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Sample records for advanced clinical solutions

  1. Test Review: Advanced Clinical Solutions for WAIS-IV and WMS-IV

    ERIC Educational Resources Information Center

    Chu, Yiting; Lai, Mark H. C.; Xu, Yining; Zhou, Yuanyuan

    2012-01-01

    The authors review the "Advanced Clinical Solutions for WAIS-IV and WMS-IV". The "Advanced Clinical Solutions (ACS) for the Wechsler Adult Intelligence Scale-Fourth Edition" (WAIS-IV; Wechsler, 2008) and the "Wechsler Memory Scale-Fourth Edition" (WMS-IV; Wechsler, 2009) was published by Pearson in 2009. It is a clinical tool for extending the…

  2. Advances in clinical cardiology.

    PubMed

    McNeice, Andrew H; McAleavey, Neil M; Menown, Ian B A

    2014-08-01

    Multiple, potentially practice-changing cardiology trials have been presented or published over the past year. In this paper, we summarize and place in clinical context, new data regarding management of acute coronary syndrome and ST-elevation myocardial infarction (copeptin assessment, otamixaban, cangrelor, prasugrel, sodium nitrite, inclacumab, ranolazine, preventive coronary intervention of non-culprit lesions, immediate thrombolytic therapy versus transfer for primary intervention), new coronary intervention data (thrombectomy, radial access, pressure wire fractional flow reserve, antiplatelet therapy duration and gene-guidance, permanent and biodegradable polymers, coronary bifurcation and strategies), and coronary artery bypass data (off pump vs. on pump). Latest trials in trans-aortic valve implantation, heart failure (eplerenone, aliskiren, spironolactone, sildenafil, dopamine, nesiritide, omecamtiv mecarbil, the algisyl left ventricular augmentation device, and echo-guided cardiac resynchronization), atrial fibrillation (edoxaban, dabigatran, and ablation), cardiac arrest (hypothermia, LUCAS™ mechanical chest compression), and cardiovascular prevention (vitamins, renal denervation for resistant hypertension, renal artery stenting, saxagliptin, alogliptin, and gastric banding) are also discussed. PMID:25074280

  3. Advanced defect and metrology solutions

    NASA Astrophysics Data System (ADS)

    Novak, Erik

    2014-05-01

    Cost, weight, performance, and lifetime requirements for precision components used throughout the aerospace and defense industries are driving innovative mechanical designs, manufacturing processes and use of new materials. In turn, these advanced components typically require tighter dimensional and surface tolerances to function as designed. Scratch testers, microscope-based systems, and other traditional metrology systems are inadequate for roughness, small-scale geometry, and defect determination on many of these parts. This talk will examine the advantages and disadvantages of some of the new technologies developed to provide more robust, versatile, and sensitive measurements of precision components for advanced manufacturing environments.

  4. Colloid solutions: a clinical update.

    PubMed

    Niemi, Tomi T; Miyashita, Ryo; Yamakage, Michiaki

    2010-12-01

    Albumin, dextran, gelatin, and hydroxyethyl starch (HES) solutions are colloids that efficiently expand the circulating blood volume. The administration of colloids restores the intravascular volume with minimal risk of tissue edema in comparison with crystalloid solutions alone. However, colloids are always given for surgical and critically ill patients. The type of the colloid, volumes applied, aggressiveness of fluid resuscitation, and the volume status at the initial phase of administration determine their clinical responses. The outcome after fluid resuscitation with various colloids in critically ill patients seems to be comparable according to systematic reviews. A randomized, adequately powered clinical trial comparing modern nonprotein colloid to albumin is still lacking. Rapidly degradable HES solutions have good hemodynamic effects, and the risk of adverse renal and coagulation effects, as well as allergic reactions, is minimal. The current investigation has also shown the beneficial effect of HES solution (especially HES 130/0.4) on inflammatory response, postoperative nausea and vomiting, and postoperative outcome. The indication of colloids with an assessment of the degree of hypovolemia and safety profiles should thus be taken into consideration before colloid administration.

  5. Advances in clinical nutrition in GI surgery.

    PubMed

    Holst, Mette; Rasmussen, Henrik H; Irtun, Oivind

    2015-04-01

    This review addresses recent relevant advances to clinical nutrition regarding gastrointestinal disease surgery. Medline Ovid, EMBASE and Central were searched systematically in April 2014. Inclusion criteria were randomized controlled trials, non-randomized controlled trials and observational studies evaluating nutritional support in gastrointestinal surgery published within 5 years. The review included 56 relevant studies. Themes were: nutrition screening and risk factors predict outcome; preoperative nutritional support; shortening fasting periods and including carbohydrate solutions; early nutrition after surgery; immune modulating nutrition; synbiotics, growth hormone, omega-3 and oral, enteral and parenteral nutrition in combination. Screening for nutritional risk is profound, with special focus on dietary intake in the past week. Age and severity of disease need to be included in the screening system. Patients at severe nutritional risk benefit from nutritional therapy before surgery. New standards are developing quickly and clinical guidelines on surgery should include updated knowledge within clinical nutrition.

  6. Positive solutions of advanced differential systems.

    PubMed

    Diblík, Josef; Kúdelčíková, Mária

    2013-01-01

    We study asymptotic behavior of solutions of general advanced differential systems y(t) = F(t, y(t)), where F : Ω → [Symbol: see text] (n) is a continuous quasi-bounded functional which satisfies a local Lipschitz condition with respect to the second argument and Ω is a subset in [Symbol: see text] × C(r)(n), C(r)(n) := C([0, r], [Symbol: see text] (n)), y t [Symbol: see text]C(r)(n), and y t (θ) = y(t + θ), θ [Symbol: see text] [0, r]. A monotone iterative method is proposed to prove the existence of a solution defined for t → ∞ with the graph coordinates lying between graph coordinates of two (lower and upper) auxiliary vector functions. This result is applied to scalar advanced linear differential equations. Criteria of existence of positive solutions are given and their asymptotic behavior is discussed.

  7. Rapid solute transport in the peritoneum: physiologic and clinical consequences.

    PubMed

    Cueto-Manzano, Alfonso M

    2009-02-01

    This review focuses on the physiologic and clinical consequences of rapid solute transport in the peritoneum. The concept, the current understanding of related factors, and the possible causes implicated in rapid solute transport are discussed first. Then, the consequences, with particular emphasis on mortality, are highlighted. Finally, based on recent advances and clinical studies, some strategies for the treatment of fast peritoneal transport are reviewed.

  8. A framework for advanced clinical practice.

    PubMed

    Kaur, Sukvinder; Radford, Mark; Arblaster, Gillian

    The NHS needs a skilled, knowledgeable workforce of advanced clinical practitioners, who require multidisciplinary approach to their postgraduate development. To meet these demands we set up a regional programme to help clinical practitioners move into these new and demanding roles. As a result, health professionals who want to progress their career and advance their practice have an opportunity in the West Midlands to qualify as advanced clinical practitioners. PMID:27328598

  9. [Clinical trials with advanced therapy medicinal products].

    PubMed

    Schüssler-Lenz, M; Schneider, C K

    2010-01-01

    For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.

  10. Clinical Application and Research Advances of CT Myocardial Perfusion Imaging.

    PubMed

    2016-06-10

    Computed tomography (CT)-based myocardial perfusion imaging (CTP)has been widely recognized as a one-station solution for the imaging of myocardial ischemia-related diseases. This article reviews the clinical scanning protocols,analytical methods,and research advances of CTP in recent years and briefly discusses its limitations and future development. PMID:27469926

  11. Placebo Effects: Biological, Clinical and Ethical Advances

    PubMed Central

    Kaptchuk, Ted J; Miller, Franklin; Benedetti, Fabrizio

    2010-01-01

    For many years, placebos have been conceptualised by their inert content and their use as controls in clinical trials and treatments in clinical practice. Recent research demonstrates that placebo effects are genuine psychobiological phenomenon attributable to the overall therapeutic context, and that placebo effects can be robust in both laboratory and clinical settings. Evidence has also emerged that placebo effects can exist in clinical practice, even if no placebo is given. Further promotion and integration of laboratory and clinical research will allow advances in the ethical harnessing of placebo mechanisms that are inherent in routine clinical care and the potential use of treatments to primarily promote placebo effects. PMID:20171404

  12. Advances in clinical analysis 2012.

    PubMed

    Couchman, Lewis; Mills, Graham A

    2013-01-01

    A report on the meeting organized by The Chromatographic Society and the Separation Science Group, Analytical Division of the Royal Society of Chemistry. Over 60 delegates and commercial exhibitors attended this event, held to celebrate the careers of Robert Flanagan and David Perrett, and acknowledge their extensive contributions in the field of clinical analysis. PMID:23330556

  13. Scientifically advanced solutions for chestnut ink disease.

    PubMed

    Choupina, Altino Branco; Estevinho, Letícia; Martins, Ivone M

    2014-05-01

    On the north regions of Portugal and Spain, the Castanea sativa Mill. culture is extremely important. The biggest productivity and yield break occurs due to the ink disease, the causal agent being the oomycete Phytophthora cinnamomi. This oomycete is also responsible for the decline of many other plant species in Europe and worldwide. P. cinnamomi and Phytophthora cambivora are considered, by the generality of the authors, as the C. sativa ink disease causal agents. Most Phytophthora species secrete large amounts of elicitins, a group of unique highly conserved proteins that are able to induce hypersensitive response (HR) and enhances plant defense responses in a systemic acquired resistance (SAR) manner against infection by different pathogens. Some other proteins involved in mechanisms of infection by P. cinnamomi were identified by our group: endo-1,3-beta-glucanase (complete cds); exo-glucanase (partial cds) responsible by adhesion, penetration, and colonization of host tissues; glucanase inhibitor protein (GIP) (complete cds) responsible by the suppression of host defense responses; necrosis-inducing Phytophthora protein 1 (NPP1) (partial cds); and transglutaminase (partial cds) which inducts defense responses and disease-like symptoms. In this mini-review, we present some scientifically advanced solutions that can contribute to the resolution of ink disease.

  14. Towards advanced OCT clinical applications

    NASA Astrophysics Data System (ADS)

    Kirillin, Mikhail; Panteleeva, Olga; Agrba, Pavel; Pasukhin, Mikhail; Sergeeva, Ekaterina; Plankina, Elena; Dudenkova, Varvara; Gubarkova, Ekaterina; Kiseleva, Elena; Gladkova, Natalia; Shakhova, Natalia; Vitkin, Alex

    2015-07-01

    In this paper we report on our recent achievement in application of conventional and cross-polarization OCT (CP OCT) modalities for in vivo clinical diagnostics in different medical areas including gynecology, dermatology, and stomatology. In gynecology, CP OCT was employed for diagnosing fallopian tubes and cervix; in dermatology OCT for monitoring of treatment of psoriasis, scleroderma and atopic dermatitis; and in stomatology for diagnosis of oral diseases. For all considered application, we propose and develop different image processing methods which enhance the diagnostic value of the technique. In particular, we use histogram analysis, Fourier analysis and neural networks, thus calculating different tissue characteristics as revealed by OCT's polarization evolution. These approaches enable improved OCT image quantification and increase its resultant diagnostic accuracy.

  15. Advancements to the theory of free solution electrophoresis of polyelectrolytes

    NASA Astrophysics Data System (ADS)

    McCormick, Laurette

    Capillary electrophoresis (CE) is the workhorse of countless analytical laboratories and is used routinely in various industries including pharmaceutical, forensic and clinical applications. Basically, CE is a method for separating charged molecular species in a buffer-filled capillary by the application of an electric field; the analytes move from one end of the capillary to the detector at the other end at speeds determined by their charge, size and shape. Generally, in free solution CE uniformly charged polyelectrolytes (such as DNA) are free-draining, meaning that their speed is independent of their size. Hence, until recently, a gel or other sieving medium has been necessary for the separation of polyelectrolytes; however, modifying uniformly charged polymers on the molecular level, via conjugation to uncharged polymers, allows for separation in free solution CE. In this thesis, advancements to the theory of free solution electrophoresis of polyelectrolytes, in particular, to the theories for two new free solution electrophoresis methods relying on conjugation, are presented. The first method, called End Labelled Free Solution Electrophoresis (ELFSE), can be used to sequence DNA, a negatively charged polymer in solution. Two different means of improving the resolution of ELFSE are predicted, one based on the molecular end effect, the other based on using a controlled electro-osmotic flow. In addition, a theory for the segregation of the DNA and label coils in ELFSE is presented. The second method is called Free Solution Conjugate Electrophoresis (FSCE); it allows for characterization of a sample of neutral polymers differing in length. The relevant theory, developed herein, elucidates how to accurately determine the molar mass distribution of the sample through FSCE measurements. In addition, supporting theories are developed that clarify the correct equation for the diffusion coefficient of molecules undergoing free solution electrophoresis, as well as

  16. Clinical implications of advances in liver regeneration.

    PubMed

    Kwon, Yong Jin; Lee, Kyeong Geun; Choi, Dongho

    2015-03-01

    Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases.

  17. Advances in clinical research methodology for pain clinical trials.

    PubMed

    Farrar, John T

    2010-11-01

    Pain is a ubiquitous phenomenon, but the experience of pain varies considerably from person to person. Advances in understanding of the growing number of pathophysiologic mechanisms that underlie the generation of pain and the influence of the brain on the experience of pain led to the investigation of numerous compounds for treating pain. Improved knowledge of the subjective nature of pain, the variations in the measurement of pain, the mind-body placebo effect and the impact of differences in the conduct of a clinical trial on the outcome have changed approaches to design and implement studies. Careful consideration of how these concepts affect the choice of study population, the randomization and blinding process, the measurement and collection of data, and the analysis and interpretation of results should improve the quality of clinical trials for potential pain therapies.

  18. Final Scientific Report - Wireless and Sensing Solutions Advancing Industrial Efficiency

    SciTech Connect

    Budampati, Rama; McBrady, Adam; Nusseibeh, Fouad

    2009-09-28

    The project team's goal for the Wireless and Sensing Solution Advancing Industrial Efficiency award (DE-FC36-04GO14002) was to develop, demonstrate, and test a number of leading edge technologies that could enable the emergence of wireless sensor and sampling systems for the industrial market space. This effort combined initiatives in advanced sensor development, configurable sampling and deployment platforms, and robust wireless communications to address critical obstacles in enabling enhanced industrial efficiency.

  19. A flexible architecture for advanced process control solutions

    NASA Astrophysics Data System (ADS)

    Faron, Kamyar; Iourovitski, Ilia

    2005-05-01

    Advanced Process Control (APC) is now mainstream practice in the semiconductor manufacturing industry. Over the past decade and a half APC has evolved from a "good idea", and "wouldn"t it be great" concept to mandatory manufacturing practice. APC developments have primarily dealt with two major thrusts, algorithms and infrastructure, and often the line between them has been blurred. The algorithms have evolved from very simple single variable solutions to sophisticated and cutting edge adaptive multivariable (input and output) solutions. Spending patterns in recent times have demanded that the economics of a comprehensive APC infrastructure be completely justified for any and all cost conscious manufacturers. There are studies suggesting integration costs as high as 60% of the total APC solution costs. Such cost prohibitive figures clearly diminish the return on APC investments. This has limited the acceptance and development of pure APC infrastructure solutions for many fabs. Modern APC solution architectures must satisfy the wide array of requirements from very manual R&D environments to very advanced and automated "lights out" manufacturing facilities. A majority of commercially available control solutions and most in house developed solutions lack important attributes of scalability, flexibility, and adaptability and hence require significant resources for integration, deployment, and maintenance. Many APC improvement efforts have been abandoned and delayed due to legacy systems and inadequate architectural design. Recent advancements (Service Oriented Architectures) in the software industry have delivered ideal technologies for delivering scalable, flexible, and reliable solutions that can seamlessly integrate into any fabs" existing system and business practices. In this publication we shall evaluate the various attributes of the architectures required by fabs and illustrate the benefits of a Service Oriented Architecture to satisfy these requirements. Blue

  20. Advanced selective plating with AeroNikl solutions

    NASA Astrophysics Data System (ADS)

    Smith, Gary W.

    1989-03-01

    This paper presents the latest technical data on nickel deposits on complex areas of engine components, obtained by the selective (brush) plating of nickel sulfamate solutions (AeroNikl-250, -400, and -575). Current applications for these coatings, and advancements in application technology, are described. Particular attention is given to a controlled velocity gap plating process developed for high-speed selective deposition in bores.

  1. Some recent advances in the numerical solution of differential equations

    NASA Astrophysics Data System (ADS)

    D'Ambrosio, Raffaele

    2016-06-01

    The purpose of the talk is the presentation of some recent advances in the numerical solution of differential equations, with special emphasis to reaction-diffusion problems, Hamiltonian problems and ordinary differential equations with discontinuous right-hand side. As a special case, in this short paper we focus on the solution of reaction-diffusion problems by means of special purpose numerical methods particularly adapted to the problem: indeed, following a problem oriented approach, we propose a modified method of lines based on the employ of finite differences shaped on the qualitative behavior of the solutions. Constructive issues and a brief analysis are presented, together with some numerical experiments showing the effectiveness of the approach and a comparison with existing solvers.

  2. [Standardization and archiving of clinical reviews: search for optimal solutions].

    PubMed

    Bezuglaia, M V

    2013-12-01

    The article refers to the necessity of the optimization processes for standardization and archiving of clinical examinations at the different stages of care, including also outpatient care. The compromise solution to the problem has been offered in the article.

  3. Advanced clinical KCD scanner for digital radiography

    NASA Astrophysics Data System (ADS)

    DiBianca, Frank A.; Davis, Keana M.; Jordan, Lawrence M.; Laughter, Joseph S.; Krishnamurthy, Anand; Hu, Bo

    1998-07-01

    One of the goals of medical imaging scientists and bioengineers remains the development of digital electronic technologies that can replace film-based methods of acquiring x-ray images. With the achievement of this goal, all diagnostic imaging technologies would be based on digital techniques with all the attending benefits. Based on the performance of numerous research prototype small-field and one large-field Kinestatic Charge Detector (KCD) system for digital radiography, a large-field clinical KCD scanner is currently being designed and built for technical evaluation and for clinical evaluation of 200 volunteer patients (including clinical comparisons with film, storage phosphor, and other available clinical systems). The state of development of this clinical KCD system, including detector, data-acquisition system and scanning gantry design, is reviewed in this paper.

  4. Positioning advanced practice nurses for financial success in clinical practice.

    PubMed

    Kennerly, Susan

    2006-01-01

    Advanced practice nurses (APNs) are well prepared for patient care, but not for the financial aspects of clinical practice. A lack of reimbursement knowledge and skills limits the prospects for APNs to be key players in business and practice ventures. Faculty are challenged to strengthen the advanced practice reimbursement component of the financial management core to promote the reimbursement competency of APNs. The author discusses 4 primary content categories that are critical to financial success in clinical practice.

  5. Advances in clinical study of curcumin.

    PubMed

    Yang, Chunfen; Su, Xun; Liu, Anchang; Zhang, Lin; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

    2013-01-01

    Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies. PMID:23116307

  6. How Physicians Integrate Advances into Clinical Practices.

    ERIC Educational Resources Information Center

    Lockyer, Jocelyn M.; And Others

    1985-01-01

    Family physicians and specialists were asked to identify the sources of information they used in the process of making changes in their clinical practices. An average of 3.08 sources of information were utilized for each change and over 50 percent of the changes were complete in less than one year. (CT)

  7. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  8. Advanced solutions in combustion-based WtE technologies.

    PubMed

    Martin, Johannes J E; Koralewska, Ralf; Wohlleben, Andreas

    2015-03-01

    Thermal treatment of waste by means of combustion in grate-based systems has gained world-wide acceptance as the preferred method for sustainable management and safe disposal of residual waste. In order to maintain this position and to address new challenges and/or priorities, these systems need to be further developed with a view to energy conservation, resource and climate protection and a reduction in the environmental impact in general. MARTIN GmbH has investigated continuously how the implementation of innovative concepts in essential parts of its grate-based Waste-to-Energy (WtE) combustion technology can be used to meet the above-mentioned requirements. As a result of these efforts, new "advanced solutions" were developed, four examples of which are shown in this article. PMID:25305685

  9. Clinical Research Informatics: Recent Advances and Future Directions

    PubMed Central

    2015-01-01

    Summary Objectives To summarize significant developments in Clinical Research Informatics (CRI) over the past two years and discuss future directions. Methods Survey of advances, open problems and opportunities in this field based on exploration of current literature. Results Recent advances are structured according to three use cases of clinical research: Protocol feasibility, patient identification/recruitment and clinical trial execution. Discussion CRI is an evolving, dynamic field of research. Global collaboration, open metadata, content standards with semantics and computable eligibility criteria are key success factors for future developments in CRI. PMID:26293865

  10. Autosomal dominant polycystic kidney disease: recent advances in clinical management.

    PubMed

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C M

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 (th) century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 (st) century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  11. Autosomal dominant polycystic kidney disease: recent advances in clinical management

    PubMed Central

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C. M.

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 st century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  12. Personalizing Drug Selection Using Advanced Clinical Decision Support

    PubMed Central

    Pestian, John; Spencer, Malik; Matykiewicz, Pawel; Zhang, Kejian; Vinks, Alexander A.; Glauser, Tracy

    2009-01-01

    This article describes the process of developing an advanced pharmacogenetics clinical decision support at one of the United States’ leading pediatric academic medical centers. This system, called CHRISTINE, combines clinical and genetic data to identify the optimal drug therapy when treating patients with epilepsy or Attention Deficit Hyperactivity Disorder. In the discussion a description of clinical decision support systems is provided, along with an overview of neurocognitive computing and how it is applied in this setting. PMID:19898682

  13. Recent advances in dengue pathogenesis and clinical management.

    PubMed

    Simmons, Cameron P; McPherson, Kirsty; Van Vinh Chau, Nguyen; Hoai Tam, D T; Young, Paul; Mackenzie, Jason; Wills, Bridget

    2015-12-10

    This review describes and commentates on recent advances in the understanding of dengue pathogenesis and immunity, plus clinical research on vaccines and therapeutics. We expand specifically on the role of the dermis in dengue virus infection, the contribution of cellular and humoral immune responses to pathogenesis and immunity, NS1 and mechanisms of virus immune evasion. Additionally we review a series of therapeutic intervention trials for dengue, as well as recent clinical research aimed at improving clinical diagnosis, risk prediction and disease classification.

  14. Recent advances in basic and clinical nanomedicine.

    PubMed

    Morrow, K John; Bawa, Raj; Wei, Chiming

    2007-09-01

    Nanomedicine is a global business enterprise. Industry and governments clearly are beginning to envision nanomedicine's enormous potential. A clear definition of nanotechnology is an issue that requires urgent attention. This problem exists because nanotechnology represents a cluster of technologies, each of which may have different characteristics and applications. Although numerous novel nanomedicine-related applications are under development or nearing commercialization, the process of converting basic research in nanomedicine into commercially viable products will be long and difficult. Although realization of the full potential of nanomedicine may be years or decades away, recent advances in nanotechnology-related drug delivery, diagnosis, and drug development are beginning to change the landscape of medicine. Site-specific targeted drug delivery and personalized medicine are just a few concepts that are on the horizon.

