomorphology, cytogenetics, and individual molecular methods which can be included in a diagnostic algorithm.

Microfluidic droplet enrichment for targeted sequencing

PubMed Central

Eastburn, Dennis J.; Huang, Yong; Pellegrino, Maurizio; Sciambi, Adam; Ptáček, Louis J.; Abate, Adam R.

2015-01-01

Targeted sequence enrichment enables better identification of genetic variation by providing increased sequencing coverage for genomic regions of interest. Here, we report the development of a new target enrichment technology that is highly differentiated from other approaches currently in use. Our method, MESA (Microfluidic droplet Enrichment for Sequence Analysis), isolates genomic DNA fragments in microfluidic droplets and performs TaqMan PCR reactions to identify droplets containing a desired target sequence. The TaqMan positive droplets are subsequently recovered via dielectrophoretic sorting, and the TaqMan amplicons are removed enzymatically prior to sequencing. We demonstrated the utility of this approach by generating an average 31.6-fold sequence enrichment across 250 kb of targeted genomic DNA from five unique genomic loci. Significantly, this enrichment enabled a more comprehensive identification of genetic polymorphisms within the targeted loci. MESA requires low amounts of input DNA, minimal prior locus sequence information and enriches the target region without PCR bias or artifacts. These features make it well suited for the study of genetic variation in a number of research and diagnostic applications. PMID:25873629

Structure and Computation in Immunoreagent Design: From Diagnostics to Vaccines.

PubMed

Gourlay, Louise; Peri, Claudio; Bolognesi, Martino; Colombo, Giorgio

2017-12-01

Novel immunological tools for efficient diagnosis and treatment of emerging infections are urgently required. Advances in the diagnostic and vaccine development fields are continuously progressing, with reverse vaccinology and structural vaccinology (SV) methods for antigen identification and structure-based antigen (re)design playing increasingly relevant roles. SV, in particular, is predicted to be the front-runner in the future development of diagnostics and vaccines targeting challenging diseases such as AIDS and cancer. We review state-of-the-art methodologies for structure-based epitope identification and antigen design, with specific applicative examples. We highlight the implications of such methods for the engineering of biomolecules with improved immunological properties, potential diagnostic and/or therapeutic uses, and discuss the perspectives of structure-based rational design for the production of advanced immunoreagents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses.

PubMed

González, Víctor M; Martín, M Elena; Fernández, Gerónimo; García-Sacristán, Ana

2016-12-16

Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers' properties as a real tool for viral infection detection and treatment.

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

PubMed Central

González, Víctor M.; Martín, M. Elena; Fernández, Gerónimo; García-Sacristán, Ana

2016-01-01

Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment. PMID:27999271

The Future of Molecular Analysis in Melanoma: Diagnostics to Direct Molecularly Targeted Therapy.

PubMed

Akabane, Hugo; Sullivan, Ryan J

2016-02-01

Melanoma is a malignancy of pigment-producing cells that is driven by a variety of genetic mutations and aberrations. In most cases, this leads to upregulation of the mitogen-activated protein kinase (MAPK) pathway through activating mutations of upstream mediators of the pathway including BRAF and NRAS. With the advent of effective MAPK pathway inhibitors, including the US FDA-approved BRAF inhibitors vemurafenib and dabrafenib and MEK inhibitor trametinib, molecular analysis has become an integral part of the care of patients with metastatic melanoma. In this article, the key molecular targets and strategies to inhibit these targets therapeutically are presented, and the techniques of identifying these targets, in both tissue and blood, are discussed.

Design and testing of a magnetically driven implosion peak current diagnostic

NASA Astrophysics Data System (ADS)

Hess, M. H.; Peterson, K. J.; Ampleford, D. J.; Hutsel, B. T.; Jennings, C. A.; Gomez, M. R.; Dolan, D. H.; Robertson, G. K.; Payne, S. L.; Stygar, W. A.; Martin, M. R.; Sinars, D. B.

2018-04-01

A critical component of the magnetically driven implosion experiments at Sandia National Laboratories is the delivery of high-current, 10s of MA, from the Z pulsed power facility to a target. In order to assess the performance of the experiment, it is necessary to measure the current delivered to the target. Recent Magnetized Liner Inertial Fusion (MagLIF) experiments have included velocimetry diagnostics, such as PDV (Photonic Doppler Velocimetry) or Velocity Interferometer System for Any Reflector, in the final power feed section in order to infer the load current as a function of time. However, due to the nonlinear volumetrically distributed magnetic force within a velocimetry flyer, a complete time-dependent load current unfold is typically a time-intensive process and the uncertainties in the unfold can be difficult to assess. In this paper, we discuss how a PDV diagnostic can be simplified to obtain a peak current by sufficiently increasing the thickness of the flyer. This effectively keeps the magnetic force localized to the flyer surface, resulting in fast and highly accurate measurements of the peak load current. In addition, we show the results of experimental peak load current measurements from the PDV diagnostic in recent MagLIF experiments.

Plasmonic SERS nanochips and nanoprobes for medical diagnostics and bio-energy applications

NASA Astrophysics Data System (ADS)

Ngo, Hoan T.; Wang, Hsin-Neng; Crawford, Bridget M.; Fales, Andrew M.; Vo-Dinh, Tuan

2017-02-01

The development of rapid, easy-to-use, cost-effective, high accuracy, and high sensitive DNA detection methods for molecular diagnostics has been receiving increasing interest. Over the last five years, our laboratory has developed several chip-based DNA detection techniques including the molecular sentinel-on-chip (MSC), the multiplex MSC, and the inverse molecular sentinel-on-chip (iMS-on-Chip). In these techniques, plasmonic surface-enhanced Raman scattering (SERS) Nanowave chips were functionalized with DNA probes for single-step DNA detection. Sensing mechanisms were based on hybridization of target sequences and DNA probes, resulting in a distance change between SERS reporters and the Nanowave chip's gold surface. This distance change resulted in change in SERS intensity, thus indicating the presence and capture of the target sequences. Our techniques were single-step DNA detection techniques. Target sequences were detected by simple delivery of sample solutions onto DNA probe-functionalized Nanowave chips and SERS signals were measured after 1h - 2h incubation. Target sequence labeling or washing to remove unreacted components was not required, making the techniques simple, easy-to-use, and cost effective. The usefulness of the techniques for medical diagnostics was illustrated by the detection of genetic biomarkers for respiratory viral infection and of dengue virus 4 DNA.

High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.

PubMed

Metzger, Katja; Vogel, Sebastian; Chatterjee, Madhumita; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Geisler, Tobias; Lang, Florian; Langer, Harald; Rheinlaender, Johannes; Schäffer, Tilman E; Gawaz, Meinrad

2015-01-01

Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interpretation of diagnostic data: 5. How to do it with simple maths.

PubMed

1983-11-01

The use of simple maths with the likelihood ratio strategy fits in nicely with our clinical views. By making the most out of the entire range of diagnostic test results (i.e., several levels, each with its own likelihood ratio, rather than a single cut-off point and a single ratio) and by permitting us to keep track of the likelihood that a patient has the target disorder at each point along the diagnostic sequence, this strategy allows us to place patients at an extremely high or an extremely low likelihood of disease. Thus, the numbers of patients with ultimately false-positive results (who suffer the slings of labelling and the arrows of needless therapy) and of those with ultimately false-negative results (who therefore miss their chance for diagnosis and, possibly, efficacious therapy) will be dramatically reduced. The following guidelines will be useful in interpreting signs, symptoms and laboratory tests with the likelihood ratio strategy: Seek out, and demand from the clinical or laboratory experts who ought to know, the likelihood ratios for key symptoms and signs, and several levels (rather than just the positive and negative results) of diagnostic test results. Identify, when feasible, the logical sequence of diagnostic tests. Estimate the pretest probability of disease for the patient, and, using either the nomogram or the conversion formulas, apply the likelihood ratio that corresponds to the first diagnostic test result. While remembering that the resulting post-test probability or odds from the first test becomes the pretest probability or odds for the next diagnostic test, repeat the process for all the pertinent symptoms, signs and laboratory studies that pertain to the target disorder. However, these combinations may not be independent, and convergent diagnostic tests, if treated as independent, will combine to overestimate the final post-test probability of disease. You are now far more sophisticated in interpreting diagnostic tests than most of

Interpretation of diagnostic data: 5. How to do it with simple maths.

PubMed Central

1983-01-01

The use of simple maths with the likelihood ratio strategy fits in nicely with our clinical views. By making the most out of the entire range of diagnostic test results (i.e., several levels, each with its own likelihood ratio, rather than a single cut-off point and a single ratio) and by permitting us to keep track of the likelihood that a patient has the target disorder at each point along the diagnostic sequence, this strategy allows us to place patients at an extremely high or an extremely low likelihood of disease. Thus, the numbers of patients with ultimately false-positive results (who suffer the slings of labelling and the arrows of needless therapy) and of those with ultimately false-negative results (who therefore miss their chance for diagnosis and, possibly, efficacious therapy) will be dramatically reduced. The following guidelines will be useful in interpreting signs, symptoms and laboratory tests with the likelihood ratio strategy: Seek out, and demand from the clinical or laboratory experts who ought to know, the likelihood ratios for key symptoms and signs, and several levels (rather than just the positive and negative results) of diagnostic test results. Identify, when feasible, the logical sequence of diagnostic tests. Estimate the pretest probability of disease for the patient, and, using either the nomogram or the conversion formulas, apply the likelihood ratio that corresponds to the first diagnostic test result. While remembering that the resulting post-test probability or odds from the first test becomes the pretest probability or odds for the next diagnostic test, repeat the process for all the pertinent symptoms, signs and laboratory studies that pertain to the target disorder. However, these combinations may not be independent, and convergent diagnostic tests, if treated as independent, will combine to overestimate the final post-test probability of disease. You are now far more sophisticated in interpreting diagnostic tests than most of

Integrated diagnostics

NASA Technical Reports Server (NTRS)

Hunthausen, Roger J.

1988-01-01

Recently completed projects in which advanced diagnostic concepts were explored and/or demonstrated are summarized. The projects begin with the design of integrated diagnostics for the Army's new gas turbine engines, and advance to the application of integrated diagnostics to other aircraft subsystems. Finally, a recent project is discussed which ties together subsystem fault monitoring and diagnostics with a more complete picture of flight domain knowledge.

Applications of Diagnostic Classification Models: A Literature Review and Critical Commentary

ERIC Educational Resources Information Center

Sessoms, John; Henson, Robert A.

2018-01-01

Diagnostic classification models (DCMs) classify examinees based on the skills they have mastered given their test performance. This classification enables targeted feedback that can inform remedial instruction. Unfortunately, applications of DCMs have been criticized (e.g., no validity support). Generally, these evaluations have been brief and…

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.

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics.

PubMed

Paschke, Ralf; Cantara, Silvia; Crescenzi, Anna; Jarzab, Barbara; Musholt, Thomas J; Sobrinho Simoes, Manuel

2017-07-01

Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF , NRAS , HRAS , KRAS , PAX8/PPARG , RET/PTC ) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation.

European Thyroid Association Guidelines regarding Thyroid Nodule Molecular Fine-Needle Aspiration Cytology Diagnostics

PubMed Central

Paschke, Ralf; Cantara, Silvia; Crescenzi, Anna; Jarzab, Barbara; Musholt, Thomas J.; Sobrinho Simoes, Manuel

2017-01-01

Molecular fine-needle aspiration (FNA) cytology diagnostics has the potential to address the inherent limitation of FNA cytology which is an indeterminate (atypia of undetermined significance/follicular lesion of undetermined significance follicular neoplasm) cytology. Because of the emerging role of molecular FNA cytology diagnostics, the European Thyroid Association convened a panel of international experts to review methodological aspects, indications, results, and limitations of molecular FNA cytology diagnostics. The panel reviewed the evidence for the diagnostic value of mutation panel assessment (including at least BRAF, NRAS, HRAS, KRAS, PAX8/PPARG, RET/PTC) of targeted next generation sequencing and of a microarray gene expression classifier (GEC) test in the diagnostic assessment of an indeterminate cytology thyroid nodule. Moreover, possible surgical consequences of molecular FNA diagnostic results of thyroid nodules and the evidence that analysis of a molecular FNA diagnostic panel of somatic mutations or a microarray GEC test can alter the follow-up were reviewed. Molecular tests may help clinicians to drive patient care and the surgical decision if the analysis is performed in specialized laboratories. These molecular tests require standardization of performance characteristics and appropriate calibration as well as analytic validation before clinical interpretation. PMID:28785538

Optical biosensor technologies for molecular diagnostics at the point-of-care

NASA Astrophysics Data System (ADS)

Schotter, Joerg; Schrittwieser, Stefan; Muellner, Paul; Melnik, Eva; Hainberger, Rainer; Koppitsch, Guenther; Schrank, Franz; Soulantika, Katerina; Lentijo-Mozo, Sergio; Pelaz, Beatriz; Parak, Wolfgang; Ludwig, Frank; Dieckhoff, Jan

2015-05-01

Label-free optical schemes for molecular biosensing hold a strong promise for point-of-care applications in medical research and diagnostics. Apart from diagnostic requirements in terms of sensitivity, specificity, and multiplexing capability, also other aspects such as ease of use and manufacturability have to be considered in order to pave the way to a practical implementation. We present integrated optical waveguide as well as magnetic nanoparticle based molecular biosensor concepts that address these aspects. The integrated optical waveguide devices are based on low-loss photonic wires made of silicon nitride deposited by a CMOS compatible plasma-enhanced chemical vapor deposition (PECVD) process that allows for backend integration of waveguides on optoelectronic CMOS chips. The molecular detection principle relies on evanescent wave sensing in the 0.85 μm wavelength regime by means of Mach-Zehnder interferometers, which enables on-chip integration of silicon photodiodes and, thus, the realization of system-on-chip solutions. Our nanoparticle-based approach is based on optical observation of the dynamic response of functionalized magneticcore/ noble-metal-shell nanorods (`nanoprobes') to an externally applied time-varying magnetic field. As target molecules specifically bind to the surface of the nanoprobes, the observed dynamics of the nanoprobes changes, and the concentration of target molecules in the sample solution can be quantified. This approach is suitable for dynamic real-time measurements and only requires minimal sample preparation, thus presenting a highly promising point-of-care diagnostic system. In this paper, we present a prototype of a diagnostic device suitable for highly automated sample analysis by our nanoparticle-based approach.

Note: Neutron bang time diagnostic system on Shenguang-III prototype

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

Tang, Qi; Chen, Jiabin; Liu, Zhongjie

A neutron bang time (NBT) diagnostic system has been implemented on Shenguang-III prototype. The bang time diagnostic system is based on a sensitive fusion neutron detector, which consists of a plastic scintillator and a micro-channel plate photomultiplier tube (PMT). An optical fiber bundle is used to couple the scintillator and the PMT. The bang time system is able to measure bang time above a neutron yield of 10{sup 7}. Bang times and start time of laser were related by probing x-ray pulses produced by 200 ps laser irradiating golden targets. Timing accuracy of the NBT is better than 60 ps.

Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

PubMed Central

Bleeker, Jonathan S.; Hogan, William J.

2011-01-01

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665

Kepler Data Validation I—Architecture, Diagnostic Tests, and Data Products for Vetting Transiting Planet Candidates

NASA Astrophysics Data System (ADS)

Twicken, Joseph D.; Catanzarite, Joseph H.; Clarke, Bruce D.; Girouard, Forrest; Jenkins, Jon M.; Klaus, Todd C.; Li, Jie; McCauliff, Sean D.; Seader, Shawn E.; Tenenbaum, Peter; Wohler, Bill; Bryson, Stephen T.; Burke, Christopher J.; Caldwell, Douglas A.; Haas, Michael R.; Henze, Christopher E.; Sanderfer, Dwight T.

2018-06-01

The Kepler Mission was designed to identify and characterize transiting planets in the Kepler Field of View and to determine their occurrence rates. Emphasis was placed on identification of Earth-size planets orbiting in the Habitable Zone of their host stars. Science data were acquired for a period of four years. Long-cadence data with 29.4 min sampling were obtained for ∼200,000 individual stellar targets in at least one observing quarter in the primary Kepler Mission. Light curves for target stars are extracted in the Kepler Science Data Processing Pipeline, and are searched for transiting planet signatures. A Threshold Crossing Event is generated in the transit search for targets where the transit detection threshold is exceeded and transit consistency checks are satisfied. These targets are subjected to further scrutiny in the Data Validation (DV) component of the Pipeline. Transiting planet candidates are characterized in DV, and light curves are searched for additional planets after transit signatures are modeled and removed. A suite of diagnostic tests is performed on all candidates to aid in discrimination between genuine transiting planets and instrumental or astrophysical false positives. Data products are generated per target and planet candidate to document and display transiting planet model fit and diagnostic test results. These products are exported to the Exoplanet Archive at the NASA Exoplanet Science Institute, and are available to the community. We describe the DV architecture and diagnostic tests, and provide a brief overview of the data products. Transiting planet modeling and the search for multiple planets on individual targets are described in a companion paper. The final revision of the Kepler Pipeline code base is available to the general public through GitHub. The Kepler Pipeline has also been modified to support the Transiting Exoplanet Survey Satellite (TESS) Mission which is expected to commence in 2018.

Kepler Data Validation I: Architecture, Diagnostic Tests, and Data Products for Vetting Transiting Planet Candidates

NASA Technical Reports Server (NTRS)

Twicken, Joseph D.; Catanzarite, Joseph H.; Clarke, Bruce D.; Giroud, Forrest; Jenkins, Jon M.; Klaus, Todd C.; Li, Jie; McCauliff, Sean D.; Seader, Shawn E.; Tennenbaum, Peter;

MFP scanner diagnostics using a self-printed target to measure the modulation transfer function

NASA Astrophysics Data System (ADS)

Wang, Weibao; Bauer, Peter; Wagner, Jerry; Allebach, Jan P.

2014-01-01

In the current market, reduction of warranty costs is an important avenue for improving profitability by manufacturers of printer products. Our goal is to develop an autonomous capability for diagnosis of printer and scanner caused defects with mid-range laser multifunction printers (MFPs), so as to reduce warranty costs. If the scanner unit of the MFP is not performing according to specification, this issue needs to be diagnosed. If there is a print quality issue, this can be diagnosed by printing a special test page that is resident in the firmware of the MFP unit, and then scanning it. However, the reliability of this process will be compromised if the scanner unit is defective. Thus, for both scanner and printer image quality issues, it is important to be able to properly evaluate the scanner performance. In this paper, we consider evaluation of the scanner performance by measuring its modulation transfer function (MTF). The MTF is a fundamental tool for assessing the performance of imaging systems. Several ways have been proposed to measure the MTF, all of which require a special target, for example a slanted-edge target. It is unacceptably expensive to ship every MFP with such a standard target, and to expect that the customer can keep track of it. To reduce this cost, in this paper, we develop new approach to this task. It is based on a self-printed slanted-edge target. Then, we propose algorithms to improve the results using a self-printed slanted-edge target. Finally, we present experimental results for MTF measurement using self-printed targets and compare them to the results obtained with standard targets.

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.

Global and targeted metabolomics of esophageal squamous cell carcinoma discovers potential diagnostic and therapeutic biomarkers.

PubMed

Xu, Jing; Chen, Yanhua; Zhang, Ruiping; Song, Yongmei; Cao, Jianzhong; Bi, Nan; Wang, Jingbo; He, Jiuming; Bai, Jinfa; Dong, Lijia; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

2013-05-01

Diagnostic and therapeutic biomarkers useful for esophageal squamous cell carcinoma (ESCC) have the ability to increase the long term survival of cancer patients. A metabolomics study, using plasma from four groups including ESCC patients before, during, and after chemoradiotherapy (CRT) and healthy controls, was originally carried out by LC-MS to determine global alterations in the metabolic profiles and find biomarkers potentially applicable to diagnosis and monitoring treatment effects. It is worth pointing out that a clear clustering and separation of metabolic data from the four groups was observed, which indicated that disease status and treatment intervention resulted in specific metabolic perturbations in the patients. A series of metabolites were found to be significantly altered in ESCC patients versus healthy controls and in pre- versus post-treatment patients based on multivariate statistical data analysis (MVDA). To further validate the reliability of these potential biomarkers, an independent validation was performed by using the selected reaction monitoring (SRM) based targeted approach. Finally, 18 most significantly altered plasma metabolites in ESCC patients, relative to healthy controls, were tentatively identified as lysophosphatidylcholines (lysoPCs), fatty acids, l-carnitine, acylcarnitines, organic acids, and a sterol metabolite. The classification performance of these metabolites were analyzed by receiver operating characteristic (ROC)(1) analysis and a biomarker panel was generated. Together, biological significance of these metabolites was discussed. Comparison between pre- and post-treatment patients generated 11 metabolites as potential therapeutic biomarkers that were tentatively identified as amino acids, acylcarnitines, and lysoPCs. Levels of three of these (octanoylcarnitine, lysoPC(16:1), and decanoylcarnitine) were closely correlated with treatment effect. Moreover, variation of these three potential biomarkers was investigated

Heated probe diagnostic inside of the gas aggregation nanocluster source

NASA Astrophysics Data System (ADS)

Kolpakova, Anna; Shelemin, Artem; Kousal, Jaroslav; Kudrna, Pavel; Tichy, Milan; Biederman, Hynek; Surface; Plasma Science Team

2016-09-01

Gas aggregation cluster sources (GAS) usually operate outside common working conditions of most magnetrons and the size of nanoparticles created in GAS is below that commonly studied in dusty plasmas. Therefore, experimental data obtained inside the GAS are important for better understanding of process of nanoparticles formation. In order to study the conditions inside the gas aggregation chamber, special ``diagnostic GAS'' has been constructed. It allows simultaneous monitoring (or spatial profiling) by means of optical emission spectroscopy, mass spectrometry and probe diagnostic. Data obtained from Langmuir and heated probes map the plasma parameters in two dimensions - radial and axial. Titanium has been studied as an example of metal for which the reactive gas in the chamber starts nanoparticles production. Three basic situations were investigated: sputtering from clean titanium target in argon, sputtering from partially pre-oxidized target and sputtering with oxygen introduced into the discharge. It was found that during formation of nanoparticles the plasma parameters differ strongly from the situation without nanoparticles. These experimental data will support the efforts of more realistic modeling of the process. Czech Science Foundation 15-00863S.

Targeted Endoscopic Imaging

PubMed Central

Li, Meng; Wang, Thomas D

2011-01-01

Summary Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before. PMID:19423025

MicroRNAs in Leukemias: Emerging Diagnostic Tools and Therapeutic Targets

PubMed Central

Mian, Yousaf A.; Zeleznik-Le, Nancy J.

2010-01-01

MicroRNAs (miRNA) are small non-coding RNAs of ~22 nucleotides that regulate the translation and stability of mRNA to control different functions of the cell. Misexpression of miRNA has been linked to disruption of normal cellular functions, which results in various disorders including cancers such as leukemias. MicroRNA involvement in disease has been the subject of much attention and is increasing our current understanding of disease biology. Such linkages have been determined by high-throughput studies, which provide a framework for characterizing differential miRNA expression levels correlating to different cytogenetic abnormalities and their corresponding malignancies. In addition, functional studies of particular miRNAs have begun to define the effects of miRNA on predicted mRNA targets. It is clear that miRNAs can serve as molecular markers of leukemias and the hope is that they can also serve as new therapeutic targets. Studies are beginning to elucidate how to deliver therapeutic antagonists to attenuate overexpressed miRNAs and to replace underexpressed miRNAs. In this review, we: i) discuss the current understanding of miRNA function and expression in normal hematopoiesis, ii) provide examples of miRNAs that are misregulated in leukemias, and iii) evaluate the current status and potential future directions for the burgeoning field of antisense oligonucleotides and other therapeutic attempts to intervene in miRNA disregulation in leukemias. PMID:20370647

Targeted RNA-Sequencing with Competitive Multiplex-PCR Amplicon Libraries

PubMed Central

Blomquist, Thomas M.; Crawford, Erin L.; Lovett, Jennie L.; Yeo, Jiyoun; Stanoszek, Lauren M.; Levin, Albert; Li, Jia; Lu, Mei; Shi, Leming; Muldrew, Kenneth; Willey, James C.

2013-01-01

Whole transcriptome RNA-sequencing is a powerful tool, but is costly and yields complex data sets that limit its utility in molecular diagnostic testing. A targeted quantitative RNA-sequencing method that is reproducible and reduces the number of sequencing reads required to measure transcripts over the full range of expression would be better suited to diagnostic testing. Toward this goal, we developed a competitive multiplex PCR-based amplicon sequencing library preparation method that a) targets only the sequences of interest and b) controls for inter-target variation in PCR amplification during library preparation by measuring each transcript native template relative to a known number of synthetic competitive template internal standard copies. To determine the utility of this method, we intentionally selected PCR conditions that would cause transcript amplification products (amplicons) to converge toward equimolar concentrations (normalization) during library preparation. We then tested whether this approach would enable accurate and reproducible quantification of each transcript across multiple library preparations, and at the same time reduce (through normalization) total sequencing reads required for quantification of transcript targets across a large range of expression. We demonstrate excellent reproducibility (R2 = 0.997) with 97% accuracy to detect 2-fold change using External RNA Controls Consortium (ERCC) reference materials; high inter-day, inter-site and inter-library concordance (R2 = 0.97–0.99) using FDA Sequencing Quality Control (SEQC) reference materials; and cross-platform concordance with both TaqMan qPCR (R2 = 0.96) and whole transcriptome RNA-sequencing following “traditional” library preparation using Illumina NGS kits (R2 = 0.94). Using this method, sequencing reads required to accurately quantify more than 100 targeted transcripts expressed over a 107-fold range was reduced more than 10,000-fold, from 2.3×109 to 1

Diagnostic uncertainty, guilt, mood, and disability in back pain.

PubMed

Serbic, Danijela; Pincus, Tamar; Fife-Schaw, Chris; Dawson, Helen

2016-01-01

In the majority of patients a definitive cause for low back pain (LBP) cannot be established, and many patients report feeling uncertain about their diagnosis, accompanied by guilt. The relationship between diagnostic uncertainty, guilt, mood, and disability is currently unknown. This study tested 3 theoretical models to explore possible pathways between these factors. In Model 1, diagnostic uncertainty was hypothesized to correlate with pain-related guilt, which in turn would positively correlate with depression, anxiety and disability. Two alternative models were tested: (a) a path from depression and anxiety to guilt, from guilt to diagnostic uncertainty, and finally to disability; (b) a model in which depression and anxiety, and independently, diagnostic uncertainty, were associated with guilt, which in turn was associated with disability. Structural equation modeling was employed on data from 413 participants with chronic LBP. All 3 models showed a reasonable-to-good fit with the data, with the 2 alternative models providing marginally better fit indices. Guilt, and especially social guilt, was associated with disability in all 3 models. Diagnostic uncertainty was associated with guilt, but only moderately. Low mood was also associated with guilt. Two newly defined factors, pain related guilt and diagnostic uncertainty, appear to be linked to disability and mood in people with LBP. The causal path of these links cannot be established in this cross sectional study. However, pain-related guilt especially appears to be important, and future research should examine whether interventions directly targeting guilt improve outcomes. (c) 2015 APA, all rights reserved).

Dielectrophoresis-based microfluidic platforms for cancer diagnostics.

PubMed

Chan, Jun Yuan; Ahmad Kayani, Aminuddin Bin; Md Ali, Mohd Anuar; Kok, Chee Kuang; Yeop Majlis, Burhanuddin; Hoe, Susan Ling Ling; Marzuki, Marini; Khoo, Alan Soo-Beng; Ostrikov, Kostya Ken; Ataur Rahman, Md; Sriram, Sharath

2018-01-01

The recent advancement of dielectrophoresis (DEP)-enabled microfluidic platforms is opening new opportunities for potential use in cancer disease diagnostics. DEP is advantageous because of its specificity, low cost, small sample volume requirement, and tuneable property for microfluidic platforms. These intrinsic advantages have made it especially suitable for developing microfluidic cancer diagnostic platforms. This review focuses on a comprehensive analysis of the recent developments of DEP enabled microfluidic platforms sorted according to the target cancer cell. Each study is critically analyzed, and the features of each platform, the performance, added functionality for clinical use, and the types of samples, used are discussed. We address the novelty of the techniques, strategies, and design configuration used in improving on existing technologies or previous studies. A summary of comparing the developmental extent of each study is made, and we conclude with a treatment of future trends and a brief summary.

Basis for molecular diagnostics and immunotherapy for esophageal cancer.

PubMed

Abdo, Joe; Agrawal, Devendra K; Mittal, Sumeet K

2017-01-01

Esophageal cancer (EC) is an extremely aggressive neoplasm, diagnosed in about 17,000 Americans every year with a mortality rate of more than 80% within five years and a median overall survival of just 13 months. For decades, the go-to regimen for esophageal cancer patients has been the use of taxane and platinum-based chemotherapy regimens, which has yielded the field's most dire survival statistics. Areas covered: Combination immunotherapy and a more robust molecular diagnostic platform for esophageal tumors could improve patient management strategies and potentially extend lives beyond the current survival figures. Analyzing a panel of biomarkers including those affiliated with taxane and platinum resistance (ERCC1 and TUBB3) as well as immunotherapy effectiveness (PD-L1) would provide oncologists more information on how to optimize first-line therapy for EC. Expert commentary: Of the 12 FDA-approved therapies in EC, zero target the genome. A majority of the approved drugs either target or are effected by proteomic expression. Therefore, a broader understanding of diagnostic biomarkers could give more clarity and direction in treating esophageal cancer in concert with a greater use of immunotherapy.

Basis for molecular diagnostics and immunotherapy for esophageal cancer

PubMed Central

Abdo, Joe; Agrawal, Devendra K.; Mittal, Sumeet K.

2017-01-01

Introduction Esophageal cancer is an extremely aggressive neoplasm, diagnosed in about 17,000 Americans every year with a mortality rate of more than 80% within five years and a median overall survival of just 13 months. For decades, the go-to regimen for esophageal cancer patients has been the use of taxane and platinum-based chemotherapy regimens, which has yielded the field’s most dire survival statistics. Areas covered Combination immunotherapy and a more robust molecular diagnostic platform for esophageal tumors could improve patient management strategies and potentially extend lives beyond the current survival figures. Analyzing a panel of biomarkers including those affiliated with taxane and platinum resistance (ERCC1 and TUBB3) as well as immunotherapy effectiveness (PD-L1) would provide oncologists more information on how to optimize first-line therapy for esophageal cancer. Expert commentary Of the 12 FDA-approved therapies in esophageal cancer, zero target the genome. A majority of the approved drugs either target or are effected by proteomic expression. Therefore, a broader understanding of diagnostic biomarkers could give more clarity and direction in treating esophageal cancer in concert with a greater use of immunotherapy. PMID:27838937

Accelerated Photobleaching of a Cyanine Dye in the Presence of a Ternary Target DNA, PNA Probe, Dye Catalytic Complex: A Molecular Diagnostic

PubMed Central

Wang, M.; Holmes-Davis, R.; Rafinski, Z.; Jedrzejewska, B.; Choi, K. Y.; Zwick, M.; Bupp, C.; Izmailov, A.; Paczkowski, J.; Warner, B.; Koshinsky, H.