  15. Advances in kinase targeting: current clinical use and clinical trials.

    PubMed

    Rask-Andersen, Mathias; Zhang, Jin; Fabbro, Doriano; Schiöth, Helgi B

    2014-11-01

    Phosphotransferases, also known as kinases, are the most intensively studied protein drug target category in current pharmacological research, as evidenced by the vast number of kinase-targeting agents enrolled in active clinical trials. This development has emerged following the great success of small-molecule, orally available protein kinase inhibitors for the treatment of cancer, starting with the introduction of imatinib (Gleevec®) in 2003. The pharmacological utility of kinase-targeting has expanded to include treatment of inflammatory diseases, and rapid development is ongoing for kinase-targeted therapies in a broad array of indications in ophthalmology, analgesia, central nervous system (CNS) disorders, and the complications of diabetes, osteoporosis, and otology. In this review we highlight specifically the kinase drug targets and kinase-targeting agents being explored in current clinical trials. This analysis is based on a recent estimate of all established and clinical trial drug mechanisms of action, utilizing private and public databases to create an extensive dataset detailing aspects of more than 3000 approved and experimental drugs. PMID:25312588

  16. Advances in myelofibrosis: a clinical case approach

    PubMed Central

    Mascarenhas, John O.; Orazi, Attilio; Bhalla, Kapil N.; Champlin, Richard E.; Harrison, Claire; Hoffman, Ronald

    2013-01-01

    Primary myelofibrosis is a member of the myeloproliferative neoplasms, a diverse group of bone marrow malignancies. Symptoms of myelofibrosis, particularly those associated with splenomegaly (abdominal distention and pain, early satiety, dyspnea, and diarrhea) and constitutional symptoms, represent a substantial burden to patients. Most patients eventually die from the disease, with a median survival ranging from approximately 5–7 years. Mutations in Janus kinase 2 (JAK2), a kinase that is essential for the normal development of erythrocytes, granulocytes, and platelets, notably the V617F mutation, have been identified in approximately 50% of patients with myelofibrosis. The approval of a JAK2 inhibitor in 2011 has improved the outlook of many patients with myelofibrosis and has changed the treatment landscape. This article focuses on some of the important issues in current myelofibrosis treatment management, including differentiation of myelofibrosis from essential thrombocythemia and polycythemia vera, up-dated data on the results of JAK2 inhibitor therapy, the role of epigenetic mechanisms in myelofibrosis pathogenesis, investigational therapies for myelofibrosis, and advances in hematopoietic stem cell transplant. Three myelofibrosis cases are included to underscore the issues in diagnosing and treating this complex disease. PMID:24091929

  17. Advancing cell wall inhibitors towards clinical applications.

    PubMed

    Maffioli, Sonia I; Cruz, João C S; Monciardini, Paolo; Sosio, Margherita; Donadio, Stefano

    2016-03-01

    Natural products represent a major source of approved drugs and still play an important role in supplying chemical diversity. Consistently, 2014 has seen new, natural product-derived antibiotics approved for human use by the US Food and Drug Administration. One of the recently approved second-generation glycopeptides is dalbavancin, a semi-synthetic derivative of the natural product A40,926. This compound inhibits bacterial growth by binding to lipid intermediate II (Lipid II), a key intermediate in peptidoglycan biosynthesis. Like other recently approved antibiotics, dalbavancin has a complex history of preclinical and clinical development, with several companies contributing to different steps in different years. While our work on dalbavancin development stopped at the previous company, intriguingly our current pipeline includes two more Lipid II-binding natural products or derivatives thereof. In particular, we will focus on the properties of NAI-107 and related lantibiotics, which originated from recent screening and characterization efforts. PMID:26515981

  18. Advancing cell wall inhibitors towards clinical applications.

    PubMed

    Maffioli, Sonia I; Cruz, João C S; Monciardini, Paolo; Sosio, Margherita; Donadio, Stefano

    2016-03-01

    Natural products represent a major source of approved drugs and still play an important role in supplying chemical diversity. Consistently, 2014 has seen new, natural product-derived antibiotics approved for human use by the US Food and Drug Administration. One of the recently approved second-generation glycopeptides is dalbavancin, a semi-synthetic derivative of the natural product A40,926. This compound inhibits bacterial growth by binding to lipid intermediate II (Lipid II), a key intermediate in peptidoglycan biosynthesis. Like other recently approved antibiotics, dalbavancin has a complex history of preclinical and clinical development, with several companies contributing to different steps in different years. While our work on dalbavancin development stopped at the previous company, intriguingly our current pipeline includes two more Lipid II-binding natural products or derivatives thereof. In particular, we will focus on the properties of NAI-107 and related lantibiotics, which originated from recent screening and characterization efforts.

  19. Advance modern medicine with clinical case reports

    PubMed Central

    2014-01-01

    Randomized clinical trial (RCT) can fail to demonstrate the richness of individual patient characteristics. Given the unpredictable nature of medicine, a patient may present in an unusual way, have a strange new pathology, or react to a medical intervention in a manner not seen before. The publication of these novelties as case reports is a fundamental way of conveying medical knowledge. Throughout history there have been famous case studies that shaped the way we view health and disease. Case reports can have the following functions: (I) descriptions of new diseases; (II) study of mechanisms; (III) discovery new therapies; (IV) recognition of side effects; and (V) education. Before submitting a case report, it is worthwhile to refer to the Case Report Check Sheet described by Green and Johnson [2006]. PMID:25525572

  20. Advances in Clinical PET/MRI Instrumentation.

    PubMed

    Herzog, Hans; Lerche, Christoph

    2016-04-01

    In 2010, the first whole-body PET/MRI scanners installed for clinical use were the sequential Philips PET/MRI with PMT-based, TOF-capable technology and the integrated simultaneous Siemens PET/MRI. Avalanche photodiodes as non-magneto-sensitive readout electronics allowed PET integrated within the MRI. The experiences with these scanners showed that improvements of software aspects, such as attenuation correction, were necessary and that efficient protocols combining optimally PET and MRI must be still developed. In 2014, General Electric issued an integrated PET/MRI with SiPM-based PET detectors, allowing TOF-PET. Looking at the MRI components of current PET/MR imaging systems, primary improvements come from sequences and new coils.

  1. Advances in Clinical Management of Eosinophilic Esophagitis

    PubMed Central

    Dellon, Evan S.; Liacouras, Chris A.

    2014-01-01

    EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines—EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885

  2. Construction of databases: advances and significance in clinical research.

    PubMed

    Long, Erping; Huang, Bingjie; Wang, Liming; Lin, Xiaoyu; Lin, Haotian

    2015-12-01

    Widely used in clinical research, the database is a new type of data management automation technology and the most efficient tool for data management. In this article, we first explain some basic concepts, such as the definition, classification, and establishment of databases. Afterward, the workflow for establishing databases, inputting data, verifying data, and managing databases is presented. Meanwhile, by discussing the application of databases in clinical research, we illuminate the important role of databases in clinical research practice. Lastly, we introduce the reanalysis of randomized controlled trials (RCTs) and cloud computing techniques, showing the most recent advancements of databases in clinical research. PMID:27215009

  3. Symposium on research advances in clinical PET. Final performance report

    SciTech Connect

    J. Michael McGehee

    1992-01-01

    The Institute for Clinical PET and the U.S. Department of Energy (DOE) co-sponsored a symposium entitled 'Research in PET: International and Institutional Perspectives' that highlighted the activities of many leading investigators in the U.S. and throughout the world. Research programs at the DOE were discussed as were potential directions of PET research. International as well as institutional perspectives on PET research were presented. This symposium was successful in reaching those interested in research advances of clinical PET.

  4. Intravenous balanced solutions: from physiology to clinical evidence.

    PubMed

    Langer, Thomas; Santini, Alessandro; Scotti, Eleonora; Van Regenmortel, Niels; Malbrain, Manu L N G; Caironi, Pietro

    2015-01-01

    "Balanced" solutions are commonly defined as intravenous fluids having an electrolyte composition close to that of plasma. As such, they should minimally affect acid-base equilibrium, as compared to the commonly reported 0.9% NaCl-related hyperchloremic metabolic acidosis. Recently, the term "balanced" solution has been also employed to indicate intravenous fluids with low chloride content, being the concentration of this electrolyte the most altered and supra-physiologic in 0.9% NaCl as compared to plasma, and based upon a suggested detrimental effect on renal function associated with hyperchloremia. Despite efforts for its identification, the ideal balanced solution, with minimal effects on acid-base status, low chloride content, and adequate tonicity, is not yet available. After the accumulation of pre-clinical and clinical physiologic data, in the last three years, several clinical trials, mostly observational and retrospective, have addressed the question of whether the use of balanced solutions has beneficial effects as compared to the standard of care, sometimes even suggesting an improvement in survival. Nonetheless, the first large randomized controlled trial comparing the effects of a balanced vs. unbalanced solution on renal function in critically-ill patients (SPLIT trial, the 0.9% Saline vs Plasma-Lyte 148 for Intensive Cate Unit Fluid Therapy), just recently published, showed identical equipoise between the two treatments. In the present review, we offer a comprehensive and updated summary on this issue, firstly, by providing a full physiological background of balanced solutions, secondly, by summarizing their potential pathophysiologic effects, and lastly, by presenting the clinical evidence available to support, at the moment, their use. PMID:26588483

  5. Introducing Advanced Clinical Reasoning to an Adult Learning Disability Service

    ERIC Educational Resources Information Center

    Stansfield, Jois; Matthews, Alison

    2014-01-01

    The advanced clinical reasoning approach is widely adopted in speech and language therapy practice. This article reports on the introduction of the approach across a multidisciplinary adult learning disability service and staff reports on the impact of this initiative. Staff and team managers reported that the training had a positive impact on…

  6. Advancing your career in clinical engineering or biomedical technology.

    PubMed

    Brush, L C

    1991-01-01

    Career advancement options available to the aspiring biomedical technician, clinical engineer or supervisor are described. "Paths" to professional development include: obtaining additional education, getting certified, joining professional associations, finding a mentor, on-the-job training and improving working style. Suggestions are offered on how to start this process in one's own career. PMID:10115432

  7. Recent advances in dengue pathogenesis and clinical management.

    PubMed

    Simmons, Cameron P; McPherson, Kirsty; Van Vinh Chau, Nguyen; Hoai Tam, D T; Young, Paul; Mackenzie, Jason; Wills, Bridget

    2015-12-10

    This review describes and commentates on recent advances in the understanding of dengue pathogenesis and immunity, plus clinical research on vaccines and therapeutics. We expand specifically on the role of the dermis in dengue virus infection, the contribution of cellular and humoral immune responses to pathogenesis and immunity, NS1 and mechanisms of virus immune evasion. Additionally we review a series of therapeutic intervention trials for dengue, as well as recent clinical research aimed at improving clinical diagnosis, risk prediction and disease classification. PMID:26458808

  8. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  9. Wireless Sensor Network for Advanced Energy Management Solutions

    SciTech Connect

    Peter J. Theisen; Bin Lu, Charles J. Luebke

    2009-09-23

    Eaton has developed an advanced energy management solution that has been deployed to several Industries of the Future (IoF) sites. This demonstrated energy savings and reduced unscheduled downtime through an improved means for performing predictive diagnostics and energy efficiency estimation. Eaton has developed a suite of online, continuous, and inferential algorithms that utilize motor current signature analysis (MCSA) and motor power signature analysis (MPSA) techniques to detect and predict the health condition and energy usage condition of motors and their connect loads. Eaton has also developed a hardware and software platform that provided a means to develop and test these advanced algorithms in the field. Results from lab validation and field trials have demonstrated that the developed advanced algorithms are able to detect motor and load inefficiency and performance degradation. Eaton investigated the performance of Wireless Sensor Networks (WSN) within various industrial facilities to understand concerns about topology and environmental conditions that have precluded broad adoption by the industry to date. A Wireless Link Assessment System (WLAS), was used to validate wireless performance under a variety of conditions. Results demonstrated that wireless networks can provide adequate performance in most facilities when properly specified and deployed. Customers from various IoF expressed interest in applying wireless more broadly for selected applications, but continue to prefer utilizing existing, wired field bus networks for most sensor based applications that will tie into their existing Computerized Motor Maintenance Systems (CMMS). As a result, wireless technology was de-emphasized within the project, and a greater focus placed on energy efficiency/predictive diagnostics. Commercially available wireless networks were only utilized in field test sites to facilitate collection of motor wellness information, and no wireless sensor network products were

  10. Confocal microscopy of skin cancers: Translational advances toward clinical utility

    PubMed Central

    Rajadhyaksha, Milind

    2014-01-01

    Recent advances in translational research in and technology for confocal microscopy of skin cancers, toward clinical applications, are described. Advances in translational research are in diagnosis of melanoma in vivo, pre-operative mapping of lentigo maligna melanoma margins to guide surgery and intra-operative imaging of residual basal cell carcinomas to guide shave-biopsy. Advances in technology include mosaicing microscopy for detection of basal cell carcinomas in large areas of excised tissue, toward rapid pathology-at-the-bedside, and development of small, simple and low-cost line-scanning confocal microscopes for worldwide use in diverse primary healthcare settings. Current limitations and future opportunities and challenges for both clinicians and technologists are discussed. PMID:19964286

  11. Clinical utility of ramucirumab in advanced gastric cancer.

    PubMed

    Chan, Matthew Mk; Sjoquist, Katrin M; Zalcberg, John R

    2015-01-01

    Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF) pathway including anti-VEGF antibody therapy (eg, bevacizumab), inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib), and inhibitors of vascular endothelial growth factor receptors (VEGFRs) (eg, ramucirumab). Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer.

  12. Technological advances in perioperative monitoring: Current concepts and clinical perspectives.

    PubMed

    Chilkoti, Geetanjali; Wadhwa, Rachna; Saxena, Ashok Kumar

    2015-01-01

    Minimal mandatory monitoring in the perioperative period recommended by Association of Anesthetists of Great Britain and Ireland and American Society of Anesthesiologists are universally acknowledged and has become an integral part of the anesthesia practice. The technologies in perioperative monitoring have advanced, and the availability and clinical applications have multiplied exponentially. Newer monitoring techniques include depth of anesthesia monitoring, goal-directed fluid therapy, transesophageal echocardiography, advanced neurological monitoring, improved alarm system and technological advancement in objective pain assessment. Various factors that need to be considered with the use of improved monitoring techniques are their validation data, patient outcome, safety profile, cost-effectiveness, awareness of the possible adverse events, knowledge of technical principle and ability of the convenient routine handling. In this review, we will discuss the new monitoring techniques in anesthesia, their advantages, deficiencies, limitations, their comparison to the conventional methods and their effect on patient outcome, if any.

  13. Rewards and advancements for clinical pharmacy practitioners. American College of Clinical Pharmacy.

    PubMed

    1995-01-01

    It is important to recognize that pharmacy practice models are changing quickly. Although the concepts of pharmaceutical care depict all pharmacists as clinical practitioners, there are still significant opportunities for individuals to develop advanced and refined skills and knowledge, and to seek recognition. Criteria for professional advancement need to be reevaluated and modified periodically. As departments become more effective in implementing pharmaceutical care, and practice skills advance, criteria for advancement must be updated. Recognition and advancement within newer models of practice such as patient focus units, clinical path teams, and quality improvement teams complicate assessment and evaluation strategies. In the future, pharmacy managers will need to look at reward and advancement systems that incorporate the recommendations of the team manager or members for these newer models of practice. Perhaps there will be a shift in responsibility for recognition to the team manager. Career ladders may need to provide for new roles, and reward practitioners for behaviors not currently represented in most departmental performance evaluations. Performance evaluation, standards of practice, and advancement criteria will need to be carefully reviewed and integrated with the patient focus team's objectives, structure, and processes to assure that appropriate recognition is given to pharmacists in this exciting new environment. Career ladders provide one form of reward and advancement for practitioners. Institutions can include many elements of career ladder process, function, and structure, as well as implement many other management tools for reward and recognition, without implementing a complete career ladder.

  14. Mentoring for retention and advancement in the multigenerational clinical laboratory.

    PubMed

    Laudicina, R J

    2001-01-01

    Retention of recent graduates and other laboratory practitioners in the workplace will play a key role in addressing current and projected shortages of clinical laboratory scientists (CLS) and technicians (CLT). In addition, with overrepresentation of the aging Baby Boomer generation in laboratory supervisory and management positions, it is crucial not only to retain younger practitioners, but to prepare them for assuming these important functions in the future. Mentoring, a practice commonly employed in other professions, is widely considered to be useful in employee retention and career advancement. Mentoring has probably been used in the clinical laboratory profession, but has not been well documented. In the clinical laboratory environment, potential mentors are in the Veteran and Baby Boomer generations, and new practitioners who could benefit from mentoring are in Generation X. Generational differences among these groups may present challenges to the use of mentoring. This article will attempt to provide a better understanding of generational differences and show how mentoring can be applied in the setting of the clinical laboratory in order to increase retention and promote career advancement of younger practitioners. A panel of five laboratory managers provided examples of mentoring strategies. Definitions, benefits, and examples of mentoring are addressed in the accompanying article, "Passing the Torch: Mentoring the Next Generation of Laboratory Professionals". PMID:15633495

  15. Mentoring for retention and advancement in the multigenerational clinical laboratory.

    PubMed

    Laudicina, R J

    2001-01-01

    Retention of recent graduates and other laboratory practitioners in the workplace will play a key role in addressing current and projected shortages of clinical laboratory scientists (CLS) and technicians (CLT). In addition, with overrepresentation of the aging Baby Boomer generation in laboratory supervisory and management positions, it is crucial not only to retain younger practitioners, but to prepare them for assuming these important functions in the future. Mentoring, a practice commonly employed in other professions, is widely considered to be useful in employee retention and career advancement. Mentoring has probably been used in the clinical laboratory profession, but has not been well documented. In the clinical laboratory environment, potential mentors are in the Veteran and Baby Boomer generations, and new practitioners who could benefit from mentoring are in Generation X. Generational differences among these groups may present challenges to the use of mentoring. This article will attempt to provide a better understanding of generational differences and show how mentoring can be applied in the setting of the clinical laboratory in order to increase retention and promote career advancement of younger practitioners. A panel of five laboratory managers provided examples of mentoring strategies. Definitions, benefits, and examples of mentoring are addressed in the accompanying article, "Passing the Torch: Mentoring the Next Generation of Laboratory Professionals".

  16. CRC Clinical Trials Management System (CTMS): An Integrated Information Management Solution for Collaborative Clinical Research

    PubMed Central

    Payne, Philip R.O.; Greaves, Andrew W.; Kipps, Thomas J.

    2003-01-01

    The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. To enable the CRC’s clinical research efforts, a system providing for real-time collaboration was required. CTMS provides such functionality, and demonstrates that the use of novel data modeling, web-application platforms, and management strategies provides for the deployment of an extensible, cost effective solution in such an environment. PMID:14728471

  17. Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research Past ... very emotional." Should You Be Interested in a Clinical Trial People volunteer to take part in clinical trials ...

  18. Coronary Stents: The Impact of Technological Advances on Clinical Outcomes.

    PubMed

    Mennuni, Marco G; Pagnotta, Paolo A; Stefanini, Giulio G

    2016-02-01

    Percutaneous coronary interventions (PCI) were proposed in the late 1970s as an alternative to surgical coronary artery bypass grafting for the treatment of coronary artery disease. Important technological progress has been made since. Balloon angioplasty was replaced by bare metal stents, which allowed to permanently scaffold the coronary vessel avoiding acute recoil and abrupt occlusion. Thereafter, the introduction of early generation drug-eluting stents (DES) has significantly improved clinical outcomes, primarily by markedly reducing the risk of restenosis. New generation DES with thinner stent struts, novel durable or biodegradable polymer coatings, and new limus antiproliferative agents, have further improved upon the safety and efficacy profile of early generation DES. The present article aims to review the impact of technological advances on clinical outcomes in the field of PCI with coronary stents, and to provide a brief overview on clinical margins of improvement and unmet needs of available DES.

  19. Advanced Methods for the Solution of Differential Equations.

    ERIC Educational Resources Information Center

    Goldstein, Marvin E.; Braun, Willis H.

    This is a textbook, originally developed for scientists and engineers, which stresses the actual solutions of practical problems. Theorems are precisely stated, but the proofs are generally omitted. Sample contents include first-order equations, equations in the complex plane, irregular singular points, and numerical methods. A more recent idea,…

  20. Clinical utility of 3% diquafosol ophthalmic solution in the treatment of dry eyes

    PubMed Central

    Koh, Shizuka

    2015-01-01

    Diquafosol is a drug used for dry eye treatment with a novel mechanism of action. It stimulates the secretion of tear fluid and mucin on the ocular surface, thus enabling us to selectively treat the tear film layer, playing an important role in the establishment of the concept of “Tear Film Oriented Therapy (TFOT)”, an effective therapeutic approach to dry eye in Japan. The 3% diquafosol ophthalmic solution has been widely used for the treatment of dry eye in clinical practice, and it is currently available in Japan and South Korea. This review provides an overview of the clinical utility of 3% diquafosol ophthalmic solution, focusing on the results of clinical studies on various types of dry eye, including aqueous-deficient dry eye, short tear film breakup time-type dry eye, and post dry eye after laser in situ keratomileusis. It also introduces the additive effect of diquafosol on sodium hyaluronate monotherapy for dry eye, and the effect of 3% diquafosol ophthalmic solution for dry eye-related conditions. Additionally, it summarizes the ocular effects of diquafosol in healthy human eyes. Lastly, the importance of improving tear film stability in dry eye treatment, as well as general advances in dry eye treatments, are described. PMID:26028958

  1. Recent developments in choledochoscopy: technical and clinical advances

    PubMed Central

    Xu, Ming-Ming; Kahaleh, Michel

    2016-01-01

    Peroral cholangioscopy has become an important tool in the diagnosis and treatment of a variety of biliary diseases, ranging from indeterminate biliary strictures to bile duct stones. Although the first cholangioscopy was performed in the 1970s, recent technological advances have provided us with cholangioscopes that yield high-resolution images, possess single-operator capability, and have ultrathin design to allow easier maneuverability and detailed imaging of the biliary tract. We review here the currently available devices for peroral cholangioscopy, their clinical applications, limitations, and complications. PMID:27274300

  2. Clinical perspectives on lupus genetics: advances and opportunities.

    PubMed

    James, Judith A

    2014-08-01

    In recent years, genome-wide association studies have led to an expansion in the identification of regions containing confirmed genetic risk variants within complex human diseases, such as systemic lupus erythematosus (SLE). Many of the strongest SLE genetic associations can be divided into groups based on their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination, DNA degradation, innate immunity, cellular immunity, lymphocyte development, and antigen presentation. Recent advances have also shown several genetic associations with SLE subphenotypes and subcriteria. Many areas for further exploration remain to move lupus genetic studies toward clinically informative end points.

  3. Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies.

    PubMed

    Hu, Che-Ming J; Fang, Ronnie H; Luk, Brian T; Zhang, Liangfang

    2014-01-01

    Long-circulating polymeric nanotherapeutics have garnered increasing interest in research and in the clinic owing to their ability to improve the solubility and pharmacokinetics of therapeutic cargoes. Modulation of carrier properties promises more effective drug localization at the disease sites and can lead to enhanced drug safety and efficacy. In the present review, we highlight the current development of polymeric nanotherapeutics in the clinic. In light of the importance of stealth properties in therapeutic nanoparticles, we also review the advances in stealth functionalization strategies and examine the performance of different stealth polymers in the literature. In addition, we discuss the recent development of biologically inspired "self" nanoparticles, which present a differing stealth concept from conventional approaches.

  4. Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies

    NASA Astrophysics Data System (ADS)

    Hu, Che-Ming J.; Fang, Ronnie H.; Luk, Brian T.; Zhang, Liangfang

    2013-12-01

    Long-circulating polymeric nanotherapeutics have garnered increasing interest in research and in the clinic owing to their ability to improve the solubility and pharmacokinetics of therapeutic cargoes. Modulation of carrier properties promises more effective drug localization at the disease sites and can lead to enhanced drug safety and efficacy. In the present review, we highlight the current development of polymeric nanotherapeutics in the clinic. In light of the importance of stealth properties in therapeutic nanoparticles, we also review the advances in stealth functionalization strategies and examine the performance of different stealth polymers in the literature. In addition, we discuss the recent development of biologically inspired ``self'' nanoparticles, which present a differing stealth concept from conventional approaches.

  5. Implementing clinical governance in Isfahan hospitals: Barriers and solutions, 2014

    PubMed Central

    Ferdosi, Masoud; Ziyari, Farhad Bahman; Ollahi, Mehran Nemat; Salmani, Amaneh Rahim; Niknam, Noureddin

    2016-01-01

    Introduction: In the new approach, all health care providers have been obligated to maintain and improve the quality and have been accountable for it. One of the ways is the implementation of clinical governance (CG). More accurate understanding of its challenges can help to improve its performance. Aims: In this study, barriers of CG implementation are investigated from the perspective of the hospitals involved. Besides, some solutions are suggested based on stakeholders’ opinions. Materials and Methods: This study used combined method (qualitative content analysis and questionnaire) in hospitals affiliated to Isfahan University of Medical Sciences in 2014. First, experts, and stakeholders talked about CG implementation obstacles in a semi-structured interview. Interviews were confirmed by the interviewee (double check). After analyzing the interviews using reduction coding the questionnaire was drawn up. The questionnaire “validity was confirmed by Cronbach's alpha (0/891)” and its reliability was obtained using experts confirmation. Data analyzing was performed using SPSS (18) software. Results: According to results staffing and management factors were the main obstacles. After them, were factors related to organizational culture, infrastructure elements, information, sociocultural and then process factors. The learning barriers were in final rank. Thirty-four solutions was proposed by experts and divided into subset of eight major barriers. Most solutions were offered on modifying processes and minimal solutions about modifying of organizational culture, sociocultural, and educational factors. Conclusion: Removing the obstacles, especially management and human resource factors can be effective by facilitating and accelerating CG. Furthermore, use of experts and stakeholders opinions can help to remove CG barriers. PMID:27500173

  6. Methods and Applications for Advancing Distance Education Technologies: International Issues and Solutions

    ERIC Educational Resources Information Center

    Syed, Mahbubur Rahman, Ed.

    2009-01-01

    The emerging field of advanced distance education delivers academic courses across time and distance, allowing educators and students to participate in a convenient learning method. "Methods and Applications for Advancing Distance Education Technologies: International Issues and Solutions" demonstrates communication technologies, intelligent…

  7. The biology of infertility: research advances and clinical challenges

    PubMed Central

    Matzuk, Martin M; Lamb, Dolores J

    2013-01-01

    Reproduction is required for the survival of all mammalian species, and thousands of essential ‘sex’ genes are conserved through evolution. Basic research helps to define these genes and the mechanisms responsible for the development, function and regulation of the male and female reproductive systems. However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. For other individuals with a known etiology, effective cures are lacking, although their infertility is often bypassed with assisted reproductive technologies (ART), some accompanied by safety or ethical concerns. Certainly, progress in the field of reproduction has been realized in the twenty-first century with advances in the understanding of the regulation of fertility, with the production of over 400 mutant mouse models with a reproductive phenotype and with the promise of regenerative gonadal stem cells. Indeed, the past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility. Translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples. Additionally, new approaches to contraception remain elusive. Nevertheless, the basic and clinical advances in the understanding of the molecular controls of reproduction are impressive and will ultimately improve patient care. PMID:18989307

  8. Major clinical research advances in gynecologic cancer in 2014.

    PubMed

    Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

    2015-04-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

  9. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  10. [Advanced data analysis and visualization for clinical laboratory].

    PubMed

    Inada, Masanori; Yoneyama, Akiko

    2011-01-01

    This paper describes visualization techniques that help identify hidden structures in clinical laboratory data. The visualization of data is helpful for a rapid and better understanding of the characteristics of data sets. Various charts help the user identify trends in data. Scatter plots help prevent misinterpretations due to invalid data by identifying outliers. The representation of experimental data in figures is always useful for communicating results to others. Currently, flexible methods such as smoothing methods and latent structure analysis are available owing to the presence of advanced hardware and software. Principle component analysis, which is a well-known technique used to reduce multidimensional data sets, can be carried out on a personal computer. These methods could lead to advanced visualization with regard to exploratory data analysis. In this paper, we present 3 examples in order to introduce advanced data analysis. In the first example, a smoothing spline was fitted to a time-series from the control chart which is not in a state of statistical control. The trend line was clearly extracted from the daily measurements of the control samples. In the second example, principal component analysis was used to identify a new diagnostic indicator for Graves' disease. The multi-dimensional data obtained from patients were reduced to lower dimensions, and the principle components thus obtained summarized the variation in the data set. In the final example, a latent structure analysis for a Gaussian mixture model was used to draw complex density functions suitable for actual laboratory data. As a result, 5 clusters were extracted. The mixed density function of these clusters represented the data distribution graphically. The methods used in the above examples make the creation of complicated models for clinical laboratories more simple and flexible.

  11. Solution of a Two-Dimensional Diffusion Equation Using an Advanced Spreadsheet Program.

    ERIC Educational Resources Information Center

    Kharab, Abdelwahab

    1997-01-01

    Spreadsheet programs are used increasingly by engineering students to solve problems, especially problems requiring repetitive calculations, as they provide rapid and simple numerical solutions. This article shows how advanced spreadsheet programs are used in the learning of numerical solutions of two-dimensional diffusion equation using the…

  12. Engineering novel infrared glass ceramics for advanced optical solutions

    NASA Astrophysics Data System (ADS)

    Richardson, K.; Buff, A.; Smith, C.; Sisken, L.; Musgraves, J. David; Wachtel, P.; Mayer, T.; Swisher, A.; Pogrebnyakov, A.; Kang, M.; Pantano, C.; Werner, D.; Kirk, A.; Aiken, S.; Rivero-Baleine, C.

    2016-05-01

    Advanced photonic devices require novel optical materials that serve specified optical function but also possess attributes which can be tailored to accommodate specific optical design, manufacturing or component/device integration constraints. Multi-component chalcogenide glass (ChG) materials have been developed which exhibit broad spectral transparency with a range of physical properties that can be tuned to vary with composition, material microstructure and form. Specific tradeoffs that highlight the impact of material morphology and optical properties including transmission, loss and refractive index, are presented. This paper reports property evolution in a representative 20 GeSe2-60 As2Se3-20 PbSe glass material including a demonstration of a 1D GRIN profile through the use of controlled crystallization.

  13. Review: Coastal groundwater optimization—advances, challenges, and practical solutions

    NASA Astrophysics Data System (ADS)

    Ketabchi, Hamed; Ataie-Ashtiani, Behzad

    2015-09-01

    Decision models are essential tools for coastal groundwater management (CGM). A combined simulation-optimization framework is employed to develop these models. One of the main barriers in the widespread application of these models for real-world cases is their large computational burden. Recent advances in efficient computational approaches and robust optimization methods can crack this barrier. This study surveys the scientific basis of CGM to provide an overview on this subject and reviews the-state-of-the-art to clarify recent developments and to outline ideas for improving the computational performance. Key details are presented on the performance and choice of possible robust tools such as efficient evolutionary algorithms (EAs), surrogate models, and parallel processing techniques. Then, the potential challenges remaining in this context are scrutinized, demonstrating open fields for further research, which include issues related to advances in simulating and optimizing phases such as introducing new robust algorithms and considering multi-objective purposes, implementing novel and high-performance tools, considering global concerns (e.g. climate change impacts), enhancing the existing models to fit the real world, and taking into account the complexities of real-world applications (e.g. uncertainties in the modeling parameters, and data acquisition). Finally, the outcomes of the systematic review are applied to solve a real-world CGM problem in Iran, to quantitatively examine the performance of combined implementation of some of the suggested tools. It is revealed that the required computational time is considerably reduced by as much as three orders of magnitude when correct combinations of robust EAs, surrogate model, and parallelization technique are utilized.

  14. Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

    PubMed

    Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

    2016-11-01

    The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc.

  15. Advances in functional magnetic resonance imaging: technology and clinical applications.

    PubMed

    Dickerson, Bradford C

    2007-07-01

    Functional MRI (fMRI) is a valuable method for use by clinical investigators to study task-related brain activation in patients with neurological or neuropsychiatric illness. Despite the relative infancy of the field, the rapid adoption of this functional neuroimaging technology has resulted from, among other factors, its ready availability, its relatively high spatial and temporal resolution, and its safety as a noninvasive imaging tool that enables multiple repeated scans over the course of a longitudinal study, and thus may lend itself well as a measure in clinical drug trials. Investigators have used fMRI to identify abnormal functional brain activity during task performance in a variety of patient populations, including those with neurodegenerative, demyelinating, cerebrovascular, and other neurological disorders that highlight the potential utility of fMRI in both basic and clinical spheres of research. In addition, fMRI studies reveal processes related to neuroplasticity, including compensatory hyperactivation, which may be a universally-occurring, adaptive neural response to insult. Functional MRI is being used to study the modulatory effects of genetic risk factors for neurological disease on brain activation; it is being applied to differential diagnosis, as a predictive biomarker of disease course, and as a means to identify neural correlates of neurotherapeutic interventions. Technological advances are rapidly occurring that should provide new applications for fMRI, including improved spatial resolution, which promises to reveal novel insights into the function of fine-scale neural circuitry of the human brain in health and disease.

  16. Advanced titania buffer layer architectures prepared by chemical solution deposition

    NASA Astrophysics Data System (ADS)

    Kunert, J.; Bäcker, M.; Brunkahl, O.; Wesolowski, D.; Edney, C.; Clem, P.; Thomas, N.; Liersch, A.

    2011-08-01

    Chemical solution deposition (CSD) was used to grow high-quality (100) oriented films of SrTiO3 (STO) on CSD CaTiO3 (CTO), Ba0.1Ca0.9TiO3 (BCT) and STO seed and template layers. These template films bridge the lattice misfit between STO and the nickel-tungsten (NiW) substrate, assisting in dense growth of textured STO. Additional niobium (Nb) doping of the STO buffer layer reduces oxygen diffusion which is necessary to avoid undesired oxidation of the NiW. The investigated templates offer suitable alternatives to established standard buffer systems like La2Zr2O7 (LZO) and CeO2 for coated conductors.

  17. Climate Solutions based on advanced scientific discoveries of Allatra physics

    NASA Astrophysics Data System (ADS)

    Vershigora, Valery

    2016-05-01

    Global climate change is one of the most important international problems of the 21st century. The overall rapid increase in the dynamics of cataclysms, which have been observed in recent decades, is particularly alarming. Howdo modern scientists predict the occurrence of certain events? In meteorology, unusually powerful cumulonimbus clouds are one of the main conditions for the emergence of a tornado. The former, in their turn, are formed during the invasion of cold air on the overheated land surface. The satellite captures the cloud front, and, based on these pictures, scientists make assumptions about the possibility of occurrence of the respective natural phenomena. In fact, mankind visually observes and draws conclusions about the consequences of the physical phenomena which have already taken place in the invisible world, so the conclusions of scientists are assumptions by their nature, rather than precise knowledge of the causes of theorigin of these phenomena in the physics of microcosm. The latest research in the field of the particle physics and neutrino astrophysics, which was conducted by a working team of scientists of ALLATRA International Public Movement (hereinafter ALLATRA SCIENCE group) allatra-science.org, last accessed 10 April 2016. , offers increased opportunities for advanced fundamental and applied research in climatic engineering.

  18. Advanced techniques in reliability model representation and solution

    NASA Technical Reports Server (NTRS)

    Palumbo, Daniel L.; Nicol, David M.

    1992-01-01

    The current tendency of flight control system designs is towards increased integration of applications and increased distribution of computational elements. The reliability analysis of such systems is difficult because subsystem interactions are increasingly interdependent. Researchers at NASA Langley Research Center have been working for several years to extend the capability of Markov modeling techniques to address these problems. This effort has been focused in the areas of increased model abstraction and increased computational capability. The reliability model generator (RMG) is a software tool that uses as input a graphical object-oriented block diagram of the system. RMG uses a failure-effects algorithm to produce the reliability model from the graphical description. The ASSURE software tool is a parallel processing program that uses the semi-Markov unreliability range evaluator (SURE) solution technique and the abstract semi-Markov specification interface to the SURE tool (ASSIST) modeling language. A failure modes-effects simulation is used by ASSURE. These tools were used to analyze a significant portion of a complex flight control system. The successful combination of the power of graphical representation, automated model generation, and parallel computation leads to the conclusion that distributed fault-tolerant system architectures can now be analyzed.

  19. Troll oil pipeline: Advanced landfall solution at Mongstad

    SciTech Connect

    Sintini, G.L.; Bernardi, M.; Doerheim, M.K.; Kjosavik, J.K.

    1996-12-01

    The landfall of the 16-in. Troll Oil Pipeline is achieved by means of a 30-in. cased borehole routed through hard metamorphic rock using up-to-date technology for drilling, down hole directional control and path survey. The borehole, which extends over a total length of 760 m, starts in a clear area inside the Mongstad Refinery and pierces in the lowermost part of Fensfjord`s southern steep sided cliff at 314 m water depth. The deep waters at th4e offshore end required completely diverless operations. Pipeline installation inside the borehole was carried out as part of the pipelay start-up with the aid of an onshore located pull-in winch. Main topics faced during the design and the adopted technical solutions are presented, notably: borehole route and size; borehole approach route and intervention works, corrosion protection system; and auxiliary devices such as the bellmouth at the offshore end and the anchor block at the onshore end. Experience feedback from construction activities is discussed focusing on technology performance, contingencies and remedial actions.

  20. Clinical relevance of advanced glycation endproducts for vascular surgery.

    PubMed

    Meerwaldt, R; van der Vaart, M G; van Dam, G M; Tio, R A; Hillebrands, J-L; Smit, A J; Zeebregts, C J

    2008-08-01

    Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery. PMID:18356091

  1. [Anticoagulant therapy clinic: moving towards Advanced Nursing Practice].

    PubMed

    Romero Ruiz, Adolfo; Parrado Borrego, Gema; Rodríguez González, José; Caparrós Miranda, Isabel S; Vargas Lirio, M Isabel; Ortiz Fernández, Primitiva

    2014-01-01

    There is currently around one million people receiving oral anticoagulants in Spain. The drug most used is acenocoumarol, which requires coagulation monitoring to ensure that the patient is within its normal therapeutic range. Patients usually start this treatment in a hospital clinic and, when they are stabilised, they are referred to primary care, where they are followed-up by their community nurses. The usual practice is that nurses are responsible for changes in the dose when the patients are outside the range. This practice is not performed by hospital nurses, despite having sufficient experience and knowledge to adequately manage these types of patients. An Advanced Nursing Practice model has been introduced into the Haematology management unit of the Hospital Universitario Virgen de la Victoria, Málaga. This involves various aspects of attention and care of patients on anticoagulant therapy, and includes adjusting the doses of their treatment following a catalogue of therapeutic and diagnostic ranges.

  2. Clinical relevance of advanced glycation endproducts for vascular surgery.

    PubMed

    Meerwaldt, R; van der Vaart, M G; van Dam, G M; Tio, R A; Hillebrands, J-L; Smit, A J; Zeebregts, C J

    2008-08-01

    Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery.

  3. Radiotherapy for lung cancer: clinical impact of recent technical advances.

    PubMed

    Haasbeek, Cornelis J A; Slotman, Ben J; Senan, Suresh

    2009-04-01

    Radiation oncology plays an important role in the curative treatment of patients with lung cancer. New technological developments have enabled delivery of higher radiation doses while better sparing surrounding normal tissues, thereby increasing the likelihood of local control without increased toxicity. Multi-modality imaging enables better target definition, improved planning software allows for correct calculation of delivered doses, and tools to verify accurate treatment delivery are now available. A good example of the results of applying these developments is the high local control rates achieved in stage I NSCLC with stereotactic radiotherapy (SRT). These advances are rapidly becoming available outside academic institutions, and pulmonologists, surgeons and medical oncologists need to understand and critically assess the potential impact of such developments in the routine care of their patients. Aspects of cost-effectiveness of technical innovations, as well as the level of evidence required before widespread clinical implementation, will be addressed.

  4. Major clinical research advances in gynecologic cancer in 2014.

    PubMed

    Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

    2015-04-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review. PMID:25872896

  5. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T.

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behavior and most important, in their response to certain anti-tumor treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume. PMID:23582916

  6. Mineralization of paracetamol in aqueous solution with advanced oxidation processes.

    PubMed

    Torun, Murat; Gültekin, Özge; Şolpan, Dilek; Güven, Olgun

    2015-01-01

    Paracetamol is a common analgesic drug widely used in all regions of the world more than hundred tonnes per year and it poses a great problem for the aquatic environment. Its phenolic intermediates are classified as persistent organic pollutants and toxic for the environment as well as human beings. In the present study, the irradiation of aqueous solutions of paracetamol with 60Co gamma-rays was examined on a laboratory scale and its degradation path was suggested with detected radiolysis products. The synergic effect of ozone on gamma-irradiation was investigated by preliminary ozonation before irradiation which reduced the irradiation dose from 5 to 3 kGy to completely remove paracetamol and its toxic intermediate hydroquinone from 6 to 4 kGy as well as increasing the radiation chemical yield (Gi values 1.36 and 1.66 in the absence and presence of ozone, respectively). The observed amount of formed hydroquinone was also decreased in the presence of ozone. There is a decrease in pH from 6.4 to 5.2 and dissolved oxygen consumed, which is up to 0.8 mg l(-1), to form some peroxyl radicals used for oxidation. Analytical measurements were carried out with gas chromatography/mass spectrometry and ion chromatography (IC) both qualitatively and quantitatively. Amounts of paracetamol and hydroquinone were measured with gas chromatography after trimethylsilane derivatization. Small aliphatic acids, such as acetic acid, formic acid and oxalic acid, were measured quantitatively with IC as well as inorganic ions (nitrite and nitrate) in which their yields increase with irradiation.

  7. Mineralization of paracetamol in aqueous solution with advanced oxidation processes.

    PubMed

    Torun, Murat; Gültekin, Özge; Şolpan, Dilek; Güven, Olgun

    2015-01-01

    Paracetamol is a common analgesic drug widely used in all regions of the world more than hundred tonnes per year and it poses a great problem for the aquatic environment. Its phenolic intermediates are classified as persistent organic pollutants and toxic for the environment as well as human beings. In the present study, the irradiation of aqueous solutions of paracetamol with 60Co gamma-rays was examined on a laboratory scale and its degradation path was suggested with detected radiolysis products. The synergic effect of ozone on gamma-irradiation was investigated by preliminary ozonation before irradiation which reduced the irradiation dose from 5 to 3 kGy to completely remove paracetamol and its toxic intermediate hydroquinone from 6 to 4 kGy as well as increasing the radiation chemical yield (Gi values 1.36 and 1.66 in the absence and presence of ozone, respectively). The observed amount of formed hydroquinone was also decreased in the presence of ozone. There is a decrease in pH from 6.4 to 5.2 and dissolved oxygen consumed, which is up to 0.8 mg l(-1), to form some peroxyl radicals used for oxidation. Analytical measurements were carried out with gas chromatography/mass spectrometry and ion chromatography (IC) both qualitatively and quantitatively. Amounts of paracetamol and hydroquinone were measured with gas chromatography after trimethylsilane derivatization. Small aliphatic acids, such as acetic acid, formic acid and oxalic acid, were measured quantitatively with IC as well as inorganic ions (nitrite and nitrate) in which their yields increase with irradiation. PMID:25263253

  8. Advances in process overlay: alignment solutions for future technology nodes

    NASA Astrophysics Data System (ADS)

    Megens, Henry; van Haren, Richard; Musa, Sami; Doytcheva, Maya; Lalbahadoersing, Sanjay; van Kemenade, Marc; Lee, Hyun-Woo; Hinnen, Paul; van Bilsen, Frank

    2007-03-01

    Semiconductor industry has an increasing demand for improvement of the total lithographic overlay performance. To improve the level of on-product overlay control the number of alignment measurements increases. Since more mask levels will be integrated, more alignment marks need to be printed when using direct-alignment (also called layer-to-layer alignment). Accordingly, the alignment mark size needs to become smaller, to fit all marks into the scribelane. For an in-direct alignment scheme, e.g. a scheme that aligns to another layer than the layer to which overlay is being measured, the number of needed alignment marks can be reduced. Simultaneously there is a requirement to reduce the size of alignment mark sub-segmentations without compromising the alignment and overlay performance. Smaller features within alignment marks can prevent processing issues like erosion, dishing and contamination. However, when the sub-segmentation size within an alignment mark becomes comparable to the critical dimension, and thus smaller than the alignment-illuminating wavelength, polarization effects might start to occur. Polarization effects are a challenge for optical alignment systems to maintain mark detectability. Nevertheless, this paper shows how to actually utilize those effects in order to obtain enhanced alignment and overlay performance to support future technology nodes. Finally, another challenge to be met for new semiconductor product technologies is the ability to align through semi-opaque materials, like for instance new hard-mask materials. Enhancement of alignment signal strength can be reached by adapting to new alignment marks that generate a higher alignment signal. This paper provides a description of an integral alignment solution that meets with these emerging customer application requirements. Complying with these requirements will significantly enhance the flexibility in production strategies while maintaining or improving the alignment and overlay

  9. Cancer stem cells and immunoresistance: clinical implications and solutions

    PubMed Central

    Rosell, Rafael

    2015-01-01

    Tumor cells can be contained, but not eliminated, by traditional cancer therapies. A cell minor subpopulation is able to evade attack from therapies and may have cancer stem cell (CSC) characteristics, including self-renewal, multiple differentiation and tumor initiation (tumor initiating cells, or TICs). Thus, CSCs/TICs, aided by the microenvironment, produce more differentiated, metastatic cancer cells which the immune system detects and interacts with. There are three phases to this process: elimination, equilibrium and escape. In the elimination phase the immune system recognizes and destroys most of the tumor cells. Then the latency phase begins, consisting of equilibrium between immunological elimination and tumor cell growth. Finally, a minor attack-resistant subpopulation escapes and forms a clinically detectable tumor mass. Herein we review current knowledge of immunological characterization of CSCs/TICs. Due to the correlation between CTCs/TICs and drug resistance and metastasis, we also comment on the crucial role of key molecules involved in controlling CSCs/TICs properties; such molecules are essential to detect and destroy CSCs/TICs. Monoclonal antibodies, antibody constructs and vaccines have been designed to act against CSCs/TICs, with demonstrated efficacy in human cancer xenografts and some antitumor activity in human clinical studies. Therefore, therapeutic strategies that selectively target CSCs/TICs warrant further investigation. Better understanding of the interaction between CSCs and tumor immunology may help to identify strategies to eradicate the minor subpopulation that escapes conventional therapy attack, thus providing a solution to the problem of drug resistance and metastasis. PMID:26798578

  10. Targeting ALK in neuroblastoma--preclinical and clinical advancements.

    PubMed

    Carpenter, Erica L; Mossé, Yael P

    2012-07-01

    Despite improvements in cancer therapies in the past 50 years, neuroblastoma remains a devastating clinical problem and a leading cause of childhood cancer deaths. Advances in treatments for children with high-risk neuroblastoma have, until recently, involved addition of cytotoxic therapy to dose-intensive regimens. In this era of targeted therapies, substantial efforts have been made to identify optimal targets for different types of cancer. The discovery of hereditary and somatic activating mutations in the oncogene ALK has now placed neuroblastoma among other cancers, such as melanoma and non-small-cell lung cancer (NSCLC), which benefit from therapies with oncogene-specific small-molecule tyrosine kinase inhibitors. Crizotinib, a small-molecule inhibitor of ALK, has transformed the landscape for the treatment of NSCLC harbouring ALK translocations and has demonstrated activity in preclinical models of ALK-driven neuroblastomas. However, inhibition of mutated ALK is complex when compared with translocated ALK and remains a therapeutic challenge. This Review discusses the biology of ALK in the development of neuroblastoma, preclinical and clinical progress with the use of ALK inhibitors and immunotherapy, challenges associated with resistance to such therapies and the steps being taken to overcome some of these hurdles.

  11. Artificial placenta: Recent advances and potential clinical applications.

    PubMed

    Metelo-Coimbra, Catarina; Roncon-Albuquerque, Roberto

    2016-06-01

    Lung immaturity remains a major cause of morbidity and mortality in extremely premature infants. Positive-pressure mechanical ventilation, the method of choice for respiratory support in premature infants, frequently promotes by itself lung injury and a negative impact in the circulatory function. Extracorporeal lung support has been proposed for more than 50 years as a potential alternative to mechanical ventilation in the treatment of severe respiratory failure of extremely premature infants. Recent advances in this field included the development of miniaturized centrifugal pumps and polymethylpentene oxygenators, as well as the successful use of pump-assisted veno-venous extracorporeal gas exchange systems in experimental artificial placenta models. This review, which includes studies published from 1958 to 2015, presents an update on the artificial placenta concept and its potential clinical applications. Special focus will be devoted to the milestones achieved so far and to the limitations that must be overcome before its clinical application. Notwithstanding, the artificial placenta stands as a promising alternative to mechanical ventilation in extremely premature infants. Pediatr Pulmonol. 2016;51:643-649. © 2016 Wiley Periodicals, Inc.

  12. Breast cancer stem cells: current advances and clinical implications.

    PubMed

    Luo, Ming; Clouthier, Shawn G; Deol, Yadwinder; Liu, Suling; Nagrath, Sunitha; Azizi, Ebrahim; Wicha, Max S

    2015-01-01

    There is substantial evidence that many cancers, including breast cancer, are driven by a population of cells that display stem cell properties. These cells, termed cancer stem cells (CSCs) or tumor initiating cells, not only drive tumor initiation and growth but also mediate tumor metastasis and therapeutic resistance. In this chapter, we summarize current advances in CSC research with a major focus on breast CSCs (BCSCs). We review the prevailing methods to isolate and characterize BCSCs and recent evidence documenting their cellular origins and phenotypic plasticity that enables them to transition between mesenchymal and epithelial-like states. We describe in vitro and clinical evidence that these cells mediate metastasis and treatment resistance in breast cancer, the development of novel strategies to isolate circulating tumor cells (CTCs) that contain CSCs and the use of patient-derived xenograft (PDX) models in preclinical breast cancer research. Lastly, we highlight several signaling pathways that regulate BCSC self-renewal and describe clinical implications of targeting these cells for breast cancer treatment. The development of strategies to effectively target BCSCs has the potential to significantly improve the outcomes for patients with breast cancer.

  13. [Clinical studies and accepted therapies of advanced melanoma].

    PubMed

    Liszkay, Gabriella

    2016-03-01

    The objective of the work is presentation of the available therapeutic results of the clinical trials with anti CTLA-4 and anti PD-1 treatment, which are operating on the immune checkpoints registered in advanced melanoma, and the results of T-VEC vaccination (NCT00094653, NCT00324155, KEYNOTE-001, -002, -006, CheckMate-066, -037, -067, NCT00769704). With ipilimumab therapy, long-term survival can be achieved in the case of 20% of patients, with low (10%) therapeutic response, and grade 3-4 treatment related, predominantly autoimmune adverse events occurring in 10-15% of patients. Anti-PD-1 therapy proved more effective compared to ipilimumab, resulting in 21-40% therapeutic response, with 60-74% one-year survival rate and significantly less severe and frequent side effects. Progression-free survival achieved with ipilimumab/nivolumab combination was 11.5 months with grade 3-4 side effects occurring in 55% of patients. T-VEC therapy resulted in 26.4% objective response rate without a significant survival advantage. In the possession of the new immunotherapeutic possibilities, knowledge of the results of clinical studies is essential for the optimal complex therapy of melanoma. PMID:26934345

  14. Recent technological advances in computed tomography and the clinical impact therein.

    PubMed

    Runge, Val M; Marquez, Herman; Andreisek, Gustav; Valavanis, Anton; Alkadhi, Hatem

    2015-02-01

    Current technological advances in CT, specifically those with a major impact on clinical imaging, are discussed. The intent was to provide for both medical physicists and practicing radiologists a summary of the clinical impact of each advance, offering guidance in terms of utility and day-to-day clinical implementation, with specific attention to radiation dose reduction.