2009-01-01

In many settings, molecular testing is needed but unavailable due to complexity and cost. Simple, rapid, and specific DNA detection technologies would provide important alternatives to existing detection methods. Here we report a novel, rapid nucleic acid detection method based on the accelerated photobleaching of the light-sensitive cyanine dye, 3,3′-diethylthiacarbocyanine iodide (DiSC2(3) I−), in the presence of a target genomic DNA and a complementary peptide nucleic acid (PNA) probe. On the basis of the UV–vis, circular dichroism, and fluorescence spectra of DiSC2(3) with PNA–DNA oligomer duplexes and on characterization of a product of photolysis of DiSC2(3) I−, a possible reaction mechanism is proposed. We propose that (1) a novel complex forms between dye, PNA, and DNA, (2) this complex functions as a photosensitizer producing 1O2, and (3) the 1O2 produced promotes photobleaching of dye molecules in the mixture. Similar cyanine dyes (DiSC3(3), DiSC4(3), DiSC5(3), and DiSCpy(3)) interact with preformed PNA–DNA oligomer duplexes but do not demonstrate an equivalent accelerated photobleaching effect in the presence of PNA and target genomic DNA. The feasibility of developing molecular diagnostic assays based on the accelerated photobleaching (the smartDNA assay) that results from the novel complex formed between DiSC2(3) and PNA–DNA is under way. PMID:19231844

Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

PubMed

Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

2014-11-21

In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

Laboratory Diagnostics of Botulism

PubMed Central

Lindström, Miia; Korkeala, Hannu

2006-01-01

Botulism is a potentially lethal paralytic disease caused by botulinum neurotoxin. Human pathogenic neurotoxins of types A, B, E, and F are produced by a diverse group of anaerobic spore-forming bacteria, including Clostridium botulinum groups I and II, Clostridium butyricum, and Clostridium baratii. The routine laboratory diagnostics of botulism is based on the detection of botulinum neurotoxin in the patient. Detection of toxin-producing clostridia in the patient and/or the vehicle confirms the diagnosis. The neurotoxin detection is based on the mouse lethality assay. Sensitive and rapid in vitro assays have been developed, but they have not yet been appropriately validated on clinical and food matrices. Culture methods for C. botulinum are poorly developed, and efficient isolation and identification tools are lacking. Molecular techniques targeted to the neurotoxin genes are ideal for the detection and identification of C. botulinum, but they do not detect biologically active neurotoxin and should not be used alone. Apart from rapid diagnosis, the laboratory diagnostics of botulism should aim at increasing our understanding of the epidemiology and prevention of the disease. Therefore, the toxin-producing organisms should be routinely isolated from the patient and the vehicle. The physiological group and genetic traits of the isolates should be determined. PMID:16614251

Nanolock-Nanopore Facilitated Digital Diagnostics of Cancer Driver Mutation in Tumor Tissue.

PubMed

Wang, Yong; Tian, Kai; Shi, Ruicheng; Gu, Amy; Pennella, Michael; Alberts, Lindsey; Gates, Kent S; Li, Guangfu; Fan, Hongxin; Wang, Michael X; Gu, Li-Qun

2017-07-28

Cancer driver mutations are clinically significant biomarkers. In precision medicine, accurate detection of these oncogenic changes in patients would enable early diagnostics of cancer, individually tailored targeted therapy, and precise monitoring of treatment response. Here we investigated a novel nanolock-nanopore method for single-molecule detection of a serine/threonine protein kinase gene BRAF V600E mutation in tumor tissues of thyroid cancer patients. The method lies in a noncovalent, mutation sequence-specific nanolock. We found that the nanolock formed on the mutant allele/probe duplex can separate the duplex dehybridization procedure into two sequential steps in the nanopore. Remarkably, this stepwise unzipping kinetics can produce a unique nanopore electric marker, with which a single DNA molecule of the cancer mutant allele can be unmistakably identified in various backgrounds of the normal wild-type allele. The single-molecule sensitivity for mutant allele enables both binary diagnostics and quantitative analysis of mutation occurrence. In the current configuration, the method can detect the BRAF V600E mutant DNA lower than 1% in the tumor tissues. The nanolock-nanopore method can be adapted to detect a broad spectrum of both transversion and transition DNA mutations, with applications from diagnostics to targeted therapy.

Mammalian plasma membrane proteins as potential biomarkers and drug targets.

PubMed

Rucevic, Marijana; Hixson, Douglas; Josic, Djuro

2011-06-01

Defining the plasma membrane proteome is crucial to understand the role of plasma membrane in fundamental biological processes. Change in membrane proteins is one of the first events that take place under pathological conditions, making plasma membrane proteins a likely source of potential disease biomarkers with prognostic or diagnostic potential. Membrane proteins are also potential targets for monoclonal antibodies and other drugs that block receptors or inhibit enzymes essential to the disease progress. Despite several advanced methods recently developed for the analysis of hydrophobic proteins and proteins with posttranslational modifications, integral membrane proteins are still under-represented in plasma membrane proteome. Recent advances in proteomic investigation of plasma membrane proteins, defining their roles as diagnostic and prognostic disease biomarkers and as target molecules in disease treatment, are presented. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Current trends in the use of liposomes for tumor targeting

PubMed Central

Deshpande, Pranali P; Biswas, Swati; Torchilin, Vladimir P

2013-01-01

The use of liposomes for drug delivery began early in the history of pharmaceutical nanocarriers. These nanosized, lipid bilayered vesicles have become popular as drug delivery systems owing to their efficiency, biocompatibility, nonimmunogenicity, enhanced solubility of chemotherapeutic agents and their ability to encapsulate a wide array of drugs. Passive and ligand-mediated active targeting promote tumor specificity with diminished adverse off-target effects. The current field of liposomes focuses on both clinical and diagnostic applications. Recent efforts have concentrated on the development of multifunctional liposomes that target cells and cellular organelles with a single delivery system. This review discusses the recent advances in liposome research in tumor targeting. PMID:23914966

NIF Ignition Target 3D Point Design

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

Jones, O; Marinak, M; Milovich, J

2008-11-05

We have developed an input file for running 3D NIF hohlraums that is optimized such that it can be run in 1-2 days on parallel computers. We have incorporated increasing levels of automation into the 3D input file: (1) Configuration controlled input files; (2) Common file for 2D and 3D, different types of capsules (symcap, etc.); and (3) Can obtain target dimensions, laser pulse, and diagnostics settings automatically from NIF Campaign Management Tool. Using 3D Hydra calculations to investigate different problems: (1) Intrinsic 3D asymmetry; (2) Tolerance to nonideal 3D effects (e.g. laser power balance, pointing errors); and (3) Syntheticmore » diagnostics.« less

Audible sonar images generated with proprioception for target analysis.

PubMed

Kuc, Roman B

2017-05-01

Some blind humans have demonstrated the ability to detect and classify objects with echolocation using palatal clicks. An audible-sonar robot mimics human click emissions, binaural hearing, and head movements to extract interaural time and level differences from target echoes. Targets of various complexity are examined by transverse displacements of the sonar and by target pose rotations that model movements performed by the blind. Controlled sonar movements executed by the robot provide data that model proprioception information available to blind humans for examining targets from various aspects. The audible sonar uses this sonar location and orientation information to form two-dimensional target images that are similar to medical diagnostic ultrasound tomograms. Simple targets, such as single round and square posts, produce distinguishable and recognizable images. More complex targets configured with several simple objects generate diffraction effects and multiple reflections that produce image artifacts. The presentation illustrates the capabilities and limitations of target classification from audible sonar images.

Nanoparticles target early-stage breast cancer metastasis in vivo

NASA Astrophysics Data System (ADS)

Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E.; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

2017-10-01

Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Procedural Terminology published by the American Medical Association. (vii) Diagnostic tests performed by a... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Procedural Terminology published by the American Medical Association. (vii) Diagnostic tests performed by a... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

[Companion diagnostics in the era of personalized medicine--chairmen's introductory remarks].

PubMed

Fukutsuka, Katsuhiro; Takubo, Takayuki

2014-04-01

Personalized medicine is a medical model that proposes the customization of treatment for individual patients. In this model, diagnostic tests are essential for selecting safer and more efficacious treatments. The term "companion diagnostics" has been used to describe these tests, whereby molecular assays that measure the levels of proteins or specific gene mutations are used to provide a specific therapy for an individual by stratifying the disease status, selecting the proper medication, and tailoring dosages. Examples of companion diagnostics in the field of cancer medicine for molecular targeted therapy include tests for the ALK-fusion gene in non-small cell lung cancer and expression of CCR4 in adult T-cell leukemia. For breast cancer, the expression of HER2 protein is evaluated by immunohistochemistry (IHC), and gene amplification of HER2 is tested by fluorescence in situ hybridization (FISH); both tests consist of pre-analysis, analysis, and post-analysis processes that require quality control to ensure the reliability of the results. This symposium includes: 1) future aspects of companion diagnostics addressing many of the problems that must be overcome, 2) companion diagnostics using FISH focusing on HER2 amplification and ALK alteration, 3) newly developed diagnostic tests using tumor specimens and cell-free DNA in serum, and 4) CCR4 expression detected by IHC and flow cytometry.

Upgrade of the MIT Linear Electrostatic Ion Accelerator (LEIA) for nuclear diagnostics development for Omega, Z and the NIF.

PubMed

Sinenian, N; Manuel, M J-E; Zylstra, A B; Rosenberg, M; Waugh, C J; Rinderknecht, H G; Casey, D T; Sio, H; Ruszczynski, J K; Zhou, L; Gatu Johnson, M; Frenje, J A; Séguin, F H; Li, C K; Petrasso, R D; Ruiz, C L; Leeper, R J

2012-04-01

The MIT Linear Electrostatic Ion Accelerator (LEIA) generates DD and D(3)He fusion products for the development of nuclear diagnostics for Omega, Z, and the National Ignition Facility (NIF). Significant improvements to the system in recent years are presented. Fusion reaction rates, as high as 10(7) s(-1) and 10(6) s(-1) for DD and D(3)He, respectively, are now well regulated with a new ion source and electronic gas control system. Charged fusion products are more accurately characterized, which allows for better calibration of existing nuclear diagnostics. In addition, in situ measurements of the on-target beam profile, made with a CCD camera, are used to determine the metrology of the fusion-product source for particle-counting applications. Finally, neutron diagnostics development has been facilitated by detailed Monte Carlo N-Particle Transport (MCNP) modeling of neutrons in the accelerator target chamber, which is used to correct for scattering within the system. These recent improvements have resulted in a versatile platform, which continues to support the existing nuclear diagnostics while simultaneously facilitating the development of new diagnostics in aid of the National Ignition Campaign at the National Ignition Facility. © 2012 American Institute of Physics

Voltage-Gated Potassium Channels Kv1.3--Potentially New Molecular Target in Cancer Diagnostics and Therapy.

PubMed

Teisseyre, Andrzej; Gąsiorowska, Justyna; Michalak, Krystyna

2015-01-01

Voltage-gated potassium channels, Kv1.3, which were discovered in 1984, are integral membrane proteins which are activated ("open") upon change of the cell membrane potential, enabling a passive flux of potassium ions across the cell membrane. The channels are expressed in many different tissues, both normal and cancer. Since 2005 it has been known that the channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane. The activity of Kv1.3 channels plays an important role, among others, in setting the cell resting membrane potential, cell proliferation, apoptosis and volume regulation. For some years, these channels have been considered a potentially new molecular target in both the diagnostics and therapy of some cancer diseases. This review article focuses on: 1) changes of expression of the channels in cancer disorders with special regard to correlations between the channels' expression and stage of the disease, 2) influence of inhibitors of Kv1.3 channels on proliferation and apoptosis of cancer cells, 3) possible future applications of Kv1.3 channels' inhibitors in therapy of some cancer diseases. In the last section, the results of studies performed in our Laboratory of Bioelectricity on the influence of selected biologically active plant-derived compounds from the groups of flavonoids and stilbenes and their natural and synthetic derivatives on the activity of Kv1.3 channels in normal and cancer cells are reviewed. A possible application of some compounds from these groups to support therapy of cancer diseases, such as breast, colon and lymph node cancer, and melanoma or chronic lymphocytic leukemia (B-CLL), is announced.

The effect of general anesthesia versus intravenous sedation on diagnostic yield and success in electromagnetic navigation bronchoscopy.

PubMed

Bowling, Mark R; Kohan, Matthew W; Walker, Paul; Efird, Jimmy; Ben Or, Sharon

2015-01-01

Navigational bronchoscopy is utilized to guide biopsies of peripheral lung nodules and place fiducial markers for treatment of limited stage lung cancer with stereotactic body radiotherapy. The type of sedation used for this procedure remains controversial. We performed a retrospective chart review to evaluate the differences of diagnostic yield and overall success of the procedure based on anesthesia type. Electromagnetic navigational bronchoscopy was performed using the superDimension software system. Once the targeted lesion was within reach, multiple tissue samples were obtained. Statistical analysis was used to correlate the yield with the type of sedation among other factors. A successful procedure was defined if a diagnosis was made or a fiducial marker was adequately placed. Navigational bronchoscopy was performed on a total of 120 targeted lesions. The overall complication rate of the procedure was 4.1%. The diagnostic yield and success of the procedure was 74% and 87%, respectively. Duration of the procedure was the only significant difference between the general anesthesia and IV sedation groups (mean, 58 vs. 43 min, P=0.0005). A larger tumor size was associated with a higher diagnostic yield (P=0.032). All other variables in terms of effect on diagnostic yield and an unsuccessful procedure did not meet statistical significance. Navigational bronchoscopy is a safe and effective pulmonary diagnostic tool with relatively low complication rate. The diagnostic yield and overall success of the procedure does not seem to be affected by the type of sedation used.

Composite targets in HiPIMS plasmas: Correlation of in-vacuum XPS characterization and optical plasma diagnostics

NASA Astrophysics Data System (ADS)

Layes, Vincent; Monje, Sascha; Corbella, Carles; Schulz-von der Gathen, Volker; von Keudell, Achim; de los Arcos, Teresa

2017-05-01

In-vacuum characterization of magnetron targets after High Power Impulse Magnetron Sputtering (HiPIMS) has been performed by X-ray photoelectron spectroscopy (XPS). Al-Cr composite targets (circular, 50 mm diameter) mounted in two different geometries were investigated: an Al target with a small Cr disk embedded at the racetrack position and a Cr target with a small Al disk embedded at the racetrack position. The HiPIMS discharge and the target surface composition were characterized in parallel for low, intermediate, and high power conditions, thus covering both the Ar-dominated and the metal-dominated HiPIMS regimes. The HiPIMS plasma was investigated using optical emission spectroscopy and fast imaging using a CCD camera; the spatially resolved XPS surface characterization was performed after in-vacuum transfer of the magnetron target to the XPS chamber. This parallel evaluation showed that (i) target redeposition of sputtered species was markedly more effective for Cr atoms than for Al atoms; (ii) oxidation at the target racetrack was observed even though the discharge ran in pure Ar gas without O2 admixture, the oxidation depended on the discharge power and target composition; and (iii) a bright emission spot fixed on top of the inserted Cr disk appeared for high power conditions.

Iodine Symporter Targeting with 124I/131I Theranostics.

PubMed

Nagarajah, James; Janssen, Marcel; Hetkamp, Philipp; Jentzen, Walter

2017-09-01

Theranostics, a modern approach combining therapeutics and diagnostics, is among the most promising concepts in nuclear medicine for optimizing and individualizing treatments for many cancer entities. Theranostics has been used in clinical routines in nuclear medicine for more than 60 y-as 131 I for diagnostic and therapeutic purposes in thyroid diseases. In this minireview, we provide a survey of the use of 2 different radioiodine isotopes for targeting the sodium-iodine symporter in thyroid cancer and nonthyroidal neoplasms as well as a brief summary of theranostics for neuroendocrine neoplasms and metastatic castration-refractory prostate cancer. In particular, we discuss the role of 124 I-based dosimetry in targeting of the sodium-iodine symporter and describe the clinical application of 124 I dosimetry in a patient who had radioiodine-refractory thyroid cancer and who underwent a redifferentiation treatment with the mitogen-activated extracellular signal-related kinase kinase inhibitor trametinib. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Plasma diagnostic development and UHV testing for the ALPHA collaboration at Marquette University

NASA Astrophysics Data System (ADS)

Tharp, T. D.; Alpha Collaboration

2017-10-01

At Marquette, we are developing the next generation of nonneutral plasma diagnostics for the ALPHA experiment at CERN. ALPHA is building a new vertical experiment to test the gravitational interaction of antihydrogen with Earth. This expansion requires significant changes to the design of our plasma diagnostic suites: the next generation of tools must be able to measure plasmas from two directions, and must be capable of operating in a horizontal position. The diagnostic suite includes measurements of plasma density, shape, and temperature. The hardware used includes a MicroChannel Plate (MCP), a Faraday Cup, and an electron gun. In addition, we are building a vacuum chamber to test the viability of 3-d printed components for UHV compatibility, with target pressures of 10-10 mbar.

Rotorcraft Diagnostics

NASA Technical Reports Server (NTRS)

Haste, Deepak; Azam, Mohammad; Ghoshal, Sudipto; Monte, James

2012-01-01

Health management (HM) in any engineering systems requires adequate understanding about the system s functioning; a sufficient amount of monitored data; the capability to extract, analyze, and collate information; and the capability to combine understanding and information for HM-related estimation and decision-making. Rotorcraft systems are, in general, highly complex. Obtaining adequate understanding about functioning of such systems is quite difficult, because of the proprietary (restricted access) nature of their designs and dynamic models. Development of an EIM (exact inverse map) solution for rotorcraft requires a process that can overcome the abovementioned difficulties and maximally utilize monitored information for HM facilitation via employing advanced analytic techniques. The goal was to develop a versatile HM solution for rotorcraft for facilitation of the Condition Based Maintenance Plus (CBM+) capabilities. The effort was geared towards developing analytic and reasoning techniques, and proving the ability to embed the required capabilities on a rotorcraft platform, paving the way for implementing the solution on an aircraft-level system for consolidation and reporting. The solution for rotorcraft can he used offboard or embedded directly onto a rotorcraft system. The envisioned solution utilizes available monitored and archived data for real-time fault detection and identification, failure precursor identification, and offline fault detection and diagnostics, health condition forecasting, optimal guided troubleshooting, and maintenance decision support. A variant of the onboard version is a self-contained hardware and software (HW+SW) package that can be embedded on rotorcraft systems. The HM solution comprises components that gather/ingest data and information, perform information/feature extraction, analyze information in conjunction with the dependency/diagnostic model of the target system, facilitate optimal guided troubleshooting, and offer

Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies.

PubMed

Zarschler, K; Prapainop, K; Mahon, E; Rocks, L; Bramini, M; Kelly, P M; Stephan, H; Dawson, K A

2014-06-07

For effective localization of functionalized nanoparticles at diseased tissues such as solid tumours or metastases through biorecognition, appropriate targeting vectors directed against selected tumour biomarkers are a key prerequisite. The diversity of such vector molecules ranges from proteins, including antibodies and fragments thereof, through aptamers and glycans to short peptides and small molecules. Here, we analyse the specific nanoparticle targeting capabilities of two previously suggested peptides (D4 and GE11) and a small camelid single-domain antibody (sdAb), representing potential recognition agents for the epidermal growth factor receptor (EGFR). We investigate specificity by way of receptor RNA silencing techniques and look at increasing complexity in vitro by introducing increasing concentrations of human or bovine serum. Peptides D4 and GE11 proved problematic to employ and conjugation resulted in non-receptor specific uptake into cells. Our results show that sdAb-functionalized particles can effectively target the EGFR, even in more complex bovine and human serum conditions where targeting specificity is largely conserved for increasing serum concentration. In human serum however, an inhibition of overall nanoparticle uptake is observed with increasing protein concentration. For highly affine targeting ligands such as sdAbs, targeting a receptor such as EGFR with low serum competitor abundance, receptor recognition function can still be partially realised in complex conditions. Here, we stress the value of evaluating the targeting efficiency of nanoparticle constructs in realistic biological milieu, prior to more extensive in vivo studies.

The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers

PubMed Central

Sahl, Jason W.; Vazquez, Adam J.; Hall, Carina M.; Busch, Joseph D.; Tuanyok, Apichai; Mayo, Mark; Schupp, James M.; Lummis, Madeline; Pearson, Talima; Shippy, Kenzie; Allender, Christopher J.; Theobald, Vanessa; Hutcheson, Alex; Korlach, Jonas; LiPuma, John J.; Ladner, Jason; Lovett, Sean; Koroleva, Galina; Palacios, Gustavo; Limmathurotsakul, Direk; Wuthiekanun, Vanaporn; Wongsuwan, Gumphol; Currie, Bart J.

2016-01-01

ABSTRACT Whole-genome sequence (WGS) data are commonly used to design diagnostic targets for the identification of bacterial pathogens. To do this effectively, genomics databases must be comprehensive to identify the strict core genome that is specific to the target pathogen. As additional genomes are analyzed, the core genome size is reduced and there is erosion of the target-specific regions due to commonality with related species, potentially resulting in the identification of false positives and/or false negatives. PMID:27651357

Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy

NASA Astrophysics Data System (ADS)

Kühnemund, Malte; Wei, Qingshan; Darai, Evangelia; Wang, Yingjie; Hernández-Neuta, Iván; Yang, Zhao; Tseng, Derek; Ahlford, Annika; Mathot, Lucy; Sjöblom, Tobias; Ozcan, Aydogan; Nilsson, Mats

2017-01-01

Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies.

A Quantitative Assessment of Factors Affecting the Technological Development and Adoption of Companion Diagnostics

PubMed Central

Luo, Dee; Smith, James A.; Meadows, Nick A.; Schuh, A.; Manescu, Katie E.; Bure, Kim; Davies, Benjamin; Horne, Rob; Kope, Mike; DiGiusto, David L.; Brindley, David A.

2016-01-01

Rapid innovation in (epi)genetics and biomarker sciences is driving a new drug development and product development pathway, with the personalized medicine era dominated by biologic therapeutics and companion diagnostics. Companion diagnostics (CDx) are tests and assays that detect biomarkers and specific mutations to elucidate disease pathways, stratify patient populations, and target drug therapies. CDx can substantially influence the development and regulatory approval for certain high-risk biologics. However, despite the increasingly important role of companion diagnostics in the realization of personalized medicine, in the USA, there are only 23 Food and Drug Administration (FDA) approved companion diagnostics on the market for 11 unique indications. Personalized medicines have great potential, yet their use is currently constrained. A major factor for this may lie in the increased complexity of the companion diagnostic and corresponding therapeutic development and adoption pathways. Understanding the market dynamics of companion diagnostic/therapeutic (CDx/Rx) pairs is important to further development and adoption of personalized medicine. Therefore, data collected on a variety of factors may highlight incentives or disincentives driving the development of companion diagnostics. Statistical analysis for 36 hypotheses resulted in two significant relationships and 34 non-significant relationships. The sensitivity of the companion diagnostic was the only factor that significantly correlated with the price of the companion diagnostic. This result indicates that while there is regulatory pressure for the diagnostic and pharmaceutical industry to collaborate and co-develop companion diagnostics for the approval of personalized therapeutics, there seems to be a lack of parallel economic collaboration to incentivize development of companion diagnostics. PMID:26858745

A Quantitative Assessment of Factors Affecting the Technological Development and Adoption of Companion Diagnostics.

PubMed

Luo, Dee; Smith, James A; Meadows, Nick A; Schuh, A; Manescu, Katie E; Bure, Kim; Davies, Benjamin; Horne, Rob; Kope, Mike; DiGiusto, David L; Brindley, David A

2015-01-01

Rapid innovation in (epi)genetics and biomarker sciences is driving a new drug development and product development pathway, with the personalized medicine era dominated by biologic therapeutics and companion diagnostics. Companion diagnostics (CDx) are tests and assays that detect biomarkers and specific mutations to elucidate disease pathways, stratify patient populations, and target drug therapies. CDx can substantially influence the development and regulatory approval for certain high-risk biologics. However, despite the increasingly important role of companion diagnostics in the realization of personalized medicine, in the USA, there are only 23 Food and Drug Administration (FDA) approved companion diagnostics on the market for 11 unique indications. Personalized medicines have great potential, yet their use is currently constrained. A major factor for this may lie in the increased complexity of the companion diagnostic and corresponding therapeutic development and adoption pathways. Understanding the market dynamics of companion diagnostic/therapeutic (CDx/Rx) pairs is important to further development and adoption of personalized medicine. Therefore, data collected on a variety of factors may highlight incentives or disincentives driving the development of companion diagnostics. Statistical analysis for 36 hypotheses resulted in two significant relationships and 34 non-significant relationships. The sensitivity of the companion diagnostic was the only factor that significantly correlated with the price of the companion diagnostic. This result indicates that while there is regulatory pressure for the diagnostic and pharmaceutical industry to collaborate and co-develop companion diagnostics for the approval of personalized therapeutics, there seems to be a lack of parallel economic collaboration to incentivize development of companion diagnostics.

The market trend analysis and prospects of cancer molecular diagnostics kits.

PubMed

Seo, Ju Hwan; Lee, Joon Woo; Cho, Daemyeong

2018-01-01

The molecular diagnostics market can be broadly divided into PCR (rt-PCR, d-PCR), NGS(Next Generation Sequencing), Microarray, FISH(Fluorescent in situ-hybridization) and other categories, based on the diagnostic technique. Also, depending on the disease being diagnosed, the market can also be divided into cancer, infectious diseases, HIV/STDs (herpes, syphilis), and women's health issues such as breast cancer, cervical cancer, ovarian cancer, HPV(human papillomavirus), and vaginitis.Chromosome analysis (including Fluorescent In-situ Hybridization) is one type of blood cancer diagnostic method, which involves the direct detection of individual cells with chromosomal translocation, but there have been problems of sensitivity when using this method. PCR targeting individual genes or the RT (reverse transcription)-PCR method offers outstanding sensitivity, but one drawback is the risk of false-positive reaction caused by contamination of samples, etc. Blood cancer molecular diagnostics kits allow us to overcome these shortcomings, and related products have been under development, with a focus on improving detection sensitivity, enabling multiple tests, and reducing the cost and diagnostic time. Blood cancer molecular diagnostics is usually performed based on platforms such as PCR. The global market for blood cancer molecular diagnostics kits is $ 335.9 million as of 2016 and is expected to reach $ 6980 million in 2026 with an average annual growth rate of 32.9%. The market in South Korea is anticipated to grow at an average annual rate of 28.9%, from $ 3.75 million as of 2016 to $ 60.89 million in 2026. The Market for blood cancer molecular diagnostics kits is judged to be higher in growth possibility due to the increase in the number of cancer patients.

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

DOE PAGES

Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.; ...

2017-12-19

Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

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

Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.

Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

CHANGING OUR DIAGNOSTIC PARADIGM: MOVEMENT SYSTEM DIAGNOSTIC CLASSIFICATION

PubMed Central

Kamonseki, Danilo H.; Staker, Justin L.; Lawrence, Rebekah L.; Braman, Jonathan P.

2017-01-01

Proper diagnosis is a first step in applying best available treatments, and prognosticating outcomes for clients. Currently, the majority of musculoskeletal diagnoses are classified according to pathoanatomy. However, the majority of physical therapy treatments are applied toward movement system impairments or pain. While advocated within the physical therapy profession for over thirty years, diagnostic classification within a movement system framework has not been uniformly developed or adopted. We propose a basic framework and rationale for application of a movement system diagnostic classification for atraumatic shoulder pain conditions, as a case for the broader development of movement system diagnostic labels. Shifting our diagnostic paradigm has potential to enhance communication, improve educational efficiency, facilitate research, directly link to function, improve clinical care, and accelerate preventive interventions. PMID:29158950

Diagnostic emulation: Implementation and user's guide

NASA Technical Reports Server (NTRS)

Becher, Bernice

1987-01-01

The Diagnostic Emulation Technique was developed within the System Validation Methods Branch as a part of the development of methods for the analysis of the reliability of highly reliable, fault tolerant digital avionics systems. This is a general technique which allows for the emulation of a digital hardware system. The technique is general in the sense that it is completely independent of the particular target hardware which is being emulated. Parts of the system are described and emulated at the logic or gate level, while other parts of the system are described and emulated at the functional level. This algorithm allows for the insertion of faults into the system, and for the observation of the response of the system to these faults. This allows for controlled and accelerated testing of system reaction to hardware failures in the target machine. This document describes in detail how the algorithm was implemented at NASA Langley Research Center and gives instructions for using the system.

Molecular Diagnostics in Pathology: Time for a Next-Generation Pathologist?

PubMed

Fassan, Matteo

2018-03-01

- Comprehensive molecular investigations of mainstream carcinogenic processes have led to the use of effective molecular targeted agents in most cases of solid tumors in clinical settings. - To update readers regarding the evolving role of the pathologist in the therapeutic decision-making process and the introduction of next-generation technologies into pathology practice. - Current literature on the topic, primarily sourced from the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database, were reviewed. - Adequate evaluation of cytologic-based and tissue-based predictive diagnostic biomarkers largely depends on both proper pathologic characterization and customized processing of biospecimens. Moreover, increased requests for molecular testing have paralleled the recent, sharp decrease in tumor material to be analyzed-material that currently comprises cytology specimens or, at minimum, small biopsies in most cases of metastatic/advanced disease. Traditional diagnostic pathology has been completely revolutionized by the introduction of next-generation technologies, which provide multigene, targeted mutational profiling, even in the most complex of clinical cases. Combining traditional and molecular knowledge, pathologists integrate the morphological, clinical, and molecular dimensions of a disease, leading to a proper diagnosis and, therefore, the most-appropriate tailored therapy.

Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy

PubMed Central

Kühnemund, Malte; Wei, Qingshan; Darai, Evangelia; Wang, Yingjie; Hernández-Neuta, Iván; Yang, Zhao; Tseng, Derek; Ahlford, Annika; Mathot, Lucy; Sjöblom, Tobias; Ozcan, Aydogan; Nilsson, Mats

2017-01-01

Molecular diagnostics is typically outsourced to well-equipped centralized laboratories, often far from the patient. We developed molecular assays and portable optical imaging designs that permit on-site diagnostics with a cost-effective mobile-phone-based multimodal microscope. We demonstrate that targeted next-generation DNA sequencing reactions and in situ point mutation detection assays in preserved tumour samples can be imaged and analysed using mobile phone microscopy, achieving a new milestone for tele-medicine technologies. PMID:28094784

Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs.

PubMed

Tibau, Ariadna; Díez-González, Laura; Navarro, Beatriz; Galán-Moya, Eva M; Templeton, Arnoud J; Seruga, Bostjan; Pandiella, Atanasio; Amir, Eitan; Ocana, Alberto

2017-06-01

Companion diagnostics permit the selection of patients likely to respond to targeted anticancer drugs; however, it is unclear if the drug development process differs between drugs developed with or without companion diagnostics. Identification of differences in study design could help future clinical development. Anticancer drugs approved for use in solid tumors between 28 September 2000 and 4 January 2014 were identified using a search of the US FDA website. Phase III trials supporting registration were extracted from the drug label. Each published study was reviewed to obtain information about the phase I and II trials used for the development of the respective drug. We identified 35 drugs and 59 phase III randomized trials supporting regulatory approval. Fifty-three phase I trials and 47 phase II trials were cited in the studies and were used to support the design of these phase III trials. The approval of drugs using a companion diagnostic has increased over time (p for trend 0.01). Expansion cohorts were more frequently observed with drugs developed with a companion diagnostic (62 vs. 20%; p = 0.005). No differences between drugs developed with or without a companion diagnostic were observed for the design of phase I and II studies. The approval of drugs developed with a companion diagnostic has increased over time. The availability of a companion diagnostic was associated with more frequent use of phase I expansion cohorts comprising patients selected by the companion diagnostic.

Tomographic diagnostic of the hydrogen beam from a negative ion source

NASA Astrophysics Data System (ADS)

Agostini, M.; Brombin, M.; Serianni, G.; Pasqualotto, R.