  15. Risk of discontinuation of Advanced Therapy Medicinal Products clinical trials

    PubMed Central

    Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Objective Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. Methods We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Results Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. Conclusion No failure risk rate per development phase is available for ATMPs. The discontinuation rate may

  16. Clinical implications of hepatitis B virus mutations: Recent advances

    PubMed Central

    Lazarevic, Ivana

    2014-01-01

    Hepatitis B virus (HBV) infection is a major cause of acute and chronic hepatitis, and of its long-term complications. It is the most variable among DNA viruses, mostly because of its unique life cycle which includes the activity of error-prone enzyme, reverse transcriptase, and the very high virion production per day. In last two decades, numerous research studies have shown that the speed of disease progression, reliability of diagnostic methods and the success of antiviral therapy and immunization are all influenced by genetic variability of this virus. It was shown that mutations in specific regions of HBV genome could be responsible for unwanted clinical outcomes or evasion of detection by diagnostic tools, thus making the monitoring for these mutations a necessity in proper evaluation of patients. The success of the vaccination programs has now been challenged by the discovery of mutant viruses showing amino acid substitutions in hepatitis B surface antigen (HBsAg), which may lead to evasion of vaccine-induced immunity. However, the emergence of these mutations has not yet raised concern since it was shown that they develop slowly. Investigations of HBV genetic variability and clinical implications of specific mutations have resulted in significant advances over the past decade, particularly in regard to management of resistance to antiviral drugs. In the era of drugs with high genetic barrier for resistance, on-going monitoring for possible resistance is still essential since prolonged therapy is often necessary. Understanding the frequencies and clinical implications of viral mutations may contribute to improvement of diagnostic procedures, more proper planning of immunization programs and creating the most efficient therapeutic protocols. PMID:24976703

  17. Clinical registered dietitians, employers, and educators are interested in advanced practice education and professional doctorate degrees in clinical nutrition.

    PubMed

    Skipper, Annalynn; Lewis, Nancy M

    2006-12-01

    A subset of registered dietitians (RDs) is known to practice at an advanced level, but a clear educational pathway supporting advanced medical nutrition therapy practice has not been identified. Thus, an electronic survey was designed to investigate interest of clinical RDs, employers, and educators in advanced practice competencies and professional doctorate degree programs in clinical nutrition. Usable responses were obtained from 440 of 978 (45%) RDs, 61 of 107 (57%) employers, and 76 of 114 (67%) educators. Mean interest (5 = very interested, 1 = very uninterested) in obtaining advanced practice education was highest among RDs (3.93+/-1.01) and was significantly different (P < 0.01) from employers (3.74 +/-1.28) and educators (2.76+/-1.33). Interest in completing a professional doctorate in clinical nutrition was significantly (P < 0.01) different among RDs (3.05+/-1.28), employers (3.18+/-1.30), and educators (2.3+/-1.34). Employers' mean interest score for hiring RDs with a professional doctorate in clinical nutrition was 4.02+/-0.93. A subset of clinical RDs appears to be interested in obtaining advanced practice competency and enrolling in professional doctorate degrees in clinical nutrition. Clinical nutrition managers in academic medical centers may be interested in hiring advanced practice clinical RDs with professional doctorate degrees. Opportunities exist for educators to develop advanced practice educational experiences and professional doctorate degree programs.

  18. Advancing Porous Silicon Biosensor Technology for Use in Clinical Diagnostics

    NASA Astrophysics Data System (ADS)

    Bonanno, Lisa Marie

    Inexpensive and robust analytical techniques for detecting molecular recognition events are in great demand in healthcare, food safety, and environmental monitoring. Despite vast research in this area, challanges remain to develop practical biomolecular platforms that, meet the rigorous demands of real-world applications. This includes maintaining low-cost devices that are sensitive and specific in complex test specimens, are stable after storage, have short assay time, and possess minimal complexity of instrumentation for readout. Nanostructured porous silicon (PSi) material has been identified as an ideal candidate towards achieving these goals and the past decade has seen diverse proof-of-principle studies developing optical-based sensing techniques. In Part 1 of this thesis, the impact of surface chemistry and PSi morphology on detection sensitivity of target molecules is investigated. Initial proof-of-concept that PSi devices facilitate detection of protein in whole blood is demonstrated. This work highlights the importance of material stability and blocking chemistry for sensor use in real world biological samples. In addition, the intrinisic filtering capability of the 3-D PSi morphology is shown as an advantage in complex solutions, such as whole blood. Ultimately, this initial work identified a need to improve detection sensitivity of the PSI biosensor technique to facilitate clinical diagnostic use over relevant target concentration ranges. The second part of this thesis, builds upon sensitivity challenges that are highlighted in the first part of the thesis and development of a surface-bound competitive inhibition immunoassay facilitated improved detection sensitivity of small molecular weight targets (opiates) over a relevant clinical concentration range. In addition, optimization of assay protocol addressed issues of maintaining stability of sensors after storage. Performance of the developed assay (specificity and sensitivity) was then validated in a

  19. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

    Cancer.gov

    Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

  20. Hairy cell leukemia: clinical features and therapeutic advances.

    PubMed

    Lembersky, B C; Golomb, H M

    1987-01-01

    Hairy cell leukemia (HCL) is a rare chronic lymphoproliferative disorder which has been extensively studied over the past decade. Much has been learned regarding the diagnosis, natural history, biology, and treatment of this unique neoplasm. The disease most commonly affects middle aged men and characteristic clinical features include splenomegaly, cytopenias, and usually the presence in the peripheral blood of distinctive 'hairy cells' with irregular cytoplasmic projections. Diagnosis can usually be confirmed by bone marrow biopsy. Although the natural history can be extremely variable among patients, complications are usually referable to the cytopenias, with anemia and infection being most frequent. In addition to pyogenic infections, patients are susceptible to unusual organisms including atypical mycobacterium, legionella, and fungi. The requirement of red blood cell transfusion, severe granulocytopenia or thrombocytopenia, frequent infections, or painful splenomegaly are all indications for treatment. Splenectomy is the standard initial treatment of choice. However, in the past few years there have been exciting major advances in the therapeutic modalities for HCL. Recombinant alpha-interferon is highly effective, with beneficial responses occurring in close to 90% of patients. The Food and Drug Administration has recently approved the use of interferon for HCL. This represents the first time a biological response modifier has been approved for the treatment of human disease. In addition, preliminary results with the adenosine deaminase inhibitor, 2'deoxycoformycin (dcf), have been encouraging. Further clinical trials are required in order to determine the optimal sequential treatment strategy for HCL. The exact mechanisms of action of both interferon and dcf in HCL remain to be elucidated. A better understanding of the unusual features of the hairy cell and the underlying biological effect of these two agents in HCL may have important applications in other

  1. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group.

    PubMed Central

    1991-01-01

    OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients. PMID:1834291

  2. Advances, practice, and clinical perspectives in high-throughput sequencing.

    PubMed

    Park, S-J; Saito-Adachi, M; Komiyama, Y; Nakai, K

    2016-07-01

    Remarkable advances in high-throughput sequencing technologies have fundamentally changed our understanding of the genetic and epigenetic molecular bases underlying human health and diseases. As these technologies continue to revolutionize molecular biology leading to fresh perspectives, it is imperative to thoroughly consider the enormous excitement surrounding the technologies by highlighting the characteristics of platforms and their global trends as well as potential benefits and limitations. To date, with a variety of platforms, the technologies provide an impressive range of applications, including sequencing of whole genomes and transcriptomes, identifying of genome modifications, and profiling of protein interactions. Because these applications produce a flood of data, simultaneous development of bioinformatics tools is required to efficiently deal with the big data and to comprehensively analyze them. This review covers the major achievements and performances of the high-throughput sequencing and further summarizes the characteristics of their applications along with introducing applicable bioinformatics tools. Moreover, a step-by-step procedure for a practical transcriptome analysis is described employing an analytical pipeline. Clinical perspectives with special consideration to human oral health and diseases are also covered. PMID:26602181

  3. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  4. Bioinformatics Methods and Tools to Advance Clinical Care

    PubMed Central

    Lecroq, T.

    2015-01-01

    Summary Objectives To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care. Method We provide a synopsis of the articles selected for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,594 articles and the evaluation results were merged for retaining 15 articles for peer-review. Results The selection and evaluation process of this Yearbook’s section on Bioinformatics and Translational Informatics yielded four excellent articles regarding data management and genome medicine that are mainly tool-based papers. In the first article, the authors present PPISURV a tool for uncovering the role of specific genes in cancer survival outcome. The second article describes the classifier PredictSNP which combines six performing tools for predicting disease-related mutations. In the third article, by presenting a high-coverage map of the human proteome using high resolution mass spectrometry, the authors highlight the need for using mass spectrometry to complement genome annotation. The fourth article is also related to patient survival and decision support. The authors present datamining methods of large-scale datasets of past transplants. The objective is to identify chances of survival. Conclusions The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care. Indeed, there is a need for powerful tools for managing and interpreting complex, large-scale genomic and biological datasets, but also a need for user-friendly tools developed for the clinicians in their

  5. Advances in endodontics: Potential applications in clinical practice

    PubMed Central

    Kishen, Anil; Peters, Ove A.; Zehnder, Matthias; Diogenes, Anibal R.; Nair, Madhu K.

    2016-01-01

    Contemporary endodontics has seen an unprecedented advance in technology and materials. This article aimed to review some of the challenges and advances in the following sections: (1) endodontic imaging, (2) root canal preparation, (3) root canal disinfection, (4) root canal filling, and (4) regenerative endodontic procedures (REPs). Jointly, these advances are aimed at improving the state of the art and science of root canal treatment. PMID:27217630

  6. Advances in endodontics: Potential applications in clinical practice.

    PubMed

    Kishen, Anil; Peters, Ove A; Zehnder, Matthias; Diogenes, Anibal R; Nair, Madhu K

    2016-01-01

    Contemporary endodontics has seen an unprecedented advance in technology and materials. This article aimed to review some of the challenges and advances in the following sections: (1) endodontic imaging, (2) root canal preparation, (3) root canal disinfection, (4) root canal filling, and (4) regenerative endodontic procedures (REPs). Jointly, these advances are aimed at improving the state of the art and science of root canal treatment. PMID:27217630

  7. A Two Stage Solution Procedure for Production Planning System with Advance Demand Information

    NASA Astrophysics Data System (ADS)

    Ueno, Nobuyuki; Kadomoto, Kiyotaka; Hasuike, Takashi; Okuhara, Koji

    We model for ‘Naiji System’ which is a unique corporation technique between a manufacturer and suppliers in Japan. We propose a two stage solution procedure for a production planning problem with advance demand information, which is called ‘Naiji’. Under demand uncertainty, this model is formulated as a nonlinear stochastic programming problem which minimizes the sum of production cost and inventory holding cost subject to a probabilistic constraint and some linear production constraints. By the convexity and the special structure of correlation matrix in the problem where inventory for different periods is not independent, we propose a solution procedure with two stages which are named Mass Customization Production Planning & Management System (MCPS) and Variable Mesh Neighborhood Search (VMNS) based on meta-heuristics. It is shown that the proposed solution procedure is available to get a near optimal solution efficiently and practical for making a good master production schedule in the suppliers.

  8. Solutions to an advanced functional partial differential equation of the pantograph type

    PubMed Central

    Zaidi, Ali A.; Van Brunt, B.; Wake, G. C.

    2015-01-01

    A model for cells structured by size undergoing growth and division leads to an initial boundary value problem that involves a first-order linear partial differential equation with a functional term. Here, size can be interpreted as DNA content or mass. It has been observed experimentally and shown analytically that solutions for arbitrary initial cell distributions are asymptotic as time goes to infinity to a certain solution called the steady size distribution. The full solution to the problem for arbitrary initial distributions, however, is elusive owing to the presence of the functional term and the paucity of solution techniques for such problems. In this paper, we derive a solution to the problem for arbitrary initial cell distributions. The method employed exploits the hyperbolic character of the underlying differential operator, and the advanced nature of the functional argument to reduce the problem to a sequence of simple Cauchy problems. The existence of solutions for arbitrary initial distributions is established along with uniqueness. The asymptotic relationship with the steady size distribution is established, and because the solution is known explicitly, higher-order terms in the asymptotics can be readily obtained. PMID:26345391

  9. The Effect of Solution Heat Treatment on an Advanced Nickel-Base Disk Alloy

    NASA Technical Reports Server (NTRS)

    Gayda, J.; Gabb, T. P.; Kantzos, P. T.

    2004-01-01

    Five heat treat options for an advanced nickel-base disk alloy, LSHR, have been investigated. These included two conventional solution heat treat cycles, subsolvus/oil quench and supersolvus/fan cool, which yield fine grain and coarse grain microstructure disks respectively, as well as three advanced dual microstructure heat treat (DMHT) options. The DMHT options produce disks with a fine grain bore and a coarse grain rim. Based on an overall evaluation of the mechanical property data, it was evident that the three DMHT options achieved a desirable balance of properties in comparison to the conventional solution heat treatments for the LSHR alloy. However, one of the DMHT options, SUB/DMHT, produced the best set of properties, largely based on dwell crack growth data. Further evaluation of the SUB/DMHT option in spin pit experiments on a generic disk shape demonstrated the advantages and reliability of a dual grain structure at the component level.

  10. Developing more open and equitable relationships with industry to improve advancements in clinical research in dermatology.

    PubMed

    Campa, M; Ryan, C; Menter, A

    2016-06-01

    Relationships between physicians, scientists, and the pharmaceutical industry can be complicated by conflicts of interest. Honest and equitable relationships, however, are essential to the advancement of dermatologic clinical research. Several factors can increase transparency in clinical trials including preregistration of clinical trials, reporting of all data produced from clinical trials, non-industry ownership of clinical trial data, clarity of statistical methods and publication of both positive and negative results. Through collaborative, scientifically rigorous studies, physicians and industry can achieve significant advances in dermatologic care. PMID:27317287

  11. Answering Physicians' Clinical Questions: Obstacles and Potential Solutions

    PubMed Central

    Ely, John W.; Osheroff, Jerome A.; Chambliss, M. Lee; Ebell, Mark H.; Rosenbaum, Marcy E.

    2005-01-01

    Objective: To identify the most frequent obstacles preventing physicians from answering their patient-care questions and the most requested improvements to clinical information resources. Design: Qualitative analysis of questions asked by 48 randomly selected generalist physicians during ambulatory care. Measurements: Frequency of reported obstacles to answering patient-care questions and recommendations from physicians for improving clinical information resources. Results: The physicians asked 1,062 questions but pursued answers to only 585 (55%). The most commonly reported obstacle to the pursuit of an answer was the physician's doubt that an answer existed (52 questions, 11%). Among pursued questions, the most common obstacle was the failure of the selected resource to provide an answer (153 questions, 26%). During audiotaped interviews, physicians made 80 recommendations for improving clinical information resources. For example, they requested comprehensive resources that answer questions likely to occur in practice with emphasis on treatment and bottom-line advice. They asked for help in locating information quickly by using lists, tables, bolded subheadings, and algorithms and by avoiding lengthy, uninterrupted prose. Conclusion: Physicians do not seek answers to many of their questions, often suspecting a lack of usable information. When they do seek answers, they often cannot find the information they need. Clinical resource developers could use the recommendations made by practicing physicians to provide resources that are more useful for answering clinical questions. PMID:15561792

  12. Clinical ladder to professional advancement program. An evolutionary process.

    PubMed

    Goodloe, L R; Sampson, R C; Munjas, B; Whitworth, T R; Lantz, C D; Tangley, E; Miller, W

    1996-06-01

    Since the early 1970s, clinical ladder programs have been a method of defining, recognizing, and rewarding nursing practice. As clinical practice in an institution grows and evolves, so must the program that supports the development of the practitioner. An in-depth evaluation of one clinical ladder program was conducted to determine if it was reflective of current practice. The authors discuss the method of evaluation, findings, and the revised program.

  13. [Electrochemical regeneration of dialysis solution in experimental and clinical conditions].

    PubMed

    Eventov, V L; Andrianova, M I; Maksimenko, V A; Nefedkin, S I; Ostodi, T

    1997-01-01

    The authors have created a new system for electrochemical regeneration of dialysis solution and conducted 67 experiments using a model solution. Two groups of patients with terminal renal failure were treated. The regeneration system was applied in the treatment of Group 1 patients (n = 14), the traditional acetate hemodialysis procedure was used in Group 2 (n = 11). Hemodialysis with electrochemical regeneration of dialysis fluid removed creatinine and potassium ions from critically ill patients' blood as effectively as the traditional hemodialysis procedure. During electrochemical hemodialysis, middle-molecular toxins were removed better those with the traditional one, but urea and inorganic phosphorus were eliminated slowler. Electrochemical regeneration provided continuous purification of dialysis fluid. The regenerator block can be used many times. Sodium hypochlorite ensured self-sterilization of the system. The use of electrochemical regeneration does not require water purification, water communications and dialysis concentrate, which enables the detoxification procedure to be performed outside the specially equipped rooms. PMID:9376743

  14. Recent advances towards the clinical application of DNA vaccines.

    PubMed

    Bins, A D; van den Berg, J H; Oosterhuis, K; Haanen, J B A G

    2013-04-01

    DNA vaccination is an attractive method for therapeutic vaccination against intracellular pathogens and cancer. This review provides an introduction into the DNA vaccination field and discusses the pre-clinical successes and most interesting clinical achievements thus far. Furthermore, general attributes, mechanism of action and safety of DNA vaccination will be discussed. Since clinical results with DNA vaccination so far show room for improvement, possibilities to improve the delivery and immunogenicity of DNA vaccines are reviewed. In the coming years, these new developments should show whether DNA vaccination is able to induce clinically relevant responses in patients.

  15. An Academic-Business Partnership for Advancing Clinical Informatics.

    ERIC Educational Resources Information Center

    Connors, Helen R.; Weaver, Charlotte; Warren, Judith; Miller, Karen L.

    2002-01-01

    A partnership between a university school of nursing and a health care information technology supplier resulted in the Simulated E-hEalth Delivery System (SEEDS). This program enables nursing students to learn clinical skills in a state-of-the-art environment using a live-production, clinical information system designed for care delivery. (JOW)

  16. Statin non-adherence: clinical consequences and proposed solutions

    PubMed Central

    Rosenson, Robert S.

    2016-01-01

    Large controlled clinical trials have demonstrated reductions with statin therapy in cardiovascular events in patients presenting with acute coronary syndromes and stable coronary heart disease and individuals at high risk of a cardiovascular event. In trials of acute coronary syndromes and stable coronary heart disease, high-intensity statin therapy is more effective in the prevention of recurrent cardiovascular events than low-intensity statin therapy. Thus, evidence-based guidelines recommend in-hospital initiation of high-intensity statin therapy for all acute coronary syndrome patients. Clinical trials report high adherence to and low discontinuation of high-intensity statin therapy; however, in clinical practice, high-intensity statins are prescribed to far fewer patients, who often discontinue their statin after the first refill. A coordinated effort among the patient, provider, pharmacist, health system, and insurer is necessary to improve utilization and persistence of prescribed medications. The major cause for statin discontinuations reported by patients is perceived adverse events. Evaluation of potential adverse events requires validated tools to distinguish between statin-associated adverse events versus non-specific complaints. Treatment options for statin-intolerant patients include the use of a different statin, often at a lower dose or frequency. In order to lower LDL cholesterol, lower doses of statins may be combined with ezetimibe or bile acid sequestrants. Newer treatment options for patients with statin-associated muscle symptoms may include proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors. PMID:27134737

  17. Statin non-adherence: clinical consequences and proposed solutions.

    PubMed

    Rosenson, Robert S

    2016-01-01

    Large controlled clinical trials have demonstrated reductions with statin therapy in cardiovascular events in patients presenting with acute coronary syndromes and stable coronary heart disease and individuals at high risk of a cardiovascular event. In trials of acute coronary syndromes and stable coronary heart disease, high-intensity statin therapy is more effective in the prevention of recurrent cardiovascular events than low-intensity statin therapy. Thus, evidence-based guidelines recommend in-hospital initiation of high-intensity statin therapy for all acute coronary syndrome patients. Clinical trials report high adherence to and low discontinuation of high-intensity statin therapy; however, in clinical practice, high-intensity statins are prescribed to far fewer patients, who often discontinue their statin after the first refill. A coordinated effort among the patient, provider, pharmacist, health system, and insurer is necessary to improve utilization and persistence of prescribed medications. The major cause for statin discontinuations reported by patients is perceived adverse events. Evaluation of potential adverse events requires validated tools to distinguish between statin-associated adverse events versus non-specific complaints. Treatment options for statin-intolerant patients include the use of a different statin, often at a lower dose or frequency. In order to lower LDL cholesterol, lower doses of statins may be combined with ezetimibe or bile acid sequestrants. Newer treatment options for patients with statin-associated muscle symptoms may include proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors. PMID:27134737

  18. The Advancing Clinical Impact of Molecular Imaging in Cardiovascular Disease

    PubMed Central

    Osborn, Eric A; Jaffer, Farouc A

    2013-01-01

    Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (PET, SPECT, MRI), as well in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g. the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in Phase II clinical trials. Here we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term. PMID:24332285

  19. Advancing description and explanation in clinical linguistics: a legacy of Martin J. Ball.

    PubMed

    Damico, Jack S; Damico, Holly L; Nelson, Ryan L

    2011-11-01

    This article asserts the importance of explication of order and disorder in language as a privileged objective of clinical linguistics and service delivery and reviews the contributions of Martin Ball in advancing this agenda.

  20. Advances in Clinical and Biomedical Applications of Photoacoustic Imaging

    PubMed Central

    Su, Jimmy L.; Wang, Bo; Wilson, Katheryne E.; Bayer, Carolyn L.; Chen, Yun-Sheng; Kim, Seungsoo; Homan, Kimberly A.; Emelianov, Stanislav Y.

    2010-01-01

    Importance of the field Photoacoustic imaging is an imaging modality that derives image contrast from the optical absorption coefficient of the tissue being imaged. The imaging technique is able to differentiate between healthy and diseased tissue with either deeper penetration or higher resolution than other functional imaging modalities currently available. From a clinical standpoint, photoacoustic imaging has demonstrated safety and effectiveness in diagnosing diseased tissue regions using either endogenous tissue contrast or exogenous contrast agents. Furthermore, the potential of photoacoustic imaging has been demonstrated in various therapeutic interventions ranging from drug delivery and release to image-guided therapy and monitoring. Areas covered in this review This article reviews the current state of photoacoustic imaging in biomedicine from a technological perspective, highlights various biomedical and clinical applications of photoacoustic imaging, and gives insights on future directions. What the reader will gain Readers will learn about the various applications of photoacoustic imaging, as well as the various contrast agents that can be used to assist photoacoustic imaging. This review will highlight both pre-clinical and clinical uses for photoacoustic imaging, as well as discuss some of the challenges that must be addressed to move photoacoustic imaging into the clinical realm. Take home message Photoacoustic imaging offers unique advantages over existing imaging modalities. The imaging field is broad with many exciting applications for detecting and diagnosing diseased tissue or processes. Photoacoustics is also used in therapeutic applications to identify and characterize the pathology and then to monitor the treatment. Although the technology is still in its infancy, much work has been done in the pre-clinical arena, and photoacoustic imaging is fast approaching the clinical setting. PMID:21344060

  1. Medical Physics: Forming and testing solutions to clinical problems.

    PubMed

    Tsapaki, Virginia; Bayford, Richard

    2015-11-01

    According to the European Federation of Organizations for Medical Physics (EFOMP) policy statement No. 13, "The rapid advance in the use of highly sophisticated equipment and procedures in the medical field increasingly depends on information and communication technology. In spite of the fact that the safety and quality of such technology is vigorously tested before it is placed on the market, it often turns out that the safety and quality is not sufficient when used under hospital working conditions. To improve safety and quality for patient and users, additional safeguards and related monitoring, as well as measures to enhance quality, are required. Furthermore a large number of accidents and incidents happen every year in hospitals and as a consequence a number of patients die or are injured. Medical Physicists are well positioned to contribute towards preventing these kinds of events". The newest developments related to this increasingly important medical speciality were presented during the 8th European Conference of Medical Physics 2014 which was held in Athens, 11-13 September 2014 and hosted by the Hellenic Association of Medical Physicists (HAMP) in collaboration with the EFOMP and are summarized in this issue.