2011-10-01

In this paper the tomographic diagnostic developed to characterize the 2D density distribution of a particle beam from a negative ion source is described. In particular, the reliability of this diagnostic has been tested by considering the geometry of the source for the production of ions of deuterium extracted from an rf plasma (SPIDER). SPIDER is a low energy prototype negative ion source for the international thermonuclear experimental reactor (ITER) neutral beam injector, aimed at demonstrating the capability to create and extract a current of D- (H-) ions up to 50 A (60 A) accelerated at 100 kV. The ions are extracted over a wide surface (1.52×0.56m2) with a uniform plasma density which is prescribed to remain within 10% of the mean value. The main target of the tomographic diagnostic is the measurement of the beam uniformity with sufficient spatial resolution and of its evolution throughout the pulse duration. To reach this target, a tomographic algorithm based on the simultaneous algebraic reconstruction technique is developed and the geometry of the lines of sight is optimized so as to cover the whole area of the beam. Phantoms that reproduce different experimental beam configurations are simulated and reconstructed, and the role of the noise in the signals is studied. The simulated phantoms are correctly reconstructed and their two-dimensional spatial nonuniformity is correctly estimated, up to a noise level of 10% with respect to the signal.

Electromagnetic navigation diagnostic bronchoscopy for small peripheral lung lesions.

PubMed

Makris, D; Scherpereel, A; Leroy, S; Bouchindhomme, B; Faivre, J-B; Remy, J; Ramon, P; Marquette, C-H

2007-06-01

The present study prospectively evaluated the diagnostic yield and safety of electromagnetic navigation-guided bronchoscopy biopsy, for small peripheral lung lesions in patients where standard techniques were nondiagnostic. The study was conducted in a tertiary medical centre on 40 consecutive patients considered unsuitable for straightforward surgery or computed tomography (CT)-guided transthoracic needle aspiration biopsy, due to comorbidities. The lung lesion diameter was mean+/-sem 23.5+/-1.5 mm and the depth from the visceral-costal pleura was 14.9+/-2 mm. Navigation was facilitated by an electromagnetic tracking system which could detect a position sensor incorporated into a flexible catheter advanced through a bronchoscope. Information obtained during bronchoscopy was superimposed on previously acquired CT data. Divergence between CT data and data obtained during bronchoscopy was calculated by the system's software as a measure of navigational accuracy. All but one of the target lesions was reached and the overall diagnostic yield was 62.5% (25-40). Diagnostic yield was significantly affected by CT-to-body divergence; yield was 77.2% when estimated divergence was diagnostic yield of transbronchial biopsies without additional fluoroscopic guidance, and may be useful in the early diagnosis of lung cancer, particularly in nonoperable patients.

Upgrade of the MIT Linear Electrostatic Ion Accelerator (LEIA) for nuclear diagnostics development for Omega, Z and the NIF

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

Sinenian, N.; Manuel, M. J.-E.; Zylstra, A. B.

2012-04-15

The MIT Linear Electrostatic Ion Accelerator (LEIA) generates DD and D{sup 3}He fusion products for the development of nuclear diagnostics for Omega, Z, and the National Ignition Facility (NIF). Significant improvements to the system in recent years are presented. Fusion reaction rates, as high as 10{sup 7} s{sup -1} and 10{sup 6} s{sup -1} for DD and D{sup 3}He, respectively, are now well regulated with a new ion source and electronic gas control system. Charged fusion products are more accurately characterized, which allows for better calibration of existing nuclear diagnostics. In addition, in situ measurements of the on-target beam profile,more » made with a CCD camera, are used to determine the metrology of the fusion-product source for particle-counting applications. Finally, neutron diagnostics development has been facilitated by detailed Monte Carlo N-Particle Transport (MCNP) modeling of neutrons in the accelerator target chamber, which is used to correct for scattering within the system. These recent improvements have resulted in a versatile platform, which continues to support the existing nuclear diagnostics while simultaneously facilitating the development of new diagnostics in aid of the National Ignition Campaign at the National Ignition Facility.« less

Nucleic Acid Aptamer-Guided Cancer Therapeutics and Diagnostics: the Next Generation of Cancer Medicine

PubMed Central

Xiang, Dongxi; Shigdar, Sarah; Qiao, Greg; Wang, Tao; Kouzani, Abbas Z.; Zhou, Shu-Feng; Kong, Lingxue; Li, Yong; Pu, Chunwen; Duan, Wei

2015-01-01

Conventional anticancer therapies, such as chemo- and/or radio-therapy are often unable to completely eradicate cancers due to abnormal tumor microenvironment, as well as increased drug/radiation resistance. More effective therapeutic strategies for overcoming these obstacles are urgently in demand. Aptamers, as chemical antibodies that bind to targets with high affinity and specificity, are a promising new and novel agent for both cancer diagnostic and therapeutic applications. Aptamer-based cancer cell targeting facilitates the development of active targeting in which aptamer-mediated drug delivery could provide promising anticancer outcomes. This review is to update the current progress of aptamer-based cancer diagnosis and aptamer-mediated active targeting for cancer therapy in vivo, exploring the potential of this novel form of targeted cancer therapy. PMID:25553096

Nucleic acid aptamer-guided cancer therapeutics and diagnostics: the next generation of cancer medicine.

PubMed

Xiang, Dongxi; Shigdar, Sarah; Qiao, Greg; Wang, Tao; Kouzani, Abbas Z; Zhou, Shu-Feng; Kong, Lingxue; Li, Yong; Pu, Chunwen; Duan, Wei

2015-01-01

Conventional anticancer therapies, such as chemo- and/or radio-therapy are often unable to completely eradicate cancers due to abnormal tumor microenvironment, as well as increased drug/radiation resistance. More effective therapeutic strategies for overcoming these obstacles are urgently in demand. Aptamers, as chemical antibodies that bind to targets with high affinity and specificity, are a promising new and novel agent for both cancer diagnostic and therapeutic applications. Aptamer-based cancer cell targeting facilitates the development of active targeting in which aptamer-mediated drug delivery could provide promising anticancer outcomes. This review is to update the current progress of aptamer-based cancer diagnosis and aptamer-mediated active targeting for cancer therapy in vivo, exploring the potential of this novel form of targeted cancer therapy.

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

Aptamers and aptamer targeted delivery

PubMed Central

Yan, Amy C.; Levy, Matthew

2014-01-01

When aptamers first emerged almost two decades ago, most were RNA species that bound and tagged or inhibited simple target ligands. Very soon after, the ‘selectionologists’ developing aptamer technology quickly realized more potential for the aptamer. In recent years, advances in aptamer techniques have enabled the use of aptamers as small molecule inhibitors, diagnostic tools and even therapeutics. Aptamers are now being employed in novel applications. We review, herein, some of the recent and exciting applications of aptamers in cell-specific recognition and delivery. PMID:19458497

Surveillance for Emerging Diseases with Multiplexed Point-of-Care Diagnostics

DOE PAGES

Deshpande, Alina; McMahon, Benjamin; Daughton, Ashlynn Rae; ...

2016-06-17

Here, we present an analysis of the diagnostic technologies that were used to identify historical outbreaks of ebola virus disease and consider systematic surveillance strategies that may greatly reduce the peak size of future epidemics. We observe that clinical signs and symptoms alone are often insufficient to recognize index cases of diseases of global concern against the considerable background infectious disease burden that is present throughout the developing world. We propose a simple sampling strategy to enrich in especially dangerous pathogens with a low background for molecular diagnostics by targeting blood borne pathogens in the healthiest age groups. With existingmore » multiplexed diagnostic technologies, such a system could be combined with existing public health screening and reference laboratory systems for malaria, dengue, and common bacteremia or be used to develop such an infrastructure in less-developed locations. Because the needs for valid samples and accurate recording of patient attributes are aligned with needs for global biosurveillance, local public health needs, and improving patient care, co-development of these capabilities appears to be quite natural, flexible, and extensible as capabilities, technologies, and needs evolve over time. Furthermore, implementation of multiplexed diagnostic technologies to enhance fundamental clinical lab capacity will increase public health monitoring and biosurveillance as a natural extension.« less

Surveillance for Emerging Diseases with Multiplexed Point-of-Care Diagnostics

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

Deshpande, Alina; McMahon, Benjamin; Daughton, Ashlynn Rae

Here, we present an analysis of the diagnostic technologies that were used to identify historical outbreaks of ebola virus disease and consider systematic surveillance strategies that may greatly reduce the peak size of future epidemics. We observe that clinical signs and symptoms alone are often insufficient to recognize index cases of diseases of global concern against the considerable background infectious disease burden that is present throughout the developing world. We propose a simple sampling strategy to enrich in especially dangerous pathogens with a low background for molecular diagnostics by targeting blood borne pathogens in the healthiest age groups. With existingmore » multiplexed diagnostic technologies, such a system could be combined with existing public health screening and reference laboratory systems for malaria, dengue, and common bacteremia or be used to develop such an infrastructure in less-developed locations. Because the needs for valid samples and accurate recording of patient attributes are aligned with needs for global biosurveillance, local public health needs, and improving patient care, co-development of these capabilities appears to be quite natural, flexible, and extensible as capabilities, technologies, and needs evolve over time. Furthermore, implementation of multiplexed diagnostic technologies to enhance fundamental clinical lab capacity will increase public health monitoring and biosurveillance as a natural extension.« less

Biopsy of Liver Target Lesions under Contrast-Enhanced Ultrasound Guidance - A Multi-Center Study.

PubMed

Francica, Giampiero; Meloni, Maria Franca; de Sio, Ilario; Terracciano, Fulvia; Caturelli, Eugenio; Riccardi, Laura; Roselli, Paola; Iadevaia, Maddalena Diana; Scaglione, Mariano; Lenna, Giovanni; Chiang, Jason; Pompili, Maurizio

2017-12-12

Purpose  To retrospectively characterize the prevalence and impact of contrast-enhanced ultrasound (CEUS) as a guidance technique for the biopsy of liver target lesions (LTLs) at six interventional ultrasound centers. Materials and Methods  The six participating centers retrospectively selected all patients in whom biopsy needles were positioned in LTLs during CEUS. The prevalence of CEUS-guided biopsies at each center between 2005 and 2016, contrast agent consumption, procedure indications, diagnostic yield and complications were assessed. Informed consent was obtained for all patients. Results  CEUS-guided biopsy of LTLs was carried out in 103 patients (68 M/35 F, median age: 69 yrs) with 103 liver target lesions (median size: 20 mm) using cutting needles (18 - 20 g) in 94 cases (91.2 %). CEUS-guided biopsy represented 2.6 % (range: 0.8 - 7.7 %) of 3818 biopsies on LTLs carried out at the participating centers. Indications to CEUS-guided biopsy were: a target lesion not visible on non-enhanced US (27.2 %), improvement of conspicuity of the target (33 %), choice of non-necrotic area inside the target (39.8 %). 26 patients (25.2 %) had a previously non-diagnostic cyto-histological exam. The diagnostic accuracy of the technique was 99 %. No major complications followed infusion of contrast agent or biopsy performance. Conclusion  The indications for CEUS-guided biopsy for LTLs are limited, but CEUS can be useful in challenging clinical scenarios, e. g. poorly visualized or invisible lesions or sampling of non-necrotic areas in the target lesions. There is also a potential advantage in using CEUS to guide repeat biopsies after unsuccessful sampling performed using the standard ultrasound technique. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics.

PubMed

Steyer, Andrej; Jevšnik, Monika; Petrovec, Miroslav; Pokorn, Marko; Grosek, Štefan; Fratnik Steyer, Adela; Šoba, Barbara; Uršič, Tina; Cerar Kišek, Tjaša; Kolenc, Marko; Trkov, Marija; Šparl, Petra; Duraisamy, Raja; Lipkin, W Ian; Terzić, Sara; Kolnik, Mojca; Mrvič, Tatjana; Kapoor, Amit; Strle, Franc

2016-09-01

Twenty-five percent to 50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. Two hundred ninety seven children ≤6 years of age, admitted to hospital in Slovenia, October 2011 to October 2012, with AGE, and 88 ≤6 years old healthy children were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing, and a potential viral pathogen was detected in 17 additional samples (5.8%). Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens.

Fasting target for hyperglycaemia in pregnancy.

PubMed

Moses, Robert G; Wong, Veronica C K; Lambert, Kelly; Morris, Gary J

2016-10-01

Knowledge of the fasting plasma glucose of healthy women may assist in the setting of treatment targets for women with hyperglycaemia in pregnancy (HIP). This study examines the pregnancy glucose tolerance test results of 3344 women without HIP collected over a three-year period. The median fasting plasma glucose was 4.4 mmol/L with an interquartile range of 4.2-4.6 mmol/L and a 5th to 95th centile of 3.8-4.9 mmol/L. As the diagnostic fasting glucose level for HIP is ≥5.1 mmol/L, these data support a treatment target of ≤5.0 mmol/L. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

In situ synthesis of luminescent carbon nanoparticles toward target bioimaging

NASA Astrophysics Data System (ADS)

Sharker, Shazid Md.; Kim, Sung Min; Lee, Jung Eun; Jeong, Ji Hoon; in, Insik; Lee, Kang Dea; Lee, Haeshin; Park, Sung Young

2015-03-01

This paper describes the in situ synthesis of single fluorescence carbon nanoparticles (FCNs) for target bioimaging applications derived from biocompatible hyaluronic acid (HA) without using common conjugation processes. FCNs formed via the dehydration of hyaluronic acid, which were obtained by carbonizing HA, and partially carbonized HA fluorescence carbon nanoparticles (HA-FCNs), formed by a lower degree of carbonization, show good aqueous solubility, small particle size (<20 nm) and different fluorescence intensities with a red shift. After confirming the cytotoxicity of HA-FCNs and FCNs, we carried out in vitro and in vivo bioimaging studies where HA-FCNs themselves functioned as single particle triggers in target imaging. The converted nanocrystal carbon particles from HA provide outstanding features for in vitro and in vivo new targeted delivery and diagnostic tools.This paper describes the in situ synthesis of single fluorescence carbon nanoparticles (FCNs) for target bioimaging applications derived from biocompatible hyaluronic acid (HA) without using common conjugation processes. FCNs formed via the dehydration of hyaluronic acid, which were obtained by carbonizing HA, and partially carbonized HA fluorescence carbon nanoparticles (HA-FCNs), formed by a lower degree of carbonization, show good aqueous solubility, small particle size (<20 nm) and different fluorescence intensities with a red shift. After confirming the cytotoxicity of HA-FCNs and FCNs, we carried out in vitro and in vivo bioimaging studies where HA-FCNs themselves functioned as single particle triggers in target imaging. The converted nanocrystal carbon particles from HA provide outstanding features for in vitro and in vivo new targeted delivery and diagnostic tools. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07422j

Recent Developments in the VISRAD 3-D Target Design and Radiation Simulation Code

NASA Astrophysics Data System (ADS)

Macfarlane, Joseph; Golovkin, Igor; Sebald, James

2017-10-01

The 3-D view factor code VISRAD is widely used in designing HEDP experiments at major laser and pulsed-power facilities, including NIF, OMEGA, OMEGA-EP, ORION, Z, and LMJ. It simulates target designs by generating a 3-D grid of surface elements, utilizing a variety of 3-D primitives and surface removal algorithms, and can be used to compute the radiation flux throughout the surface element grid by computing element-to-element view factors and solving power balance equations. Target set-up and beam pointing are facilitated by allowing users to specify positions and angular orientations using a variety of coordinates systems (e.g., that of any laser beam, target component, or diagnostic port). Analytic modeling for laser beam spatial profiles for OMEGA DPPs and NIF CPPs is used to compute laser intensity profiles throughout the grid of surface elements. VISRAD includes a variety of user-friendly graphics for setting up targets and displaying results, can readily display views from any point in space, and can be used to generate image sequences for animations. We will discuss recent improvements to conveniently assess beam capture on target and beam clearance of diagnostic components, as well as plans for future developments.

Tumor target amplification: Implications for nano drug delivery systems.

PubMed

Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

2018-04-10

Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea.

PubMed

Lim, Eun-A; Lee, Haeyoung; Bae, Eunmi; Lim, Jaeok; Shin, Young Kee; Choi, Sang-Eun

2016-01-01

As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer's perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy.

Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

PubMed

Marquet, Pierre; Longeray, Pierre-Henry; Barlesi, Fabrice; Ameye, Véronique; Augé, Pascale; Cazeneuve, Béatrice; Chatelut, Etienne; Diaz, Isabelle; Diviné, Marine; Froguel, Philippe; Goni, Sylvia; Gueyffier, François; Hoog-Labouret, Natalie; Mourah, Samia; Morin-Surroca, Michèle; Perche, Olivier; Perin-Dureau, Florent; Pigeon, Martine; Tisseau, Anne; Verstuyft, Céline

2015-01-01

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Diagnostic molecular microbiology: a 2013 snapshot.

PubMed

Fairfax, Marilynn Ransom; Salimnia, Hossein

2013-12-01

Molecular testing has a large and increasing role in the diagnosis of infectious diseases. It has evolved significantly since the first probe tests were FDA approved in the early 1990s. This article highlights the uses of molecular techniques in diagnostic microbiology, including "older," as well as innovative, probe techniques, qualitative and quantitative RT-PCR, highly multiplexed PCR panels, some of which use sealed microfluidic test cartridges, MALDI TOF, and nuclear magnetic resonance. Tests are grouped together by technique and target. Tests with similar roles for similar analytes are compared with respect to benefits, drawbacks, and possible problems. Copyright © 2013 Elsevier Inc. All rights reserved.

Assembling Amperometric Biosensors for Clinical Diagnostics

PubMed Central

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

2008-01-01

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

Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques

NASA Astrophysics Data System (ADS)

Ballard, John R.; Casper, Andrew J.; Liu, Dalong; Haritonova, Alyona; Shehata, Islam A.; Troutman, Mitchell; Ebbini, Emad S.

2012-11-01

A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-2000 msec duration were performed at several planes in the plaque. During therapy, pulsed HIFU was interleaved with single transmit focus imaging from the DMUA and M2D imaging from the diagnostic transducer for further analysis of lesion formation. After therapy, the swine's were recovered and later sacrificed after 4 and 7 days for histological analysis of lesion formation. At sacrifice, the lower half of the swine was perfused and the femoral artery with adjoining muscle was fixed and stained with H&E to characterize HIFU-induced lesions. Histology has confirmed that localized thermal lesion formation within the plaque was achieved according to the planned lesion maps. Furthermore, the damage was confined to the plaque tissue without damage to the intima. These results offer the promise of a new treatment potentially suited for vulnerable plaques. The results also provide the first real-time demonstration of DMUA technology in targeting fine tissue structures for

Newer diagnostic approaches to intestinal protozoa.

PubMed

van Lieshout, Lisette; Verweij, Jaco J

2010-10-01

To update the reader on the latest developments in the laboratory diagnosis of intestinal protozoa. Correct identification of a diarrhoea causing pathogens is essential for the choice of treatment in an individual patient as well as to map the aetiology of diarrhoea in a variety of patient populations. Classical diagnosis of diarrhoea causing protozoa by microscopic examination of a stool sample lacks both sensitivity and specificity. Alternative diagnostic platforms are discussed. Recent literature on the diagnosis of intestinal protozoa has focused mainly on nucleic acid-based assays, in particular the specific detection of parasite DNA in stool samples using real-time PCR. In addition, the trend has been moving from single pathogen detection to a multiplex approach, allowing simultaneous identification of multiple parasites. Different combinations of targets can be used within a routine diagnostic setting, depending on the patient population, such as children, immunocompromised individuals and those who have been travelling to tropical regions. Large-scale monitoring and evaluation of control strategies become feasible due to automation and high-throughput facilities. Improved technology also has become available for differentiating protozoa subspecies, which facilitates outbreak investigations and extensive research in molecular epidemiology.

Molecular diagnostics for hereditary hearing loss in children.

PubMed

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

2017-08-01

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

Magnetic nanoparticles in magnetic resonance imaging and diagnostics.

PubMed

Rümenapp, Christine; Gleich, Bernhard; Haase, Axel

2012-05-01

Magnetic nanoparticles are useful as contrast agents for magnetic resonance imaging (MRI). Paramagnetic contrast agents have been used for a long time, but more recently superparamagnetic iron oxide nanoparticles (SPIOs) have been discovered to influence MRI contrast as well. In contrast to paramagnetic contrast agents, SPIOs can be functionalized and size-tailored in order to adapt to various kinds of soft tissues. Although both types of contrast agents have a inducible magnetization, their mechanisms of influence on spin-spin and spin-lattice relaxation of protons are different. A special emphasis on the basic magnetism of nanoparticles and their structures as well as on the principle of nuclear magnetic resonance is made. Examples of different contrast-enhanced magnetic resonance images are given. The potential use of magnetic nanoparticles as diagnostic tracers is explored. Additionally, SPIOs can be used in diagnostic magnetic resonance, since the spin relaxation time of water protons differs, whether magnetic nanoparticles are bound to a target or not.

Microfluidic Purification and Concentration of Malignant Pleural Effusions for Improved Molecular and Cytomorphological Diagnostics

PubMed Central

Go, Derek E.; Talati, Ish; Ying, Yong; Rao, Jianyu; Kulkarni, Rajan P.; Di Carlo, Dino

2013-01-01

Evaluation of pleural fluids for metastatic cells is a key component of diagnostic cytopathology. However, a large background of smaller leukocytes and/or erythrocytes can make accurate diagnosis difficult and reduce specificity in identification of mutations of interest for targeted anti-cancer therapies. Here, we describe an automated microfluidic system (Centrifuge Chip) which employs microscale vortices for the size-based isolation and concentration of cancer cells and mesothelial cells from a background of blood cells. We are able to process non-diluted pleural fluids at 6 mL/min and enrich target cells significantly over the background; we achieved improved purity in all patient samples analyzed. The resulting isolated and viable cells are readily available for immunostaining, cytological analysis, and detection of gene mutations. To demonstrate the utility towards aiding companion diagnostics, we also show improved detection accuracy of KRAS gene mutations in lung cancer cells processed using the Centrifuge Chip, leading to an increase in the area under the curve (AUC) of the receiver operating characteristic from 0.90 to 0.99. The Centrifuge Chip allows for rapid concentration and processing of large volumes of bodily fluid samples for improved cytological diagnosis and purification of cells of interest for genetic testing, which will be helpful for enhancing diagnostic accuracy. PMID:24205153

Beamlet diagnostics

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

Theys, M.

1994-05-06

Beamlet is a high power laser currently being built at Lawrence Livermore National Lab as a proof of concept for the National Ignition Facility (NIF). Beamlet is testing several areas of laser advancements, such as a 37cm Pockels cell, square amplifier, and propagation of a square beam. The diagnostics on beamlet tell the operators how much energy the beam has in different locations, the pulse shape, the energy distribution, and other important information regarding the beam. This information is being used to evaluate new amplifier designs, and extrapolate performance to the NIF laser. In my term at Lawrence Livermore Nationalmore » Laboratory I have designed and built a diagnostic, calibrated instruments used on diagnostics, setup instruments, hooked up communication lines to the instruments, and setup computers to control specific diagnostics.« less

Species separation and modification of neutron diagnostics in inertial-confinement fusion

NASA Astrophysics Data System (ADS)

Inglebert, A.; Canaud, B.; Larroche, O.

2014-09-01

The different behaviours of deuterium (D) and tritium (T) in the hot spot of marginally igniting cryogenic DT inertial-confinement fusion (ICF) targets are investigated with an ion Fokker-Planck model. With respect to an equivalent single-species model, a higher density and a higher temperature are found for T in the stagnation phase of the target implosion. In addition, the stagnating hot spot is found to be less dense but hotter than in the single-species case. As a result, the fusion reaction yield in the hot spot is significantly increased. Fusion neutron diagnostics of the implosion find a larger ion temperature as deduced from DT reactions than from DD reactions, in good agreement with NIF experimental results. ICF target designs should thus definitely take ion-kinetic effects into account.

Educational Diagnostic Assessment.

ERIC Educational Resources Information Center

Bejar, Isaac I.

1984-01-01

Approaches proposed for educational diagnostic assessment are reviewed and identified as deficit assessment and error analysis. The development of diagnostic instruments may require a reexamination of existing psychometric models and development of alternative ones. The psychometric and content demands of diagnostic assessment all but require test…

Statistical inference on censored data for targeted clinical trials under enrichment design.

PubMed

Chen, Chen-Fang; Lin, Jr-Rung; Liu, Jen-Pei

2013-01-01

For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures. Copyright © 2013 John Wiley & Sons, Ltd.

Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning.

PubMed

Nishikiori, Nobuyuki; Van Weezenbeek, Catharina

2013-02-02

Despite the progress made in the past decade, tuberculosis (TB) control still faces significant challenges. In many countries with declining TB incidence, the disease tends to concentrate in vulnerable populations that often have limited access to health care. In light of the limitations of the current case-finding approach and the global urgency to improve case detection, active case-finding (ACF) has been suggested as an important complementary strategy to accelerate tuberculosis control especially among high-risk populations. The present exercise aims to develop a model that can be used for county-level project planning. A simple deterministic model was developed to calculate the number of estimated TB cases diagnosed and the associated costs of diagnosis. The model was designed to compare cost-effectiveness parameters, such as the cost per case detected, for different diagnostic algorithms when they are applied to different risk populations. The model was transformed into a web-based tool that can support national TB programmes and civil society partners in designing ACF activities. According to the model output, tuberculosis active case-finding can be a costly endeavor, depending on the target population and the diagnostic strategy. The analysis suggests the following: (1) Active case-finding activities are cost-effective only if the tuberculosis prevalence among the target population is high. (2) Extensive diagnostic methods (e.g. X-ray screening for the entire group, use of sputum culture or molecular diagnostics) can be applied only to very high-risk groups such as TB contacts, prisoners or people living with human immunodeficiency virus (HIV) infection. (3) Basic diagnostic approaches such as TB symptom screening are always applicable although the diagnostic yield is very limited. The cost-effectiveness parameter was sensitive to local diagnostic costs and the tuberculosis prevalence of target populations. The prioritization of appropriate target

Nucleic acid aptamers: research tools in disease diagnostics and therapeutics.

PubMed

Santosh, Baby; Yadava, Pramod K

2014-01-01

Aptamers are short sequences of nucleic acid (DNA or RNA) or peptide molecules which adopt a conformation and bind cognate ligands with high affinity and specificity in a manner akin to antibody-antigen interactions. It has been globally acknowledged that aptamers promise a plethora of diagnostic and therapeutic applications. Although use of nucleic acid aptamers as targeted therapeutics or mediators of targeted drug delivery is a relatively new avenue of research, one aptamer-based drug "Macugen" is FDA approved and a series of aptamer-based drugs are in clinical pipelines. The present review discusses the aspects of design, unique properties, applications, and development of different aptamers to aid in cancer diagnosis, prevention, and/or treatment under defined conditions.

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

PubMed Central

Chung, Eun Ji; Tirrell, Matthew

2016-01-01

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

Emergency coronary angioplasty with stenting using Cordis® diagnostic coronary catheters when there is difficulty in engaging guide catheters and bench evaluation of diagnostic and guide catheters.

PubMed

Arokiaraj, Mark Christopher

2018-02-01

Difficulty in engaging with guide catheters is not uncommon in acute emergencies. We aimed to evaluate the use of Cordis ® INFINITI diagnostic catheters to perform angioplasty in patients in whom the coronaries cannot be engaged using standard guide catheters. In 34 cases of acute coronary syndrome, when difficulty in engagement with two standard guide catheters was encountered with reasonable manipulations, angioplasty was performed using diagnostic catheters. In total, 40 stents were placed by this technique. Pushability and trackability, distal tip flexion and three-point bending tests were performed to evaluate the performance of the guide and diagnostic catheters. Angioplasty was performed easily in a setting where it would have been very difficult to perform. Coronary dissection occurred in one patient, treated by a stent. The stent and dilatation balloons were easily passed through the diagnostic catheters. Pressure tracings were clearly preserved with certain stent delivery systems, and at angioplasty, although there was slightly reduced opacification of the respective artery, the coronary anatomy was sufficiently visualized to perform angioplasty. No periprocedural target lesion complications were seen in any cases. Pushability and trackability tests showed good force transmission along a tortuous path with diagnostic catheters, and balanced force-displacement curves from three-point bending tests and distal tip softness tests. Angioplasty with stenting can be performed safely through 6F Cordis ® infiniti diagnostic catheters when difficulty in engaging guide catheters is encountered. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Treatments and compositions targeting α-synuclein: a patent review (2010-2016).

PubMed

Jęśko, Henryk; Lenkiewicz, Anna M; Adamczyk, Agata

2017-04-01

Abnormal deposition of α-synuclein (ASN) is a hallmark and possible central mechanism of Parkinson's disease and other synucleinopathies. Their therapy is currently hampered by the lack of early, screening-compatible diagnostic methods and efficient treatments. Areas covered: Patent applications related to synucleinopathies obtained from Patentscope and Espacenet databases are described against the background of current knowledge regarding the regulatory mechanisms of ASN behavior including alternative splicing, post-translational modifications, molecular interactions, aggregation, degradation, and changes in localization. Expert opinion: As the central pathological feature and possibly one of root causes in a number of neurodegenerative diseases, deregulation of ASN is a potentially optimal diagnostic and therapeutic target. Changes in total ASN may have diagnostic value, especially if non-invasive /peripheral tissue tests can be developed. Targeting the whole ASN pool for therapeutic purposes may be problematic, however. ASN mutations, truncation, and post-translational modifications have great potential value; therapeutic approaches selective towards aggregated or aggregation-prone ASN forms may lead to more successful and safe treatments. Numerous ASN interactions with signaling pathways, protein degradation and stress mechanisms widen its potential therapeutic significance dramatically. However, significant improvement in the basic knowledge on ASN is necessary to fully exploit these opportunities.

Nanoparticles that Communicate In Vivo to Amplify Tumour Targeting

PubMed Central

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2012-01-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability for communication to improve targeting in biological systems, such inflammatory cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘Signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally active the coagulation cascade to broadcast tumour location to clot-targeted ‘Receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed from multiple types of Signalling and Receiving modules, can transmit information via multiple molecular pathways in coagulation, can operate autonomously, and can target over 40-fold higher doses of chemotherapeutics to tumours than non-communicating controls. PMID:21685903

Nanoparticles that communicate in vivo to amplify tumour targeting

NASA Astrophysics Data System (ADS)

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2011-07-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted ‘receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.

The Evolving Role of Companion Diagnostics for Breast Cancer in an Era of Next-Generation Omics.

PubMed

Rosenbaum, Jason N; Weisman, Paul

2017-10-01

A companion diagnostic is a test for a specific biomarker-approved by the United States Food and Drug Administration-qualifying a patient to receive a specific, associated therapy. As interest has grown in precision medicine over the past decade, the principle of companion diagnostics has gained increasing purchase among laboratory professionals, clinicians, regulators, and even patients. The evolution of the biomarkers used to stratify and treat breast cancer illustrates the history of companion diagnostics and provides a lens through which to examine potential challenges. As new targeted therapies and corresponding biomarkers accumulate, algorithms for diagnosis and treatment necessarily become lengthier and more complex. To accommodate future needs of breast cancer patients, the companion diagnostic model will continue to adapt and evolve. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Investigation of cAMP microdomains as a path to novel cancer diagnostics.

PubMed

Desman, Garrett; Waintraub, Caren; Zippin, Jonathan H

2014-12-01

Understanding of cAMP signaling has greatly improved over the past decade. The advent of live cell imaging techniques and more specific pharmacologic modulators has led to an improved understanding of the intricacies by which cAMP is able to modulate such a wide variety of cellular pathways. It is now appreciated that cAMP is able to activate multiple effector proteins at distinct areas in the cell leading to the activation of very different downstream targets. The investigation of signaling proteins in cancer is a common route to the development of diagnostic tools, prognostic tools, and/or therapeutic targets, and in this review we highlight how investigation of cAMP signaling microdomains driven by the soluble adenylyl cyclase in different cancers has led to the development of a novel cancer biomarker. Antibodies directed against the soluble adenylyl cyclase (sAC) are highly specific markers for melanoma especially for lentigo maligna melanoma and are being described as "second generation" cancer diagnostics, which are diagnostics that determine the 'state' of a cell and not just identify the cell type. Due to the wide presence of cAMP signaling pathways in cancer, we predict that further investigation of both sAC and other cAMP microdomains will lead to additional cancer biomarkers. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

NASA Astrophysics Data System (ADS)

Coughlin, Andrew James

Cancer accounts for nearly 1 out of every 4 deaths in the United States, and because conventional treatments are limited by morbidity and off-target toxicities, improvements in cancer management are needed. This thesis further develops nanoparticle-assisted photothermal therapy (NAPT) as a viable treatment option for cancer patients. NAPT enables localized ablation of disease because heat generation only occurs where tissue permissive near-infrared (NIR) light and absorbing nanoparticles are combined, leaving surrounding normal tissue unharmed. Two principle approaches were investigated to improve the specificity of this technique: multimodal imaging and molecular targeting. Multimodal imaging affords the ability to guide NIR laser application for site-specific NAPT and more holistic characterization of disease by combining the advantages of several diagnostic technologies. Towards the goal of image-guided NAPT, gadolinium-conjugated gold-silica nanoshells were engineered and demonstrated to enhance imaging contrast across a range of diagnostic modes, including T1-weighted magnetic resonance imaging, X-Ray, optical coherence tomography, reflective confocal microscopy, and two-photon luminescence in vitro as well as within an animal tumor model. Additionally, the nanoparticle conjugates were shown to effectively convert NIR light to heat for applications in photothermal therapy. Therefore, the broad utility of gadolinium-nanoshells for anatomic localization of tissue lesions, molecular characterization of malignancy, and mediators of ablation was established. Molecular targeting strategies may also improve NAPT by promoting nanoparticle uptake and retention within tumors and enhancing specificity when malignant and normal tissue interdigitate. Here, ephrinA1 protein ligands were conjugated to nanoshell surfaces for particle homing to overexpressed EphA2 receptors on prostate cancer cells. In vitro, successful targeting and subsequent photothermal ablation of

Panel-based Genetic Diagnostic Testing for Inherited Eye Diseases is Highly Accurate and Reproducible and More Sensitive for Variant Detection Than Exome Sequencing

PubMed Central

Bujakowska, Kinga M.; Sousa, Maria E.; Fonseca-Kelly, Zoë D.; Taub, Daniel G.; Janessian, Maria; Wang, Dan Yi; Au, Elizabeth D.; Sims, Katherine B.; Sweetser, David A.; Fulton, Anne B.; Liu, Qin; Wiggs, Janey L.; Gai, Xiaowu; Pierce, Eric A.

2015-01-01

Purpose Next-generation sequencing (NGS) based methods are being adopted broadly for genetic diagnostic testing, but the performance characteristics of these techniques have not been fully defined with regard to test accuracy and reproducibility. Methods We developed a targeted enrichment and NGS approach for genetic diagnostic testing of patients with inherited eye disorders, including inherited retinal degenerations, optic atrophy and glaucoma. In preparation for providing this Genetic Eye Disease (GEDi) test on a CLIA-certified basis, we performed experiments to measure the sensitivity, specificity, reproducibility as well as the clinical sensitivity of the test. Results The GEDi test is highly reproducible and accurate, with sensitivity and specificity for single nucleotide variant detection of 97.9% and 100%, respectively. The sensitivity for variant detection was notably better than the 88.3% achieved by whole exome sequencing (WES) using the same metrics, due to better coverage of targeted genes in the GEDi test compared to commercially available exome capture sets. Prospective testing of 192 patients with IRDs indicated that the clinical sensitivity of the GEDi test is high, with a diagnostic rate of 51%. Conclusion The data suggest that based on quantified performance metrics, selective targeted enrichment is preferable to WES for genetic diagnostic testing. PMID:25412400

Overview of Target Fabrication in Support of Sandia National Laboratories

NASA Astrophysics Data System (ADS)

Schroen, Diana; Breden, Eric; Florio, Joseph; Grine-Jones, Suzi; Holt, Randy; Krych, Wojtek; Metzler, James; Russell, Chris; Stolp, Justin; Streit, Jonathan; Youngblood, Kelly

2004-11-01

Sandia National Laboratories has succeeded in making its pulsed power driver, the Z machine, a valuable testbed for a great variety of experiments. These experiments include ICF, weapon physics, Equation of State and astrophysics. There are four main target types: Dynamic Hohlraum, Double Pinch, Fast Igniter and EOS. The target sizes are comparable to projected NIF sizes. For example, capsules up to 5 mm have been fielded. This talk will focus on the assembly challenges and the use of foams to create these targets. For many targets, diagnostics and capsules are embedded in the foams, and foam dopants have been added. It is the 14 mg/cc foam target with an embedded capsule (containing deuterium) that has reproducibly produced thermonuclear neutrons. For all target types, the characterization and documentation has had to develop to ensure understanding of target performance. To achieve the required resolution we are using a Nikon automated microscope and a custom OMEGA/NIF target assembly system. Our drive for quality has lead us develop a management system that been registered to ISO 9001.

Diagnostic Lumbar Puncture

PubMed Central

Doherty, Carolynne M; Forbes, Raeburn B

2014-01-01

Diagnostic Lumbar Puncture is one of the most commonly performed invasive tests in clinical medicine. Evaluation of an acute headache and investigation of inflammatory or infectious disease of the nervous system are the most common indications. Serious complications are rare, and correct technique will minimise diagnostic error and maximise patient comfort. We review the technique of diagnostic Lumbar Puncture including anatomy, needle selection, needle insertion, measurement of opening pressure, Cerebrospinal Fluid (CSF) specimen handling and after care. We also make some quality improvement suggestions for those designing services incorporating diagnostic Lumbar Puncture. PMID:25075138

Location of core diagnostic information across various sequences in brain MRI and implications for efficiency of MRI scanner utilization.

PubMed

Sharma, Aseem; Chatterjee, Arindam; Goyal, Manu; Parsons, Matthew S; Bartel, Seth

2015-04-01

Targeting redundancy within MRI can improve its cost-effective utilization. We sought to quantify potential redundancy in our brain MRI protocols. In this retrospective review, we aggregated 207 consecutive adults who underwent brain MRI and reviewed their medical records to document clinical indication, core diagnostic information provided by MRI, and its clinical impact. Contributory imaging abnormalities constituted positive core diagnostic information whereas absence of imaging abnormalities constituted negative core diagnostic information. The senior author selected core sequences deemed sufficient for extraction of core diagnostic information. For validating core sequences selection, four readers assessed the relative ease of extracting core diagnostic information from the core sequences. Potential redundancy was calculated by comparing the average number of core sequences to the average number of sequences obtained. Scanning had been performed using 9.4±2.8 sequences over 37.3±12.3 minutes. Core diagnostic information was deemed extractable from 2.1±1.1 core sequences, with an assumed scanning time of 8.6±4.8 minutes, reflecting a potential redundancy of 74.5%±19.1%. Potential redundancy was least in scans obtained for treatment planning (14.9%±25.7%) and highest in scans obtained for follow-up of benign diseases (81.4%±12.6%). In 97.4% of cases, all four readers considered core diagnostic information to be either easily extractable from core sequences or the ease to be equivalent to that from the entire study. With only one MRI lacking clinical impact (0.48%), overutilization did not seem to contribute to potential redundancy. High potential redundancy that can be targeted for more efficient scanner utilization exists in brain MRI protocols.

Molecular engineering of antibodies for therapeutic and diagnostic purposes

PubMed Central

Ducancel, Frédéric; Muller, Bruno H.

2012-01-01

During the past ten years, monoclonal antibodies (mAbs) have taken center stage in the field of targeted therapy and diagnosis. This increased interest in mAbs is due to their binding accuracy (affinity and specificity) together with the original molecular and structural rules that govern interactions with their cognate antigen. In addition, the effector properties of antibodies constitute a second major advantage associated with their clinical use. The development of molecular and structural engineering and more recently of in vitro evolution of antibodies has opened up new perspectives in the de novo design of antibodies more adapted to clinical and diagnostic use. Thus, efforts are regularly made by researchers to improve or modulate antibody recognition properties, to adapt their pharmacokinetics, engineer their stability, and control their immunogenicity. This review presents the latest molecular engineering results on mAbs with therapeutic and diagnostic applications. PMID:22684311

Economic evaluation of targeted cancer interventions: critical review and recommendations.

PubMed

Elkin, Elena B; Marshall, Deborah A; Kulin, Nathalie A; Ferrusi, Ilia L; Hassett, Michael J; Ladabaum, Uri; Phillips, Kathryn A

2011-10-01

Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening, and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. In this study, we describe the importance of this principle by reviewing published cost-effectiveness analyses of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationships among the method of targeting, the accuracy of the targeting test, and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that cost-effectiveness analyses of targeted interventions explicitly consider costs and outcomes of the method of targeting.

Direct Reading of Bona Fide Barcode Assays for Diagnostics with Smartphone Apps.

PubMed

Wong, Jessica X H; Li, Xiaochun; Liu, Frank S F; Yu, Hua-Zhong

2015-06-30

The desire to develop new point-of-care (POC) diagnostic tools has led to the adaptation of smartphones to tackle limitations in state-of-the-art instrumentation and centralized laboratory facilities. Today's smartphones possess the computer-like ability to image and process data using mobile apps; barcode scanners are one such type of apps. We demonstrate herein that a diagnostic assay can be performed by patterning immunoassay strips in a bona fide barcode format such that after target binding and signal enhancement, the linear barcode can be read directly with a standard smartphone app. Quantitative analysis can then be performed based on the grayscale intensities with a customized mobile app. This novel diagnostic concept has been validated for a real-world application, i.e., the detection of human chorionic gonadotropin, a pregnancy hormone. With the possibility of multiplex detection, the barcode assay protocol promises to boost POC diagnosis research by the direct adaptation of mobile devices and apps.

Direct Reading of Bona Fide Barcode Assays for Diagnostics with Smartphone Apps

PubMed Central

Wong, Jessica X. H.; Li, Xiaochun; Liu, Frank S. F.; Yu, Hua-Zhong

2015-01-01

The desire to develop new point-of-care (POC) diagnostic tools has led to the adaptation of smartphones to tackle limitations in state-of-the-art instrumentation and centralized laboratory facilities. Today’s smartphones possess the computer-like ability to image and process data using mobile apps; barcode scanners are one such type of apps. We demonstrate herein that a diagnostic assay can be performed by patterning immunoassay strips in a bona fide barcode format such that after target binding and signal enhancement, the linear barcode can be read directly with a standard smartphone app. Quantitative analysis can then be performed based on the grayscale intensities with a customized mobile app. This novel diagnostic concept has been validated for a real-world application, i.e., the detection of human chorionic gonadotropin, a pregnancy hormone. With the possibility of multiplex detection, the barcode assay protocol promises to boost POC diagnosis research by the direct adaptation of mobile devices and apps. PMID:26122608

Direct Reading of Bona Fide Barcode Assays for Diagnostics with Smartphone Apps

NASA Astrophysics Data System (ADS)

Wong, Jessica X. H.; Li, Xiaochun; Liu, Frank S. F.; Yu, Hua-Zhong

2015-06-01

The desire to develop new point-of-care (POC) diagnostic tools has led to the adaptation of smartphones to tackle limitations in state-of-the-art instrumentation and centralized laboratory facilities. Today’s smartphones possess the computer-like ability to image and process data using mobile apps; barcode scanners are one such type of apps. We demonstrate herein that a diagnostic assay can be performed by patterning immunoassay strips in a bona fide barcode format such that after target binding and signal enhancement, the linear barcode can be read directly with a standard smartphone app. Quantitative analysis can then be performed based on the grayscale intensities with a customized mobile app. This novel diagnostic concept has been validated for a real-world application, i.e., the detection of human chorionic gonadotropin, a pregnancy hormone. With the possibility of multiplex detection, the barcode assay protocol promises to boost POC diagnosis research by the direct adaptation of mobile devices and apps.

Developing a Multi-Dimensional Early Elementary Mathematics Screener and Diagnostic Tool: The Primary Mathematics Assessment.

PubMed

Brendefur, Jonathan L; Johnson, Evelyn S; Thiede, Keith W; Strother, Sam; Severson, Herb H

2018-01-01

There is a critical need to identify primary level students experiencing difficulties in mathematics to provide immediate and targeted instruction that remediates their deficits. However, most early math screening instruments focus only on the concept of number, resulting in inadequate and incomplete information for teachers to design intervention efforts. We propose a mathematics assessment that screens and provides diagnostic information in six domains that are important to building a strong foundation in mathematics. This article describes the conceptual framework and psychometric qualities of a web-based assessment tool, the Primary Math Assessment (PMA). The PMA includes a screener to identify students at risk for poor math outcomes and a diagnostic tool to provide a more in-depth profile of children's specific strengths and weaknesses in mathematics. The PMA allows teachers and school personnel to make better instructional decisions by providing more targeted analyses.

DVA as a Diagnostic Test for Vestibulo-Ocular Reflex Function

NASA Technical Reports Server (NTRS)

Wood, Scott J.; Appelbaum, Meghan

2010-01-01

The vestibulo-ocular reflex (VOR) stabilizes vision on earth-fixed targets by eliciting eyes movements in response to changes in head position. How well the eyes perform this task can be functionally measured by the dynamic visual acuity (DVA) test. We designed a passive, horizontal DVA test to specifically study the acuity and reaction time when looking in different target locations. Visual acuity was compared among 12 subjects using a standard Landolt C wall chart, a computerized static (no rotation) acuity test and dynamic acuity test while oscillating at 0.8 Hz (+/-60 deg/s). In addition, five trials with yaw oscillation randomly presented a visual target in one of nine different locations with the size and presentation duration of the visual target varying across trials. The results showed a significant difference between the static and dynamic threshold acuities as well as a significant difference between the visual targets presented in the horizontal plane versus those in the vertical plane when comparing accuracy of vision and reaction time of the response. Visual acuity increased proportional to the size of the visual target and increased between 150 and 300 msec duration. We conclude that dynamic visual acuity varies with target location, with acuity optimized for targets in the plane of rotation. This DVA test could be used as a functional diagnostic test for visual-vestibular and neuro-cognitive impairments by assessing both accuracy and reaction time to acquire visual targets.

Choosing the right diagnostic imaging modality in musculoskeletal diagnosis.

PubMed

Aagesen, Andrea L; Melek, Maged

2013-12-01

Radiological studies can confirm or rule out competing diagnoses for musculoskeletal injuries and pain. Obtaining a detailed history and physical examination is pivotal for localizing the pain generator and choosing the most appropriate imaging studies, based on the suspected injured tissue. Judicious use of imaging is important to avoid unnecessary radiation exposure, minimize cost, and avoid therapy targeting asymptomatic imaging abnormalities. This article compares and contrasts the diagnostic imaging commonly used for detecting musculoskeletal injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

Fluorescent imaging of cancerous tissues for targeted surgery

PubMed Central

Bu, Lihong; Shen, Baozhong; Cheng, Zhen

2014-01-01

To maximize tumor excision and minimize collateral damage is the primary goal of cancer surgery. Emerging molecular imaging techniques have to “image-guided surgery” developing into “molecular imaging-guided surgery”, which is termed “targeted surgery” in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling “targeted surgery” to be a component of “targeted therapy”. Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields. PMID:25064553

A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands.

PubMed

Das, Samir; Nag, Arundhati; Liang, JingXin; Bunck, David N; Umeda, Aiko; Farrow, Blake; Coppock, Matthew B; Sarkes, Deborah A; Finch, Amethist S; Agnew, Heather D; Pitram, Suresh; Lai, Bert; Yu, Mary Beth; Museth, A Katrine; Deyle, Kaycie M; Lepe, Bianca; Rodriguez-Rivera, Frances P; McCarthy, Amy; Alvarez-Villalonga, Belen; Chen, Ann; Heath, John; Stratis-Cullum, Dimitra N; Heath, James R

2015-11-02

We describe a general synthetic strategy for developing high-affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full-length protein to identify the best binder. We describe development of epitope-targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Thalassaemia diagnostics].

PubMed

Kusters, Elske; Kerkhoffs, Jean-Louis H; van Rossum, André P

2014-01-01

The thalassaemias are characterised by quantitative aberrations in the production of the globin chains that make up haemoglobin, and are a subgroup of the haemoglobinopathies. In this LabQuiz we show how thalassaemia carrier status can be indicated in the results of regular laboratory tests, and discuss the laboratory diagnostics that can confirm or rule out thalassaemia. In these two cases we will present a man of Moroccan descent, and two brothers of Filipino descent, all with anaemia and microcytosis. We show it is possible to differentiate between iron-deficiency anaemia and thalassaemia carrier status on the basis of a complete blood count and measurement of ferritin levels, and which laboratory diagnostics can be subsequently performed in order to confirm a suspicion of thalassaemia. The background section discusses the properties and pitfalls of routine laboratory diagnostics for the thalassaemias, and thalassaemia diagnostics in the Dutch newborn screening programme.

Tracking of multimodal therapeutic nanocomplexes targeting breast cancer in vivo.

PubMed

Bardhan, Rizia; Chen, Wenxue; Bartels, Marc; Perez-Torres, Carlos; Botero, Maria F; McAninch, Robin Ward; Contreras, Alejandro; Schiff, Rachel; Pautler, Robia G; Halas, Naomi J; Joshi, Amit

2010-12-08

Nanoparticle-based therapeutics with local delivery and external electromagnetic field modulation holds extraordinary promise for soft-tissue cancers such as breast cancer; however, knowledge of the distribution and fate of nanoparticles in vivo is crucial for clinical translation. Here we demonstrate that multiple diagnostic capabilities can be introduced in photothermal therapeutic nanocomplexes by simultaneously enhancing both near-infrared fluorescence and magnetic resonance imaging (MRI). We track nanocomplexes in vivo, examining the influence of HER2 antibody targeting on nanocomplex distribution over 72 h. This approach provides valuable, detailed information regarding the distribution and fate of complex nanoparticles designed for specific diagnostic and therapeutic functions.

Tracking of Multimodal Therapeutic Nanocomplexes Targeting Breast Cancer in Vivo

PubMed Central

Bardhan, Rizia; Chen, Wenxue; Bartels, Marc; Perez-Torres, Carlos; Botero, Maria F.; McAninch, Robin Ward; Contreras, Alejandro; Schiff, Rachel; Pautler, Robia G.; Halas, Naomi J.; Joshi, Amit

2014-01-01

Nanoparticle-based therapeutics with local delivery and external electromagnetic field modulation holds extraordinary promise for soft-tissue cancers such as breast cancer; however, knowledge of the distribution and fate of nanoparticles in vivo is crucial for clinical translation. Here we demonstrate that multiple diagnostic capabilities can be introduced in photothermal therapeutic nanocomplexes by simultaneously enhancing both near-infrared fluorescence and magnetic resonance imaging (MRI). We track nanocomplexes in vivo, examining the influence of HER2 antibody targeting on nanocomplex distribution over 72 h. This approach provides valuable, detailed information regarding the distribution and fate of complex nanoparticles designed for specific diagnostic and therapeutic functions. PMID:21090693

Molecular phylogenetic analysis of Enterobius vermicularis and development of an 18S ribosomal DNA-targeted diagnostic PCR.

PubMed

Zelck, Ulrike E; Bialek, Ralf; Weiss, Michael

2011-04-01

We genetically characterized pinworms obtained from 37 children from different regions of Germany and established new species-specific molecular diagnostic tools. No ribosomal DNA diversity was found; the phylogenetic position of Enterobius vermicularis within the Oxyurida order and its close relationship to the Ascaridida and Spirurida orders was confirmed.

Demise of Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry as an Infectious Diseases Diagnostic Tool.

PubMed

Özenci, Volkan; Patel, Robin; Ullberg, Måns; Strålin, Kristoffer

2018-01-18

Although there are several US Food and Drug Administration (FDA)-approved/cleared molecular microbiology diagnostics for direct analysis of patient samples, all are single target or panel-based tests. There is no FDA-approved/cleared diagnostic for broad microbial detection. Polymerase chain reaction (PCR)/electrospray ionization-mass spectrometry (PCR/ESI-MS), commercialized as the IRIDICA system (Abbott) and formerly PLEX-ID, had been under development for over a decade and had become CE-marked and commercially available in Europe in 2014. Capable of detecting a large number of microorganisms, it was under review at the FDA when, in April 2017, Abbott discontinued it. This turn of events represents not only the loss of a potential diagnostic tool for infectious diseases but may be a harbinger of similar situations with other emerging and expensive microbial diagnostics, especially genomic tests. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Diagnostic potential of Raman spectroscopy in Barrett's esophagus

NASA Astrophysics Data System (ADS)

Wong Kee Song, Louis-Michel; Molckovsky, Andrea; Wang, Kenneth K.; Burgart, Lawrence J.; Dolenko, Brion; Somorjai, Rajmund L.; Wilson, Brian C.

2005-04-01

Patients with Barrett's esophagus (BE) undergo periodic endoscopic surveillance with random biopsies in an effort to detect dysplastic or early cancerous lesions. Surveillance may be enhanced by near-infrared Raman spectroscopy (NIRS), which has the potential to identify endoscopically-occult dysplastic lesions within the Barrett's segment and allow for targeted biopsies. The aim of this study was to assess the diagnostic performance of NIRS for identifying dysplastic lesions in BE in vivo. Raman spectra (Pexc=70 mW; t=5 s) were collected from Barrett's mucosa at endoscopy using a custom-built NIRS system (λexc=785 nm) equipped with a filtered fiber-optic probe. Each probed site was biopsied for matching histological diagnosis as assessed by an expert pathologist. Diagnostic algorithms were developed using genetic algorithm-based feature selection and linear discriminant analysis, and classification was performed on all spectra with a bootstrap-based cross-validation scheme. The analysis comprised 192 samples (112 non-dysplastic, 54 low-grade dysplasia and 26 high-grade dysplasia/early adenocarcinoma) from 65 patients. Compared with histology, NIRS differentiated dysplastic from non-dysplastic Barrett's samples with 86% sensitivity, 88% specificity and 87% accuracy. NIRS identified 'high-risk' lesions (high-grade dysplasia/early adenocarcinoma) with 88% sensitivity, 89% specificity and 89% accuracy. In the present study, NIRS classified Barrett's epithelia with high and clinically-useful diagnostic accuracy.

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective.

PubMed

Chen, Guoli; Yang, Zhaohai; Eshleman, James R; Netto, George J; Lin, Ming-Tseh

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional "one test-one drug" assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective

PubMed Central

Chen, Guoli; Yang, Zhaohai; Eshleman, James R.; Netto, George J.

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional “one test-one drug” assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC. PMID:27699178

Recent Advances in Aptamers Targeting Immune System.

PubMed

Hu, Piao-Ping

2017-02-01

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

Drug-induced amplification of nanoparticle targeting to tumors

PubMed Central

Lin, Kevin Y.; Kwon, Ester J.; Lo, Justin H.; Bhatia, Sangeeta N.

2018-01-01

Summary Nanomedicines have the potential to significantly impact cancer therapy by improving drug efficacy and decreasing off-target effects, yet our ability to efficiently home nanoparticles to disease sites remains limited. One frequently overlooked constraint of current active targeting schemes is the relative dearth of targetable antigens within tumors, which restricts the amount of cargo that can be delivered in a tumor-specific manner. To address this limitation, we exploit tumor-specific responses to drugs to construct a cooperative targeting system where a small molecule therapeutic modulates the disease microenvironment to amplify nanoparticle recruitment in vivo. We first administer a vascular disrupting agent, ombrabulin, which selectively affects tumors and leads to locally elevated presentation of the stress-related protein, p32. This increase in p32 levels provides more binding sites for circulating p32-targeted nanoparticles, enhancing their delivery of diagnostic or therapeutic cargos to tumors. We show that this cooperative targeting system recruits over five times higher doses of nanoparticles to tumors and decreases tumor burden when compared with non-cooperative controls. These results suggest that using nanomedicine in conjunction with drugs that enhance the presentation of target antigens in the tumor environment may be an effective strategy for improving the diagnosis and treatment of cancer. PMID:29731806

Quatrième conférence consensuelle sur le diagnostic et le traitement de la démence

PubMed Central

Moore, Ainsley; Patterson, Christopher; Lee, Linda; Vedel, Isabelle; Bergman, Howard

2014-01-01

Résumé Objectif Revoir les stratégies diagnostiques de la maladie d’Alzheimer, actualiser les recommandations concernant le traitement des symptômes de démence et proposer une approche thérapeutique à la démence d’apparition précoce et d’évolution rapide. Composition du comité Des spécialistes et des délégués de diverses régions du Canada et représentant diverses disciplines pertinentes ont discuté et se sont mis d’accord sur les révisions à apporter aux lignes directrices de 2006. Méthodologie On a eu recours au système GRADE (grading of recommendations, assessment, development, and evaluation) pour évaluer le consensus concernant les recommandations, lequel était défini comme suit : lorsque 80 % ou plus des participants ont voté en faveur de la recommandation. La cote des données probantes est rapportée lorsque cela est possible. Rapport important pour les médecins de famille, malgré les progrès effectués dans les domaines des biomarqueurs liquidiens et de la neuro-imagerie, le diagnostic de démence au Canada demeure fondamentalement clinique. De nouveaux critères cliniques essentiels de diagnostic de la maladie d’Alzheimer en reconnaissent dorénavant les formes moins fréquentes et non amnestiques. La démence précoce, une affection rare, mais importante, devrait inciter les médecins à aiguiller les patients vers un spécialiste ayant accès à des conseillers en génétique. La démence d’évolution rapide, mal définie dans la littérature, faciliterait le dépistage de cette affection rare, mais importante. Les inhibiteurs de la cholinestérase sont maintenant indiqués pour le traitement d’affections autres que la maladie d’Alzheimer. Des lignes directrices concernant l’arrêt du traitement, lesquelles n’existaient pas auparavant, sont également apparues. De nouvelles données probantes sur le recours à la mémantine, aux antidépresseurs et à d’autres agents psychotropes dans le traitement de la

Electro-optic analysis of the influence of target geometry on electromagnetic pulses generated by petawatt laser-matter interactions

NASA Astrophysics Data System (ADS)

Robinson, Timothy; Giltrap, Samuel; Eardley, Samuel; Consoli, Fabrizio; De Angelis, Riccardo; Ingenito, Francesco; Stuart, Nicholas; Verona, Claudio; Smith, Roland A.

2018-01-01

We present an analysis of strong laser-driven electromagnetic pulses using novel electro-optic diagnostic techniques. A range of targets were considered, including thin plastic foils (20-550 nm) and mass-limited, optically-levitated micro-targets. Results from foils indicate a dependence of EMP on target thickness, with larger peak electric fields observed with thinner targets. Spectral analysis suggests high repeatability between shots, with identified spectral features consistently detected with <1 MHz standard deviations of the peak position. This deviation is reduced for shots taken on the same day, suggesting that local conditions, such as movement of metal objects within the target chamber, are more likely to lead to minor spectral modifications, highlighting the role of the local environment in determining the details of EMP production. Levitated targets are electrically isolated from their environment, hence these targets should be unable to draw a neutralization current from the earth following ejection of hot electrons from the plasma, in contrast to predictions for pin-mounted foils in the Poyé EMP generation model. With levitated targets, no EMP was measurable above the noise threshold of any diagnostic, despite observation of protons accelerated to >30 MeV energies, suggesting the discharge current contribution to EMP is dominant.

Neoplastic Meningitis from Solid Tumors: New Diagnostic and Therapeutic Approaches

PubMed Central

Zustovich, Fable; Farina, Patrizia; Della Puppa, Alessandro; Manara, Renzo; Cecchin, Diego; Brunello, Antonella; Cappetta, Alessandro; Zagonel, Vittorina

2011-01-01

Neoplastic meningitis is a result of the spread of malignant cells to the leptomeninges and subarachnoid space and their dissemination within the cerebrospinal fluid. This event occurs in 4%–15% of all patients with solid tumors and represents an important prognostic factor for poor survival. Neoplastic meningitis should be diagnosed in the early stages of disease to prevent important neurological deficits and to provide the most appropriate treatment. Despite new diagnostic approaches developed in recent years, such as positron emission tomography–computed tomography and new biological markers, the combination of magnetic resonance imaging without and with gadolinium enhancement and cytology still has the greatest diagnostic sensitivity. Recently, no new randomized studies comparing intrathecal (i.t.) with systemic treatment have been performed, yet there have been a few small phase II studies and case reports about new molecularly targeted substances whose successful i.t. or systemic application has been reported. Trastuzumab, gefitinib, and sorafenib are examples of possible future treatments for neoplastic meningitis, in order to better individualize therapy thus allowing better outcomes. In this review, we analyze the most recent and interesting developments on diagnostic and therapeutic approaches. PMID:21795431

A tuberculosis biomarker database: the key to novel TB diagnostics.

PubMed

Yerlikaya, Seda; Broger, Tobias; MacLean, Emily; Pai, Madhukar; Denkinger, Claudia M

2017-03-01

New diagnostic innovations for tuberculosis (TB), including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this 'biomarker pipeline problem', FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs) for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... in the 80000 series of the Current Procedural Terminology published by the American Medical... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

42 CFR 410.32 - Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Procedural Terminology published by the American Medical Association. (3) Levels of supervision. Except where... & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services § 410.32 Diagnostic x-ray tests, diagnostic laboratory...

Molecular Phylogenetic Analysis of Enterobius vermicularis and Development of an 18S Ribosomal DNA-Targeted Diagnostic PCR▿

PubMed Central

Zelck, Ulrike E.; Bialek, Ralf; Weiß, Michael

2011-01-01

We genetically characterized pinworms obtained from 37 children from different regions of Germany and established new species-specific molecular diagnostic tools. No ribosomal DNA diversity was found; the phylogenetic position of Enterobius vermicularis within the Oxyurida order and its close relationship to the Ascaridida and Spirurida orders was confirmed. PMID:21248085

Diagnostic Tests to Support Late-Stage Control Programs for Schistosomiasis and Soil-Transmitted Helminthiases.

PubMed

Hawkins, Kenneth R; Cantera, Jason L; Storey, Helen L; Leader, Brandon T; de Los Santos, Tala

2016-12-01

Global efforts to address schistosomiasis and soil-transmitted helminthiases (STH) include deworming programs for school-aged children that are made possible by large-scale drug donations. Decisions on these mass drug administration (MDA) programs currently rely on microscopic examination of clinical specimens to determine the presence of parasite eggs. However, microscopy-based methods are not sensitive to the low-intensity infections that characterize populations that have undergone MDA. Thus, there has been increasing recognition within the schistosomiasis and STH communities of the need for improved diagnostic tools to support late-stage control program decisions, such as when to stop or reduce MDA. Failure to adequately address the need for new diagnostics could jeopardize achievement of the 2020 London Declaration goals. In this report, we assess diagnostic needs and landscape potential solutions and determine appropriate strategies to improve diagnostic testing to support control and elimination programs. Based upon literature reviews and previous input from experts in the schistosomiasis and STH communities, we prioritized two diagnostic use cases for further exploration: to inform MDA-stopping decisions and post-MDA surveillance. To this end, PATH has refined target product profiles (TPPs) for schistosomiasis and STH diagnostics that are applicable to these use cases. We evaluated the limitations of current diagnostic methods with regards to these use cases and identified candidate biomarkers and diagnostics with potential application as new tools. Based on this analysis, there is a need to develop antigen-detecting rapid diagnostic tests (RDTs) with simplified, field-deployable sample preparation for schistosomiasis. Additionally, there is a need for diagnostic tests that are more sensitive than the current methods for STH, which may include either a field-deployable molecular test or a simple, low-cost, rapid antigen-detecting test.