  2. Clinical applications of advanced lipoprotein testing in diabetes mellitus

    PubMed Central

    Moin, Danyaal S; Rohatgi, Anand

    2011-01-01

    Traditional lipid profiles often fail to fully explain the elevated cardiovascular risk of individuals with diabetes mellitus. Advanced lipoprotein testing offers a novel means to evaluate dyslipidemia and refine risk estimation. Numerous observational studies have demonstrated a characteristic pattern of elevated levels of small, dense LDL particles, out of proportion to traditional lipid levels, in patients with both diabetes mellitus and the metabolic syndrome. Commonly used glucose and lipid-lowering agents have varied effects in patients with diabetes on both LDL and HDL subfractions. The exact role of advanced lipoprotein testing in patients with diabetes mellitus and the metabolic syndrome remains unclear but may offer improved assessment of cardiovascular risk compared with traditional lipid measurements. PMID:22162979

  3. Dermatotoxicologic clinical solutions: textile dye dermatitis patch testing.

    PubMed

    Coman, Garrett; Blickenstaff, Nicholas; Edwards, Ashley; Maibach, Howard

    2015-03-01

    The authors provide a framework for working up and counseling a patient with suspected textile dermatitis, focusing on identifying which textile materials are most likely to be the cause of the eczematous lesions, the current clinical guidelines, the utility and appropriateness of patch testing, the limitations of these guidelines, and our pro tempore recommendations. While there are many challenges to correctly identify and counsel patients on how to avoid the offending textile products in a patient with suspected textile dye dermatitis, there is value in following the guidelines set forth to help identify the causative textile(s). Although patch tests can be useful, dermatologists should understand the limitations of standardized patch testing for patients with suspected textile dye-induced dermatitis. These guidelines are expected to increase the likelihood of identifying the causative textile(s), so that patch testing can be supplemented with swatch testing and chemical dye extraction to help discover the allergenic dye.

  4. Clinical imaging guidelines part 2: Risks, benefits, barriers, and solutions.

    PubMed

    Malone, James; del Rosario-Perez, Maria; Van Bladel, Lodewijk; Jung, Seung Eun; Holmberg, Ola; Bettmann, Michael A

    2015-02-01

    A recent international meeting was convened by two United Nations bodies to focus on international collaboration on clinical appropriateness/referral guidelines for use in medical imaging. This paper, the second of 4 from this technical meeting, addresses barriers to the successful development/deployment of clinical imaging guidelines and means of overcoming them. It reflects the discussions of the attendees, and the issues identified are treated under 7 headings: ■ Practical Strategy for Development and Deployment of Guidelines; ■ Governance Arrangements and Concerns with Deployment of Guidelines; ■ Finance, Sustainability, Reimbursement, and Related Issues; ■ Identifying Benefits and Radiation Risks from Radiological Examinations; ■ Information Given to Patients and the Public, and Consent Issues; ■ Special Concerns Related to Pregnancy; and ■ The Research Agenda. Examples of topics identified include the observation that guideline development is a global task and there is no case for continuing it as the project of the few professional organizations that have been brave enough to make the long-term commitment required. Advocacy for guidelines should include the expectations that they will facilitate: (1) better health care delivery; (2) lower cost of that delivery; with (3) reduced radiation dose and associated health risks. Radiation protection issues should not be isolated; rather, they should be integrated with the overall health care picture. The type of dose/radiation risk information to be provided with guidelines should include the uncertainty involved and advice on application of the precautionary principle with patients. This principle may be taken as an extension of the well-established medical principle of "first do no harm." PMID:25652302

  5. Major clinical research advances in gynecologic cancer in 2015

    PubMed Central

    2016-01-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

  6. Developing and validating advanced divertor solutions on DIII-D for next-step fusion devices

    DOE PAGES

    Guo, H. Y.; Hill, D. N.; Leonard, A. W.; Allen, S. L.; Stangeby, P. C.; Thomas, D.; Unterberg, E. A.; Abrams, T.; Boedo, J.; Briesemeister, A. R.; et al

    2016-09-14

    A major challenge facing the design and operation of next-step high-power steady-state fusion devices is to develop a viable divertor solution with order-of-magnitude increases in power handling capability relative to present experience, while having acceptable divertor target plate erosion and being compatible with maintaining good core plasma confinement. A new initiative has been launched on DIII-D to develop the scientific basis for design, installation, and operation of an advanced divertor to evaluate boundary plasma solutions applicable to next step fusion experiments beyond ITER. Developing the scientific basis for fusion reactor divertor solutions must necessarily follow three lines of research, whichmore » we plan to pursue in DIII-D: (1) Advance scientific understanding and predictive capability through development and comparison between state-of-the art computational models and enhanced measurements using targeted parametric scans; (2) Develop and validate key divertor design concepts and codes through innovative variations in physical structure and magnetic geometry; (3) Assess candidate materials, determining the implications for core plasma operation and control, and develop mitigation techniques for any deleterious effects, incorporating development of plasma-material interaction models. These efforts will lead to design, installation, and evaluation of an advanced divertor for DIII-D to enable highly dissipative divertor operation at core density (n e/n GW), neutral fueling and impurity influx most compatible with high performance plasma scenarios and reactor relevant plasma facing components (PFCs). In conclusion, this paper highlights the current progress and near-term strategies of boundary/PMI research on DIII-D.« less

  7. Developing and validating advanced divertor solutions on DIII-D for next-step fusion devices

    NASA Astrophysics Data System (ADS)

    Guo, H. Y.; Hill, D. N.; Leonard, A. W.; Allen, S. L.; Stangeby, P. C.; Thomas, D.; Unterberg, E. A.; Abrams, T.; Boedo, J.; Briesemeister, A. R.; Buchenauer, D.; Bykov, I.; Canik, J. M.; Chrobak, C.; Covele, B.; Ding, R.; Doerner, R.; Donovan, D.; Du, H.; Elder, D.; Eldon, D.; Lasa, A.; Groth, M.; Guterl, J.; Jarvinen, A.; Hinson, E.; Kolemen, E.; Lasnier, C. J.; Lore, J.; Makowski, M. A.; McLean, A.; Meyer, B.; Moser, A. L.; Nygren, R.; Owen, L.; Petrie, T. W.; Porter, G. D.; Rognlien, T. D.; Rudakov, D.; Sang, C. F.; Samuell, C.; Si, H.; Schmitz, O.; Sontag, A.; Soukhanovskii, V.; Wampler, W.; Wang, H.; Watkins, J. G.

    2016-12-01

    A major challenge facing the design and operation of next-step high-power steady-state fusion devices is to develop a viable divertor solution with order-of-magnitude increases in power handling capability relative to present experience, while having acceptable divertor target plate erosion and being compatible with maintaining good core plasma confinement. A new initiative has been launched on DIII-D to develop the scientific basis for design, installation, and operation of an advanced divertor to evaluate boundary plasma solutions applicable to next step fusion experiments beyond ITER. Developing the scientific basis for fusion reactor divertor solutions must necessarily follow three lines of research, which we plan to pursue in DIII-D: (1) Advance scientific understanding and predictive capability through development and comparison between state-of-the art computational models and enhanced measurements using targeted parametric scans; (2) Develop and validate key divertor design concepts and codes through innovative variations in physical structure and magnetic geometry; (3) Assess candidate materials, determining the implications for core plasma operation and control, and develop mitigation techniques for any deleterious effects, incorporating development of plasma-material interaction models. These efforts will lead to design, installation, and evaluation of an advanced divertor for DIII-D to enable highly dissipative divertor operation at core density (n e/n GW), neutral fueling and impurity influx most compatible with high performance plasma scenarios and reactor relevant plasma facing components (PFCs). This paper highlights the current progress and near-term strategies of boundary/PMI research on DIII-D.

  8. Evaluation of a commercial AdvancedTCA board management controller solution (IPMC)

    NASA Astrophysics Data System (ADS)

    Mendez, J.; Bobillier, V.; Haas, S.; Joos, M.; Vasey, F.

    2016-02-01

    The MicroTCA (MTCA) and AdvancedTCA (ATCA) industry standards have been selected as the hardware platform for the upgrade of the electronic systems of some of the experiments at the Large Hadron Collider (LHC) . In this context, the electronics support group for experiments at CERN is running a project to perform technical evaluations of MTCA and ATCA equipment. As part of this activity, a commercial solution for an Intelligent Platform Management Controller (IPMC), an essential component of any ATCA blade design, is being evaluated. We validated the supported IPMC features, checked the interoperability and adapted the reference design for use on an existing ATCA carrier board.

  9. Clinical Curriculum Reform and Advanced Care Training at the New England College of Optometry.

    ERIC Educational Resources Information Center

    Wilson, Roger

    1998-01-01

    Discusses how the New England College of Optometry has expanded clinical education so graduates are equipped to handle new and advanced clinical and patient-care responsibilities and meet the changing standards of professional entry-level competency. The reform process, third- and fourth-year curriculum components, rotations, and plans for…

  10. Opioid-induced constipation: advances and clinical guidance

    PubMed Central

    Nelson, Alfred D.; Camilleri, Michael

    2016-01-01

    Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain. PMID:26977281

  11. Advanced Chinese NiTi alloy wire and clinical observations.

    PubMed

    Chen, R; Zhi, Y F; Arvystas, M G

    1992-01-01

    Chinese NiTi wire was studied on the bench with six other nickel-titanium-alloy wires. Bending and torsional tests were conducted and temperatures of phase transformation compared. The Chinese NiTi wire was found to have a low stiffness, high springback and constant bending and torsional moments on unloading, in a very large deformation region. It can produce a gentle, nearly constant force. These factors make it desirable for clinical application. Included in this paper are clinical observations of case selected from over 100 patients in current treatment with Chinese NiTi wires. Chinese NiTi wire reduced the leveling and alignment phase of treatment without discomfort to the patient. Chinese NiTi wire can be used in both children and adults. PMID:1445516

  12. Recent Advances in Understanding Xenotransplantation: Implications for the Clinic

    PubMed Central

    Cooper, David K. C.; Bottino, Rita

    2016-01-01

    Summary The results of organ and cell allotransplantation continue to improve, but the field remains limited by a lack of deceased donor organs. Xenotransplantation, e.g., between pig and human, offers unlimited organs and cells for clinical transplantation. The immune barriers include a strong innate immune response in addition to the adaptive T cell response. The innate response has largely been overcome by the transplantation of organs from pigs with genetic modifications that protect their tissues from this response. T cell-mediated rejection can be controlled by immunosuppressive agents that inhibit costimulation. Coagulation dysfunction between the pig and primate remains problematic but is being overcome by the transplantation of organs from pigs that express human coagulation-regulatory proteins. The remaining barriers will be resolved by the introduction of novel genetically-engineered pigs. Limited clinical trials of pig islet and corneal transplantation are already underway. PMID:26548357

  13. Reverse phase protein microarrays advance to use in clinical trials

    PubMed Central

    Mueller, Claudius; Liotta, Lance A.; Espina, Virginia

    2010-01-01

    Individualizing cancer therapy for molecular targeted inhibitors requires a new class of molecular profiling technology that can map the functional state of the cancer cell signal pathways containing the drug targets. Reverse phase protein microarrays (RPMA) are a technology platform designed for quantitative, multiplexed analysis of specific phosphorylated, cleaved, or total (phosphorylated and non-phosphorylated) forms of cellular proteins from a limited amount of sample. This class of microarray can be used to interrogate tissue samples, cells, serum, or body fluids. RPMA were previously a research tool; now this technology has graduated to use in research clinical trials with clinical grade sensitivity and precision. In this review we describe the application of RPMA for multiplexed signal pathway analysis in therapeutic monitoring, biomarker discovery, and evaluation of pharmaceutical targets, and conclude with a summary of the technical aspects of RPMA construction and analysis. PMID:20974554

  14. Hereditary spastic paraplegia: clinical principles and genetic advances.

    PubMed

    Fink, John K

    2014-07-01

    Hereditary spastic paraplegia (HSP) refers to inherited disorders in which spastic gait is either the only feature or is a major syndrome feature. There are more than 70 genetic types of HSP. Neuropathological studies, albeit limited to only a few genetic types of HSP, have identified axon degeneration involving the distal ends of the corticospinal tracts and fasciculus gracilis fibers. In this review, the author highlights the clinical and genetic features of HSP.

  15. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.

    PubMed

    Detappe, Alexandre; Kunjachan, Sijumon; Sancey, Lucie; Motto-Ros, Vincent; Biancur, Douglas; Drane, Pascal; Guieze, Romain; Makrigiorgos, G Mike; Tillement, Olivier; Langer, Robert; Berbeco, Ross

    2016-09-28

    Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment. PMID:27423325

  16. Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

    PubMed

    Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

    2015-01-01

    In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

  17. Enabling the 14nm node contact patterning using advanced RET solutions

    NASA Astrophysics Data System (ADS)

    Zeggaoui, N.; Landie, G.; Villaret, A.; Farys, V.; Yesilada, E.; Tritchkov, A.; Word, J.

    2015-09-01

    The 14nm node designs is getting more sophisticated, and printability issues become more critical which need more advanced techniques to fix. One of the most critical processes is the contact patterning due to the very aggressive design rules and the process window which becomes quickly limited. Despite the large number of RET applied, some hotspot configurations remain challenging. It becomes increasingly challenging to achieve sufficient process windows around the hot spots just using conventional process such as OPC and rule-based SRAF insertion. Although, it might be desirable to apply Inverse Lithography Technique (ILT) on all hot spots to guarantee ideal mask quality. However, because of the high number of hot spots to repair in the design, that solution might be much time consuming in term of OPC and mask processing. In this paper we present a hybrid OPC solution based on local ILT usage around hot spots. It is named as Local Printability Enhancement (LPE) flow. First, conventional OPC and SRAF placement is applied on the whole design. Then, we apply LPE solution only on the remaining problematic hot spots of the design. The LPE flow also takes into account the mask rules so that it maintains the mask rule check (MRC) compliance through the borders of the repaired hot spot's areas. We will demonstrate that the LPE flow enlarges the process window around hot spots and gives better lithography quality than baseline. The simulation results are confirmed on silicon wafer where all the hot spots are printed. We will demonstrate that LPE flow enlarges the depth of focus of the most challenging hot spot by 30nm compared to POR conventional solution. Because the proposed flow applies ILT solution on very local hot spot areas, the total OPC run time remains acceptable from manufacturing side.

  18. Hyperprolactinemia--a review of recent clinical advances.

    PubMed

    Kirby, R W; Kotchen, T A; Rees, E D

    1979-12-01

    Since the radioimmunoassay for serum prolactin became available eight years ago, prolactin has become a hormone of considerable clinical interest. An elevated serum prolactin concentration is the most frequent hormone marker for pituitary tumors. Secreted in excess, prolactin causes dysfunction of the hypothalamic-pituitary axis, the gonads, and the adrenal cortex. In women, menstrual disturbances, galactorrhea, infertility, and hirsutism result. Impotence, oligospermia, and decreased libido are common in men. These metabolic abnormalities attributed to prolactin excess are corrected when prolactin concentrations are lowered by either medical or surgical therapy. The availability of effective therapy mandates early recognition and proper management of the patient with hyperprolactinemia.

  19. Advancing Clostridia to Clinical Trial: Past Lessons and Recent Progress

    PubMed Central

    Mowday, Alexandra M.; Guise, Christopher P.; Ackerley, David F.; Minton, Nigel P.; Lambin, Philippe; Dubois, Ludwig J.; Theys, Jan; Smaill, Jeff B.; Patterson, Adam V.

    2016-01-01

    Most solid cancers contain regions of necrotic tissue. The extent of necrosis is associated with poor survival, most likely because it reflects aggressive tumour outgrowth and inflammation. Intravenously injected spores of anaerobic bacteria from the genus Clostridium infiltrate and selectively germinate in these necrotic regions, providing cancer-specific colonisation. The specificity of this system was first demonstrated over 60 years ago and evidence of colonisation has been confirmed in multiple tumour models. The use of “armed” clostridia, such as in Clostridium Directed Enzyme Prodrug Therapy (CDEPT), may help to overcome some of the described deficiencies of using wild-type clostridia for treatment of cancer, such as tumour regrowth from a well-vascularised outer rim of viable cells. Successful preclinical evaluation of a transferable gene that metabolises both clinical stage positron emission tomography (PET) imaging agents (for whole body vector visualisation) as well as chemotherapy prodrugs (for conditional enhancement of efficacy) would be a valuable early step towards the prospect of “armed” clostridia entering clinical evaluation. The ability to target the immunosuppressive hypoxic tumour microenvironment using CDEPT may offer potential for synergy with recently developed immunotherapy strategies. Ultimately, clostridia may be most efficacious when combined with conventional therapies, such as radiotherapy, that sterilise viable aerobic tumour cells. PMID:27367731

  20. Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience.

    PubMed

    Yao, James C; Phan, Alexandria T; Jehl, Valentine; Shah, Gaurav; Meric-Bernstam, Funda

    2013-03-01

    The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo.

  1. Major clinical research advances in gynecologic cancer in 2012.

    PubMed

    Suh, Dong Hoon; Kim, Jae-Weon; Kim, Kidong; Kim, Hak Jae; Lee, Kyung-Hun

    2013-01-01

    Ten topics were chosen among major clinical research achievements in gynecologic oncology in 2012. For ovarian cancer, comprehensive review of the history of bevacizumab studies was followed by poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors and other molecular targeted agents such as epidermal growth factor receptor tyrosine kinase inhibitor and AMG 386. For the development of genomic study in gynecologic cancers, BRCA and DICER1 mutations were covered in epithelial and nonepithelial ovarian cancer, respectively. For endometrial cancer, targeted agents including mammalian target of rapamycin (mTOR) inhibitors and bevacizumab were discussed. Radiation therapy "sandwiched" between combination chemotherapy schedules for the treatment of uterine papillary serous carcinoma was also reviewed. Preoperative prediction of lymph node metastasis, definition of low-risk group, and recurrence and survival outcomes of laparoscopic approaches were addressed. For cervical cancer, we reviewed long-term benefit of human papillomavirus test and efficacy of paclitaxel/carboplatin versus paclitaxel/cisplatin in stage IVB, persistent or recurrent disease. In addition, the effect of three dimensional image-based high-dose rate brachytherapy was also reviewed. For vulvar cancer, the diagnostic value of sentinel lymph node biopsy was discussed. For breast cancer, positive results of three outstanding phase III randomized clinical trials, CLEOPATRA, EMILIA, and BOLERO-2 were introduced. Lastly, updates of major practice guidelines were summarized.

  2. Lost in Translation: The Gap in Scientific Advancements and Clinical Application.

    PubMed

    Fernandez-Moure, Joseph S

    2016-01-01

    The evolution of medicine and medical technology hinges on the successful translation of basic science research from the bench to clinical implementation at the bedside. Out of the increasing need to facilitate the transfer of scientific knowledge to patients, translational research has emerged. Significant leaps in improving global health, such as antibiotics, vaccinations, and cancer therapies, have all seen successes under this paradigm, yet today, it has become increasingly difficult to realize this ideal scenario. As hospital revenue demand increases, and financial support declines, clinician-protected research time has been limited. Researchers, likewise, have been forced to abandon time- and resource-consuming translational research to focus on publication-generating work to maintain funding and professional advancement. Compared to the surge in scientific innovation and new fields of science, realization of transformational scientific findings in device development and materials sciences has significantly lagged behind. Herein, we describe: how the current scientific paradigm struggles in the new health-care landscape; the obstacles met by translational researchers; and solutions, both public and private, to overcoming those obstacles. We must rethink the old dogma of academia and reinvent the traditional pathways of research in order to truly impact the health-care arena and ultimately those that matter most: the patient. PMID:27376058

  3. Lost in Translation: The Gap in Scientific Advancements and Clinical Application

    PubMed Central

    Fernandez-Moure, Joseph S.

    2016-01-01

    The evolution of medicine and medical technology hinges on the successful translation of basic science research from the bench to clinical implementation at the bedside. Out of the increasing need to facilitate the transfer of scientific knowledge to patients, translational research has emerged. Significant leaps in improving global health, such as antibiotics, vaccinations, and cancer therapies, have all seen successes under this paradigm, yet today, it has become increasingly difficult to realize this ideal scenario. As hospital revenue demand increases, and financial support declines, clinician-protected research time has been limited. Researchers, likewise, have been forced to abandon time- and resource-consuming translational research to focus on publication-generating work to maintain funding and professional advancement. Compared to the surge in scientific innovation and new fields of science, realization of transformational scientific findings in device development and materials sciences has significantly lagged behind. Herein, we describe: how the current scientific paradigm struggles in the new health-care landscape; the obstacles met by translational researchers; and solutions, both public and private, to overcoming those obstacles. We must rethink the old dogma of academia and reinvent the traditional pathways of research in order to truly impact the health-care arena and ultimately those that matter most: the patient. PMID:27376058

  4. Lost in Translation: The Gap in Scientific Advancements and Clinical Application.

    PubMed

    Fernandez-Moure, Joseph S

    2016-01-01

    The evolution of medicine and medical technology hinges on the successful translation of basic science research from the bench to clinical implementation at the bedside. Out of the increasing need to facilitate the transfer of scientific knowledge to patients, translational research has emerged. Significant leaps in improving global health, such as antibiotics, vaccinations, and cancer therapies, have all seen successes under this paradigm, yet today, it has become increasingly difficult to realize this ideal scenario. As hospital revenue demand increases, and financial support declines, clinician-protected research time has been limited. Researchers, likewise, have been forced to abandon time- and resource-consuming translational research to focus on publication-generating work to maintain funding and professional advancement. Compared to the surge in scientific innovation and new fields of science, realization of transformational scientific findings in device development and materials sciences has significantly lagged behind. Herein, we describe: how the current scientific paradigm struggles in the new health-care landscape; the obstacles met by translational researchers; and solutions, both public and private, to overcoming those obstacles. We must rethink the old dogma of academia and reinvent the traditional pathways of research in order to truly impact the health-care arena and ultimately those that matter most: the patient.

  5. Clinical holistic health: advanced tools for holistic medicine.

    PubMed

    Ventegodt, Søren; Clausen, Birgitte; Nielsen, May Lyck; Merrick, Joav

    2006-02-24

    According to holistic medical theory, the patient will heal when old painful moments, the traumatic events of life that are often called "gestalts", are integrated in the present "now". The advanced holistic physician's expanded toolbox has many different tools to induce this healing, some that are more dangerous and potentially traumatic than others. The more intense the therapeutic technique, the more emotional energy will be released and contained in the session, but the higher also is the risk for the therapist to lose control of the session and lose the patient to his or her own dark side. To avoid harming the patient must be the highest priority in holistic existential therapy, making sufficient education and training an issue of highest importance. The concept of "stepping up" the therapy by using more and more "dramatic" methods to get access to repressed emotions and events has led us to a "therapeutic staircase" with ten steps: (1) establishing the relationship; (2) establishing intimacy, trust, and confidentiality; (3) giving support and holding; (4) taking the patient into the process of physical, emotional, and mental healing; (5) social healing of being in the family; (6) spiritual healing--returning to the abstract wholeness of the soul; (7) healing the informational layer of the body; (8) healing the three fundamental dimensions of existence: love, power, and sexuality in a direct way using, among other techniques, "controlled violence" and "acupressure through the vagina"; (9) mind-expanding and consciousness-transformative techniques like psychotropic drugs; and (10) techniques transgressing the patient's borders and, therefore, often traumatizing (for instance, the use of force against the will of the patient). We believe that the systematic use of the staircase will greatly improve the power and efficiency of holistic medicine for the patient and we invite a broad cooperation in scientifically testing the efficiency of the advanced holistic

  6. Recent Advances in Clinical Glycoproteomics of Immunoglobulins (Igs)*

    PubMed Central

    Plomp, Rosina; Bondt, Albert; de Haan, Noortje; Rombouts, Yoann; Wuhrer, Manfred

    2016-01-01

    Antibody glycosylation analysis has seen methodological progress resulting in new findings with regard to antibody glycan structure and function in recent years. For example, antigen-specific IgG glycosylation analysis is now applicable for clinical samples because of the increased sensitivity of measurements, and this has led to new insights in the relationship between IgG glycosylation and various diseases. Furthermore, many new methods have been developed for the purification and analysis of IgG Fc glycopeptides, notably multiple reaction monitoring for high-throughput quantitative glycosylation analysis. In addition, new protocols for IgG Fab glycosylation analysis were established revealing autoimmune disease-associated changes. Functional analysis has shown that glycosylation of IgA and IgE is involved in transport across the intestinal epithelium and receptor binding, respectively. PMID:27009965

  7. Recent Advances in the Clinical Management of Lead Poisoning.

    PubMed

    Kianoush, Sina; Sadeghi, Mahmood; Balali-Mood, Mahdi

    2015-01-01

    Lead poisoning is a historic universal disease. Acute or chronic lead exposure may cause reversible or even permanent damages in human beings. Environmental lead exposure is a global health concern in children. Occupational lead poisoning is still a health issue, particularly in developing countries. During the last decades, new methods and medications have been advocated for the prevention and treatment of lead poisoning. This review deals mainly with recent developments in the management of lead poisoning. Sources of lead exposure are introduced, and methods for the primary prevention of lead poisoning are discussed. Details for the screening of adults and children are also explained to serve as a practical guideline for the secondary prevention. Standard chelation therapy in different groups and up-to-date less toxic new medications for the treatment of lead poisoning are finally discussed. Our published clinical research on the therapeutic effects of garlic tablets in mild to moderate occupational lead poisoning will also be discussed.