Socioeconomic and Behavioral Factors Associated with Tuberculosis Diagnostic Delay in Lima, Peru.

PubMed

Bonadonna, Lily V; Saunders, Matthew J; Guio, Heinner; Zegarra, Roberto; Evans, Carlton A

2018-06-01

Early detection and diagnosis of tuberculosis (TB) is a global priority. Prolonged symptom duration before TB diagnosis is associated with increased morbidity, mortality, and risk of transmission. We aimed to determine socioeconomic and behavioral factors associated with diagnostic delays among patients with TB. Data were collected from 105 patients with TB using a semi-structured interview guide in Lima, Peru. Factors associated with diagnostic delay were analyzed using negative binomial regression. The median delay from when symptoms commenced and the first positive diagnostic sample in public health facilities was 57 days (interquartile range: 28-126). In multivariable analysis, greater diagnostic delay was independently associated with patient older age, female gender, lower personal income before diagnosis, living with fewer people, and having more visits to professional health facilities before diagnosis (all P < 0.05). Patients who first sought care at a private health facility had more visits overall to professional health facilities before diagnosis than those who first sought care from public or insured employee health facilities and had longer diagnostic delay in analysis adjusted for age and gender. Patients with TB were significantly more likely to first self-medicate than to visit professional health facilities before diagnosis ( P = 0.003). Thus, diagnostic delay was prolonged, greatest among older, low-income women, and varied according to the type of care sought by individuals when their symptoms commenced. These findings suggest that TB case-finding initiatives should target vulnerable groups in informal and private health facilities, where many patients with TB first seek health care.

The Targeted Reading Intervention (TRI): A Classroom Teacher Tier 2 Intervention to Help Struggling Readers in Early Elementary School

ERIC Educational Resources Information Center

Vernon-Feagans, Lynne; Amendum, Steve; Kainz, Kirsten; Ginsburg, Marnie

2009-01-01

The two studies presented in this report were designed to test the effectiveness of a new diagnostic-based reading intervention for classroom teachers, called the Targeted Reading Intervention (TRI). This TRI Tier 2 intervention stressed diagnostic teaching as the key to helping struggling readers make rapid progress in reading in the regular…

A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium.

PubMed

Pequegnat, Brittany; Sagermann, Martin; Valliani, Moez; Toh, Michael; Chow, Herbert; Allen-Vercoe, Emma; Monteiro, Mario A

2013-06-10

Constipation and diarrhea are common in autistic patients. Treatment with antibiotics against bacteria appears to partially alleviate autistic-related symptoms. Clostridium bolteae is a bacterium that has been shown to be overabundant in the intestinal tract of autistic children suffering from gastric intestinal ailments, and as such is an organism that could potentially aggravate gastrointestinal symptoms. We set out to investigate the cell-wall polysaccharides of C. bolteae in order to evaluate their structure and immunogenicity. Our explorations revealed that C. bolteae produces a conserved specific capsular polysaccharide comprised of rhamnose and mannose units: [→3)-α-D-Manp-(1→4)-β-d-Rhap-(1→], which is immunogenic in rabbits. These findings are the first description of a C. bolteae immunogen and indicate the prospect of using this polysaccharide as a vaccine to reduce or prevent C. bolteae colonization of the intestinal tract in autistic patients, and as a diagnostic marker for the rapid detection of C. bolteae in a clinical setting. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diagnostic Opportunities Using Rasch Measurement in the Context of a Misconceptions-Based Physical Science Assessment

ERIC Educational Resources Information Center

Wind, Stefanie A.; Gale, Jessica D.

2015-01-01

Multiple-choice (MC) items that are constructed such that distractors target known misconceptions for a particular domain provide useful diagnostic information about student misconceptions (Herrmann-Abell & DeBoer, 2011, 2014; Sadler, 1998). Item response theory models can be used to examine misconceptions distractor-driven multiple-choice…

Targeted next generation sequencing identifies novel NOTCH3 gene mutations in CADASIL diagnostics patients.

PubMed

Maksemous, Neven; Smith, Robert A; Haupt, Larisa M; Griffiths, Lyn R

2016-11-24

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic, hereditary, small vessel disease of the brain causing stroke and vascular dementia in adults. CADASIL has previously been shown to be caused by varying mutations in the NOTCH3 gene. The disorder is often misdiagnosed due to its significant clinical heterogeneic manifestation with familial hemiplegic migraine and several ataxia disorders as well as the location of the currently identified causative mutations. The aim of this study was to develop a new, comprehensive and efficient single assay strategy for complete molecular diagnosis of NOTCH3 mutations through the use of a custom next-generation sequencing (NGS) panel for improved routine clinical molecular diagnostic testing. Our custom NGS panel identified nine genetic variants in NOTCH3 (p.D139V, p.C183R, p.R332C, p.Y465C, p.C597W, p.R607H, p.E813E, p.C977G and p.Y1106C). Six mutations were stereotypical CADASIL mutations leading to an odd number of cysteine residues in one of the 34 NOTCH3 gene epidermal growth factor (EGF)-like repeats, including three new typical cysteine mutations identified in exon 11 (p.C597W; c.1791C>G); exon 18 (p.C977G; c.2929T>G) and exon 20 (p.Y1106C; c.3317A>G). Interestingly, a novel missense mutation in the CACNA1A gene was also identified in one CADASIL patient. All variants identified (novel and known) were further investigated using in silico bioinformatic analyses and confirmed through Sanger sequencing. NGS provides an improved and effective methodology for the diagnosis of CADASIL. The NGS approach reduced time and cost for comprehensive genetic diagnosis, placing genetic diagnostic testing within reach of more patients.

42 CFR 415.180 - Teaching setting requirements for the interpretation of diagnostic radiology and other diagnostic...

Code of Federal Regulations, 2011 CFR

2011-10-01

... interpretation of diagnostic radiology and other diagnostic tests. 415.180 Section 415.180 Public Health CENTERS... for the interpretation of diagnostic radiology and other diagnostic tests. (a) General rule. Physician fee schedule payment is made for the interpretation of diagnostic radiology and other diagnostic tests...

42 CFR 415.180 - Teaching setting requirements for the interpretation of diagnostic radiology and other diagnostic...

Code of Federal Regulations, 2010 CFR

2010-10-01

... interpretation of diagnostic radiology and other diagnostic tests. 415.180 Section 415.180 Public Health CENTERS... for the interpretation of diagnostic radiology and other diagnostic tests. (a) General rule. Physician fee schedule payment is made for the interpretation of diagnostic radiology and other diagnostic tests...

Clinically inappropriate post hoc exclusion of study participants from test accuracy calculations: the ROMA score, an example from a recent NICE diagnostic assessment.

PubMed

Lang, Shona; Armstrong, Nigel; Deshpande, Sohan; Ramaekers, Bram; Grimm, Sabine; de Kock, Shelley; Kleijnen, Jos; Westwood, Marie

2018-01-01

Objective To explore how the definition of the target condition and post hoc exclusion of participants can limit the usefulness of diagnostic accuracy studies. Methods We used data from a systematic review, conducted for a NICE diagnostic assessment of risk scores to inform secondary care decisions about specialist referral for women with suspected ovarian cancer, to explore how the definition of the target condition and post hoc exclusion of participants can limit the usefulness of diagnostic accuracy studies to inform clinical practice. Results Fourteen of the studies evaluated the ROMA score, nine used Abbott ARCHITECT tumour marker assays, five used Roche Elecsys. The summary sensitivity estimate (Abbott ARCHITECT) was highest, 95.1% (95% CI: 92.4 to 97.1%), where analyses excluded participants with borderline tumours or malignancies other than epithelial ovarian cancer and lowest, 75.0% (95% CI: 60.4 to 86.4%), where all participants were included. Results were similar for Roche Elecsys tumour marker assays. Although the number of patients involved was small, data from studies that reported diagnostic accuracy for both the whole study population and with post hoc exclusion of those with borderline or non-epithelial malignancies suggested that patients with borderline or malignancies other than epithelial ovarian cancer accounts for between 50 and 85% of false-negative ROMA scores. Conclusions Our results illustrate the potential consequences of inappropriate population selection in diagnostic studies; women with non-epithelial ovarian cancers or non-ovarian primaries, and those borderline tumours may be disproportionately represented among those with false negative, 'low risk' ROMA scores. These observations highlight the importance of giving careful consideration to how the target condition has been defined when assessing whether the diagnostic accuracy estimates reported in clinical studies will translate into clinical utility in real-world settings.

Evaluation of Targeted Next-Generation Sequencing for Detection of Bovine Pathogens in Clinical Samples.

PubMed

Anis, Eman; Hawkins, Ian K; Ilha, Marcia R S; Woldemeskel, Moges W; Saliki, Jeremiah T; Wilkes, Rebecca P

2018-07-01

The laboratory diagnosis of infectious diseases, especially those caused by mixed infections, is challenging. Routinely, it requires submission of multiple samples to separate laboratories. Advances in next-generation sequencing (NGS) have provided the opportunity for development of a comprehensive method to identify infectious agents. This study describes the use of target-specific primers for PCR-mediated amplification with the NGS technology in which pathogen genomic regions of interest are enriched and selectively sequenced from clinical samples. In the study, 198 primers were designed to target 43 common bovine and small-ruminant bacterial, fungal, viral, and parasitic pathogens, and a bioinformatics tool was specifically constructed for the detection of targeted pathogens. The primers were confirmed to detect the intended pathogens by testing reference strains and isolates. The method was then validated using 60 clinical samples (including tissues, feces, and milk) that were also tested with other routine diagnostic techniques. The detection limits of the targeted NGS method were evaluated using 10 representative pathogens that were also tested by quantitative PCR (qPCR), and the NGS method was able to detect the organisms from samples with qPCR threshold cycle ( C T ) values in the 30s. The method was successful for the detection of multiple pathogens in the clinical samples, including some additional pathogens missed by the routine techniques because the specific tests needed for the particular organisms were not performed. The results demonstrate the feasibility of the approach and indicate that it is possible to incorporate NGS as a diagnostic tool in a cost-effective manner into a veterinary diagnostic laboratory. Copyright © 2018 Anis et al.

Evaluation of 64Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer's Disease.

PubMed

Bandara, Nilantha; Sharma, Anuj K; Krieger, Stephanie; Schultz, Jason W; Han, Byung Hee; Rogers, Buck E; Mirica, Liviu M

2017-09-13

Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer's disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides 11 C (20.4 min) and 18 F (109.8 min) may limit the widespread use of these imaging agents. Therefore, we have begun to evaluate novel AD diagnostic agents that can be radiolabeled with 64 Cu, a radionuclide with a half-life of 12.7 h, ideal for PET imaging. Described herein are a series of bifunctional chelators (BFCs), L 1 -L 5 , that were designed to tightly bind 64 Cu and shown to interact with Aβ aggregates both in vitro and in transgenic AD mouse brain sections. Importantly, biodistribution studies show that these compounds exhibit promising brain uptake and rapid clearance in wild-type mice, and initial microPET imaging studies of transgenic AD mice suggest that these compounds could serve as lead compounds for the development of improved diagnostic agents for AD.

Optical diagnostics on the Magnetized Shock Experiment (MSX)

NASA Astrophysics Data System (ADS)

Boguski, J. C.; Weber, T. E.; Intrator, T. P.; Smith, R. J.; Dunn, J. P.; Hutchinson, T. M.; Gao, K. W.

2013-10-01

The Magnetized Shock Experiment (MSX) at Los Alamos National Laboratory was built to investigate the physics of high Alfvén Mach number, supercritical, magnetized shocks through the acceleration and subsequent stagnation of a Field Reversed Configuration (FRC) plasmoid against a magnetic mirror and/or plasma target. A suite of optical diagnostics has recently been fielded on MSX to characterize plasma conditions during the formation, acceleration, and stagnation phases of the experiment. CCD-backed streak and framing cameras, and a fiber-based visible light array, provide information regarding FRC shape, velocity, and instability growth. Time-resolved narrow and broadband spectroscopy provides information on pre-shock plasma temperature, impurity levels, shock location, and non-thermal ion distributions within the shock region. Details of the diagnostic design, configuration, and characterization will be presented along with initial results. This work is supported by the Center for Magnetic Self Organization, DoE OFES and NNSA under LANS contract DE-AC52-06NA25369. Approved for public release: LA-UR- 13-25190.

Aptamers in Diagnostics and Treatment of Viral Infections

PubMed Central

Wandtke, Tomasz; Woźniak, Joanna; Kopiński, Piotr

2015-01-01

Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases. PMID:25690797

Exploration of the medical periodic table: towards new targets.

PubMed

Barry, Nicolas P E; Sadler, Peter J

2013-06-07

Metallodrugs offer potential for unique mechanisms of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. We discuss recent progress in identifying new target sites and elucidating the mechanisms of action of anti-cancer, anti-bacterial, anti-viral, anti-parasitic, anti-inflammatory, and anti-neurodegenerative agents, as well as in the design of metal-based diagnostic agents. Progress in identifying and defining target sites has been accelerated recently by advances in proteomics, genomics and metal speciation analysis. Examples of metal compounds and chelating agents (enzyme inhibitors) currently in clinical use, clinical trials or preclinical development are highlighted.

Final Report on X-ray Yields from OMEGA II Targets

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

Fournier, K B; May, M J; MacLaren, S A

2007-06-20

We present details about X-ray yields measured with Lawrence Livermore National Laboratory (LLNL) and Sandia National Laboratories (SNL) diagnostics in soft and moderately hard X-ray bands from laser-driven, doped-aerogel targets shot on 07/14/06 during the OMEGA II test series. Yields accurate to {+-}25% in the 5-15 keV band are measured with Livermore's HENWAY spectrometer. Yields in the sub-keV to 3.2 keV band are measured with LLNL's DANTE diagnostic, the DANTE yields are accurate to 10-15%. SNL ran a PCD-based diagnostic that also measured X-ray yields in the spectral region above 4 keV, and also down to the sub-keV range. Themore » PCD and HENWAY and DANTE numbers are compared. The time histories of the moderately hard (h{nu} > 4 keV) X-ray signals are measured with LLNL's H11 PCD, and from two SNL PCDs with comparable filtration. There is general agreement between the H11 PCD and SNL PCD measured FWHM except for two of the shorter-laser-pulse shots, which is shown not to be due to analysis techniques. The recommended X-ray waveform is that from the SNL PCD p66k10, which was recorded on a fast, high-bandwidth TDS 6804 oscilloscope. X-ray waveforms from target emission in two softer spectral bands are also shown; the X-ray emissions have increasing duration as the spectral content gets softer.« less

Development of internally controlled duplex real-time NASBA diagnostics assays for the detection of microorganisms associated with bacterial meningitis.

PubMed

Clancy, Eoin; Coughlan, Helena; Higgins, Owen; Boo, Teck Wee; Cormican, Martin; Barrett, Louise; Smith, Terry J; Reddington, Kate; Barry, Thomas

2016-08-01

Three duplex molecular beacon based real-time Nucleic Acid Sequence Based Amplification (NASBA) assays have been designed and experimentally validated targeting RNA transcripts for the detection and identification of Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae respectively. Each real-time NASBA diagnostics assay includes an endogenous non-competitive Internal Amplification Control (IAC) to amplify the splice variant 1 mRNA of the Homo sapiens TBP gene from human total RNA. All three duplex real-time NASBA diagnostics assays were determined to be 100% specific for the target species tested for. Also the Limits of Detection (LODs) for the H. influenzae, N. meningitidis and S. pneumoniae duplex real-time NASBA assays were 55.36, 0.99, and 57.24 Cell Equivalents (CE) respectively. These robust duplex real-time NASBA diagnostics assays have the potential to be used in a clinical setting for the rapid (<60min) specific detection and identification of the most prominent microorganisms associated with bacterial meningitis in humans. Copyright © 2016 Elsevier B.V. All rights reserved.

Targeted surveillance for postnatal hearing loss: a program evaluation.

PubMed

Beswick, Rachael; Driscoll, Carlie; Kei, Joseph; Glennon, Shirley

2012-07-01

The importance of monitoring hearing throughout early childhood cannot be understated. However, there is a lack of evidence available regarding the most effective method of monitoring hearing following the newborn screen. The goal of this study was to describe a targeted surveillance program using a risk factor registry to identify children with a postnatal hearing loss. All children who were born in Queensland, Australia between September 2004 and December 2009, received a bilateral 'pass' on newborn hearing screening, and had at least one risk factor, were referred for targeted surveillance and were included in this study. The cohort was assessed throughout early childhood in accordance with Queensland's diagnostic assessment protocols. During the study period, 7320 (2.8% of 261,328) children were referred for targeted surveillance, of which 56 were identified with a postnatal hearing loss (0.77%). Of these, half (50.0%) were identified with a mild hearing loss, and 64.3% were identified with a sensorineural hearing loss. In regards to risk factors, syndrome, craniofacial anomalies, and severe asphyxia had the highest yield of positive cases of postnatal hearing loss for children referred for targeted surveillance, whereas, low birth weight, bacterial meningitis, and professional concern had a particularly low yield. Limitations of the targeted surveillance program were noted and include: (1) a lost contact rate of 32.4%; (2) delays in first surveillance assessment; (3) a large number of children who required on-going monitoring; and (4) extensive diagnostic assessments were completed on children with normal hearing. Examination of the lost contact rate revealed indigenous children were more likely to be documented as lost contact. In addition, children with one risk factor only were significantly more likely to not attend a surveillance appointment. Positive cases of postnatal hearing loss were detected through the targeted surveillance program. However, the

Peptide drugs to target G protein-coupled receptors.

PubMed

Bellmann-Sickert, Kathrin; Beck-Sickinger, Annette G

2010-09-01

Major indications for use of peptide-based therapeutics include endocrine functions (especially diabetes mellitus and obesity), infectious diseases, and cancer. Whereas some peptide pharmaceuticals are drugs, acting as agonists or antagonists to directly treat cancer, others (including peptide diagnostics and tumour-targeting pharmaceuticals) use peptides to 'shuttle' a chemotherapeutic agent or a tracer to the tumour and allow sensitive imaging or targeted therapy. Significant progress has been made in the last few years to overcome disadvantages in peptide design such as short half-life, fast proteolytic cleavage, and low oral bioavailability. These advances include peptide PEGylation, lipidisation or multimerisation; the introduction of peptidomimetic elements into the sequences; and innovative uptake strategies such as liposomal, capsule or subcutaneous formulations. This review focuses on peptides targeting G protein-coupled receptors that are promising drug candidates or that have recently entered the pharmaceutical market. Copyright 2010 Elsevier Ltd. All rights reserved.

Peptide targeting of quantum dots to human breast cancer cells

NASA Astrophysics Data System (ADS)

Haglund, Emily M.; Seale-Goldsmith, Mary-Margaret; Dhawan, Deepika; Stewart, Jane; Ramos-Vara, Jose; Cooper, Christy L.; Reece, Lisa M.; Husk, Timothy; Bergstrom, Donald; Knapp, Deborah; Leary, James F.

2008-02-01

Nanomedical approaches to diseases such as cancer provide great promise with respect to diagnostic and therapeutic applications. The impact of nanomedicine versus conventional therapies will be realized with regard to their specific cell targeting capabilities. Semiconductor nanoparticles have distinct advantages due to their chemical conjugation and detection characteristics. The attachment of a peptide sequence, LTVSPWY, was completed. These nanoparticles successfully targeted in vitro and in vivo systems. This technology can be utilized as a base mechanism for the construction of a multifunctional nanomedical system. Nanomedicine has great potential for impacting the treatment of specific diseases and healthcare delivery methods.

The role of diagnostic laboratories in support of animal disease surveillance systems.

PubMed

Zepeda, C

2007-01-01

Diagnostic laboratories are an essential component of animal disease surveillance systems. To understand the occurrence of disease in populations, surveillance systems rely on random or targeted surveys using three approaches: clinical, serological and virological surveillance. Clinical surveillance is the basis for early detection of disease and is usually centered on the detection of syndromes and clinical findings requiring confirmation by diagnostic laboratories. Although most of the tests applied usually perform to an acceptable standard, several have not been properly validated in terms of their diagnostic sensitivity and specificity. Sensitivity and specificity estimates can vary according to local conditions and, ideally, should be determined by national laboratories where the tests are to be applied. The importance of sensitivity and specificity estimates in the design and interpretation of statistically based surveys and risk analysis is fundamental to establish appropriate disease control and prevention strategies. The World Organisation for Animal Health's (OIE) network of reference laboratories acts as centers of expertise for the diagnosis of OIE listed diseases and have a role in promoting the validation of OIE prescribed tests for international trade. This paper discusses the importance of the epidemiological evaluation of diagnostic tests and the role of the OIE Reference Laboratories and Collaborating Centres in this process.

Diffusion of Molecular Diagnostic Lung Cancer Tests: A Survey of German Oncologists

PubMed Central

Steffen, Julius Alexander

2014-01-01

This study was aimed at examining the diffusion of diagnostic lung cancer tests in Germany. It was motivated by the high potential of detecting and targeting oncogenic drivers. Recognizing that the diffusion of diagnostic tests is a conditio sine qua non for the success of personalized lung cancer therapies, this study analyzed the diffusion of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tests in Germany. Qualitative and quantitative research strategies were combined in a mixed-method design. A literature review and subsequent Key Opinion Leader interviews identified a set of qualitative factors driving the diffusion process, which were then translated into an online survey. The survey was conducted among a sample of 961 oncologists (11.34% response rate). The responses were analyzed in a multiple linear regression which identified six statistically significant factors driving the diffusion of molecular diagnostic lung cancer tests: reimbursement, attitude towards R&D, information self-assessment, perceived attitudes of colleagues, age and test-pathway strategies. Besides the important role of adequate reimbursement and relevant guidelines, the results of this study suggest that an increasing usage of test-pathway strategies, especially in an office-based setting, can increase the diffusion of molecular diagnostic lung cancer tests in the future. PMID:25562146

Enhanced cytotoxic effect of cisplatin using diagnostic ultrasound and microbubbles in vitro

NASA Astrophysics Data System (ADS)

Sasaki, Noboru; Nakamura, Kensuke; Murakami, Masahiro; Lim, Sue Yee; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2012-10-01

Diagnostic ultrasound has accomplished drug and gene delivery by ultrasound targeted microbubble destruction (UTMD). However, the efficacy of delivery is still relatively low. Therefore, we optimized conditions of UTMD using diagnostic ultrasound and ultrasound contrast agent microbubbles. Canine thyroid adenocarcinoma cells were cultured in a 96-well plate. After addition of cisplatin and Sonazoid®, the plate was inverted to raise microbubbles near cells and incubated. Cells were exposed to diagnostic ultrasound using a linear probe operated in the contrast harmonic imaging mode. The center frequency was 2.5 MHz with a mechanical index of 1.33 and a frame rate of 48 frames/sec. Cytotoxic effect of cisplatin was evaluated 24h after exposure using trypan blue dye exclusion test. We optimized incubation duration, cisplatin concentration, and the relationship between microbubble concentration and exposure duration. The optimum enhancement was observed at incubation duration of 5min, cisplatin concentration of 1 μg/ml, and microbubble concentration of 2.4 × 105 microbubbles/ml. Exposure duration did not influence the enhancement at the microbubble concentration of 2.4 × 105 microbubbles/ml. Our results suggest that relative low concentrations of drug and microbubbles with short exposure duration might be sufficient for drug delivery by UTMD using diagnostic ultrasound.

A Novel PCR Assay for Listeria welshimeri Targeting Transcriptional Regulator Gene lwe1801

USDA-ARS?s Scientific Manuscript database

Transcriptional regulator genes encode a group of specialized molecules that play essential roles in microbial responses to changing external conditions. These genes have been shown to possess species or group specificity and are useful as detection targets for diagnostic application. The present st...

Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship.

PubMed

Messacar, Kevin; Parker, Sarah K; Todd, James K; Dominguez, Samuel R

2017-03-01

New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics. Copyright © 2017 American Society for Microbiology.

Erotic target location errors: an underappreciated paraphilic dimension.

PubMed

Lawrence, Anne A

2009-01-01

Based on studies of heterosexual male fetishists, transvestites, and transsexuals, Blanchard (1991) proposed the existence of a hitherto unrecognized paraphilic dimension, erotic target location errors (ETLEs), involving the erroneous location of erotic targets in the environment. ETLEs can involve preferential attention to a peripheral or inessential part of an erotic target, manifesting as fetishism, or mislocation of an erotic target in one's own body, manifesting as the desire to impersonate or become a facsimile of the erotic target (e.g., transvestism or transsexualism). Despite its potential clinical and heuristic value, the concept that ETLEs define a paraphilic dimension is underappreciated. This review summarizes the studies leading to the concept of ETLEs and describes how ETLEs are believed to manifest in men whose preferred erotic targets are women, children, men, amputees, plush animals, and real animals. This review also describes ETLEs in women; discusses possible etiologies of ETLEs; considers the implications of the ETLE concept for psychoanalytic theories of transvestism and male-to-female transsexualism, as well as for the forthcoming revision of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; suggests reasons why the concept of ETLEs has been underappreciated; and describes what might result if the concept were more widely appreciated.

Array CGH Analysis and Developmental Delay: A Diagnostic Tool for Neurologists.

PubMed

Cameron, F; Xu, J; Jung, J; Prasad, C

2013-11-01

Developmental delay occurs in 1-3% of the population, with unknown etiology in approximately 50% of cases. Initial genetic work up for developmental delay previously included chromosome analysis and subtelomeric FISH (fluorescent in situ hybridization). Array Comparative Genomic Hybridization (aCGH) has emerged as a tool to detect genetic copy number changes and uniparental disomy and is the most sensitive test in providing etiological diagnosis in developmental delay. aCGH allows for the provision of prognosis and recurrence risks, improves access to resources, helps limit further investigations and may alter medical management in many cases. aCGH has led to the delineation of novel genetic syndromes associated with developmental delay. An illustrative case of a 31-year-old man with long standing global developmental delay and recently diagnosed 4q21 deletion syndrome with a deletion of 20.8 Mb genomic interval is provided. aCGH is now recommended as a first line test in children and adults with undiagnosed developmental delay and congenital anomalies. Puce d'hybridation génomique comparative et retard de développement : un outil diagnostic pour les neurologues. Le retard de développement survient chez 1 à 3% de la population et son étiologie est inconnue chez à peu près 50% des cas. L'évaluation génétique initiale pour un retard de développement incluait antérieurement une analyse chromosomique et une analyse par FISH (hybridation in situ en fluorescence) de régions subtélomériques. La puce d'hybridation génomique comparative (CGHa) est devenue un outil de détection des changements du nombre de copies géniques ainsi que de la disomie uniparentale et elle est le test le plus sensible pour fournir un diagnostic étiologique dans le retard de développement. Le CGHa permet d'offrir un pronostic et un risque de récurrence, améliore l'accès aux ressources, aide à limiter les évaluations et peut modifier le traitement médical dans bien des cas

Test target for characterizing 3D resolution of optical coherence tomography

NASA Astrophysics Data System (ADS)

Hu, Zhixiong; Hao, Bingtao; Liu, Wenli; Hong, Baoyu; Li, Jiao

2014-12-01

Optical coherence tomography (OCT) is a non-invasive 3D imaging technology which has been applied or investigated in many diagnostic fields including ophthalmology, dermatology, dentistry, cardiovasology, endoscopy, brain imaging and so on. Optical resolution is an important characteristic that can describe the quality and utility of an image acquiring system. We employ 3D printing technology to design and fabricate a test target for characterizing 3D resolution of optical coherence tomography. The test target which mimics USAF 1951 test chart was produced with photopolymer. By measuring the 3D test target, axial resolution as well as lateral resolution of a spectral domain OCT system was evaluated. For comparison, conventional microscope and surface profiler were employed to characterize the 3D test targets. The results demonstrate that the 3D resolution test targets have the potential of qualitatively and quantitatively validating the performance of OCT systems.

LHRH-Targeted Drug Delivery Systems for Cancer Therapy.

PubMed

Li, Xiaoning; Taratula, Oleh; Taratula, Olena; Schumann, Canan; Minko, Tamara

2017-01-01

Targeted delivery of therapeutic and diagnostic agents to cancer sites has significant potential to improve the therapeutic outcome of treatment while minimizing severe side effects. It is widely accepted that decoration of the drug delivery systems with targeting ligands that bind specifically to the receptors on the cancer cells is a promising strategy that may substantially enhance accumulation of anticancer agents in the tumors. Due to the transformed cellular nature, cancer cells exhibit a variety of overexpressed cell surface receptors for peptides, hormones, and essential nutrients, providing a significant number of target candidates for selective drug delivery. Among others, luteinizing hormonereleasing hormone (LHRH) receptors are overexpressed in the majority of cancers, while their expression in healthy tissues, apart from pituitary cells, is limited. The recent studies indicate that LHRH peptides can be employed to efficiently guide anticancer and imaging agents directly to cancerous cells, thereby increasing the amount of these substances in tumor tissue and preventing normal cells from unnecessary exposure. This manuscript provides an overview of the targeted drug delivery platforms that take advantage of the LHRH receptors overexpression by cancer cells.

Telomere biology: Rationale for diagnostics and therapeutics in cancer.

PubMed

Rousseau, Philippe; Autexier, Chantal

2015-01-01

The key step of carcinogenesis is the malignant transformation which is fundamentally a telomere biology dysfunction permitting cells to bypass the Hayflick limit and to divide indefinitely and uncontrollably. Thus all partners and structures involved in normal and abnormal telomere maintenance, protection and lengthening can be considered as potential anti-cancer therapeutic targets. In this Point of View we discuss, highlight and provide new perspectives from the current knowledge and understanding to position the different aspects of telomere biology and dysfunction as diagnostic, preventive and curative tools in the field of cancer.