  8. [Research advance on clinical blood transfusion and tumor therapy].

    PubMed

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  9. Leveraging advanced data analytics, machine learning, and metrology models to enable critical dimension metrology solutions for advanced integrated circuit nodes

    NASA Astrophysics Data System (ADS)

    Rana, Narender; Zhang, Yunlin; Kagalwala, Taher; Bailey, Todd

    2014-10-01

    Integrated circuit (IC) technology is changing in multiple ways: 193i to extreme ultraviolet exposure, planar to nonplanar device architecture, from single exposure lithography to multiple exposure and directed self-assembly (DSA) patterning, and so on. Critical dimension (CD) control requirement is becoming stringent and more exhaustive: CD and process windows are shrinking, three-sigma CD control of <2 nm is required in complex geometries, and a metrology uncertainty of <0.2 nm is required to achieve the target CD control for advanced IC nodes (e.g., 14, 10, and 7 nm nodes). There are fundamental capability and accuracy limits in all the metrology techniques that are detrimental to the success of advanced IC nodes. Reference or physical CD metrology is provided by atomic force microscopy (CD-AFM) and TEM while workhorse metrology is provided by CD-SEM, scatterometry, and model-based infrared reflectrometry (MBIR). Precision alone is not sufficient for moving forward. No single technique is sufficient to ensure the required accuracy of patterning. The accuracy of CD-AFM is ˜1 nm and the precision in TEM is poor due to limited statistics. CD scanning electron microscopy (CD-SEM), scatterometry, and MBIR need to be calibrated by reference measurements for ensuring the accuracy of patterned CDs and patterning models. There is a dire need for a measurement with <0.5 nm accuracy and the industry currently does not have that capability with inline measurements. Being aware of the capability gaps for various metrology techniques, we have employed data processing techniques and predictive data analytics, along with patterning simulation and metrology models and data integration techniques to selected applications demonstrating the potential solution and practicality of such an approach to enhance CD metrology accuracy. Data from multiple metrology techniques have been analyzed in multiple ways to extract information with associated uncertainties and integrated to extract

  10. Vision 20/20: Automation and advanced computing in clinical radiation oncology

    SciTech Connect

    Moore, Kevin L. Moiseenko, Vitali; Kagadis, George C.; McNutt, Todd R.; Mutic, Sasa

    2014-01-15

    This Vision 20/20 paper considers what computational advances are likely to be implemented in clinical radiation oncology in the coming years and how the adoption of these changes might alter the practice of radiotherapy. Four main areas of likely advancement are explored: cloud computing, aggregate data analyses, parallel computation, and automation. As these developments promise both new opportunities and new risks to clinicians and patients alike, the potential benefits are weighed against the hazards associated with each advance, with special considerations regarding patient safety under new computational platforms and methodologies. While the concerns of patient safety are legitimate, the authors contend that progress toward next-generation clinical informatics systems will bring about extremely valuable developments in quality improvement initiatives, clinical efficiency, outcomes analyses, data sharing, and adaptive radiotherapy.

  11. Clinical advances in molecular biomarkers for cancer diagnosis and therapy.

    PubMed

    Sethi, Seema; Ali, Shadan; Philip, Philip A; Sarkar, Fazlul H

    2013-07-16

    Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer. Moreover, deregulating their activity offers novel cancer therapeutic approaches. The availability of high throughput techniques for the identification of altered cellular molecules allowed their use in cancer diagnosis. Their application to a variety of body specimens from blood to tissues has been helpful for appreciating their use in the clinical context. The development of innovative antibodies for immunohistochemical detection of proteins also assists in diagnosis and risk stratification. Overall, the novel cancer diagnostic tools have extended their application as prognostic risk factors and can be used as targets for personalized medicine.

  12. Advanced clinical monitoring: considerations for real-time hemodynamic diagnostics.

    PubMed

    Goldman, J M; Cordova, M J

    1994-01-01

    In an effort to ease staffing burdens and potentially improve patient outcome in an intensive care unit (ICU) environment, we are developing a real-time system to accurately and efficiently diagnose cardiopulmonary emergencies. The system is being designed to utilize all relevant routinely-monitored physiological data in order to automatically diagnose potentially fatal events. The initial stage of this project involved formulating the overall system design and appropriate methods for real-time data acquisition, data storage, data trending, waveform analysis, and implementing diagnostic rules. Initially, we defined a conceptual analysis of the minimum physiologic data set, and the monitoring time-frames (trends) which would be required to diagnose cardiopulmonary emergencies. Following that analysis, we used a fuzzy logic diagnostic engine to analyze physiological data during a simulated arrhythmic cardiac arrest (ACA) in order to assess the validity of our diagnostic methodology. We used rate, trend, and morphologic data extracted from the following signals: expired CO2 time-concentration curve (capnogram), electrocardiogram, and arterial blood pressure. The system performed well: The fuzzy logic engine effectively diagnosed the likelihood of ACA from the subtle hemodynamic trends which preceded the complete arrest. As the clinical picture worsened, the fuzzy logic-based system accurately indicated the change in patient condition. Termination of the simulated arrest was rapidly detected by the diagnostic engine. In view of the effectiveness of this fuzzy logic implementation, we plan to develop additional fuzzy logic modules to diagnose other cardiopulmonary emergencies.

  13. Differential reinforcement of alternative behavior increases resistance to extinction: clinical demonstration, animal modeling, and clinical test of one solution.

    PubMed

    Mace, F Charles; McComas, Jennifer J; Mauro, Benjamin C; Progar, Patrick R; Taylor, Bridget; Ervin, Ruth; Zangrillo, Amanda N

    2010-05-01

    Basic research with pigeons on behavioral momentum suggests that differential reinforcement of alternative behavior (DRA) can increase the resistance of target behavior to change. This finding suggests that clinical applications of DRA may inadvertently increase the persistence of target behavior even as it decreases its frequency. We conducted three coordinated experiments to test whether DRA has persistence-strengthening effects on clinically significant target behavior and then tested the effectiveness of a possible solution to this problem in both a nonhuman and clinical study. Experiment 1 compared resistance to extinction following baseline rates of reinforcement versus higher DRA rates of reinforcement in a clinical study. Resistance to extinction was substantially greater following DRA. Experiment 2 tested a rat model of a possible solution to this problem. Training an alternative response in a context without reinforcement of the target response circumvented the persistence-strengthening effects of DRA. Experiment 3 translated the rat model into a novel clinical application of DRA. Training an alternative response with DRA in a separate context resulted in lower resistance to extinction than employing DRA in the context correlated with reinforcement of target behavior. The value of coordinated bidirectional translational research is discussed.

  14. Clinical and radiographic evaluation of maxillary central incisors exposure in patients undergoing maxillary advancement

    PubMed Central

    Trento, Guilherme dos Santos; Bernabé, Felipe Bueno Rosettti; da Costa, Delson João; Rebellato, Nelson Luis Barbosa; Klüppel, Leandro Eduardo; Scariot, Rafaela

    2015-01-01

    Abstract Introduction: Patients with dentofacial deformities may undergo orthodontic or orthodontic-surgical treatment. Both modalities can affect esthetics. Objective: This study aims to evaluate clinical and radiographic changes in exposure of maxillary central incisors occurring after orthognathic surgery for maxillary advancement. Methods: A total of 17 patients who underwent orthognathic surgery for maxillary advancement between September, 2010 and July, 2011 were selected. Exposure of maxillary central incisors was evaluated clinically and by lateral cephalograms. Measurements were taken one week before and three months after surgery. Data were paired in terms of sex, age, nasolabial angle, height and thickness of the upper lip, the amount of maxillary advancement, clinical exposure and inclination of maxillary central incisor by statistical tests (CI 95%). Results: After maxillary advancement, incisor clinical exposure had increased even with relaxed lips and under forced smile. Moreover, there was a mean increase of 23.33% revealed by lateral cephalograms. There was an inverse correlation between upper lip thickness and incisors postsurgical exposure revealed by radiographic images (p = 0.002). Conclusions: Significant changes in the exposure of maxillary central incisors occur after maxillary advancement, under the influence of some factors, especially lip thickness. PMID:26691970

  15. Advances in basic and clinical immunology in 2014.

    PubMed

    Chinen, Javier; Notarangelo, Luigi D; Shearer, William T

    2015-05-01

    Genetic identification of immunodeficiency syndromes has become more efficient with the availability of whole-exome sequencing, expediting the identification of relevant genes and complementing traditional linkage analysis and homozygosity mapping. New genes defects causing immunodeficiency include phophoglucomutase 3 (PGM3), cytidine 5' triphosphate synthase 1 (CTPS1), nuclear factor κB-inducing kinase (NIK), cytotoxic T lymphocyte-associated antigen 4 (CTLA4), B-cell chronic lymphocytic leukemia/lymphoma 10 (BCL10), phosphoinositide-3 kinase regulatory subunit 1 (PIK3R1), IL21, and Jagunal homolog 1 (JAGN1). New case reports expanded the clinical spectrum of gene defects. For example, a specific recombination-activating gene 1 variant protein with partial recombinant activity might produce Omenn syndrome or a common variable immunodeficiency phenotype. Central and peripheral B-cell tolerance was investigated in patients with several primary immunodeficiencies, including common variable immunodeficiency and Wiskott-Aldrich syndrome, to explain the occurrence of autoimmunity and inflammatory disorders. The role of IL-12 and IL-15 in the enhancement of natural killer cell activity was reported. Newborn screening for T-cell deficiency is being implemented in more states and is achieving its goal of defining the true incidence of severe combined immunodeficiency and providing early treatment that offers the highest survival for these patients. Definitive treatment of severe immunodeficiency with both hematopoietic stem cell transplantation and gene therapy was reported to be successful, with increasing definition of conditions needed for optimal outcomes. Progress in HIV infection is directed toward the development of an effective vaccine and the eradication of hidden latent virus reservoirs.

  16. [Clinical competence certification for advanced heart failure: an emerging need also in Italy?].

    PubMed

    Marini, Marco; Pini, Daniela; Russo, Giulia; Milli, Massimo; De Maria, Renata; Di Tano, Giuseppe; Aspromonte, Nadia

    2015-02-01

    Advanced heart failure (HF) is a deadly condition. Fortunately, an increasing array of effective (but often expensive) therapies has become available. The management of patients with advanced HF is complex and requires a high level of expertise. The American Board of Internal Medicine was the first regulatory board to recognize the need for a subspecialty in Advanced HF and Transplant Cardiology. More recently, the HF Association of the European Society of Cardiology has proposed a curriculum for HF specialists that includes the optional module of advanced HF therapy. However, the successful completion of such a curriculum does not result in a European Certification in Heart Failure, because no European Board of Medicine does exist. While in some European countries the secondary specialty of HF has been implemented, no country has a subspecialty in advanced HF. The ANMCO HF Area has proposed a survey to 25 Italian centers with accredited programs for heart transplant or ventricular assist device implant as destination therapy with the aim to assess the actual need of a certification of clinical competence in advanced HF and a certification of institutional competence for the centers with the highest expertise in advanced HF management. The survey indicated that there is a perceived need. A first step towards education of advanced HF specialists could be the implementation of CME courses by Scientific Societies. As regards certification of institutional competence for the centers with the highest expertise in advanced HF management, the government appears to be the only entity that can grant it.

  17. Recent clinical and translational advances in pediatric hypertension.

    PubMed

    Falkner, Bonita

    2015-05-01

    Epidemiological reports describe a child population increase in BP level and an increase in prevalence of hypertension, that is largely, but not entirely, driven by a concurrent increase in childhood obesity. Given current estimates, ≈10% of adolescents have hypertension or prehypertension. In addition to obesity, dietary salt intake and waist circumference, a marker of visceral obesity, are found to be independently associated with the rise in BP among children and adolescents. Dietary salt intake in urban children is well above recommended levels largely because of consumption of processed and fast foods. Childhood exposures, such as stress,52 salt, and fructose, as well as lifestyles, including food sources, sleep patterns, and reductions in physical activity may have a role in obesity-high BP associations. In addition, clinical and translational evidence is mounting that intrauterine exposures alter can effect changes in fetal development that have an enduring effect on cardiovascular and metabolic function later in life. These effects can be detected even in children who are products of a term otherwise normal pregnancy. Hypertension in childhood has been defined statistically (BP ≥ 95th percentile) because of lack of outcome data that links a BP level with heightened risk for future cardiovascular events. Therefore, primary hypertension had been considered a risk factor for later hypertension in adulthood. Intermediate markers of TOD, including cardiac hypertrophy, vascular stiffness, and increases in cIMT, are detectable in adolescents with primary hypertension. Evidence that vascular injury is present in the early phase of hypertension and even in prehypertension warrants consideration on the current definition of pediatric hypertension. With further studies on TOD and other risk factors in addition to high BP, it may be possible to shift from a statistical definition to a definition of childhood hypertension that is evidence based. Preventing or

  18. Recent clinical and translational advances in pediatric hypertension.

    PubMed

    Falkner, Bonita

    2015-05-01

    Epidemiological reports describe a child population increase in BP level and an increase in prevalence of hypertension, that is largely, but not entirely, driven by a concurrent increase in childhood obesity. Given current estimates, ≈10% of adolescents have hypertension or prehypertension. In addition to obesity, dietary salt intake and waist circumference, a marker of visceral obesity, are found to be independently associated with the rise in BP among children and adolescents. Dietary salt intake in urban children is well above recommended levels largely because of consumption of processed and fast foods. Childhood exposures, such as stress,52 salt, and fructose, as well as lifestyles, including food sources, sleep patterns, and reductions in physical activity may have a role in obesity-high BP associations. In addition, clinical and translational evidence is mounting that intrauterine exposures alter can effect changes in fetal development that have an enduring effect on cardiovascular and metabolic function later in life. These effects can be detected even in children who are products of a term otherwise normal pregnancy. Hypertension in childhood has been defined statistically (BP ≥ 95th percentile) because of lack of outcome data that links a BP level with heightened risk for future cardiovascular events. Therefore, primary hypertension had been considered a risk factor for later hypertension in adulthood. Intermediate markers of TOD, including cardiac hypertrophy, vascular stiffness, and increases in cIMT, are detectable in adolescents with primary hypertension. Evidence that vascular injury is present in the early phase of hypertension and even in prehypertension warrants consideration on the current definition of pediatric hypertension. With further studies on TOD and other risk factors in addition to high BP, it may be possible to shift from a statistical definition to a definition of childhood hypertension that is evidence based. Preventing or

  19. Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches

    PubMed Central

    Snyder, Hannah R.; Miyake, Akira; Hankin, Benjamin L.

    2015-01-01

    Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science. PMID:25859234

  20. What clinical activities do advanced-practice registered dietitian nutritionists perform? Results of a Delphi study.

    PubMed

    Brody, Rebecca A; Byham-Gray, Laura; Touger-Decker, Riva; Passannante, Marian R; Rothpletz Puglia, Pamela; O'Sullivan Maillet, Julie

    2014-05-01

    Activities performed by advanced-practice registered dietitian nutritionists (RDNs) have yet to be clearly elucidated. The study aimed to gain consensus on the practice activities of advanced-practice RDNs who provide direct clinical nutrition care. A three-round Delphi study was conducted. Purposive sampling identified 117 RDN experts working as clinicians and/or managers in direct care settings that met inclusion criteria for advanced-level practice. In Round 1, 85 experts provided open-ended advanced-level practice activities linked to the Nutrition Care Process sections. Using content analysis, the responses were coded into activity statements. In Round 2, experts rated the essentiality of these activities. In Round 3, experts re-rated statements not reaching consensus while viewing their previous rating, the group median, and comments. Median ratings of 1.0 to 3.0 were defined as essential, 4.0 were neither essential nor nonessential, and 5.0 to 7.0 were nonessential. Consensus was reached when the interquartile range of responses to each question was <2.0. Seventy-six (89.4%) experts completed all rounds. From 770 comments, 129 activity statements were generated. All statements reached consensus: 97.7% as essential; 0.8% as nonessential; and 1.5% as neither. Of essential activities, 67.5% were highly essential with limited variability (median=1.0; interquartile range≤2.0). Advanced-practice RDNs' tasks are patient-centered and reflect complex care; involve a comprehensive and discriminating approach; are grounded in advanced knowledge and expertise in clinical nutrition; include use of advanced interviewing, education, and counseling strategies; and require communication with patient, families, and the health care team. The high-level of consensus from experts suggest advanced-level clinical nutrition practice exists and can be defined.

  1. Translating Advances from the Basic Biology of Aging into Clinical Application

    PubMed Central

    Kirkland, James L.

    2013-01-01

    Recently, lifespan and healthspan have been extended in experimental animals using interventions that are potentially translatable into humans. A great deal of thought and work are needed beyond the usual steps in drug development to advance these findings into clinical application. Realistic pre-clinical and clinical trials paradigms need to be devised. Focusing on subjects with symptoms of age-related diseases or frailty or who are at imminent risk of developing these problems, measuring effects on short-term, clinically relevant outcomes, as opposed to long-term outcomes such as healthspan or lifespan, and developing biomarkers and outcome measures acceptable to regulatory agencies will be important. Research funding is a major roadblock, as is lack of investigators with combined expertise in the basic biology of aging, clinical geriatrics, and conducting investigational new drug clinical trials. Options are reviewed for developing a path from the bench to the bedside for interventions that target fundamental aging processes. PMID:23237984

  2. Peritoneal dialysis solutions low in glucose degradation products: clinical experience and outcomes.

    PubMed

    Diaz-Buxo, Jose A

    2007-01-01

    The latest literature describing clinical experiences with peritoneal dialysis solutions low in glucose degradation products (GDPs) is mostly consistent with previous reports suggesting less inflammation, better peritoneal mesothelial mass preservation, a lower rate of decline of residual renal function, and improved patient survival. The data suggest stable peritoneal transport rates, but no definite evidence has yet emerged of superior membrane preservation. Most studies have reported very low peritonitis rates, but without significant differences as compared with rates in patients exposed to conventional solutions. New, appropriately powered randomized clinical trials are needed to confirm the potential benefits of low-GDP solutions and to establish the role of renal function preservation with regard to those benefits.

  3. Contact Lens Care Solutions: A Pilot Study of Ethnic Differences in Clinical Signs and Symptoms

    PubMed Central

    Lin, Meng C.; Yuen, Jenny; Graham, Andrew D.

    2014-01-01

    Objectives To determine whether Asian and Caucasian subjects differ in clinical signs or subjective symptoms in response to use of different biguanide-preserved contact lens care solutions. Methods Forty-two subjects (15 Asian, 27 Caucasian) wearing lotrafilcon B silicone hydrogel contact lenses used a preservative-free lens care solution (Clear Care®, CIBA VISION, Atlanta, GA, USA) bilaterally for 2 weeks, then used 2 biguanide-preserved solutions (Solution 1: ReNu MPS®, Bausch & Lomb, Rochester, NY, USA; Solution 2: AQuify MPS®, CIBA VISION, Atlanta, GA, USA) contralaterally in randomly assigned eyes for 4 weeks. Comprehensive ocular surface exams were performed and symptomatology questionnaires were administered every 2 weeks. Investigators were masked as to solution assignment during examinations, while subjects were not in order to avoid potential difficulties in compliance with the protocol. Results With Solution 1, the majority of both Asian and Caucasian subjects had grade 2 or greater corneal staining after 2 weeks (67% and 59%, respectively) and 4 weeks (60% and 67%, respectively). With Solution 2, grade 2 or greater corneal staining occurred in 40% of Asians after 2 weeks and in 13% after 4 weeks, but in only 4% of Caucasians after 2 weeks and 0% after 4 weeks. Caucasians reported significantly better average comfort (p = 0.046) and less dryness (p < 0.001) than did Asians. Conclusions Asians and Caucasians differ in both ocular response to use of contact lens care solutions and in reporting of subjective symptoms. Racial and ethnic differences should be considered when evaluating and treating contact lens patients in a clinical setting. PMID:24887209

  4. Advances in circulating tumor cells (ACTC): from basic research to clinical practice

    PubMed Central

    2013-01-01

    The first 'Advances in Circulating Tumor Cells (ACTC): from Basic Research to Clinical Practice' meeting was held in Athens, Greece, September 26–29, 2012 (abstracts, presentations and a more detailed meeting report are freely available online: http://www.actc2012.org). We summarize in this report most major findings presented and the main conclusions derived during the expert panel sessions. PMID:24314311

  5. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  6. Identifying components of advanced-level clinical nutrition practice: a Delphi study.

    PubMed

    Brody, Rebecca A; Byham-Gray, Laura; Touger-Decker, Riva; Passannante, Marian R; O'Sullivan Maillet, Julie

    2012-06-01

    The dietetics profession lacks a comprehensive definition of advanced-level practice. Using a three-round Delphi study with mailed surveys, expert consensus on four dimensions of advanced-level practice that define advanced practice registered dietitians (RDs) in clinical nutrition was explored. Purposive sampling identified 117 RDs who met advanced-level practice criteria. In round 1, experts rated the essentiality of statements on a 7-point ordinal scale and generated open-ended practice activity statements regarding the following four dimensions of advanced-level practice: professional knowledge, abilities and skills, approaches to practice, roles and relationships, and practice behaviors. Median ratings of 1.0 to 3.0 were defined as essential, 4.0 was neutral, and 5.0 to 7.0 were nonessential. In rounds 2 and 3, experts re-rated statements not reaching consensus by evaluating their previous responses, group median rating, and comments. Consensus was reached when the interquartile range of responses to a statement was ≤2.0. Eighty-five experts enrolled (72.6%); 76 (89.4%) completed all rounds. In total, 233 statements were rated, with 100% achieving consensus; 211 (90.6%) were essential to advanced practice RD clinical practice. Having a master's degree; completing an advanced practice residency; research coursework; and advanced continuing education were essential, as were having 8 years of experience; clinical nutrition knowledge/expertise; specialization; participation in research activities; and skills in technology and communication. Highly essential approaches to practice were systematic yet adaptable and used critical thinking and intuition and highly essential values encompassed professional growth and service to patients. Roles emphasized patient care and leadership. Essential practice activities within the nutrition care process included provision of complex patient-centered nutrition care using application of advanced knowledge/expertise and

  7. Clinical cancer advances 2007: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Gralow, Julie; Ozols, Robert F; Bajorin, Dean F; Cheson, Bruce D; Sandler, Howard M; Winer, Eric P; Bonner, James; Demetri, George D; Curran, Walter; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory H; Sawaya, Raymond; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Davidson, Nancy E; Schilsky, Richard L; Lichter, Allen S

    2008-01-10

    A MESSAGE FROM ASCO'S PRESIDENT: For the third year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO publishes this report to demonstrate the important progress being made on the front lines of clinical cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and organizations, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on the use of magnetic resonance imaging for breast cancer screening, the association between hormone replacement therapy and breast cancer incidence, the link between human papillomavirus and head and neck cancers, and the use of radiation therapy to prevent lung cancer from spreading. They also report on effective new targeted therapies for cancers that have been historically difficult to treat, such as liver cancer and kidney cancer, among many others. A total of 24 advances are featured in this year's report. These advances and many more over the past several years show that the nation's long-term investment in cancer research is paying off. But there are disturbing signs that progress could slow. We are now in the midst of the longest sustained period of flat government funding for cancer research in history. The budgets for the National Institutes of Health and the National Cancer Institute (NCI) have been unchanged for four years. When adjusted for inflation, cancer research funding has actually declined 12% since 2004. These budget constraints limit the NCI's ability to fund promising cancer research. In the past several years the number of grants that the NCI has been able to fund has significantly decreased; this year, in response to just the

  8. Integrating first-line treatment options into clinical practice: what's new in advanced melanoma?

    PubMed

    Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Larkin, James; Lebbé, Celeste; Hauschild, Axel

    2015-12-01

    Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients. PMID:26426764

  9. The Clinical Impact of Recent Advances in LC-MS for Cancer Biomarker Discovery and Verification

    SciTech Connect

    Wang, Hui; Shi, Tujin; Qian, Weijun; Liu, Tao; Kagan, Jacob; Srivastava, Sudhir; Smith, Richard D.; Rodland, Karin D.; Camp, David G.

    2016-01-01

    Mass spectrometry-based proteomics has become an indispensable tool in biomedical research with broad applications ranging from fundamental biology, systems biology, and biomarker discovery. Recent advances in LC-MS have made it become a major technology in clinical applications, especially in cancer biomarker discovery and verification. To overcome the challenges associated with the analysis of clinical samples, such as extremely wide dynamic range of protein concentrations in biofluids and the need to perform high throughput and accurate quantification, significant efforts have been devoted to improve the overall performance of LC-MS bases clinical proteomics. In this review, we summarize the recent advances in LC-MS in the aspect of cancer biomarker discovery and quantification, and discuss its potentials, limitations, and future perspectives.

  10. Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis

    PubMed Central

    Mowery, D.; South, B. R.; Kvist, M.; Dalianis, H.

    2015-01-01

    Summary Objectives We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. Methods We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Results Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. Conclusions There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices. PMID:26293867

  11. Advancing medicine one research note at a time: the educational value in clinical case reports

    PubMed Central

    2012-01-01

    A case report—a brief written note that describes unique aspects of a clinical case—provides a significant function in medicine given its rapid, succinct, and educational contributions to scientific literature and clinical practice. Despite the growth of, and emphasis on, randomized clinical trials and evidenced-based medicine, case reports continue to provide novel and exceptional knowledge in medical education. The journal BMC Research Notes introduces a new “case reports” section to provide the busy clinician with a forum in which to document any authentic clinical case that provide educational value to current clinical practice. The aim is for this article type to be reviewed, wherever possible, by specialized Associate Editors for the journal, in order to provide rapid but thorough decision making. New ideas often garnered by and documented in case reports will support the advancement of medical science — one research note at a time. PMID:22697904

  12. Advanced ensemble modelling of flexible macromolecules using X-ray solution scattering.

    PubMed

    Tria, Giancarlo; Mertens, Haydyn D T; Kachala, Michael; Svergun, Dmitri I

    2015-03-01

    Dynamic ensembles of macromolecules mediate essential processes in biology. Understanding the mechanisms driving the function and molecular interactions of 'unstructured' and flexible molecules requires alternative approaches to those traditionally employed in structural biology. Small-angle X-ray scattering (SAXS) is an established method for structural characterization of biological macromolecules in solution, and is directly applicable to the study of flexible systems such as intrinsically disordered proteins and multi-domain proteins with unstructured regions. The Ensemble Optimization Method (EOM) [Bernadó et al. (2007 ▶). J. Am. Chem. Soc. 129, 5656-5664] was the first approach introducing the concept of ensemble fitting of the SAXS data from flexible systems. In this approach, a large pool of macromolecules covering the available conformational space is generated and a sub-ensemble of conformers coexisting in solution is selected guided by the fit to the experimental SAXS data. This paper presents a series of new developments and advancements to the method, including significantly enhanced functionality and also quantitative metrics for the characterization of the results. Building on the original concept of ensemble optimization, the algorithms for pool generation have been redesigned to allow for the construction of partially or completely symmetric oligomeric models, and the selection procedure was improved to refine the size of the ensemble. Quantitative measures of the flexibility of the system studied, based on the characteristic integral parameters of the selected ensemble, are introduced. These improvements are implemented in the new EOM version 2.0, and the capabilities as well as inherent limitations of the ensemble approach in SAXS, and of EOM 2.0 in particular, are discussed.

  13. Quality assurance issues in conducting multi-institutional advanced technology clinical trials.

    PubMed

    Purdy, James A

    2008-01-01

    The National Cancer Institute-sponsored Advanced Technology Quality Assurance (QA) Consortium, which consisted of the Image-Guided Therapy QA Center, Radiation Therapy Oncology Group, Radiological Physics Center, Quality Assurance Review Center, and Resource Center for Emerging Technologies, has pioneered the development of an infrastructure and QA method for advanced technology clinical trials that requires volumetric digital data submission of a protocol patient's treatment plan and verification data. In particular, the Image-Guided Therapy QA Center has nearly 15 years experience in facilitating QA review for Radiation Therapy Oncology Group advanced technology clinical trials. This QA process includes (1) a data integrity review for completeness of protocol required elements, the format of data, and possible data corruption, and recalculation of dose-volume histograms; (2) a review of compliance with target volume and organ-at-risk contours by study chairs; and (3) a review of dose prescription and dose heterogeneity compliance by the Radiation Therapy Oncology Group Headquarters Dosimetry Group or the Radiological Physics Center dosimetrists (for brachytherapy protocols). This report reviews the lessons learned and the QA challenges presented by the use of advanced treatment modalities in clinical trials requiring volumetric digital data submission.

  14. Quality Assurance Issues in Conducting Multi-Institutional Advanced Technology Clinical Trials

    SciTech Connect

    Purdy, James A.

    2008-05-01

    The National Cancer Institute-sponsored Advanced Technology Quality Assurance (QA) Consortium, which consisted of the Image-Guided Therapy QA Center, Radiation Therapy Oncology Group, Radiological Physics Center, Quality Assurance Review Center, and Resource Center for Emerging Technologies, has pioneered the development of an infrastructure and QA method for advanced technology clinical trials that requires volumetric digital data submission of a protocol patient's treatment plan and verification data. In particular, the Image-Guided Therapy QA Center has nearly 15 years experience in facilitating QA review for Radiation Therapy Oncology Group advanced technology clinical trials. This QA process includes (1) a data integrity review for completeness of protocol required elements, the format of data, and possible data corruption, and recalculation of dose-volume histograms; (2) a review of compliance with target volume and organ-at-risk contours by study chairs; and (3) a review of dose prescription and dose heterogeneity compliance by the Radiation Therapy Oncology Group Headquarters Dosimetry Group or the Radiological Physics Center dosimetrists (for brachytherapy protocols). This report reviews the lessons learned and the QA challenges presented by the use of advanced treatment modalities in clinical trials requiring volumetric digital data submission.

  15. Quality assurance issues in conducting multi-institutional advanced technology clinical trials.

    PubMed

    Purdy, James A

    2008-01-01

    The National Cancer Institute-sponsored Advanced Technology Quality Assurance (QA) Consortium, which consisted of the Image-Guided Therapy QA Center, Radiation Therapy Oncology Group, Radiological Physics Center, Quality Assurance Review Center, and Resource Center for Emerging Technologies, has pioneered the development of an infrastructure and QA method for advanced technology clinical trials that requires volumetric digital data submission of a protocol patient's treatment plan and verification data. In particular, the Image-Guided Therapy QA Center has nearly 15 years experience in facilitating QA review for Radiation Therapy Oncology Group advanced technology clinical trials. This QA process includes (1) a data integrity review for completeness of protocol required elements, the format of data, and possible data corruption, and recalculation of dose-volume histograms; (2) a review of compliance with target volume and organ-at-risk contours by study chairs; and (3) a review of dose prescription and dose heterogeneity compliance by the Radiation Therapy Oncology Group Headquarters Dosimetry Group or the Radiological Physics Center dosimetrists (for brachytherapy protocols). This report reviews the lessons learned and the QA challenges presented by the use of advanced treatment modalities in clinical trials requiring volumetric digital data submission. PMID:18406941

  16. Advances in clinical research in gynecologic radiation oncology: an RTOG symposium.

    PubMed

    Gaffney, David; Mundt, Arno; Schwarz, Julie; Eifel, Patricia

    2012-05-01

    There have been inexorable improvements in gynecologic radiation oncology through technologically advances, 3-dimensional imaging, and clinical research. Investment in these 3 critical areas has improved, and will continue to improve, the lives of patients with gynecologic cancer. Advanced technology delivery in gynecologic radiation oncology is challenging owing to the following: (1) setup difficulties, (2) managing considerable internal organ motion, and (3) responding to tumor volume reduction during treatment. Image guidance is a potential route to solve these problems and improve delivery to tumor and sparing organs at risk. Imaging with positron emission tomography-computed tomography and magnetic resonance imaging are contributing significantly to improved accuracy in diagnosis, treatment, and follow-up in cancer of the cervix. Functional imaging by exploiting tumor biology may improve prognosis and treatment. Clinical trials have been the greatest mechanism to improve and establish standards of care in women with vulvar, endometrial, and cervical cancer. There have been multiple technological advances and practice changing trials within the past several decades. Many important questions remain in optimizing care for women with gynecologic malignancies. The performance of clinical trials will be advanced with the use of consistent language (ie, similar staging system and criteria), eligibility criteria that fit the research question, end points that matter, adequate statistical power, complete follow-up, and prompt publication of mature results. PMID:22398709

  17. Selective Extraction of Heavy and Light Lanthanides from Aqueous Solution by Advanced Magnetic Nanosorbents.

    PubMed

    Zhang, Huijin; McDowell, Rocklan G; Martin, Leigh R; Qiang, You

    2016-04-13

    Rare earth elements (REEs) make unique and vital contributions to our current world of technology. Separating and recycling REEs is of great importance to diversify the sources of REEs and advance the efficient use of REE resources when the supply is limited. In light of separation nanotechnology, diethylenetriamine-pentaacetic acid (DTPA) functionalized magnetic nanosorbents have been synthesized and investigated for the highly selective extraction of heavy (Sm-Ho) and light (La-Nd) lanthanides (Ln) from aqueous solutions. The results demonstrated that the separation factor (SF) between heavy-Ln and light-Ln groups reached the maximal value of 11.5 at low pH value of 2.0 in 30 min. For example, the SFs of Gd/La and Dy/La pairs were up to 10 times higher than that reported by other studies. Besides the excellent selectivity, our double-coated magnetic nanoparticles coupled with diethylenetriaminepentaacetic acid (dMNP-DTPA) nanosorbents are more advantageous in that the Ln(III) sorption was effectively and quickly (in 30 min) achieved in acid solutions with pH values as low as 2.0. Such attributes ensure a stronger adaptability to the harsh environments of REE recycling processes. Displacement phenomena were subsequently observed between the heavy-Ln and light-Ln ions that were coexisting in solution and competing for the same sorption sites, causing the increase in sorption capacity of heavy Ln on the surface of nanosorbents with time. The order of affinity of Ln(III) to DTPA-functionalized magnetic nanosorbents perfectly followed the corresponding stability constants between Ln(III) and nonimmobilized DTPA. Displacement phenomena and lanthanide contraction, as well as the surface nanostructures of DTPA-functionalized nanosorbents, significantly improved the separation factors of heavy-Ln/light-Ln pairs. The Ln(III) interaction with DTPA-functionalized magnetic nanosorbents followed the pseudo-second-order kinetics with a correlation coefficient extremely high and

  18. Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

    PubMed

    Vogelzang, Nicholas J; Benowitz, Steven I; Adams, Sylvia; Aghajanian, Carol; Chang, Susan Marina; Dreyer, Zoann Eckert; Janne, Pasi A; Ko, Andrew H; Masters, Greg A; Odenike, Olatoyosi; Patel, Jyoti D; Roth, Bruce J; Samlowski, Wolfram E; Seidman, Andrew D; Tap, William D; Temel, Jennifer S; Von Roenn, Jamie H; Kris, Mark G

    2012-01-01

    A message from ASCO'S President. It has been forty years since President Richard Nixon signed the National Cancer Act of 1971, which many view as the nation's declaration of the "War on Cancer." The bill has led to major investments in cancer research and significant increases in cancer survival. Today, two-thirds of patients survive at least five years after being diagnosed with cancer compared with just half of all diagnosed patients surviving five years after diagnosis in 1975. The research advances detailed in this year's Clinical Cancer Advances demonstrate that improvements in cancer screening, treatment, and prevention save and improve lives. But although much progress has been made, cancer remains one of the world's most serious health problems. In the United States, the disease is expected to become the nation's leading cause of death in the years ahead as our population ages. I believe we can accelerate the pace of progress, provided that everyone involved in cancer care works together to achieve this goal. It is this viewpoint that has shaped the theme for my presidential term: Collaborating to Conquer Cancer. In practice, this means that physicians and researchers must learn from every patient's experience, ensure greater collaboration between members of a patient's medical team, and involve more patients in the search for cures through clinical trials. Cancer advocates, insurers, and government agencies also have important roles to play. Today, we have an incredible opportunity to improve the quality of cancer care by drawing lessons from the real-world experiences of patients. The American Society of Clinical Oncology (ASCO) is taking the lead in this area, in part through innovative use of health information technology. In addition to our existing quality initiatives, ASCO is working with partners to develop a comprehensive rapid-learning system for cancer care. When complete, this system will provide physicians with personalized, real

  19. Technical solutions for mitigating security threats caused by health professionals in clinical settings.

    PubMed

    Fernandez-Aleman, Jose Luis; Belen Sanchez Garcia, Ana; Garcia-Mateos, Gines; Toval, Ambrosio

    2015-08-01

    The objective of this paper is to present a brief description of technical solutions for health information system security threats caused by inadequate security and privacy practices in healthcare professionals. A literature search was carried out in ScienceDirect, ACM Digital Library and IEEE Digital Library to find papers reporting technical solutions for certain security problems in information systems used in clinical settings. A total of 17 technical solutions were identified: measures for password security, the secure use of e-mail, the Internet, portable storage devices, printers and screens. Although technical safeguards are essential to the security of healthcare organization's information systems, good training, awareness programs and adopting a proper information security policy are particularly important to prevent insiders from causing security incidents. PMID:26736528

  20. Technical solutions for mitigating security threats caused by health professionals in clinical settings.

    PubMed

    Fernandez-Aleman, Jose Luis; Belen Sanchez Garcia, Ana; Garcia-Mateos, Gines; Toval, Ambrosio

    2015-08-01

    The objective of this paper is to present a brief description of technical solutions for health information system security threats caused by inadequate security and privacy practices in healthcare professionals. A literature search was carried out in ScienceDirect, ACM Digital Library and IEEE Digital Library to find papers reporting technical solutions for certain security problems in information systems used in clinical settings. A total of 17 technical solutions were identified: measures for password security, the secure use of e-mail, the Internet, portable storage devices, printers and screens. Although technical safeguards are essential to the security of healthcare organization's information systems, good training, awareness programs and adopting a proper information security policy are particularly important to prevent insiders from causing security incidents.

  1. Clinical thermometry: possible causes and potential solutions to electronic, digital thermometer inaccuracies.

    PubMed

    Latman, Neal S

    2003-01-01

    Previous research has indicated that the improvements in safety, speed, and ease of use of the newer electronic, digital oral and tympanic clinical thermometers have been offset by a loss in accuracy and reliability when compared with the traditional glass/mercury oral clinical thermometers. The purpose of this study was to determine possible causes of the relative lack of accuracy and reliability in these thermometers and suggest logical potential solutions. Evidence has been reviewed, which suggests that problems with the tympanic thermometers are the result of the range of normal anatomical variability. The combination of an otoscope with the tympanic thermometers is suggested and discussed as a potential solution. Evidence has been reviewed, which suggests that problems with the newer oral thermometers are the results of the size of the temperature sensors and the speed with which they respond. The small sensor size results in variability in placement relative to the primary heat source. The speed of sensor response results in too great a sensitivity to local, acute vasomotor activity (clinical temperature noise). Potential solutions, including an increase in sensor size and a reduction in response speed are discussed.

  2. A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application.

    PubMed

    Garland, Megan; Yim, Joshua J; Bogyo, Matthew

    2016-01-21

    The Precision Medicine Initiative aims to use advances in basic and clinical research to develop therapeutics that selectively target and kill cancer cells. Under the same doctrine of precision medicine, there is an equally important need to visualize these diseased cells to enable diagnosis, facilitate surgical resection, and monitor therapeutic response. Therefore, there is a great opportunity for chemists to develop chemically tractable probes that can image cancer in vivo. This review focuses on recent advances in the development of optical probes, as well as their current and future applications in the clinical management of cancer. The progress in probe development described here suggests that optical imaging is an important and rapidly developing field of study that encourages continued collaboration among chemists, biologists, and clinicians to further refine these tools for interventional surgical imaging, as well as for diagnostic and therapeutic applications. PMID:26933740

  3. [Image guided and robotic treatment--the advance of cybernetics in clinical medicine].

    PubMed

    Fosse, E; Elle, O J; Samset, E; Johansen, M; Røtnes, J S; Tønnessen, T I; Edwin, B

    2000-01-10

    The introduction of advanced technology in hospitals has changed the treatment practice towards more image guided and minimal invasive procedures. Modern computer and communication technology opens up for robot aided and pre-programmed intervention. Several robotic systems are in clinical use today both in microsurgery and in major cardiac and orthopedic operations. As this trend develops, professions which are new in this context such as physicists, mathematicians and cybernetic engineers will be increasingly important in the treatment of patients.

  4. Clinical decision support systems for brain tumor characterization using advanced magnetic resonance imaging techniques.

    PubMed

    Tsolaki, Evangelia; Kousi, Evanthia; Svolos, Patricia; Kapsalaki, Efthychia; Theodorou, Kyriaki; Kappas, Constastine; Tsougos, Ioannis

    2014-04-28

    In recent years, advanced magnetic resonance imaging (MRI) techniques, such as magnetic resonance spectroscopy, diffusion weighted imaging, diffusion tensor imaging and perfusion weighted imaging have been used in order to resolve demanding diagnostic problems such as brain tumor characterization and grading, as these techniques offer a more detailed and non-invasive evaluation of the area under study. In the last decade a great effort has been made to import and utilize intelligent systems in the so-called clinical decision support systems (CDSS) for automatic processing, classification, evaluation and representation of MRI data in order for advanced MRI techniques to become a part of the clinical routine, since the amount of data from the aforementioned techniques has gradually increased. Hence, the purpose of the current review article is two-fold. The first is to review and evaluate the progress that has been made towards the utilization of CDSS based on data from advanced MRI techniques. The second is to analyze and propose the future work that has to be done, based on the existing problems and challenges, especially taking into account the new imaging techniques and parameters that can be introduced into intelligent systems to significantly improve their diagnostic specificity and clinical application.

  5. Professional excellence and career advancement in nursing: a conceptual framework for clinical leadership development.

    PubMed

    Adeniran, Rita Kudirat; Bhattacharya, Anand; Adeniran, Anthony A

    2012-01-01

    Increasingly, stakeholders in the health care community are recognizing nursing as key to solving the nation's health care issues. This acknowledgment provides a unique opportunity for nursing to demonstrate leadership by developing clinical nurse leaders to collaborate with the multidisciplinary care team in driving evidence-based, safe quality, cost-effective health care services. One approach for nursing success is standardizing the entry-level education for nurses and developing a uniform professional development and career advancement trajectory with appropriate incentives to encourage participation. A framework to guide and provide scientific evidence of how frontline nurses can be engaged will be paramount. The model for professional excellence and career advancement provides a framework that offers a clear path for researchers to examine variables influencing nurses' professional development and career advancement in a systematic manner. Professional Excellence and Career Advancement in Nursing underscores professional preparedness of a registered nurse as central to leadership development. It also describes the elements that influence nurses' participation in professional development and career advancement under 4 main categories emphasizing mentorship and self-efficacy as essential variables.

  6. Advanced image reconstruction strategies for 4D prostate DCE-MRI: steps toward clinical practicality

    NASA Astrophysics Data System (ADS)

    Stinson, Eric G.; Borisch, Eric A.; Froemming, Adam T.; Kawashima, Akira; Young, Phillip M.; Warndahl, Brent A.; Grimm, Roger C.; Manduca, Armando; Riederer, Stephen J.; Trzasko, Joshua D.

    2015-09-01

    Dynamic contrast-enhanced (DCE) MRI is an important tool for the detection and characterization of primary and recurring prostate cancer. Advanced reconstruction strategies (e.g., sparse or low-rank regression) provide improved depiction of contrast dynamics and pharmacokinetic parameters; however, the high computation cost of reconstructing 4D (3D+time, 50+ frames) datasets typically inhibits their routine clinical use. Here, a novel alternating direction method-of-multipliers (ADMM) optimization strategy is described that enables these methods to be executed in ∠5 minutes, and thus within the standard clinical workflow. After overviewing the mechanics of this approach, high-performance implementation strategies will be discussed and demonstrated through clinical cases.

  7. Biology of Advanced Uveal Melanoma and Next Steps for Clinical Therapeutics

    PubMed Central

    Luke, Jason J.; Triozzi, Pierre L.; McKenna, Kyle C.; Van Meir, Erwin G.; Gershenwald, Jeffrey E.; Bastian, Boris C.; Gutkind, J. Silvio; Bowcock, Anne M.; Streicher, Howard Z.; Patel, Poulam M.; Sato, Takami; Sossman, Jeffery A.; Sznol, Mario; Welch, Jack; Thurin, Magdalena; Selig, Sara; Flaherty, Keith T.; Carvajal, Richard D.

    2014-01-01

    Summary Uveal melanoma is the most common intraocular malignancy though it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15 year period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease and median survival remains poor. Here, as a joint effort between CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed and next steps in the development of clinical therapeutics are discussed. PMID:25113308

  8. Engineering and clinical-oriented solution to cost-effective PACS for developing areas in China

    NASA Astrophysics Data System (ADS)

    Hu, Dake; Zhang, Hong; Zhou, Shengmin; Shao, Lin

    1997-05-01

    Although PACS has been studied in industrial countries for more than sixteen years, few effort has been made so far to apply PACS technology to such developing areas as most rural regions in CHina. Engineering and clinical problems raised from installing PACS in undeveloped areas has brought many challenges to our system design. In this study, we try to analyze the clinical need of the Chinese hospitals and find out a solution to meet most hospitals' requirements from engineering and clinical points of view, such as system cost, ease of deployment, user interface, maintenance difficulty, etc., thus provide patients with better medical serve at affordable cost. First of all, we analyzed data collected from Zhejiang Cancer Hospital (ZCH) and take hospitals' financial situation into consideration. then according to the analysis, we made our choices for hardware and software platform, digitizer and storage device. The development of mini PACS is interacted by clinicians and radiologists from ZCH. They showed great interest in the downsizing PACS that does not risk much of the system performance. It is promising that our solution will be accepted in developing areas.

  9. Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic Diseases.

    PubMed

    Oliveira, Cláudia; Ribeiro, António J; Veiga, Francisco; Silveira, Isabel

    2016-05-01

    Delivery of nucleic acids is the most promising therapy for many diseases that remain untreatable. Therefore, many research efforts have been put on finding a safe and efficient delivery system able to provide a sustained response. Viral vectors have proved to be the most efficient for delivery of nucleic acids and, thus, stand as the foremost vector used in current clinical trials. However, safety issues arise as a main concern and mitigate their use, impelling the improvement of non-viral alternatives. This review focuses on the recent advances in pre-clinical development of non-viral polyplexes and lipoplexes for nucleic acid-based delivery, in contrast with vectors being used in present clinical trials. Nucleic acid vectors for neurodegenerative ataxias, Parkinson's disease, retinitis pigmentosa, cystic fibrosis, hemophilia, pancreatic and lung cancer, and rheumatoid arthritis are discussed to illustrate current state of pre-clinical and clinical studies. Thereby, denoting the prospects for treatment of genetic diseases and elucidating the trend in non-viral vector development and improvement which is expected to significantly increase disease rescue exceeding the modest clinical successes observed so far. PMID:27305810

  10. Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic Diseases.

    PubMed

    Oliveira, Cláudia; Ribeiro, António J; Veiga, Francisco; Silveira, Isabel

    2016-05-01

    Delivery of nucleic acids is the most promising therapy for many diseases that remain untreatable. Therefore, many research efforts have been put on finding a safe and efficient delivery system able to provide a sustained response. Viral vectors have proved to be the most efficient for delivery of nucleic acids and, thus, stand as the foremost vector used in current clinical trials. However, safety issues arise as a main concern and mitigate their use, impelling the improvement of non-viral alternatives. This review focuses on the recent advances in pre-clinical development of non-viral polyplexes and lipoplexes for nucleic acid-based delivery, in contrast with vectors being used in present clinical trials. Nucleic acid vectors for neurodegenerative ataxias, Parkinson's disease, retinitis pigmentosa, cystic fibrosis, hemophilia, pancreatic and lung cancer, and rheumatoid arthritis are discussed to illustrate current state of pre-clinical and clinical studies. Thereby, denoting the prospects for treatment of genetic diseases and elucidating the trend in non-viral vector development and improvement which is expected to significantly increase disease rescue exceeding the modest clinical successes observed so far.