Telomere biology: Rationale for diagnostics and therapeutics in cancer

PubMed Central

Rousseau, Philippe; Autexier, Chantal

2015-01-01

The key step of carcinogenesis is the malignant transformation which is fundamentally a telomere biology dysfunction permitting cells to bypass the Hayflick limit and to divide indefinitely and uncontrollably. Thus all partners and structures involved in normal and abnormal telomere maintenance, protection and lengthening can be considered as potential anti-cancer therapeutic targets. In this Point of View we discuss, highlight and provide new perspectives from the current knowledge and understanding to position the different aspects of telomere biology and dysfunction as diagnostic, preventive and curative tools in the field of cancer. PMID:26291128

A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

PubMed Central

Faltermeier, Claire; Busuttil, Ronald W.; Zarrinpar, Ali

2015-01-01

Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC. PMID:28943622

Applying Diagnostics to Enhance Cable System Reliability (Cable Diagnostic Focused Initiative, Phase II)

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

Hartlein, Rick; Hampton, Nigel; Perkel, Josh

2016-02-01

The Cable Diagnostic Focused Initiative (CDFI) played a significant and powerful role in clarifying the concerns and understanding the benefits of performing diagnostic tests on underground power cable systems. This project focused on the medium and high voltage cable systems used in utility transmission and distribution (T&D) systems. While many of the analysis techniques and interpretations are applicable to diagnostics and cable systems outside of T&D, areas such as generating stations (nuclear, coal, wind, etc.) and other industrial environments were not the focus. Many large utilities in North America now deploy diagnostics or have changed their diagnostic testing approach asmore » a result of this project. Previous to the CDFI, different diagnostic technology providers individually promoted their approach as the “the best” or “the only” means of detecting cable system defects.« less

Investigation of Hypervelocity Impact Phenomena Using Real-Time Concurrent Diagnostics

NASA Astrophysics Data System (ADS)

Mihaly, Jonathan Michael

Hypervelocity impact of meteoroids and orbital debris poses a serious and growing threat to spacecraft. To study hypervelocity impact phenomena, a comprehensive ensemble of real-time concurrently operated diagnostics has been developed and implemented in the Small Particle Hypervelocity Impact Range (SPHIR) facility. This suite of simultaneously operated instrumentation provides multiple complementary measurements that facilitate the characterization of many impact phenomena in a single experiment. The investigation of hypervelocity impact phenomena described in this work focuses on normal impacts of 1.8 mm nylon 6/6 cylinder projectiles and variable thickness aluminum targets. The SPHIR facility two-stage light-gas gun is capable of routinely launching 5.5 mg nylon impactors to speeds of 5 to 7 km/s. Refinement of legacy SPHIR operation procedures and the investigation of first-stage pressure have improved the velocity performance of the facility, resulting in an increase in average impact velocity of at least 0.57 km/s. Results for the perforation area indicate the considered range of target thicknesses represent multiple regimes describing the non-monotonic scaling of target perforation with decreasing target thickness. The laser side-lighting (LSL) system has been developed to provide ultra-high-speed shadowgraph images of the impact event. This novel optical technique is demonstrated to characterize the propagation velocity and two-dimensional optical density of impact-generated debris clouds. Additionally, a debris capture system is located behind the target during every experiment to provide complementary information regarding the trajectory distribution and penetration depth of individual debris particles. The utilization of a coherent, collimated illumination source in the LSL system facilitates the simultaneous measurement of impact phenomena with near-IR and UV-vis spectrograph systems. Comparison of LSL images to concurrent IR results indicates two

Effect of specialized diagnostic assessment units on the time to diagnosis in screen-detected breast cancer patients.

PubMed

Jiang, L; Gilbert, J; Langley, H; Moineddin, R; Groome, P A

2015-05-26

The duration of the cancer diagnostic process has considerable influence on patients' psychosocial well-being. Breast diagnostic assessment units (DAUs) in Ontario, Canada are designed to improve the quality and timeliness of care during a breast cancer diagnosis. We compared the diagnostic duration of patients diagnosed through a DAU vs usual care (UC). Retrospective population-based cohort study of 2499 screen-detected breast cancers (2011) using administrative health-care databases linked to the Ontario Cancer Registry. The diagnostic interval was measured from the initial screen to cancer diagnosis. Diagnostic assessment unit use was based on the biopsy and/or surgery hospital. We compared the length of the diagnostic interval between the DAU groups using multivariable quantile regression. Diagnostic assessment units had a higher proportion of patients diagnosed within the 7-week target compared with UC (79.1% vs 70.2%, P<0.001). The median time to diagnosis at DAUs was 26 days, which was 9 days shorter compared with UC (95% CI: 6.4-11.6). This effect was reduced to 8.3 days after adjusting for all study covariates. Adjusted DAU differences were similar at the 75th and 90th percentiles of the diagnostic interval distribution. Diagnosis through an Ontario DAU was associated with a reduced time to diagnosis for screen-detected breast cancer patients, which likely reduces the anxiety and distress associated with waiting for a diagnosis.

Diagnostic Algorithm Benchmarking

NASA Technical Reports Server (NTRS)

Poll, Scott

2011-01-01

A poster for the NASA Aviation Safety Program Annual Technical Meeting. It describes empirical benchmarking on diagnostic algorithms using data from the ADAPT Electrical Power System testbed and a diagnostic software framework.

[Acute myeloid leukemia. Genetic diagnostics and molecular therapy].

PubMed

Schlenk, R F; Döhner, K; Döhner, H

2013-02-01

Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.

Mobile Diagnostics Based on Motion? A Close Look at Motility Patterns in the Schistosome Life Cycle

PubMed Central

Linder, Ewert; Varjo, Sami; Thors, Cecilia

2016-01-01

Imaging at high resolution and subsequent image analysis with modified mobile phones have the potential to solve problems related to microscopy-based diagnostics of parasitic infections in many endemic regions. Diagnostics using the computing power of “smartphones” is not restricted by limited expertise or limitations set by visual perception of a microscopist. Thus diagnostics currently almost exclusively dependent on recognition of morphological features of pathogenic organisms could be based on additional properties, such as motility characteristics recognizable by computer vision. Of special interest are infectious larval stages and “micro swimmers” of e.g., the schistosome life cycle, which infect the intermediate and definitive hosts, respectively. The ciliated miracidium, emerges from the excreted egg upon its contact with water. This means that for diagnostics, recognition of a swimming miracidium is equivalent to recognition of an egg. The motility pattern of miracidia could be defined by computer vision and used as a diagnostic criterion. To develop motility pattern-based diagnostics of schistosomiasis using simple imaging devices, we analyzed Paramecium as a model for the schistosome miracidium. As a model for invasive nematodes, such as strongyloids and filaria, we examined a different type of motility in the apathogenic nematode Turbatrix, the “vinegar eel.” The results of motion time and frequency analysis suggest that target motility may be expressed as specific spectrograms serving as “diagnostic fingerprints.” PMID:27322330

A real-time PCR diagnostic method for detection of Naegleria fowleri.

PubMed

Madarová, Lucia; Trnková, Katarína; Feiková, Sona; Klement, Cyril; Obernauerová, Margita

2010-09-01

Naegleria fowleri is a free-living amoeba that can cause primary amoebic meningoencephalitis (PAM). While, traditional methods for diagnosing PAM still rely on culture, more current laboratory diagnoses exist based on conventional PCR methods; however, only a few real-time PCR processes have been described as yet. Here, we describe a real-time PCR-based diagnostic method using hybridization fluorescent labelled probes, with a LightCycler instrument and accompanying software (Roche), targeting the Naegleria fowleriMp2Cl5 gene sequence. Using this method, no cross reactivity with other tested epidemiologically relevant prokaryotic and eukaryotic organisms was found. The reaction detection limit was 1 copy of the Mp2Cl5 DNA sequence. This assay could become useful in the rapid laboratory diagnostic assessment of the presence or absence of Naegleria fowleri. Copyright 2009 Elsevier Inc. All rights reserved.

Semiconductor nanocrystal-aptamer bioconjugate probes for specific prostate carcinoma cell targeting

NASA Astrophysics Data System (ADS)

Shieh, Felice; Lavery, Laura; Chu, Chitai T.; Richards-Kortum, Rebecca; Ellington, Andrew D.; Korgel, Brian A.

2005-04-01

Cancer of the prostate affects approximately 1 in 11 men. Current early screening for prostate cancer utilizes digital rectal examinations to detect anomalies in the prostate gland and blood test screenings for upregulated levels of prostate specific antigen (PSA). Many of these tests are invasive and can often be inconclusive as PSA levels may be heightened due to benign factors. Prostate specific membrane antigen (PSMA), a well-characterized integral membrane protein, is expressed in virtually all prostate cancers and often correlates with cancer aggressiveness. Therefore, it may be used as an indicator of cancer growth and metastases. PSMA-specific antibodies have been identified and conjugated to fluorescent markers for cancer cell targeting; however, both the antibodies and markers possess significant limitations in their pharmaceutical and diagnostic value. Here we report the use of semiconductor nanocrystals bioconjugated to PSMA-specific aptamer recognition molecules for prostate carcinoma cell targeting. The nanocrystal/aptamer bioconjugates are small biocompatible probes with the potential for color-tunability for multicolor imaging. Ongoing in vitro and in vivo research seeks to introduce these nanoparticle bioconjugates into medical diagnostics.

Comprehensive review of neurophysiologic basis and diagnostic interventions in managing chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Singh, Vijay; Derby, Richard; Fellows, Bert; Falco, Frank J E; Datta, Sukdeb; Smith, Howard S; Hirsch, Joshua A

2009-01-01

Understanding the neurophysiological basis of chronic spinal pain and diagnostic interventional techniques is crucial in the proper diagnosis and management of chronic spinal pain. Central to the understanding of the structural basis of chronic spinal pain is the provision of physical diagnosis and validation of patient symptomatology. It has been shown that history, physical examination, imaging, and nerve conduction studies in non-radicular or discogenic pain are unable to diagnose the precise cause in 85% of the patients. In contrast, controlled diagnostic blocks have been shown to determine the cause of pain in as many as 85% of the patients. To provide evidence-based clinical practice guidelines for diagnostic interventional techniques. Best evidence synthesis. Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II. Diagnostic criteria established by systematic reviews were utilized with controlled diagnostic blocks. Diagnostic criteria included at least 80% pain relief with controlled local anesthetic blocks with the ability to perform multiple maneuvers which were painful prior to the diagnostic blocks for facet joint and sacroiliac joint blocks, whereas for provocation discography, the criteria included concordant pain upon stimulation of the target disc with 2 adjacent discs producing no pain at all. The indicated level of evidence for diagnostic lumbar, cervical, and thoracic facet joint nerve blocks is Level I or II-1. The indicated evidence is Level II-2 for lumbar and cervical discography, whereas it is Level II-3 for thoracic provocation discography. The evidence for diagnostic sacroiliac joint nerve blocks is Level II-2. Level of evidence for selective nerve root blocks for diagnostic purposes is Level II-3. Limitations of this guideline preparation include a continued paucity of literature and conflicts in preparation

Rayleigh Scattering Diagnostics Workshop

NASA Technical Reports Server (NTRS)

Seasholtz, Richard (Compiler)

1996-01-01

The Rayleigh Scattering Diagnostics Workshop was held July 25-26, 1995 at the NASA Lewis Research Center in Cleveland, Ohio. The purpose of the workshop was to foster timely exchange of information and expertise acquired by researchers and users of laser based Rayleigh scattering diagnostics for aerospace flow facilities and other applications. This Conference Publication includes the 12 technical presentations and transcriptions of the two panel discussions. The first panel was made up of 'users' of optical diagnostics, mainly in aerospace test facilities, and its purpose was to assess areas of potential applications of Rayleigh scattering diagnostics. The second panel was made up of active researchers in Rayleigh scattering diagnostics, and its purpose was to discuss the direction of future work.

A closer look at diagnosis in clinical dental practice: part 1. Reliability, validity, specificity and sensitivity of diagnostic procedures.

PubMed

Pretty, Iain A; Maupomé, Gerardo

2004-04-01

Dentists are involved in diagnosing disease in every aspect of their clinical practice. A range of tests, systems, guides and equipment--which can be generally referred to as diagnostic procedures--are available to aid in diagnostic decision making. In this era of evidence-based dentistry, and given the increasing demand for diagnostic accuracy and properly targeted health care, it is important to assess the value of such diagnostic procedures. Doing so allows dentists to weight appropriately the information these procedures supply, to purchase new equipment if it proves more reliable than existing equipment or even to discard a commonly used procedure if it is shown to be unreliable. This article, the first in a 6-part series, defines several concepts used to express the usefulness of diagnostic procedures, including reliability and validity, and describes some of their operating characteristics (statistical measures of performance), in particular, specificity and sensitivity. Subsequent articles in the series will discuss the value of diagnostic procedures used in daily dental practice and will compare today's most innovative procedures with established methods.

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications

PubMed Central

Kratz, Jeremy D.; Chaddha, Ashish; Bhattacharjee, Somnath

2016-01-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD. PMID:26809711

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

PubMed

Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

2016-02-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

Diffuse Gliomas for Nonneuropathologists: The New Integrated Molecular Diagnostics.

PubMed

Lee, Sunhee C

2018-05-18

Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified. Incorporating information on a few genetic parameters (IDH, ATRX and/or p53, and chromosome 1p19q codeletion), a relatively straightforward diagnostic algorithm has been generated with robust and reproducible results that correlate with patients' survival far better than relying on conventional histology alone. Evidence also supports the conclusion that the vast majority of diffuse gliomas without IDH mutations (IDH-wild-type astrocytomas) behave like IDH-wild-type glioblastomas ("molecular GBM"). Together, these changes reflect a big shift in the practice of diagnostic neuropathology in which tumor risk stratification aligns better with molecular information than histology/grading. The purpose of this review is to provide the readers with a brief synopsis of the changes in the 2016 World Health Organization update with an emphasis on diffuse gliomas and to summarize key gene abnormalities on which these classifications are based. Practical points involved in day-to-day diagnostic workup are also discussed, along with a comparison of the various diagnostic tests, including immunohistochemistry, with an emphasis on targeted next-generation sequencing panel technology as a future universal approach.

In situ synthesis of luminescent carbon nanoparticles toward target bioimaging.

PubMed

Sharker, Shazid Md; Kim, Sung Min; Lee, Jung Eun; Jeong, Ji Hoon; In, Insik; Lee, Kang Dea; Lee, Haeshin; Park, Sung Young

2015-03-12

This paper describes the in situ synthesis of single fluorescence carbon nanoparticles (FCNs) for target bioimaging applications derived from biocompatible hyaluronic acid (HA) without using common conjugation processes. FCNs formed via the dehydration of hyaluronic acid, which were obtained by carbonizing HA, and partially carbonized HA fluorescence carbon nanoparticles (HA-FCNs), formed by a lower degree of carbonization, show good aqueous solubility, small particle size (<20 nm) and different fluorescence intensities with a red shift. After confirming the cytotoxicity of HA-FCNs and FCNs, we carried out in vitro and in vivo bioimaging studies where HA-FCNs themselves functioned as single particle triggers in target imaging. The converted nanocrystal carbon particles from HA provide outstanding features for in vitro and in vivo new targeted delivery and diagnostic tools.

New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

PubMed Central

Park, Young Gun; Roh, Young-Jung

2016-01-01

Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE-targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results. PMID:26881240

A New Spin on an Old Technology: Piezoelectric Ejecta Diagnostics for Shock Environments

NASA Astrophysics Data System (ADS)

Vogan, W. S.; Anderson, W. W.; Grover, M.; King, N. S. P.; Lamoreaux, S. K.; Morley, K. B.; Rigg, P. A.; Stevens, G. D.; Turley, W. D.; Buttler, W. T.

2006-07-01

In our investigation of ejecta, or metal particulate emitted from a surface subjected to shock-loaded conditions, we have developed a shock experiment suitable for testing new ideas in piezoelectric mass and impact detectors. High-explosive (HE) shock loading of tin targets subjected to various machined and compressed finishes results in significant trends in ejecta characteristics of interest such as areal density and velocity. Our enhanced piezoelectric diagnostic, "piezo-pins" modified for shock mitigation, have proven levels of robustness and reliability suitable for effective operation in these ejecta milieux. These field tests address questions about ejecta production from surfaces of interest; experimental results are discussed and compared with those from complementary diagnostics such as x-ray and optical attenuation visualization techniques.

Designs and adaptive analysis plans for pivotal clinical trials of therapeutics and companion diagnostics.

PubMed

Simon, Richard

2008-06-01

Developments in genomics and biotechnology provide unprecedented opportunities for the development of effective therapeutics and companion diagnostics for matching the right drug to the right patient. Effective co-development involves many new challenges with increased opportunity for success as well as delay and failure. Clinical trial designs and adaptive analysis plans for the prospective design of pivotal trials of new therapeutics and companion diagnostics are reviewed. Effective co-development requires careful prospective planning of the design and analysis strategy for pivotal clinical trials. Randomized clinical trials continue to be important for evaluating the effectiveness of new treatments, but the target populations for analysis should be prospectively specified based on the companion diagnostic. Post hoc analyses of traditionally designed randomized clinical trials are often deeply problematic. Clear separation is generally required of the data used for developing the diagnostic test, including their threshold of positivity, from the data used for evaluating treatment effectiveness in subsets determined by the test. Adaptive analysis can be used to provide flexibility to the analysis but the use of such methods requires careful planning and prospective definition in order to assure that the pivotal trial adequately limits the chance of erroneous conclusions.

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

PubMed

Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

2015-10-13

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

Exploring miRNA based approaches in cancer diagnostics and therapeutics.

PubMed

Mishra, Shivangi; Yadav, Tanuja; Rani, Vibha

2016-02-01

MicroRNAs (miRNAs), a highly conserved class of tissue specific, small non-protein coding RNAs maintain cell homeostasis by negative gene regulation. Proper controlling of miRNA expression is required for a balanced physiological environment, as these small molecules influence almost every genetic pathway from cell cycle checkpoint, cell proliferation to apoptosis, with a wide range of target genes. Deregulation in miRNAs expression correlates with various cancers by acting as tumor suppressors and oncogenes. Although promising therapies exist to control tumor development and progression, there is a lack of efficient diagnostic and therapeutic approaches for delineating various types of cancer. The molecularly different tumors can be differentiated by specific miRNA profiling as their phenotypic signatures, which can hence be exploited to surmount the diagnostic and therapeutic challenges. Present review discusses the involvement of miRNAs in oncogenesis with the analysis of patented research available on miRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Electromagnetic Navigation Diagnostic Bronchoscopy

PubMed Central

Gildea, Thomas R.; Mazzone, Peter J.; Karnak, Demet; Meziane, Moulay; Mehta, Atul C.

2006-01-01

Rationale: Electromagnetic navigation bronchoscopy using superDimension/Bronchus System is a novel method to increase diagnostic yield of peripheral and mediastinal lung lesions. Objectives: A prospective, open label, single-center, pilot study was conducted to determine the ability of electromagnetic navigation bronchoscopy to sample peripheral lung lesions and mediastinal lymph nodes with standard bronchoscopic instruments and demonstrate safety. Methods: Electromagnetic navigation bronchoscopy was performed using the superDimension/Bronchus system consisting of electromagnetic board, position sensor encapsulated in the tip of a steerable probe, extended working channel, and real-time reconstruction of previously acquired multiplanar computed tomography images. The final distance of the steerable probe to lesion, expected error based on the actual and virtual markers, and procedure yield was gathered. Measurements: 60 subjects were enrolled between December 2004 and September 2005. Mean navigation times were 7 ± 6 min and 2 ± 2 min for peripheral lesions and lymph nodes, respectively. The steerable probe tip was navigated to the target lung area in all cases. The mean peripheral lesions and lymph nodes size was 22.8 ± 12.6 mm and 28.1 ± 12.8 mm. Yield was determined by results obtained during the bronchoscopy per patient. Results: The yield/procedure was 74% and 100% for peripheral lesions and lymph nodes, respectively. A diagnosis was obtained in 80.3% of bronchoscopic procedures. A definitive diagnosis of lung malignancy was made in 74.4% of subjects. Pneumothorax occurred in two subjects. Conclusion: Electromagnetic navigation bronchoscopy is a safe method for sampling peripheral and mediastinal lesions with high diagnostic yield independent of lesion size and location. PMID:16873767

A novel diagnostic method for malaria using loop-mediated isothermal amplification (LAMP) and MinION™ nanopore sequencer.

PubMed

Imai, Kazuo; Tarumoto, Norihito; Misawa, Kazuhisa; Runtuwene, Lucky Ronald; Sakai, Jun; Hayashida, Kyoko; Eshita, Yuki; Maeda, Ryuichiro; Tuda, Josef; Murakami, Takashi; Maesaki, Shigefumi; Suzuki, Yutaka; Yamagishi, Junya; Maeda, Takuya

2017-09-13

A simple and accurate molecular diagnostic method for malaria is urgently needed due to the limitations of conventional microscopic examination. In this study, we demonstrate a new diagnostic procedure for human malaria using loop mediated isothermal amplification (LAMP) and the MinION™ nanopore sequencer. We generated specific LAMP primers targeting the 18S-rRNA gene of all five human Plasmodium species including two P. ovale subspecies (P. falciparum, P. vivax, P. ovale wallikeri, P. ovale curtisi, P. knowlesi and P. malariae) and examined human blood samples collected from 63 malaria patients in Indonesia. Additionally, we performed amplicon sequencing of our LAMP products using MinION™ nanopore sequencer to identify each Plasmodium species. Our LAMP method allowed amplification of all targeted 18S-rRNA genes of the reference plasmids with detection limits of 10-100 copies per reaction. Among the 63 clinical samples, 54 and 55 samples were positive by nested PCR and our LAMP method, respectively. Identification of the Plasmodium species by LAMP amplicon sequencing analysis using the MinION™ was consistent with the reference plasmid sequences and the results of nested PCR. Our diagnostic method combined with LAMP and MinION™ could become a simple and accurate tool for the identification of human Plasmodium species, even in resource-limited situations.

Diagnostic testing.

PubMed

Brewer, D E

2000-09-01

The results of cardiac tests must always be interpreted through the lens of pretest probabilities created by the history and the physical examination. Tests should be chosen with a clear diagnostic and prognostic purpose in mind. A clear understanding of the relationship between the history and physical examination and more technologic diagnostic testing improves the primary care physician's ability to evaluate potential cardiac disease in an efficient and cost-effective manner.

Fusion proteins in head and neck neoplasms: Clinical implications, genetics, and future directions for targeting

PubMed Central

Escalante, Derek A.; Wang, He; Fundakowski, Christopher E.

2016-01-01

ABSTRACT Fusion proteins resulting from chromosomal rearrangements are known to drive the pathogenesis of a variety of hematological and solid neoplasms such as chronic myeloid leukemia and non-small-cell lung cancer. Efforts to elucidate the role they play in these malignancies have led to important diagnostic and therapeutic triumphs, including the famous development of the tyrosine kinase inhibitor dasatinib targeting the BCR-ABL fusion. Until recently, there has been a paucity of research investigating fusion proteins harbored by head and neck neoplasms. The discovery and characterization of novel fusion proteins in neoplasms originating from the thyroid, nasopharynx, salivary glands, and midline head and neck structures offer substantial contributions to our understanding of the pathogenesis and biological behavior of these neoplasms, while raising new therapeutic and diagnostic opportunities. Further characterization of these fusion proteins promises to facilitate advances on par with those already achieved with regard to hematologic malignancies in the precise, molecularly guided diagnosis and treatment of head and neck neoplasms. The following is a subsite specific review of the clinical implications of fusion proteins in head and neck neoplasms and the future potential for diagnostic targeting. PMID:27636353

Validity and Diagnostic Accuracy of Scores from the Autism Diagnostic Observation Schedule-Generic

ERIC Educational Resources Information Center

Reid, Melissa A.

2012-01-01

The purpose of this study was to examine the internal structure, relationships with other variables, and diagnostic accuracy of scores on the Autism Diagnostic Observation Schedule-Generic (ADOS-G; Lord et al., 1999) for the purpose of diagnostic decision-making. Participants were 462 children enrolled in a public school district in the southern…

Fusion genes in solid tumors: an emerging target for cancer diagnosis and treatment.

PubMed

Parker, Brittany C; Zhang, Wei

2013-11-01

Studies over the past decades have uncovered fusion genes, a class of oncogenes that provide immense diagnostic and therapeutic advantages because of their tumor-specific expression. Originally associated with hemotologic cancers, fusion genes have recently been discovered in a wide array of solid tumors, including sarcomas, carcinomas, and tumors of the central nervous system. Fusion genes are attractive as both therapeutic targets and diagnostic tools due to their inherent expression in tumor tissue alone. Therefore, the discovery and elucidation of fusion genes in various cancer types may provide more effective therapies in the future for cancer patients.

Mobile diagnostics: next-generation technologies for in vitro diagnostics.

PubMed

Shin, Joonchul; Chakravarty, Sudesna; Choi, Wooseok; Lee, Kyungyeon; Han, Dongsik; Hwang, Hyundoo; Choi, Jaekyu; Jung, Hyo-Il

2018-03-26

The emergence of a wide range of applications of smartphones along with advances in 'liquid biopsy' has significantly propelled medical research particularly in the field of in vitro diagnostics (IVD). Herein, we have presented a detailed analysis of IVD, its associated critical concerns and probable solutions. It also demonstrates the transition in terms of analytes from minimally invasive (blood) to non-invasive (urine, saliva and sweat) and depicts how the different features of a smartphone can be integrated for specific diagnostic purposes. This review basically highlights recent advances in the applications of smartphone-based biosensors in IVD taking into account the following factors: accuracy and portability; quantitative and qualitative analysis; and centralization and decentralization tests. Furthermore, the critical concerns and future direction of diagnostics based on smartphones are also discussed.

Biocomputing nanoplatforms as therapeutics and diagnostics.

PubMed

Evans, A C; Thadani, N N; Suh, J

2016-10-28

Biocomputing nanoplatforms are designed to detect and integrate single or multiple inputs under defined algorithms, such as Boolean logic gates, and generate functionally useful outputs, such as delivery of therapeutics or release of optically detectable signals. Using sensing modules composed of small molecules, polymers, nucleic acids, or proteins/peptides, nanoplatforms have been programmed to detect and process extrinsic stimuli, such as magnetic fields or light, or intrinsic stimuli, such as nucleic acids, enzymes, or pH. Stimulus detection can be transduced by the nanomaterial via three different mechanisms: system assembly, system disassembly, or system transformation. The increasingly sophisticated suite of biocomputing nanoplatforms may be invaluable for a multitude of applications, including medical diagnostics, biomedical imaging, environmental monitoring, and delivery of therapeutics to target cell populations. Copyright © 2016 Elsevier B.V. All rights reserved.

READING DIAGNOSTIC APPROACHES.

ERIC Educational Resources Information Center

PURDY, ROBERT J.; AND OTHERS

A DIAGNOSTIC KIT DESIGNED TO HELP CLASSROOM TEACHERS DIAGNOSE READING DIFFICULTIES MORE ADEQUATELY AND MOTIVATE PUPILS MORE EFFECTIVELY IS PRESENTED. SUGGESTIONS ARE APPLICABLE TO LOWER PRIMARY CHILDREN. DIAGNOSTIC TECHNIQUES ARE OUTLINED FOR SUBJECTIVE AND OBJECTIVE OBSERVATION OF LANGUAGE ABILITY, VISUAL PERCEPTION SKILLS, AUDITORY…

Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis

PubMed Central

Willis, Sarah R; Ahmed, Hashim U; Moore, Caroline M; Donaldson, Ian; Emberton, Mark; Miners, Alec H; van der Meulen, Jan

2014-01-01

Objective To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive. Design Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making. Population A hypothetical cohort of 1000 men with suspected prostate cancer. Interventions mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men. Outcome measures We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters. Results In 1000 men, mpMRI followed by MRI-targeted biopsy ‘clinically dominates’ TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis. Conclusions Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters. PMID:24934207

Development and Application of Diagnostics in the National Schistosomiasis Control Programme in The People's Republic of China.

PubMed

Zhang, J-F; Xu, J; Bergquist, R; Yu, L-L; Yan, X-L; Zhu, H-Q; Wen, L-Y

2016-01-01

Schistosomiasis, caused by Schistosoma japonicum infection to human, has a documented history of more than 2100years in The People's Republic of China. In spite of great progress in controlling the disease, it is still one of the most serious parasitic diseases in the country. The study and use of diagnostic techniques play an important role in the targeting of chemotherapy that has been continuously applied in the national schistosomiasis control programme for several decades. This paper reviews the development and application of parasitological, immunodiagnostic and molecular diagnostic technology for S. japonicum in The People's Republic of China with a brief mention of diagnostic imagery, such as ultrasound and radiology. When analysing the efficacy and performance characteristics of the main diagnostic techniques in current use, it becomes apparent that approaches that worked well in the past are less suitable now as successful control has shifted the endemic situation towards control and interruption of transmission. The conclusion is that a mutable approach must be adopted choosing the most appropriate diagnostic technique for each control stage (and area), thus modifying the methodology according to the prevailing diagnostic needs in terms of sensitivity and specificity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Draft versus finished sequence data for DNA and protein diagnostic signature development

PubMed Central

Gardner, Shea N.; Lam, Marisa W.; Smith, Jason R.; Torres, Clinton L.; Slezak, Tom R.

2005-01-01

Sequencing pathogen genomes is costly, demanding careful allocation of limited sequencing resources. We built a computational Sequencing Analysis Pipeline (SAP) to guide decisions regarding the amount of genomic sequencing necessary to develop high-quality diagnostic DNA and protein signatures. SAP uses simulations to estimate the number of target genomes and close phylogenetic relatives (near neighbors or NNs) to sequence. We use SAP to assess whether draft data are sufficient or finished sequencing is required using Marburg and variola virus sequences. Simulations indicate that intermediate to high-quality draft with error rates of 10−3–10−5 (∼8× coverage) of target organisms is suitable for DNA signature prediction. Low-quality draft with error rates of ∼1% (3× to 6× coverage) of target isolates is inadequate for DNA signature prediction, although low-quality draft of NNs is sufficient, as long as the target genomes are of high quality. For protein signature prediction, sequencing errors in target genomes substantially reduce the detection of amino acid sequence conservation, even if the draft is of high quality. In summary, high-quality draft of target and low-quality draft of NNs appears to be a cost-effective investment for DNA signature prediction, but may lead to underestimation of predicted protein signatures. PMID:16243783

Stroma Targeting Nuclear Imaging and Radiopharmaceuticals

PubMed Central

Shetty, Dinesh; Jeong, Jae-Min; Shim, Hyunsuk

2012-01-01

Malignant transformation of tumor accompanies profound changes in the normal neighboring tissue, called tumor stroma. The tumor stroma provides an environment favoring local tumor growth, invasion, and metastatic spreading. Nuclear imaging (PET/SPECT) measures biochemical and physiologic functions in the human body. In oncology, PET/SPECT is particularly useful for differentiating tumors from postsurgical changes or radiation necrosis, distinguishing benign from malignant lesions, identifying the optimal site for biopsy, staging cancers, and monitoring the response to therapy. Indeed, PET/SPECT is a powerful, proven diagnostic imaging modality that displays information unobtainable through other anatomical imaging, such as CT or MRI. When combined with coregistered CT data, [18F]fluorodeoxyglucose ([18F]FDG)-PET is particularly useful. However, [18F]FDG is not a target-specific PET tracer. This paper will review the tumor microenvironment targeting oncologic imaging such as angiogenesis, invasion, hypoxia, growth, and homing, and also therapeutic radiopharmaceuticals to provide a roadmap for additional applications of tumor imaging and therapy. PMID:22685650

Mucin-based targeted pancreatic cancer therapy.

PubMed

Torres, Maria P; Chakraborty, Subhankar; Souchek, Joshua; Batra, Surinder K

2012-01-01

The prognosis of pancreatic cancer (PC) patients is very poor with a five-year survival of less than 5%. One of the major challenges in developing new therapies for PC is the lack of expression of specific markers by pancreatic tumor cells. Mucins are heavily Oglycosylated proteins characterized by the presence of short stretches of amino acid sequences repeated several times in tandem. The expression of several mucins including MUC1, MUC4, MUC5AC, and MUC16 is strongly upregulated in PC. Recent studies have also demonstrated a link between the aberrant expression and differential overexpression of mucin glycoproteins to the initiation, progression, and poor prognosis of the disease. These studies have led to increasing recognition of mucins as potential diagnostic markers and therapeutic targets in PC. In this focused review we present an overview of the therapies targeting mucins in PC, including immunotherapy (i.e. vaccines, antibodies, and radioimmunoconjugates), gene therapy, and other novel therapeutic strategies.

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).

Role of Metal and Metal Oxide Nanoparticles as Diagnostic and Therapeutic Tools for Highly Prevalent Viral Infections

PubMed Central

Yadavalli, Tejabhiram; Shukla, Deepak

2016-01-01

Nanotechnology is increasingly playing important roles in various fields including virology. The emerging use of metal or metal oxide nanoparticles in virus targeting formulations shows the promise of improved diagnostic or therapeutic ability of the agents while uniquely enhancing the prospects of targeted drug delivery. Although a number of nanoparticles varying in composition, size, shape, and surface properties have been approved for human use, the candidates being tested or approved for clinical diagnosis and treatment of viral infections are relatively less in number. Challenges remain in this domain due to a lack of essential knowledge regarding the in vivo comportment of nanoparticles during viral infections. This review provides a broad overview of recent advances in diagnostic, prophylactic and therapeutic applications of metal and metal oxide nanoparticles in Human Immunodeficiency Virus, Hepatitis virus, influenza virus and Herpes virus infections. Types of nanoparticles commonly used and their broad applications have been explained in this review. PMID:27575283

Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

PubMed Central

Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

2013-01-01

The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

[Diagnostic Errors in Medicine].

PubMed

Buser, Claudia; Bankova, Andriyana

2015-12-09

The recognition of diagnostic errors in everyday practice can help improve patient safety. The most common diagnostic errors are the cognitive errors, followed by system-related errors and no fault errors. The cognitive errors often result from mental shortcuts, known as heuristics. The rate of cognitive errors can be reduced by a better understanding of heuristics and the use of checklists. The autopsy as a retrospective quality assessment of clinical diagnosis has a crucial role in learning from diagnostic errors. Diagnostic errors occur more often in primary care in comparison to hospital settings. On the other hand, the inpatient errors are more severe than the outpatient errors.

Drinking correlates of DSM-IV alcohol use disorder diagnostic orphans in college students.

PubMed

Hagman, Brett T; Cohn, Amy M

2012-01-01

One major limitation of the DSM-IV criteria for alcohol abuse and dependence is that a cluster of individuals who endorse a subthreshold number of dependence criteria and no abuse criteria do not receive a formal diagnosis; despite elevated risk for alcohol-related problems relative to those with an abuse diagnosis. These individuals have been referred to as diagnostic orphans. The primary aim of this study was to examine alcohol use correlates of a group of diagnostic orphans in a sample of 396 nontreatment seeking college students who reported drinking on at least one occasion in the last 90 days. DSM-IV criteria were assessed using a modified version of the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). Diagnostic orphans represented 34.1% (n = 135) of the original sample who did not receive a formal diagnosis; with the most frequently endorsed dependence criteria being tolerance and drinking larger/longer amounts than intended. Diagnostic orphans reported a range of alcohol-related negative consequences and reported greater frequencies of social and enhancement drinking motives in comparison to coping motives. They were similar to alcohol abusers and dissimilar to those with dependence or those without a diagnosis on alcohol consumption, alcohol problem severity, drinking motives and restraint variables. The present findings indicate that diagnostic orphans in college students represent a distinct group of drinkers who may be at risk for the development of alcohol use disorders and may be in need of intervention, given their similarity to those with an abuse diagnosis. Prevention and intervention efforts across college campuses should target this group to prevent escalation of alcohol problem severity. Copyright © American Academy of Addiction Psychiatry.

Targeting breast cancer with sugar-coated carbon nanotubes

PubMed Central

Fahrenholtz, Cale D; Hadimani, Mallinath; King, S Bruce; Torti, Suzy V; Singh, Ravi

2015-01-01

Aims To evaluate the use of glucosamine functionalized multiwalled carbon nanotubes (glyco-MWCNTs) for breast cancer targeting. Materials & methods Two types of glucosamine functionalized MWCNTs were developed (covalently linked glucosamine and non-covalently phospholipid-glucosamine coated) and evaluated for their potential to bind and target breast cancer cells in vitro and in vivo. Results & conclusion Binding of glyco-MWCNTs in breast cancer cells is mediated by specific interaction with glucose transporters. Glyco-MWCNTs prepared by non-covalent coating with phospholipid-glucosamine displayed an extended blood circulation time, delayed urinary clearance, low tissue retention and increased breast cancer tumor accumulation in vivo. These studies lay the foundation for development of a cancer diagnostic agent based upon glyco-MWCNTs with the potential for superior accuracy over current radiopharmaceuticals. PMID:26296098

Development and Validation of an Immuno-PET Tracer as a Companion Diagnostic Agent for Antibody-Drug Conjugate Therapy to Target the CA6 Epitope.

PubMed

Ilovich, Ohad; Natarajan, Arutselvan; Hori, Sharon; Sathirachinda, Ataya; Kimura, Richard; Srinivasan, Ananth; Gebauer, Mathias; Kruip, Jochen; Focken, Ingo; Lange, Christian; Carrez, Chantal; Sassoon, Ingrid; Blanc, Veronique; Sarkar, Susanta K; Gambhir, Sanjiv S

2015-07-01

To develop and compare three copper 64 ((64)Cu)-labeled antibody fragments derived from a CA6-targeting antibody (huDS6) as immuno-positron emission tomography (immuno-PET)-based companion diagnostic agents for an antibody-drug conjugate by using huDS6. Three antibody fragments derived from huDS6 were produced, purified, conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and evaluated in the following ways: (a) the affinity of the fragments and the DOTA conjugates was measured via flow cytometry, (b) the stability of the labeled fragments was determined ex vivo in human serum over 24 hours, and (c) comparison of the in vivo imaging potential of the fragments was evaluated in mice bearing subcutaneous CA6-positive and CA6-negative xenografts by using serial PET imaging and biodistribution. Isotype controls with antilysozyme and anti-DM4 B-Fabs and blocking experiments with an excess of either B-Fab or huDS6 were used to determine the extent of the antibody fragment (64)Cu-DOTA-B-Fab binding specificity. Immunoreactivity and tracer kinetics were evaluated by using cellular uptake and 48-hour imaging experiments, respectively. Statistical analyses were performed by using t tests, one-way analysis of variance, and Wilcoxon and Mann-Whitney tests. The antibody fragment (64)Cu-DOTA-B-Fab was more than 95% stable after 24 hours in human serum, had an immunoreactivity of more than 70%, and allowed differentiation between CA6-positive and CA6-negative tumors in vivo as early as 6 hours after injection, with a 1.7-fold uptake ratio between tumors. Isotype and blocking studies experiments showed tracer-specific uptake in antigen-positive tumors, despite some nonspecific uptake in both tumor models. Three antibody fragments were produced and examined as potential companion diagnostic agents. (64)Cu-DOTA-B-Fab is a stable and effective immuno-PET tracer for CA6 imaging in vivo.

Search asymmetry: a diagnostic for preattentive processing of separable features.

PubMed

Treisman, A; Souther, J

1985-09-01

The search rate for a target among distractors may vary dramatically depending on which stimulus plays the role of target and which that of distractors. For example, the time required to find a circle distinguished by an intersecting line is independent of the number of regular circles in the display, whereas the time to find a regular circle among circles with lines increases linearly with the number of distractors. The pattern of performance suggests parallel processing when the target has a unique distinguishing feature and serial self-terminating search when the target is distinguished only by the absence of a feature that is present in all the distractors. The results are consistent with feature-integration theory (Treisman & Gelade, 1980), which predicts that a single feature should be detected by the mere presence of activity in the relevant feature map, whereas tasks that require subjects to locate multiple instances of a feature demand focused attention. Search asymmetries may therefore offer a new diagnostic to identify the primitive features of early vision. Several candidate features are examined in this article: Colors, line ends or terminators, and closure (in the sense of a partly or wholly enclosed area) appear to be functional features; connectedness, intactness (absence of an intersecting line), and acute angles do not.

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.

GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells.

PubMed

Wang, Ling; An, Yanli; Yuan, Chenyan; Zhang, Hao; Liang, Chen; Ding, Fengan; Gao, Qi; Zhang, Dongsheng

2015-01-01

Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy

Multifunctional Nanomaterials Utilizing Hybridization Chain Reaction for Molecular Diagnostics and Bioanalytical Applications

NASA Astrophysics Data System (ADS)

Rana, Md. Muhit

DNA nanotechnology has shown great promise in molecular diagnostic, bioanalytical and biomedical applications. The great challenge of detecting target analytes, biomarkers and small molecules, in molecular diagnostics is low yield sensitivity. To address this challenge, different nanomaterials have been used for a long time and to date there is no such cost-effective bioanalytical technique which can detect these target biomarkers (DNA, RNA, circulating DNA/miRNA) or environmental heavy metal ions (Hg2+ and Ag+) in a cost-effective and efficient manner. Herein, we initially discuss two possible bioanalytical detection methods- a) colorimetric and b) fluorometric assays which are very popular nowadays due to their distinctive spectroscopic properties. Finally, we report the promising colorimetric assay using a novel DNA based amplification strategy know as hybridization chain reaction (HCR) for potential application in the visual detection of low copies of biomarkers (miRNAs as little as 20 femtomole in an RNA pool and cell extracts in seven different combinations and Ebola virus DNA as low as 400 attomoles in liquid biopsy mimics in sixteen different combinations), environmental and biological heavy metal ions (mercury and silver concentrations as low as 10 pM in water, soil and urine samples) and also successfully applied to a molecular logic gate operation to distinguish OR and AND logic gates. No results showed any false-positive or false-negative information. On the other hand, we also discuss the future possibilities of HCR amplification technology, which is very promising for fluorometric bioanalysis. The HCR based nanoprobe technology has numerous remarkable advantages over other methods. It is re-programmable, simple, inexpensive, easy to assemble and operate and can be performed with visual and spectroscopic read-outs upon recognition of the target analytes. This rapid, specific and sensitive approach for biomarkers and heavy metal ion detection generates

Diagnostic potential of multi-targeted LAMP (loop-mediated isothermal amplification) for osteoarticular tuberculosis.

PubMed

Sharma, Kusum; Sharma, Megha; Batra, Nitya; Sharma, Aman; Dhillon, Mandeep Singh

2017-02-01

Delay in diagnosing osteoarticular tuberculosis (OATB) contributes significantly to morbidity by causing disfiguration and neurological sequelae. The delay caused by conventional culture and the expertise and expense involved in other nucleic acid based tests, make LAMP (loop-mediated isothermal amplification) assay a favorable middle path. We evaluated LAMP assay using IS6110 and MPB64 for rapid diagnosis of OATB by comparing with IS6110 PCR and culture. LAMP assay was performed on 140 synovial fluid and pus samples (10 culture-positive proven cases, 80 culture-negative probable cases, and 50 negative controls) using three set of primer pairs each for IS6110 and MPB64. LAMP assay, using two-target approach, had an overall sensitivity and specificity of 90% and 100% in detecting OATB. Sensitivity of IS6110 PCR, IS6110 LAMP, and MPB64 LAMP was 80%, 100%, and 100%, respectively, for confirmed cases and 72.5%, 81.75%, and 86.25%, respectively, for probable cases. Six additional cases were picked using two-target approach. LAMP assay utilizing IS6110 and MPB64 is a cost-effective technique for an early and reliable diagnosis of OATB. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:361-365, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Impact of the diagnostic process on the accuracy of source identification and time to antibiotics in septic emergency department patients.

PubMed

Uittenbogaard, Annemieke J M; de Deckere, Ernie R J T; Sandel, Maro H; Vis, Alice; Houser, Christine M; de Groot, Bas

2014-06-01

Timely administration of effective antibiotics is important in sepsis management. Source-targeted antibiotics are believed to be most effective, but source identification could cause time delays. First, to describe the accuracy/time delays of a diagnostic work-up and the association with time to antibiotics in septic emergency department (ED) patients. Second, to assess the fraction in which source-targeted antibiotics could have been administered solely on the basis of patient history and physical examination. Secondary analysis of the prospective observational study on septic ED patients was carried out. The time to test result availability was associated with time to antibiotics. The accuracy of the suspected source of infection in the ED was assessed. For patients with pneumosepsis, urosepsis, and abdominal sepsis, combinations of signs and symptoms were assessed to achieve a maximal positive predictive value for the sepsis source, identifying a subset of patients in whom source-targeted antibiotics could be administered without waiting for diagnostic test results. The time to antibiotics increased by 18 (95% confidence interval: 12-24) min/h delay in test result availability (n=323). In 38-79% of patients, antibiotics were administered after additional tests, whereas the ED diagnosis was correct in 68-85% of patients. The maximal positive predictive value of signs and symptoms was 0.87 for patients with pneumosepsis and urosepsis and 0.75 for those with abdominal sepsis. Use of signs and symptoms would have led to correct ED diagnosis in 33% of patients. Diagnostic tests are associated with delayed administration of antibiotics to septic ED patients while increasing the diagnostic accuracy to only 68-85%. In one-third of septic ED patients, the choice of antibiotics could have been accurately determined solely on the basis of patient history and physical examination.

Current diagnostics and treatment of fibrosarcoma –perspectives for future therapeutic targets and strategies

PubMed Central

Augsburger, Daniela; Nelson, Peter J.; Kalinski, Thomas; Udelnow, Andrej; Knösel, Thomas; Hofstetter, Monika; Qin, Ji Wei; Wang, Yan; Gupta, Arvid Sen; Bonifatius, Susanne; Li, Minglun; Bruns, Christiane J.; Zhao, Yue

2017-01-01

Adult-type fibrosarcoma is a rare and highly aggressive subtype of soft tissue sarcomas. Due to the existence of other spindle-cell shaped sarcomas, its diagnosis is always one of exclusion. The likelihood of misdiagnoses between similar tumour entities is high, and often leads to inappropriate tumour treatment. We summarize here the main features of fibrosarcoma. When fibrosarcoma is appropriately diagnosed, the patient`s overall prognosis is generally quite poor. Fibrosarcoma is characterized by its low sensitivity towards radio- and chemotherapy as well as by its high rate of tumour recurrences. Thus it is important to identify new methods to improve treatment of this tumour entity. We discuss some promising new directions in fibrosarcoma research, specifically focusing on more effective targeting of the tumour microenvironment. Communication between tumour cells and their surrounding stromal tissue play a crucial role in cancer progression, invasion, metastasis and chemosensitivity. The therapeutic potential of targeting the tumour microenvironment is addressed. PMID:29262667

Endosialin: from vascular target to biomarker for human sarcomas.

PubMed

Bagley, Rebecca G

2009-10-01

Biomarkers have been the focus of investigations to diagnose disease, track response to therapy and predict prognosis. Meanwhile, the identification of new targets for therapeutic intervention is an ongoing quest in the field of oncology. The recognition of endosialin as an antigen that is selectively overexpressed in human tumor tissues offers new strategies for treating cancer. Not only do the tumor vasculature and stromal compartments upregulate endosialin but, importantly, the malignant cells of sarcomas strongly express endosialin as well. A diagnostic assay that measures the intensity of endosialin expression in malignant tissues would assist in selecting patients that could benefit from an antiendosialin therapy. Thus, endosialin holds potential value both as a therapeutic target and as a biomarker for certain human cancers.

Microbial Diagnostic Array Workstation (MDAW): a web server for diagnostic array data storage, sharing and analysis

PubMed Central

Scaria, Joy; Sreedharan, Aswathy; Chang, Yung-Fu

2008-01-01

Background Microarrays are becoming a very popular tool for microbial detection and diagnostics. Although these diagnostic arrays are much simpler when compared to the traditional transcriptome arrays, due to the high throughput nature of the arrays, the data analysis requirements still form a bottle neck for the widespread use of these diagnostic arrays. Hence we developed a new online data sharing and analysis environment customised for diagnostic arrays. Methods Microbial Diagnostic Array Workstation (MDAW) is a database driven application designed in MS Access and front end designed in ASP.NET. Conclusion MDAW is a new resource that is customised for the data analysis requirements for microbial diagnostic arrays. PMID:18811969

Microbial Diagnostic Array Workstation (MDAW): a web server for diagnostic array data storage, sharing and analysis.

PubMed

Scaria, Joy; Sreedharan, Aswathy; Chang, Yung-Fu

2008-09-23

Microarrays are becoming a very popular tool for microbial detection and diagnostics. Although these diagnostic arrays are much simpler when compared to the traditional transcriptome arrays, due to the high throughput nature of the arrays, the data analysis requirements still form a bottle neck for the widespread use of these diagnostic arrays. Hence we developed a new online data sharing and analysis environment customised for diagnostic arrays. Microbial Diagnostic Array Workstation (MDAW) is a database driven application designed in MS Access and front end designed in ASP.NET. MDAW is a new resource that is customised for the data analysis requirements for microbial diagnostic arrays.

Development of Silicon-Coated Superparamagnetic Iron Oxide Nanoparticles for Targeted Molecular Imaging and Hyperthermic Therapy of Prostate Cancer

DTIC Science & Technology

2015-08-01

nanoparticles have received recent interest as targeted diagnostic and drug delivery vehicles, due to their biocompatibility, biodegradability , and...vivo tumor diagnosis. Cancer Research 66, 10855–10860 (2006). 20. Park, J.-H. et al. Biodegradable luminescent porous silicon nanoparticles for in...biocompatibility, biodegradability , and simple surface chemistry that is amenable to drug loading and targeting. A method of hyperpolarizing silicon particles

Neutron measurements from beam-target reactions at the ELISE neutral beam test facility

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

Xufei, X., E-mail: xiexufei@pku.edu.cn; Fan, T.; Nocente, M.

2014-11-15

Measurements of 2.5 MeV neutron emission from beam-target reactions performed at the ELISE neutral beam test facility are presented in this paper. The measurements are used to study the penetration of a deuterium beam in a copper dump, based on the observation of the time evolution of the neutron counting rate from beam-target reactions with a liquid scintillation detector. A calculation based on a local mixing model of deuterium deposition in the target up to a concentration of 20% at saturation is used to evaluate the expected neutron yield for comparison with data. The results are of relevance to understandmore » neutron emission associated to beam penetration in a solid target, with applications to diagnostic systems for the SPIDER and MITICA Neutral Beam Injection prototypes.« less

X-ray imaging spectroscopic diagnostics on Nike

NASA Astrophysics Data System (ADS)

Aglitskiy, Y.; Karasik, M.; Serlin, V.; Weaver, J. L.; Oh, J.; Obenschain, S. P.; Ralchenko, Yu.

2017-10-01

Electron temperature and density diagnostics of the laser plasma produced within the focal spot of the NRL's Nike laser are being explored with the help of X-ray imaging spectroscopy. Spectra of He-like and H-like ions were taken by Nike focusing spectrometers in a range of lower (1.8 kev, Si XIV) and higher (6.7 kev, Fe XXV) x-ray energies. Data that were obtained with spatial resolution were translated into the temperature and density as functions of distance from the target. As an example electron density was determined from He-like satellites to Ly-alpha in Si XIV. The dielectronic satellites with intensity ratios that are sensitive to collisional transfer of population between different triplet groups of double-excited states 2l2l' in Si XIII were observed with high spatial and spectral resolution Lineouts taken at different axial distances from the planar Si target show changing spectral shapes due to the different electron densities as determined by supporting non-LTE simulations. These shapes are relatively insensitive to the plasma temperature which was measured using different spectral lines. This work was supported by the US DOE/NNSA.

Loop-mediated isothermal amplification (LAMP) assay for speedy diagnosis of tubercular lymphadenitis: The multi-targeted 60-minute approach.

PubMed

Sharma, Megha; Sharma, Kusum; Sharma, Aman; Gupta, Nalini; Rajwanshi, Arvind

2016-09-01

Tuberculous lymphadenitis (TBLA), the most common presentation of tuberculosis, poses a significant diagnostic challenge in the developing countries. Timely, accurate and cost-effective diagnosis can decrease the high morbidity associated with TBLA especially in resource-poor high-endemic regions. The loop-mediated isothermal amplification assay (LAMP), using two targets, was evaluated for the diagnosis of TBLA. LAMP assay using 3 sets of primers (each for IS6110 and MPB64) was performed on 170 fine needle aspiration samples (85 confirmed, 35 suspected, 50 control cases of TBLA). Results were compared against IS6110 PCR, cytology, culture and smear. The overall sensitivity and specificity of LAMP assay, using multi-targeted approach, was 90% and 100% respectively in diagnosing TBLA. The sensitivity of multi-targeted LAMP, only MPB64 LAMP, only IS6110 LAMP and IS6110 PCR was 91.7%, 89.4%, 84.7% and 75.2%, respectively among confirmed cases and 85.7%, 77.1%, 68.5% and 60%, respectively among suspected cases of TBLA. Additional 12/120 (10%) cases were detected using multi-targeted method. The multi-targeted LAMP, with its speedy and reliable results, is a potential diagnostic test for TBLA in low-resource countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

A preface on advances in diagnostics for infectious and parasitic diseases: detecting parasites of medical and veterinary importance.

PubMed

Stothard, J Russell; Adams, Emily

2014-12-01

There are many reasons why detection of parasites of medical and veterinary importance is vital and where novel diagnostic and surveillance tools are required. From a medical perspective alone, these originate from a desire for better clinical management and rational use of medications. Diagnosis can be at the individual-level, at close to patient settings in testing a clinical suspicion or at the community-level, perhaps in front of a computer screen, in classification of endemic areas and devising appropriate control interventions. Thus diagnostics for parasitic diseases has a broad remit as parasites are not only tied with their definitive hosts but also in some cases with their vectors/intermediate hosts. Application of current diagnostic tools and decision algorithms in sustaining control programmes, or in elimination settings, can be problematic and even ill-fitting. For example in resource-limited settings, are current diagnostic tools sufficiently robust for operational use at scale or are they confounded by on-the-ground realities; are the diagnostic algorithms underlying public health interventions always understood and well-received within communities which are targeted for control? Within this Special Issue (SI) covering a variety of diseases and diagnostic settings some answers are forthcoming. An important theme, however, throughout the SI is to acknowledge that cross-talk and continuous feedback between development and application of diagnostic tests is crucial if they are to be used effectively and appropriately.

A new gamma-ray diagnostic for energetic ion distributions - The Compton tail on the neutron capture line

NASA Technical Reports Server (NTRS)

Vestrand, W. Thomas

1990-01-01

This paper presents a new radiation diagnostic for assaying the energy spectrum and the angular distribution of energetic ions incident on thick hydrogen-rich thermal targets. This diagnostic compares the number of emergent photons in the narrow neutron capture line at 2.223 MeV to the number of Compton scattered photons that form a low-energy tail on the line. It is shown that the relative strength of the tail can be used as a measure of the hardness of the incident ion-energy spectrum. Application of this diagnostic to solar flare conditions is the main thrust of the work presented here. It is examined how the strength of the Compton tail varies with flare viewing angle and the angular distribution of the flare-accelerated particles. Application to compact X-ray binary systems is also briefly discussed.

Multidisciplinary molecular diagnostics: the 9th European meeting on molecular diagnostics.

PubMed

Loonen, Anne J M; Schuurman, Rob; van den Brule, Adriaan J C

2016-01-01

This report presents a summary of the 9th European Meeting on Molecular Diagnostics held in Noordwijk, The Netherlands, 14-16 October 2015. This 3-day conference covered many relevant topics in the field of molecular diagnostics in humans, including infectious disease, oncology, outbreak management, population-based cancer screening, standardization and quality control, chronic diseases and pharmacogenetics. Beyond these different areas, shared values are new technologies and novel technical and clinical applications. Approximately 450 participants, the majority coming from European countries, attended the meeting. Besides high quality scientific presentations, more than 35 diagnostic companies presented their latest innovations, altogether in an informal and inspiring scientific ambience.

Cognitive aspect of diagnostic errors.

PubMed

Phua, Dong Haur; Tan, Nigel C K

2013-01-01

Diagnostic errors can result in tangible harm to patients. Despite our advances in medicine, the mental processes required to make a diagnosis exhibits shortcomings, causing diagnostic errors. Cognitive factors are found to be an important cause of diagnostic errors. With new understanding from psychology and social sciences, clinical medicine is now beginning to appreciate that our clinical reasoning can take the form of analytical reasoning or heuristics. Different factors like cognitive biases and affective influences can also impel unwary clinicians to make diagnostic errors. Various strategies have been proposed to reduce the effect of cognitive biases and affective influences when clinicians make diagnoses; however evidence for the efficacy of these methods is still sparse. This paper aims to introduce the reader to the cognitive aspect of diagnostic errors, in the hope that clinicians can use this knowledge to improve diagnostic accuracy and patient outcomes.

Epigenetics and Therapeutic Targets Mediating Neuroprotection

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2015-01-01

The rapidly evolving science of epigenetics is transforming our understanding of the nervous system in health and disease and holds great promise for the development of novel diagnostic and therapeutic approaches targeting neurological diseases. Increasing evidence suggests that epigenetic factors and mechanisms serve as important mediators of the pathogenic processes that lead to irrevocable neural injury and of countervailing homeostatic and regenerative responses. Epigenetics is, therefore, of considerable translational significance to the field of neuroprotection. In this brief review, we provide an overview of epigenetic mechanisms and highlight the emerging roles played by epigenetic processes in neural cell dysfunction and death and in resultant neuroprotective responses. PMID:26236020

Whole Genome Sequencing Expands Diagnostic Utility and Improves Clinical Management in Pediatric Medicine.

PubMed

Stavropoulos, Dimitri J; Merico, Daniele; Jobling, Rebekah; Bowdin, Sarah; Monfared, Nasim; Thiruvahindrapuram, Bhooma; Nalpathamkalam, Thomas; Pellecchia, Giovanna; Yuen, Ryan K C; Szego, Michael J; Hayeems, Robin Z; Shaul, Randi Zlotnik; Brudno, Michael; Girdea, Marta; Frey, Brendan; Alipanahi, Babak; Ahmed, Sohnee; Babul-Hirji, Riyana; Porras, Ramses Badilla; Carter, Melissa T; Chad, Lauren; Chaudhry, Ayeshah; Chitayat, David; Doust, Soghra Jougheh; Cytrynbaum, Cheryl; Dupuis, Lucie; Ejaz, Resham; Fishman, Leona; Guerin, Andrea; Hashemi, Bita; Helal, Mayada; Hewson, Stacy; Inbar-Feigenberg, Michal; Kannu, Peter; Karp, Natalya; Kim, Raymond; Kronick, Jonathan; Liston, Eriskay; MacDonald, Heather; Mercimek-Mahmutoglu, Saadet; Mendoza-Londono, Roberto; Nasr, Enas; Nimmo, Graeme; Parkinson, Nicole; Quercia, Nada; Raiman, Julian; Roifman, Maian; Schulze, Andreas; Shugar, Andrea; Shuman, Cheryl; Sinajon, Pierre; Siriwardena, Komudi; Weksberg, Rosanna; Yoon, Grace; Carew, Chris; Erickson, Raith; Leach, Richard A; Klein, Robert; Ray, Peter N; Meyn, M Stephen; Scherer, Stephen W; Cohn, Ronald D; Marshall, Christian R

2016-01-13

The standard of care for first-tier clinical investigation of the etiology of congenital malformations and neurodevelopmental disorders is chromosome microarray analysis (CMA) for copy number variations (CNVs), often followed by gene(s)-specific sequencing searching for smaller insertion-deletions (indels) and single nucleotide variant (SNV) mutations. Whole genome sequencing (WGS) has the potential to capture all classes of genetic variation in one experiment; however, the diagnostic yield for mutation detection of WGS compared to CMA, and other tests, needs to be established. In a prospective study we utilized WGS and comprehensive medical annotation to assess 100 patients referred to a paediatric genetics service and compared the diagnostic yield versus standard genetic testing. WGS identified genetic variants meeting clinical diagnostic criteria in 34% of cases, representing a 4-fold increase in diagnostic rate over CMA (8%) (p-value = 1.42e-05) alone and >2-fold increase in CMA plus targeted gene sequencing (13%) (p-value = 0.0009). WGS identified all rare clinically significant CNVs that were detected by CMA. In 26 patients, WGS revealed indel and missense mutations presenting in a dominant (63%) or a recessive (37%) manner. We found four subjects with mutations in at least two genes associated with distinct genetic disorders, including two cases harboring a pathogenic CNV and SNV. When considering medically actionable secondary findings in addition to primary WGS findings, 38% of patients would benefit from genetic counseling. Clinical implementation of WGS as a primary test will provide a higher diagnostic yield than conventional genetic testing and potentially reduce the time required to reach a genetic diagnosis.

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.

Automotive Diagnostic Technologies.

ERIC Educational Resources Information Center

Columbus State Community Coll., OH.

This document contains materials developed for and about the automotive diagnostic technologies tech prep program of the South-Western City Schools in Ohio. Part 1 begins with a map of the program, which begins with an automotive/diagnostic technologies program in grades 11 and 12 that leads to entry-level employment or a 2-year automotive…

Smartphone-Based Mobile Detection Platform for Molecular Diagnostics and Spatiotemporal Disease Mapping.

PubMed

Song, Jinzhao; Pandian, Vikram; Mauk, Michael G; Bau, Haim H; Cherry, Sara; Tisi, Laurence C; Liu, Changchun

2018-04-03

Rapid and quantitative molecular diagnostics in the field, at home, and at remote clinics is essential for evidence-based disease management, control, and prevention. Conventional molecular diagnostics requires extensive sample preparation, relatively sophisticated instruments, and trained personnel, restricting its use to centralized laboratories. To overcome these limitations, we designed a simple, inexpensive, hand-held, smartphone-based mobile detection platform, dubbed "smart-connected cup" (SCC), for rapid, connected, and quantitative molecular diagnostics. Our platform combines bioluminescent assay in real-time and loop-mediated isothermal amplification (BART-LAMP) technology with smartphone-based detection, eliminating the need for an excitation source and optical filters that are essential in fluorescent-based detection. The incubation heating for the isothermal amplification is provided, electricity-free, with an exothermic chemical reaction, and incubation temperature is regulated with a phase change material. A custom Android App was developed for bioluminescent signal monitoring and analysis, target quantification, data sharing, and spatiotemporal mapping of disease. SCC's utility is demonstrated by quantitative detection of Zika virus (ZIKV) in urine and saliva and HIV in blood within 45 min. We demonstrate SCC's connectivity for disease spatiotemporal mapping with a custom-designed website. Such a smart- and connected-diagnostic system does not require any lab facilities and is suitable for use at home, in the field, in the clinic, and particularly in resource-limited settings in the context of Internet of Medical Things (IoMT).

Combination of interferometry and thermography data for cultural heritage structural diagnostic research

NASA Astrophysics Data System (ADS)

Tornari, Vivi; Andrianakis, Michalis; Hatzigiannakis, Kostas; Kosma, Kiki; Detalle, Vincent; Giovanacci, David

2017-07-01

The demand for non destructive and non invasive structural diagnostic techniques able to perform on field remote structural evaluation of historical structures and works of art it faces an increased demand. The techniques must have some basic important characteristics The non destructivity, accuracy, repeatability, non physical contact, portability, resolution, broad range of applicability depending on the type of artwork and the question at hand, are all among the important requirements underlying the requirement for on-field structural diagnostics. In this respect there are two known techniques that have been developed at full to provide a suited structural diagnostic application in artwork conservation. The systems presented here but discussed in detail elsewhere are stimulated infrared thermography (SIRT) and digital holographic speckle pattern interferometry (DHSPI) the prior can be found n market at commercial devise level while the latter is at laboratory prototype level. The two systems are being exploited for their complimentary advantages and in this paper are used in combined testing on art related targets according to the above criteria to confirm the enhanced diagnostic information that their complimentary use provides. Results confirm the effectiveness of each technique alone and the combination of data of both techniques in the conservation field. Each system is first briefly described and examples are given with the aim to present the suitability and appropriateness for use in structural documentation analysis and reports. The experimental work is in laboratory work-in-progress focusing on the hybriding of data synthesis.

Development of stimulation diagnostic technology

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

Warpinski, N.R.; Lorenz, J.C.

The objective of this project is to apply Sandia's expertise and technology towards the development of stimulation diagnostic technology in the areas of in situ stress, natural fracturing, stimulation processes and instrumentation systems. Initial work has concentrated on experiment planning for a site where hydraulic fracturing could be evaluated and design models and fracture diagnostics could be validated and improved. Important issues have been defined and new diagnostics, such as inclinometers, identified. In the area of in situ stress, circumferential velocity analysis is proving to be a useful diagnostic for stress orientation. Natural fracture studies of the Frontier formation aremore » progressing; two fracture sets have been found and their relation to tectonic events have been hypothesized. Analyses of stimulation data have been performed for several sites, primarily for in situ stress information. Some new ideas in stimulation diagnostics have been proposed; these ideas may significantly improve fracture diagnostic capabilities.« less

New advances in targeted gastric cancer treatment.

PubMed

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-08-14

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.

New advances in targeted gastric cancer treatment

PubMed Central

Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

2016-01-01

Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

Using voluntary reports from physicians to learn from diagnostic errors in emergency medicine.

PubMed

Okafor, Nnaemeka; Payne, Velma L; Chathampally, Yashwant; Miller, Sara; Doshi, Pratik; Singh, Hardeep

2016-04-01

Diagnostic errors are common in the emergency department (ED), but few studies have comprehensively evaluated their types and origins. We analysed incidents reported by ED physicians to determine disease conditions, contributory factors and patient harm associated with ED-related diagnostic errors. Between 1 March 2009 and 31 December 2013, ED physicians reported 509 incidents using a department-specific voluntary incident-reporting system that we implemented at two large academic hospital-affiliated EDs. For this study, we analysed 209 incidents related to diagnosis. A quality assurance team led by an ED physician champion reviewed each incident and interviewed physicians when necessary to confirm the presence/absence of diagnostic error and to determine the contributory factors. We generated descriptive statistics quantifying disease conditions involved, contributory factors and patient harm from errors. Among the 209 incidents, we identified 214 diagnostic errors associated with 65 unique diseases/conditions, including sepsis (9.6%), acute coronary syndrome (9.1%), fractures (8.6%) and vascular injuries (8.6%). Contributory factors included cognitive (n=317), system related (n=192) and non-remedial (n=106). Cognitive factors included faulty information verification (41.3%) and faulty information processing (30.6%) whereas system factors included high workload (34.4%) and inefficient ED processes (40.1%). Non-remediable factors included atypical presentation (31.3%) and the patients' inability to provide a history (31.3%). Most errors (75%) involved multiple factors. Major harm was associated with 34/209 (16.3%) of reported incidents. Most diagnostic errors in ED appeared to relate to common disease conditions. While sustaining diagnostic error reporting programmes might be challenging, our analysis reveals the potential value of such systems in identifying targets for improving patient safety in the ED. Published by the BMJ Publishing Group Limited. For

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

21 CFR 868.1840 - Diagnostic spirometer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Diagnostic spirometer. 868.1840 Section 868.1840...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1840 Diagnostic spirometer. (a) Identification. A diagnostic spirometer is a device used in pulmonary function testing to measure the volume of...

Alzheimer's and ABC transporters--new opportunities for diagnostics and treatment.

PubMed

Pahnke, Jens; Langer, Oliver; Krohn, Markus

2014-12-01

Much has been said about the increasing number of demented patients and the main risk factor 'age'. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain's barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias. Copyright © 2014 Elsevier Inc. All rights reserved.

Alzheimer’s and ABC transporters - new opportunities for diagnostics and treatment

PubMed Central

Pahnke, Jens; Langer, Oliver; Krohn, Markus

2014-01-01

Much has been said about the increasing number of demented patients and the main risk factor ‘age’. Frustratingly, we do not know the precise pattern and all modulating factors that provoke the pathologic changes in the brains of affected elderly. We have to diagnose early to be able to stop the progression of diseases that irreversibly destroy brain substance. Familiar AD cases have mislead some researchers for almost 20 years, which has unfortunately narrowed the scientific understanding and has, thus, lead to insufficient funding of independent approaches. Therefore, basic researchers hardly have been able to develop causative treatments and clinicians still do not have access to prognostic and early diagnostic tools. During the recent years it became clear that insufficient Aβ export, physiologically facilitated by the ABC transporter superfamily at the brain’s barriers, plays a fundamental role in disease initiation and progression. Furthermore, export mechanisms that are deficient in affected elderly are new targets for activation and, thus, treatment, but ideally also for prevention. In sporadic AD disturbed clearance of β-amyloid from the brain is so far the most important factor for its accumulation in the parenchyma and vessel walls. Here, we review findings about the contribution of ABC transporters and of the perivascular drainage/glymphatic system on β-amyloid clearance. We highlight their potential value for innovative early diagnostics using PET and describe recently described, effective ABC transporter-targeting agents as potential causative treatment for neurodegenerative proteopathies/dementias. PMID:24746857

miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer.

PubMed

Corcoran, Claire; Rani, Sweta; Breslin, Susan; Gogarty, Martina; Ghobrial, Irene M; Crown, John; O'Driscoll, Lorraine

2014-03-24

While the treatment of HER2 over-expressing breast cancer with recent HER-targeted drugs has been highly effective for some patients, primary (also known as innate) or acquired resistance limits the success of these drugs. microRNAs have potential as diagnostic, prognostic and predictive biomarkers, as well as replacement therapies. Here we investigated the role of microRNA-630 (miR-630) in breast cancer progression and as a predictive biomarker for response to HER-targeting drugs, ultimately yielding potential as a therapeutic approach to add value to these drugs. We investigated the levels of intra- and extracellular miR-630 in cells and conditioned media from breast cancer cell lines with either innate- or acquired- resistance to HER-targeting lapatinib and neratinib, compared to their corresponding drug sensitive cell lines, using qPCR. To support the role of miR-630 in breast cancer, we examined the clinical relevance of this miRNA in breast cancer tumours versus matched peritumours. Transfection of miR-630 mimics and inhibitors was used to manipulate the expression of miR-630 to assess effects on response to HER-targeting drugs (lapatinib, neratinib and afatinib). Other phenotypic changes associated with cellular aggressiveness were evaluated by motility, invasion and anoikis assays. TargetScan prediction software, qPCR, immunoblotting and ELISAs, were used to assess miR-630's regulation of mRNA, proteins and their phosphorylated forms. We established that introducing miR-630 into cells with innate- or acquired- resistance to HER-drugs significantly restored the efficacy of lapatinib, neratinib and afatinib; through a mechanism which we have determined to, at least partly, involve miR-630's regulation of IGF1R. Conversely, we demonstrated that blocking miR-630 induced resistance/insensitivity to these drugs. Cellular motility, invasion, and anoikis were also observed as significantly altered by miR-630 manipulation, whereby introducing miR-630 into cells

Lyme disease: the promise of Big Data, companion diagnostics and precision medicine

PubMed Central

Stricker, Raphael B; Johnson, Lorraine

2016-01-01

Lyme disease caused by the spirochete Borrelia burgdorferi has become a major worldwide epidemic. Recent studies based on Big Data registries show that >300,000 people are diagnosed with Lyme disease each year in the USA, and up to two-thirds of individuals infected with B. burgdorferi will fail conventional 30-year-old antibiotic therapy for Lyme disease. In addition, animal and human evidence suggests that sexual transmission of the Lyme spirochete may occur. Improved companion diagnostic tests for Lyme disease need to be implemented, and novel treatment approaches are urgently needed to combat the epidemic. In particular, therapies based on the principles of precision medicine could be modeled on successful “designer drug” treatment for HIV/AIDS and hepatitis C virus infection featuring targeted protease inhibitors. The use of Big Data registries, companion diagnostics and precision medicine will revolutionize the diagnosis and treatment of Lyme disease. PMID:27672336

[Cognitive errors in diagnostic decision making].

PubMed

Gäbler, Martin

2017-10-01

Approximately 10-15% of our diagnostic decisions are faulty and may lead to unfavorable and dangerous outcomes, which could be avoided. These diagnostic errors are mainly caused by cognitive biases in the diagnostic reasoning process.Our medical diagnostic decision-making is based on intuitive "System 1" and analytical "System 2" diagnostic decision-making and can be deviated by unconscious cognitive biases.These deviations can be positively influenced on a systemic and an individual level. For the individual, metacognition (internal withdrawal from the decision-making process) and debiasing strategies, such as verification, falsification and rule out worst-case scenarios, can lead to improved diagnostic decisions making.

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.

Nanoparticle-blood interactions: the implications on solid tumour targeting.

PubMed

Lazarovits, James; Chen, Yih Yang; Sykes, Edward A; Chan, Warren C W

2015-02-18

Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem.

TFTR diagnostic vacuum controller

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

Olsen, D.; Persons, R.

1981-01-01

The TFTR diagnostic vacuum controller (DVC) provides in conjunction with the Central Instrumentation Control and Data Acquisition System (CICADA), control and monitoring for the pumps, valves and gauges associated with each individual diagnostic vacuum system. There will be approximately 50 systems on TFTR. Two standard versions of the controller (A and B) wil be provided in order to meet the requirements of two diagnostic manifold arrangements. All pump and valve sequencing, as well as protection features, will be implemented by the controller.

Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.

PubMed

Lee, Daniel J; Recabal, Pedro; Sjoberg, Daniel D; Thong, Alan; Lee, Justin K; Eastham, James A; Scardino, Peter T; Vargas, Hebert Alberto; Coleman, Jonathan; Ehdaie, Behfar

2016-09-01

We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance

MicroRNAs: A Puzzling Tool in Cancer Diagnostics and Therapy.

PubMed

D'Angelo, Barbara; Benedetti, Elisabetta; Cimini, Annamaria; Giordano, Antonio

2016-11-01

MicroRNAs (miRNAs) constitute a dominating class of small RNAs that regulate diverse cellular functions. Due the pivotal role of miRNAs in biological processes, a deregulated miRNA expression is likely involved in human cancers. MicroRNAs possess tumor suppressor capability, as well as display oncogenic characteristics. Interestingly, miRNAs exist in various biological fluids as circulating entities. Changes in the profile of circulating miRNAs are indicative of pathophysiological conditions in human cancer. This concept has led to consider circulating miRNAs valid biomarkers in cancer diagnostics. Furthermore, current research promotes the use of miRNAs as a target in cancer therapy. However, miRNAs are an evolving research field. Although miRNAs have been demonstrated to be potentially valuable tools both in cancer diagnosis and treatment, a greater effort should be made to improve our understanding of miRNAs biology. This review describes the biology of microRNAs, emphasizing on the use of miRNAs in cancer diagnostics and therapy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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.

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

Diagnostic aids: the Surgical Sieve revisited.

PubMed

Chai, Jason; Evans, Lloyd; Hughes, Tom

2017-08-01

Diagnostic errors are well documented in the literature and emphasise the need to teach diagnostic skills at an early stage in medical school to create effective and safe clinicians. Hence, there may be a place for diagnostic aids (such as the Surgical Sieve) that provide a framework for generating ideas about diagnoses. With repeated use of the Surgical Sieve in teaching sessions with students, and prompted by the traditional handheld wheels used in antenatal clinics, we developed the Compass Medicine, a handheld diagnostic wheel comprising three concentric discs attached at the centre. We report a preliminary study comparing the Surgical Sieve and the Compass Medicine in generating differential diagnoses. A total of 48 third-year medical students from Cardiff University participated in a study aimed at measuring the efficacy of diagnostic aids (Surgical Sieve and Compass Medicine) in generating diagnoses. We quantified the effect each aid had on the number of diagnoses generated, and compared the size of the effect between the two diagnostic aids. There may be a place for diagnostic aids that provide a framework for generating ideas about diagnoses RESULTS: The study suggests that both diagnostic aids prompted users to generate a greater number of diagnoses, but there was no significant difference in the size of effect between the two diagnostic aids. We hope that our study with diagnostic aids will encourage the use of robust tools to teach medical students an easily visualised framework for diagnostic thinking. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Negative symptom domain prevalence across diagnostic boundaries: The relevance of diagnostic shifts.

PubMed

Lyne, John; Renwick, Laoise; O'Donoghue, Brian; Kinsella, Anthony; Malone, Kevin; Turner, Niall; O'Callaghan, Eadbhard; Clarke, Mary

2015-08-30

Negative symptoms are included in diagnostic manuals as part of criteria for schizophrenia spectrum psychoses only, however some studies have found their presence in other diagnoses. This study sought to clarify negative symptom domain prevalence across diagnostic categories, while investigating whether negative symptoms predicted diagnostic shift over time. Scale for the Assessment of Negative Symptoms (SANS) data were collected at first presentation in 197 individuals presenting with first episode psychosis and again at one year follow-up assessment. Negative symptoms were highest among individuals with schizophrenia and among those whose diagnosis shifted from non-schizophrenia spectrum at baseline to schizophrenia spectrum at follow-up. In a non-schizophrenia spectrum group negative symptoms at baseline were not a significant predictor of diagnostic shift to schizophrenia spectrum diagnoses. The study suggests negative symptoms can present among individuals with non-schizophrenia spectrum diagnoses, although this is most relevant for individuals following diagnostic shift from non-schizophrenia spectrum to schizophrenia spectrum diagnoses. The findings support introduction of a negative symptom dimension when describing a range of psychotic illnesses, and indicate that further research investigating the evolution of negative symptoms in non-schizophrenia diagnoses is needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Transcriptomics in cancer diagnostics: developments in technology, clinical research and commercialization.

PubMed

Sager, Monica; Yeat, Nai Chien; Pajaro-Van der Stadt, Stefan; Lin, Charlotte; Ren, Qiuyin; Lin, Jimmy

2015-01-01

Transcriptomic technologies are evolving to diagnose cancer earlier and more accurately to provide greater predictive and prognostic utility to oncologists and patients. Digital techniques such as RNA sequencing are replacing still-imaging techniques to provide more detailed analysis of the transcriptome and aberrant expression that causes oncogenesis, while companion diagnostics are developing to determine the likely effectiveness of targeted treatments. This article examines recent advancements in molecular profiling research and technology as applied to cancer diagnosis, clinical applications and predictions for the future of personalized medicine in oncology.

Diagnostic grand rounds: a new teaching concept to train diagnostic reasoning.

PubMed

Stieger, Stefan; Praschinger, Andrea; Kletter, Kurt; Kainberger, Franz

2011-06-01

Diagnostic reasoning is a core skill in teaching and learning in undergraduate curricula. Diagnostic grand rounds (DGRs) as a subform of grand rounds are intended to train the students' skills in the selection of appropriate tests and in the interpretation of test results. The aim of this study was to test DGRs for their ability to improve diagnostic reasoning by using a pre-post-test design. During one winter term, all 398 fifth-year students (36.1% male, 63.9% female) solved 23 clinical cases presented in 8 DGRs. In an online questionnaire, a Diagnostic Thinking Inventory (DTI) with 41 items was evaluated for flexibility in thinking and structure of knowledge in memory. Results were correlated with those from a summative multiple-choice knowledge test and of the learning objectives in a logbook. The students' DTI scores in the post-test were significantly higher than those reported in the pre-test. DTI scores at either testing time did not correlate with medical knowledge as assessed by a multiple-choice knowledge test. Abilities acquired during clinical clerkships as documented in a logbook could only account for a small proportion of the increase in the flexibility subscale score. This effect still remained significant after accounting for potential confounders. Establishing DGRs proofed to be an effective way of successfully improving both students' diagnostic reasoning and the ability to select the appropriate test method in routine clinical practice. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Pancreatic cancer cell detection by targeted lipid microbubbles and multiphoton imaging

NASA Astrophysics Data System (ADS)

Cromey, Benjamin; McDaniel, Ashley; Matsunaga, Terry; Vagner, Josef; Kieu, Khanh Quoc; Banerjee, Bhaskar

2018-04-01

Surgical resection of pancreatic cancer represents the only chance of cure and long-term survival in this common disease. Unfortunately, determination of a cancer-free margin at surgery is based on one or two tiny frozen section biopsies, which is far from ideal. Not surprisingly, cancer is usually left behind and is responsible for metastatic disease. We demonstrate a method of receptor-targeted imaging using peptide ligands, lipid microbubbles, and multiphoton microscopy that could lead to a fast and accurate way of examining the entire cut surface during surgery. Using a plectin-targeted microbubble, we performed a blinded in-vitro study to demonstrate avid binding of targeted microbubbles to pancreatic cancer cells but not noncancerous cell lines. Further work should lead to a much-needed point-of-care diagnostic test for determining clean margins in oncologic surgery.

Universal Versus Targeted Screening for Lynch Syndrome: Comparing Ascertainment and Costs Based on Clinical Experience.

PubMed

Erten, Mujde Z; Fernandez, Luca P; Ng, Hank K; McKinnon, Wendy C; Heald, Brandie; Koliba, Christopher J; Greenblatt, Marc S

2016-10-01

Strategies to screen colorectal cancers (CRCs) for Lynch syndrome are evolving rapidly; the optimal strategy remains uncertain. We compared targeted versus universal screening of CRCs for Lynch syndrome. In 2010-2011, we employed targeted screening (age < 60 and/or Bethesda criteria). From 2012 to 2014, we screened all CRCs. Immunohistochemistry for the four mismatch repair proteins was done in all cases, followed by other diagnostic studies as indicated. We modeled the diagnostic costs of detecting Lynch syndrome and estimated the 5-year costs of preventing CRC by colonoscopy screening, using a system dynamics model. Using targeted screening, 51/175 (29 %) cancers fit criteria and were tested by immunohistochemistry; 15/51 (29 %, or 8.6 % of all CRCs) showed suspicious loss of ≥1 mismatch repair protein. Germline mismatch repair gene mutations were found in 4/4 cases sequenced (11 suspected cases did not have germline testing). Using universal screening, 17/292 (5.8 %) screened cancers had abnormal immunohistochemistry suspicious for Lynch syndrome. Germline mismatch repair mutations were found in only 3/10 cases sequenced (7 suspected cases did not have germline testing). The mean cost to identify Lynch syndrome probands was ~$23,333/case for targeted screening and ~$175,916/case for universal screening at our institution. Estimated costs to identify and screen probands and relatives were: targeted, $9798/case and universal, $38,452/case. In real-world Lynch syndrome management, incomplete clinical follow-up was the major barrier to do genetic testing. Targeted screening costs 2- to 7.5-fold less than universal and rarely misses Lynch syndrome cases. Future changes in testing costs will likely change the optimal algorithm.

Profiling of potential driver mutations in sarcomas by targeted next generation sequencing.

PubMed

Andersson, Carola; Fagman, Henrik; Hansson, Magnus; Enlund, Fredrik

2016-04-01

Comprehensive genetic profiling by massively parallel sequencing, commonly known as next generation sequencing (NGS), is becoming the foundation of personalized oncology. For sarcomas very few targeted treatments are currently in routine use. In clinical practice the preoperative diagnostic workup of soft tissue tumours largely relies on core needle biopsies. Although mostly sufficient for histopathological diagnosis, only very limited amounts of formalin fixated paraffin embedded tissue are often available for predictive mutation analysis. Targeted NGS may thus open up new possibilities for comprehensive characterization of scarce biopsies. We therefore set out to search for driver mutations by NGS in a cohort of 55 clinically and morphologically well characterized sarcomas using low input of DNA from formalin fixated paraffin embedded tissues. The aim was to investigate if there are any recurrent or targetable aberrations in cancer driver genes in addition to known chromosome translocations in different types of sarcomas. We employed a panel covering 207 mutation hotspots in 50 cancer-associated genes to analyse DNA from nine gastrointestinal stromal tumours, 14 synovial sarcomas, seven myxoid liposarcomas, 22 Ewing sarcomas and three Ewing-like small round cell tumours at a large sequencing depth to detect also mutations that are subclonal or occur at low allele frequencies. We found nine mutations in eight different potential driver genes, some of which are potentially actionable by currently existing targeted therapies. Even though no recurrent mutations in driver genes were found in the different sarcoma groups, we show that targeted NGS-based sequencing is clearly feasible in a diagnostic setting with very limited amounts of paraffin embedded tissue and may provide novel insights into mesenchymal cell signalling and potentially druggable targets. Interestingly, we also identify five non-synonymous sequence variants in 4 established cancer driver genes in DNA

The Diagnosticity of Color for Emotional Objects

PubMed Central

McMenamin, Brenton W.; Radue, Jasmine; Trask, Joanna; Huskamp, Kristin; Kersten, Daniel; Marsolek, Chad J.

2012-01-01

Object classification can be facilitated if simple diagnostic features can be used to determine class membership. Previous studies have found that simple shapes may be diagnostic for emotional content and automatically alter the allocation of visual attention. In the present study, we analyzed whether color is diagnostic of emotional content and tested whether emotionally diagnostic hues alter the allocation of visual attention. Reddish-yellow hues are more common in (i.e., diagnostic of) emotional images, particularly images with positive emotional content. An exogenous cueing paradigm was employed to test whether these diagnostic hues orient attention differently from other hues due to the emotional diagnosticity. In two experiments, we found that participants allocated attention differently to diagnostic hues than to non-diagnostic hues, in a pattern indicating a broadening of spatial attention when cued with diagnostic hues. Moreover, the attentional broadening effect was predicted by self-reported measures of affective style, linking the behavioral effect to emotional processes. These results confirm the existence and use of diagnostic features for the rapid detection of emotional content. PMID:24659831

Identification of Five Novel Variants in Chinese Oculocutaneous Albinism by Targeted Next-Generation Sequencing.

PubMed

Qiu, Biyuan; Ma, Tao; Peng, Chunyan; Zheng, Xiaoqin; Yang, Jiyun

2018-04-01

The diagnosis of oculocutaneous albinism (OCA) is established using clinical signs and symptoms. OCA is, however, a highly genetically heterogeneous disease with mutations identified in at least nineteen unique genes, many of which produce overlapping phenotypic traits. Thus, differentiating genetic OCA subtypes for diagnoses and genetic counseling is challenging, based on clinical presentation alone, and would benefit from a comprehensive molecular diagnostic. To develop and validate a more comprehensive, targeted, next-generation-sequencing-based diagnostic for the identification of OCA-causing variants. The genomic DNA samples from 28 OCA probands were analyzed by targeted next-generation sequencing (NGS), and the candidate variants were confirmed through Sanger sequencing. We observed mutations in the TYR, OCA2, and SLC45A2 genes in 25/28 (89%) patients with OCA. We identified 38 pathogenic variants among these three genes, including 5 novel variants: c.1970G>T (p.Gly657Val), c.1669A>C (p.Thr557Pro), c.2339-2A>C, and c.1349C>G (p.Thr450Arg) in OCA2; c.459_470delTTTTGCTGCCGA (p.Ala155_Phe158del) in SLC45A2. Our findings expand the mutational spectrum of OCA in the Chinese population, and the assay we developed should be broadly useful as a molecular diagnostic, and as an aid for genetic counseling for OCA patients.

Therapeutic target for protozoal diseases

DOEpatents

Rathore, Dharmendar [Blacksburg, VA; Jani, Dewal [Blacksburg, VA; Nagarkatti, Rana [Blacksburg, VA

2008-10-21

A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

PubMed Central

Brett, Maggie; McPherson, John; Zang, Zhi Jiang; Lai, Angeline; Tan, Ee-Shien; Ng, Ivy; Ong, Lai-Choo; Cham, Breana; Tan, Patrick; Rozen, Steve; Tan, Ene-Choo

2014-01-01

Developmental delay and/or intellectual disability (DD/ID) affects 1–3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81–84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism. PMID:24690944

Diagnostic Progress and Results on the Magnetized Shock Experiment

NASA Astrophysics Data System (ADS)

Smith, R. J.; Weber, T. E.

2015-11-01

The Magnetized Shock Experiment (MSX) at LANL is reliably producing Field Reversed Configuration (FRC) plasmas spanning peak densities of ~ 1021-23 m-3, combined Te +Ti of 10s-500eV and velocities of 100-300km/s as a means to producing a laboratory supercritical collision-less shock. Visible light images showing discontinuities indicative of shocks and jetting have been obtained on various targets: co-solenoid B field, a metal wall and counter-solenoidal B fields (FRC capture and reconnection). Two chord interferometry, external and internal magnetic probing are routinely employed and x-ray diagnostic capability has recently been added. The pulsed polarimetry technique is being deployed which can measure the local magnetic field using Lidar Thomson scattering. In addition, a fiber optic version of pulsed polarimetry using a new specialty fiber that enhances fiber backscatter with Fiber Bragg Gratings is being developed. Magnetic fields of order ~ 1T have been measured, however a new modified shock chamber geometry and recent machine modifications enabling operation at increased θ-coil voltage are expected to improve translation speed and hence stagnation pressures. Progress on these diagnostics and results will be presented. DOE support Grant No DE-SC00010559.

Current and future molecular diagnostics for ocular infectious diseases.

PubMed

Doan, Thuy; Pinsky, Benjamin A

2016-11-01

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

Chapter 17. Extension of endogenous primers as a tool to detect micro-RNA targets.

PubMed

Vatolin, Sergei; Weil, Robert J

2008-01-01

Mammalian cells express a large number of small, noncoding RNAs, including micro-RNAs (miRNAs), that can regulate both the level of a target mRNA and the protein produced by the target mRNA. Recognition of miRNA targets is a complicated process, as a single target mRNA may be regulated by several miRNAs. The potential for combinatorial miRNA-mediated regulation of miRNA targets complicates diagnostic and therapeutic applications of miRNAs. Despite significant progress in understanding the biology of miRNAs and advances in computational predictions of miRNA targets, methods that permit direct physical identification of miRNA-mRNA complexes in eukaryotic cells are still required. Several groups have utilized coimmunoprecipitation of RNA associated with a protein(s) that is part of the RNA silencing macromolecular complex. This chapter describes a detailed but straightforward strategy that identifies miRNA targets based on the assumption that small RNAs base paired with a complementary target mRNA can be used as a primer to synthesize cDNA that may be used for cloning, identification, and functional analysis.

Target product profiles for the diagnosis of Taenia solium taeniasis, neurocysticercosis and porcine cysticercosis.

PubMed

Donadeu, Meritxell; Fahrion, Anna S; Olliaro, Piero L; Abela-Ridder, Bernadette

2017-09-01

Target Product Profiles (TPPs) are process tools providing product requirements to guide researchers, developers and manufacturers in their efforts to develop effective and useful products such as biologicals, drugs or diagnostics. During a WHO Stakeholders Meeting on Taenia solium diagnostics, several TPPs were initiated to address diagnostic needs for different stages in the parasite's transmission (taeniasis, human and porcine cysticercosis). Following the meeting, draft TPPs were completed and distributed for consultation to 100 people/organizations, including experts in parasitology, human and pig cysticercosis, diagnostic researchers and manufacturers, international organizations working with neglected or zoonotic diseases, Ministries of Health and Ministries of Livestock in some of the endemic countries, WHO regional offices and other interested parties. There were 53 respondents. All comments and feedback received were considered and discussions were held with different experts according to their area of expertise. The comments were consolidated and final TPPs are presented here. They are considered to be live documents which are likely to undergo review and updating in the future when new knowledge and technologies become available.

Target product profiles for the diagnosis of Taenia solium taeniasis, neurocysticercosis and porcine cysticercosis

PubMed Central

Fahrion, Anna S.; Olliaro, Piero L.; Abela-Ridder, Bernadette

2017-01-01

Target Product Profiles (TPPs) are process tools providing product requirements to guide researchers, developers and manufacturers in their efforts to develop effective and useful products such as biologicals, drugs or diagnostics. During a WHO Stakeholders Meeting on Taenia solium diagnostics, several TPPs were initiated to address diagnostic needs for different stages in the parasite’s transmission (taeniasis, human and porcine cysticercosis). Following the meeting, draft TPPs were completed and distributed for consultation to 100 people/organizations, including experts in parasitology, human and pig cysticercosis, diagnostic researchers and manufacturers, international organizations working with neglected or zoonotic diseases, Ministries of Health and Ministries of Livestock in some of the endemic countries, WHO regional offices and other interested parties. There were 53 respondents. All comments and feedback received were considered and discussions were held with different experts according to their area of expertise. The comments were consolidated and final TPPs are presented here. They are considered to be live documents which are likely to undergo review and updating in the future when new knowledge and technologies become available. PMID:28892472

Regulation Effects by Programmed Molecules for Transcription-Based Diagnostic Automata towards Therapeutic Use

NASA Astrophysics Data System (ADS)

Hirabayashi, Miki; Ohashi, Hirotada; Kubo, Tai

We have presented experimental analysis on the controllability of our transcription-based diagnostic biomolecular automata by programmed molecules. Focusing on the noninvasive transcriptome diagnosis by salivary mRNAs, we already proposed the novel concept of diagnostic device using DNA computation. This system consists of the main computational element which has a stem shaped promoter region and a pseudo-loop shaped read-only memory region for transcription regulation through the conformation change caused by the recognition of disease-related biomarkers. We utilize the transcription of malachite green aptamer sequence triggered by the target recognition for observation of detection. This algorithm makes it possible to release RNA-aptamer drugs multiply, different from the digestion-based systems by the restriction enzyme which was proposed previously, for the in-vivo use, however, the controllability of aptamer release is not enough at the previous stage. In this paper, we verified the regulation effect on aptamer transcription by programmed molecules in basic conditions towards the developm! ent of therapeutic automata. These results would bring us one step closer to the realization of new intelligent diagnostic and therapeutic automata based on molecular circuits.

Prevalence of neuropathic features of back pain in clinical populations: implications for the diagnostic triage paradigm.

PubMed

Hush, Julia M; Marcuzzi, Anna

2012-07-01

SUMMARY Contemporary clinical assessment of back pain is based on the diagnostic triage paradigm. The most common diagnostic classification is nonspecific back pain, considered to be of nociceptive etiology. A small proportion are diagnosed with radicular pain, of neuropathic origin. In this study we review the body of literature on the prevalence of neuropathic features of back pain, revealing that the point prevalence is 17% in primary care, 34% in mixed clinical settings and 53% in tertiary care. There is evidence that neuropathic features of back pain are not restricted to typical clinical radicular pain phenotypes and may be under-recognized, particularly in primary care. The consequence of this is that in the clinic, diagnostic triage may erroneously classify patients with nonspecific back pain or radicular pain. A promising alternative is the development of mechanism-based pain phenotyping in patients with back pain. Timely identification of contributory pain mechanisms may enable greater opportunity to select appropriate therapeutic targets and improve patient outcomes.

A targeted illumination optical fiber probe for high resolution fluorescence imaging and optical switching

NASA Astrophysics Data System (ADS)

Shinde, Anant; Perinchery, Sandeep Menon; Murukeshan, Vadakke Matham

2017-04-01

An optical imaging probe with targeted multispectral and spatiotemporal illumination features has applications in many diagnostic biomedical studies. However, these systems are mostly adapted in conventional microscopes, limiting their use for in vitro applications. We present a variable resolution imaging probe using a digital micromirror device (DMD) with an achievable maximum lateral resolution of 2.7 μm and an axial resolution of 5.5 μm, along with precise shape selective targeted illumination ability. We have demonstrated switching of different wavelengths to image multiple regions in the field of view. Moreover, the targeted illumination feature allows enhanced image contrast by time averaged imaging of selected regions with different optical exposure. The region specific multidirectional scanning feature of this probe has facilitated high speed targeted confocal imaging.