  11. Hydrolytic pathway of 5-fluorouracil in aqueous solutions for clinical use.

    PubMed

    Legay, Rémi; Massou, Stéphane; Azéma, Joëlle; Martino, Robert; Malet-Martino, Myriam

    2014-09-01

    The purpose of the study was to investigate the degradation pathway of 5-fluorouracil (FU) in the situation of commercial formulations for clinical use, namely FU dissolved in sodium hydroxide (NaOH) solutions or Tris buffer at pH 8.5-9. Combination of data from (19)F, (1)H and (13)C NMR and in some cases MS led to the identification of 8 and 13 FU degradation products in NaOH and Tris solutions respectively. In FU NaOH solutions, the first stage of FU degradation is a stereoselective hydration of the C5-C6 double bond leading to 5,6-dihydro-5-fluoro-6-hydroxyuracil, the cis stereoisomer being predominant relative to the trans. The second stage involves either a defluorination step with formation of fluoride ion and 5-hydroxyuracil or the cleavage of the N3-C4 bond giving the two diastereoisomeric 2-fluoro-3-hydroxy-3-ureidopropanoic acids. The subsequent N1-C6 bond breakdown of these compounds releases urea and 2-fluoro-3-oxopropanoic acid (FOPA) which in turn losses easily carbon dioxide leading to the formation of fluoroacetaldehyde (Facet). The degradation pathway in FU-Tris solutions is identical, except that Tris reacts with the aldehydes FOPA and Facet to form oxazolidine adducts stable at pH 8.5 but in equilibrium with the aldehyde forms at physiological pH, whereas the high reactivity of free aldehydes leads to numerous unidentified degradation compounds all in very low amounts. The FOPA diastereoisomeric adducts react with Facet to form four diastereoisomeric fused bicyclic five-membered ring compounds. Facet and FOPA are highly cardiotoxic. In Tris formulations, they are trapped as stable oxazolidine adducts which release the free aldehydes at physiological pH thus explaining the higher cardiotoxicity of FU in Tris solutions compared to that of FU in NaOH solutions.

  12. From unmet clinical need to entrepreneurship: taking your informatics solution to market.

    PubMed

    Bowles, Kathryn H; Heil, Eric

    2014-01-01

    This paper will describe the process for taking a decision support solution to market as a start-up business. The nurse inventor and Co-Founder of RightCare Solutions, Inc. will share the steps from answering a clinical question, to registering an invention, creating a business plan and company, obtaining venture funding, and launching a commercial product. We will share positives about the experience such as how to get start-up funds, gaining national exposure and access to an excellent team, disseminating your work broadly, further enhancing the product, and obtaining equity, and financial rewards. We will discuss cons such as losing control, dilution of ownership, and conflict of interest. This paper will encourage nurse informaticians to think differently and learn about the steps in the process from an experienced team. PMID:24943561

  13. From unmet clinical need to entrepreneurship: taking your informatics solution to market.

    PubMed

    Bowles, Kathryn H; Heil, Eric

    2014-01-01

    This paper will describe the process for taking a decision support solution to market as a start-up business. The nurse inventor and Co-Founder of RightCare Solutions, Inc. will share the steps from answering a clinical question, to registering an invention, creating a business plan and company, obtaining venture funding, and launching a commercial product. We will share positives about the experience such as how to get start-up funds, gaining national exposure and access to an excellent team, disseminating your work broadly, further enhancing the product, and obtaining equity, and financial rewards. We will discuss cons such as losing control, dilution of ownership, and conflict of interest. This paper will encourage nurse informaticians to think differently and learn about the steps in the process from an experienced team.

  14. Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward clinical utility.

    PubMed

    Williams, Elsie M; Little, Rory F; Mowday, Alexandra M; Rich, Michelle H; Chan-Hyams, Jasmine V E; Copp, Janine N; Smaill, Jeff B; Patterson, Adam V; Ackerley, David F

    2015-10-15

    This review examines the vast catalytic and therapeutic potential offered by type I (i.e. oxygen-insensitive) nitroreductase enzymes in partnership with nitroaromatic prodrugs, with particular focus on gene-directed enzyme prodrug therapy (GDEPT; a form of cancer gene therapy). Important first indications of this potential were demonstrated over 20 years ago, for the enzyme-prodrug pairing of Escherichia coli NfsB and CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. However, it has become apparent that both the enzyme and the prodrug in this prototypical pairing have limitations that have impeded their clinical progression. Recently, substantial advances have been made in the biodiscovery and engineering of superior nitroreductase variants, in particular development of elegant high-throughput screening capabilities to enable optimization of desirable activities via directed evolution. These advances in enzymology have been paralleled by advances in medicinal chemistry, leading to the development of second- and third-generation nitroaromatic prodrugs that offer substantial advantages over CB1954 for nitroreductase GDEPT, including greater dose-potency and enhanced ability of the activated metabolite(s) to exhibit a local bystander effect. In addition to forging substantial progress towards future clinical trials, this research is supporting other fields, most notably the development and improvement of targeted cellular ablation capabilities in small animal models, such as zebrafish, to enable cell-specific physiology or regeneration studies.

  15. Unmet clinical needs in the management of advanced melanoma: findings from a survey of oncologists.

    PubMed

    Jones, C; Clapton, G; Zhao, Z; Barber, B; Saltman, D; Corrie, P

    2015-11-01

    Advanced melanoma is a life-threatening cancer with limited life expectancy. The recent introduction of new targeted systemic therapies has provided clinicians with the means to potentially extend survival for the first time. However, the chance of cure remains very low and treatment-induced toxicity is well described. This qualitative study was undertaken to evaluate clinicians' assessment regarding the key concerns in managing advanced melanoma following the introduction of these new treatments. Three hundred and forty-three oncologists were surveyed online between August and November 2012 (in 11 countries) and March and April 2013 (in an additional country). Analysis of free-text responses identified 23 clinical issues of concern across all countries. Of these, the most common clinical concerns were drug toxicity and tolerability, followed by limited treatment effectiveness and limited treatment options. These results suggest that despite the promise of the two new agents in the field, clinicians are still concerned about the limitations of current treatment options, recognising that there remains a significant unmet need in the treatment of advanced melanoma.

  16. mHealth Clinic Appointment PC Tablet: Implementation, Challenges and Solutions

    PubMed Central

    Smith, Carol E.; Spaulding, Ryan; Piamjariyakul, Ubolrat; Werkowitch, Marilyn; Yadrich, Donna Macan; Hooper, Dedrick; Moore, Tyson; Gilroy, Richard

    2015-01-01

    Background Patients requiring daily intravenous (IV) home parenteral nutrition (HPN) would benefit from in-home professional observation to improve self-care, to assess, detect and prevent serious complications. Aims The study aims are to assess the viability and utility of conducting mobile healthcare (mHealth) videoconference assessments with patients managing lifelong daily 12-hour IV nutrition infusions in their homes. The challenges and solutions to implementing mobile personal computer (PC) tablet based clinic appointments are described. Methods A wireless Apple iPad Mini™ mobile touch-screen tablet computer with 5 mega-pixel camera was loaned to patients. Each tablet had Polycom RealPresence software and a fourth generation (4G) mobile telecommunications data plan. These supported audio-visual mobile videoconferencing encrypted connections between health professionals in their offices and HPN patients and their family members in their homes. Patients’ and professionals’ evaluations of their mHealth clinic experiences are collected. Results Patients (mean age = 41.9, SD = 2.8 years) had been prescribed 12-hour home parenteral nutrition (HPN) infusions daily due short bowel disorders. Patients had been on HPN from 1 to 10 years (M=4, SD=3.6). Evaluation of clinic appointments revealed that 100% of the patients (n=45) and the professionals (n=6) indicated that they can clearly hear and easily see one another. The mHealth audio-visual interactions were highly rated by patients and family members. Professionals highly rated their ability to obtain a medical history and visual inspection of patients. Several challenges were identified and recommendations for resolutions are described. Discussion All patients and professionals highly rated the iPad mHealth clinic appointments for convenience and ease of communicating between homes and offices. An important challenge for all mHealth visits is the clinical professional’s ability to make clinically accurate

  17. 7th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis.

    PubMed

    Zhang, Tianyi Tee; Wang, Li; Weng, Naidong; Dong, Kelly; Valaskovic, Gary; Lee, Mike

    2016-10-01

    7th Annual Symposium on Clinical & Pharmaceutical Solutions through Analysis, Renaissance Shanghai Pudong Hotel, Shanghai, China, 20-23 April 2016 The 7th Annual Shanghai Symposium on Innovative Approaches to Reduce Attrition and Predict Clinical Outcomes (CPSA Shanghai 2016) was held on 20-23 April 2016 in Renaissance Shanghai Pudong Hotel, Shanghai, China. The meeting was featured with highly interactive events including diversified symposia, round table discussions, workshops, poster sessions and conference awards. There were over 220 participants from more than ten countries, with 61 oral presentations and 29 posters presented. In addition, the meeting included one preconference workshop and three joint sessions held with bioanalytical experts from local communities. PMID:27610924

  18. Clinical Cancer Advances 2008: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report From the American Society of Clinical Oncology

    PubMed Central

    Winer, Eric; Gralow, Julie; Diller, Lisa; Karlan, Beth; Loehrer, Patrick; Pierce, Lori; Demetri, George; Ganz, Patricia; Kramer, Barnett; Kris, Mark; Markman, Maurie; Mayer, Robert; Pfister, David; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory; Sandler, Howard; Sawaya, Raymond; Schuchter, Lynn; Sweetenham, John; Vahdat, Linda; Schilsky, Richard L.

    2009-01-01

    most significant clinical research is conducted increasingly overseas. In addition, talented young physicians in the United States, seeing less opportunity in the field of oncology, are choosing other specialties instead. Although greater investment in research is critical, the need for new therapies is only part of the challenge. Far too many people in the United States lack access to the treatments that already exist, leading to unnecessary suffering and death. Uninsured cancer patients are significantly more likely to die than those with insurance, racial disparities in cancer incidence and mortality remain stark, and even insured patients struggle to keep up with the rapidly rising cost of cancer therapies. As this annual American Society of Clinical Oncology report of the major cancer research advances during the last year demonstrates, we are making important progress against cancer. But sound public policies are essential to accelerate that progress. In 2009, we have an opportunity to reinvest in cancer research, and to support policies that will help ensure that every individual in the United States receives potentially life-saving cancer prevention, early detection, and treatment. Sincerely, Richard L. Schilsky, MD President American Society of Clinical Oncology PMID:19103723

  19. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    PubMed

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. PMID:25907434

  20. [Advances in cancer research. Cancer research and clinical oncology in the 21st century].

    PubMed

    Kanamaru, R

    1999-06-01

    It is my great pleasure to congradulate the Japanese Journal of Cancer and Chemotherapy on its 25 th anniversary. During this period, great progress has been made in cancer research, mainly owing to the advances in technology in molecular biology. Recently, not only researchers, but lay people as well have come to understand that cancer is mainly a genetic disease. Advances in the human genome project, DNA chip technology and gene technology; including gene targeting and cloning techniques, will enable us to accelerate progress forward the final goal of cancer research in the coming century. Major changes are coming in both cancer research and clinical oncology, which will completely transform the human social environment.

  1. Nanomedicine in the ROS-Mediated Pathophysiology: Applications and Clinical Advances

    PubMed Central

    Nash, Kevin M.; Ahmed, Salahuddin

    2015-01-01

    Reactive oxygen species (ROS) are important in regulating normal cell physiological functions, but when produced in excess lead to the augmented pathogenesis of various diseases. Among these ischemia reperfusion injury, Alzheimer’s disease and rheumatoid arthritis, are particularly important. Since ROS can be counteracted by a variety of antioxidants, natural and synthetic antioxidants have been developed. However, due to the ubiquitous production of ROS in living systems, poor in vivo efficiency of these agents and lack of target specificity, the current clinical modalities to treat oxidative stress damage are limited. Advances in the developing field of nanomedicine have yielded nanoparticles that can prolong antioxidant activity, and target specificity of these agents. Thus, catalytic antioxidants such as recombinant superoxide dismutase (SOD), in combination with platinum and cerium oxide nanoparticles manifest higher efficacy at smaller doses with potentially lower toxicity. This article reviews recent advances in antioxidant nanoparticles and their applications to manage oxidative stress-mediated diseases. PMID:26255114

  2. Genitourinary tumours in the targeted therapies era: new advances in clinical practice and future perspectives.

    PubMed

    Messina, Carlo; Buzzatti, Giulia; Dellepiane, Chiara; Cavo, Alessia; Tolomeo, Francesco; Cattrini, Carlo; Boccardo, Francesco

    2016-11-01

    Genitourinary cancers represent a heterogeneous group of malignancies arising from genitourinary tract, and are responsible for almost 359 000 newly diagnosed cases and 58 420 related deaths in USA. Continuous advances in cancer genetics and genomics have contributed towards changing the management paradigms of these neoplasms. Neoangiogenesis, through the activation of the tyrosine-kinase receptors signalling pathways, represents the key mediator event in promoting tumour proliferation, differentiation, invasiveness and motility. In the last decade, several treatments have been developed with the specific aim of targeting different cell pathways that have been recognized to drive tumour progression. The following review attempts to provide a comprehensive overview of the literature, focusing on new advances in targeted therapies for genitourinary tumours. Furthermore, the promising results of the latest clinical trials and future perspectives will be discussed.

  3. Overview of clinical flow cytometry data analysis: recent advances and future challenges.

    PubMed

    Pedreira, Carlos E; Costa, Elaine S; Lecrevisse, Quentin; van Dongen, Jacques J M; Orfao, Alberto

    2013-07-01

    Major technological advances in flow cytometry (FC), both for instrumentation and reagents, have emerged over the past few decades. These advances facilitate simultaneous evaluation of more parameters in single cells analyzed at higher speed. Consequently, larger and more complex data files that contain information about tens of parameters for millions of cells are generated. This increasing complexity has challenged pre-existing data analysis tools and promoted the development of new algorithms and tools for data analysis and visualization. Here, we review the currently available (conventional and newly developed) data analysis and visualization strategies that aim for easier, more objective, and robust interpretation of FC data both in biomedical research and clinical diagnostic laboratories.

  4. Right person, right skills, right job: the contribution of objective structured clinical examinations in advancing staff nurse experts.

    PubMed

    Mitchell, Marion; Strube, Petra; Vaux, Amanda; West, Nicky; Auditore, Anthony

    2013-10-01

    Recruitment processes need to discriminate among candidates to ensure that the right person with the right skills is selected for advancement opportunities. An innovative recruitment process using an objective structured clinical examination grounded in best practice guidelines resulted in improved recruitment practices for senior nursing clinical expert roles. Candidates' skills, knowledge, and attitudes in the areas of patient focus, clinical expertise, teamwork, and leadership were assessed using a clinical simulation. Candidates achieving advancement were assessed at 6 months to validate the efficacy of the process.

  5. Clinical skills assessment of procedural and advanced communication skills: performance expectations of residency program directors

    PubMed Central

    Langenau, Erik E.; Zhang, Xiuyuan; Roberts, William L.; DeChamplain, Andre F.; Boulet, John R.

    2012-01-01

    Background High stakes medical licensing programs are planning to augment and adapt current examinations to be relevant for a two-decision point model for licensure: entry into supervised practice and entry into unsupervised practice. Therefore, identifying which skills should be assessed at each decision point is critical for informing examination development, and gathering input from residency program directors is important. Methods Using data from previously developed surveys and expert panels, a web-delivered survey was distributed to 3,443 residency program directors. For each of the 28 procedural and 18 advanced communication skills, program directors were asked which clinical skills should be assessed, by whom, when, and how. Descriptive statistics were collected, and Intraclass Correlations (ICC) were conducted to determine consistency across different specialties. Results Among 347 respondents, program directors reported that all advanced communication and some procedural tasks are important to assess. The following procedures were considered ‘important’ or ‘extremely important’ to assess: sterile technique (93.8%), advanced cardiovascular life support (ACLS) (91.1%), basic life support (BLS) (90.0%), interpretation of electrocardiogram (89.4%) and blood gas (88.7%). Program directors reported that most clinical skills should be assessed at the end of the first year of residency (or later) and not before graduation from medical school. A minority were considered important to assess prior to the start of residency training: demonstration of respectfulness (64%), sterile technique (67.2%), BLS (68.9%), ACLS (65.9%) and phlebotomy (63.5%). Discussion Results from this study support that assessing procedural skills such as cardiac resuscitation, sterile technique, and phlebotomy would be amenable to assessment at the end of medical school, but most procedural and advanced communications skills would be amenable to assessment at the end of the first

  6. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    PubMed

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-01-01

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs. PMID:18840258

  7. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes

    PubMed Central

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-01-01

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs. PMID:18840258

  8. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes.

    PubMed

    Meerwaldt, Robbert; Links, Thera; Zeebregts, Clark; Tio, Rene; Hillebrands, Jan-Luuk; Smit, Andries

    2008-10-07

    Cardiovascular disease is the major cause of morbidity and mortality associated with diabetes. There is increasing evidence that advanced glycation endproducts (AGEs) play a pivotal role in atherosclerosis, in particular in diabetes. AGE accumulation is a measure of cumulative metabolic and oxidative stress, and may so represent the "metabolic memory". Furthermore, increased AGE accumulation is closely related to the development of cardiovascular complications in diabetes. This review article will focus on the clinical relevance of measuring AGE accumulation in diabetic patients by focusing on AGE formation, AGEs as predictors of long-term complications, and interventions against AGEs.

  9. Overview of the 3rd isirv-Antiviral Group Conference – advances in clinical management

    PubMed Central

    Hurt, Aeron C; Hui, David S; Hay, Alan; Hayden, Frederick G

    2015-01-01

    This review highlights the main points which emerged from the presentations and discussions at the 3rd isirv-Antiviral Group Conference - advances in clinical management. The conference covered emerging and potentially pandemic influenza viruses and discussed novel/pre-licensure therapeutics and currently approved antivirals and vaccines for the control of influenza. Current data on approved and novel treatments for non-influenza respiratory viruses such as MERS-CoV, respiratory syncytial virus (RSV) and rhinoviruses and the challenges of treating immunocompromised patients with respiratory infections was highlighted. PMID:25399715

  10. Using an Advance Organizer to Improve Knowledge Application by Medical Students in Computer-Based Clinical Simulations.

    ERIC Educational Resources Information Center

    Krahn, Corrie G.; Blanchaer, Marcel C.

    1986-01-01

    This study investigated the efficacy of using the advance organizer as a device to improve medical students' understanding of a clinical case simulation on the microcomputer and to enhance performance on a posttest. Advance organizers were found to be effective and most consistent with Mayer's assimilation theory. (MBR)

  11. Preliminary Data from an Advanced Dementia Consult Service: Integrating Research, Education, and Clinical Expertise

    PubMed Central

    Catic, Angela G.; Mitchell, Susan L.

    2013-01-01

    Hospitalized patients with advanced dementia often receive care that is of limited clinical benefit and inconsistent with preferences. We designed an Advanced Dementia Consult Service and conducted a pre and post pilot study to evaluate it in a Boston hospital. Consults were conducted by geriatricians and palliative care nurse practitioner. They consisted of structured consultation, counseling and provision of an information booklet to the family, and post-discharge follow-up with the family and primary care providers. Patients > 65 admitted with advanced dementia were identified and consults were solicited using pop-ups programmed into the computerized provider order entry (POE) system. In the initial 3-month period, patients received usual care (N=24). In the subsequent 3-month period, consults were provided to patients for whom it was requested (N=5). Data were obtained from the electronic medical record and proxies interviews (admission, 1-month post-discharge). The patients’ mean age in the combined sample (N=29) was 85.4, 58.6% were from nursing homes, and 86.2% of their proxies stated comfort was the goal of care. Nonetheless, their hospitalizations were characterized by high rates of intravenous antibiotics (86.2%), > 5 venipunctures (44.8%), and radiological exams (96.6%). Acknowledging the small sample size, there were trends towards better outcomes in the intervention group including: higher proxy knowledge of the disease, greater communication between proxies and providers, more advance care planning, lower re-hospitalization rates, and fewer feeding tube insertions after discharge. Targeted consultation for advanced dementia is feasible and may promote greater engagement of proxies and goal-directed care for patients after discharge. PMID:24219202

  12. Developing a clinical trial unit to advance research in an academic institution.

    PubMed

    Croghan, Ivana T; Viker, Steven D; Limper, Andrew H; Evans, Tamara K; Cornell, Alissa R; Ebbert, Jon O; Gertz, Morie A

    2015-11-01

    Research, clinical care, and education are the three cornerstones of academic health centers in the United States. The research climate has always been riddled with ebbs and flows, depending on funding availability. During a time of reduced funding, the number and scope of research studies have been reduced, and in some instances, a field of study has been eliminated. Recent reductions in the research funding landscape have led institutions to explore new ways to continue supporting research. Mayo Clinic in Rochester, MN has developed a clinical trial unit within the Department of Medicine, which provides shared resources for many researchers and serves as a solution for training and mentoring new investigators and study teams. By building on existing infrastructure and providing supplemental resources to existing research, the Department of Medicine clinical trial unit has evolved into an effective mechanism for conducting research. This article discusses the creation of a central unit to provide research support in clinical trials and presents the advantages, disadvantages, and required building blocks for such a unit.

  13. [Final goal and problems in clinical chemistry examination measured by advanced analytical instruments].

    PubMed

    Sasaki, M; Hashimoto, E

    1993-07-01

    In the field of clinical chemistry of Japan, the automation of analytical instruments first appeared in the 1960's with the rapid developments in electronics industry. After a series of improvements and modifications in the past thirty years, these analytical instruments became excellent with multifunctions. From the results of these developments, it is now well recognized that automated analytical instruments are indispensable to manage the modern clinical Laboratory. On the other hand, these automated analytical instruments uncovered the various problems which had been hitherto undetected when the manually-operated instruments were used. For instances, the variation of commercially available standard solutions due to the lack of government control causes the different values obtained in institutions. In addition, there are many problems such as a shortage of medical technologists, a complication to handle the sampling and an increased labor costs. Furthermore, the inadequacies in maintenance activities cause the frequent erroneous reports of laboratory findings in spite of the latest and efficient analytical instruments equipped. Thus, the working process in clinical laboratory must be systematized to create the rapidity and the effectiveness. In the present report, we review the developmental history of automation system for analytical instruments, discuss the problems to create the effective clinical laboratory and explore the ways to deal with these emerging issues for the automation technology in clinical laboratory.

  14. Developing a clinical trial unit to advance research in an academic institution.

    PubMed

    Croghan, Ivana T; Viker, Steven D; Limper, Andrew H; Evans, Tamara K; Cornell, Alissa R; Ebbert, Jon O; Gertz, Morie A

    2015-11-01

    Research, clinical care, and education are the three cornerstones of academic health centers in the United States. The research climate has always been riddled with ebbs and flows, depending on funding availability. During a time of reduced funding, the number and scope of research studies have been reduced, and in some instances, a field of study has been eliminated. Recent reductions in the research funding landscape have led institutions to explore new ways to continue supporting research. Mayo Clinic in Rochester, MN has developed a clinical trial unit within the Department of Medicine, which provides shared resources for many researchers and serves as a solution for training and mentoring new investigators and study teams. By building on existing infrastructure and providing supplemental resources to existing research, the Department of Medicine clinical trial unit has evolved into an effective mechanism for conducting research. This article discusses the creation of a central unit to provide research support in clinical trials and presents the advantages, disadvantages, and required building blocks for such a unit. PMID:26454064

  15. Advanced in Visualization of 3D Time-Dependent CFD Solutions

    NASA Technical Reports Server (NTRS)

    Lane, David A.; Lasinski, T. A. (Technical Monitor)

    1995-01-01

    Numerical simulations of complex 3D time-dependent (unsteady) flows are becoming increasingly feasible because of the progress in computing systems. Unfortunately, many existing flow visualization systems were developed for time-independent (steady) solutions and do not adequately depict solutions from unsteady flow simulations. Furthermore, most systems only handle one time step of the solutions individually and do not consider the time-dependent nature of the solutions. For example, instantaneous streamlines are computed by tracking the particles using one time step of the solution. However, for streaklines and timelines, particles need to be tracked through all time steps. Streaklines can reveal quite different information about the flow than those revealed by instantaneous streamlines. Comparisons of instantaneous streamlines with dynamic streaklines are shown. For a complex 3D flow simulation, it is common to generate a grid system with several millions of grid points and to have tens of thousands of time steps. The disk requirement for storing the flow data can easily be tens of gigabytes. Visualizing solutions of this magnitude is a challenging problem with today's computer hardware technology. Even interactive visualization of one time step of the flow data can be a problem for some existing flow visualization systems because of the size of the grid. Current approaches for visualizing complex 3D time-dependent CFD solutions are described. The flow visualization system developed at NASA Ames Research Center to compute time-dependent particle traces from unsteady CFD solutions is described. The system computes particle traces (streaklines) by integrating through the time steps. This system has been used by several NASA scientists to visualize their CFD time-dependent solutions. The flow visualization capabilities of this system are described, and visualization results are shown.

  16. Development of a new contact lens multipurpose solution: Comparative analysis of microbiological, biological and clinical performance

    PubMed Central

    Kilvington, Simon; Huang, Ling; Kao, Eugenia; Powell, Charles H.

    2010-01-01

    Purpose Antimicrobial, cytotoxicity and clinical performance of a new soft contact lens multi-purpose solution (COMPLETE® RevitaLens) based on polyquaternium-1 and alexidine dihydrochloride (NuMPS) was evaluated. Methods Antimicrobial efficacy was assessed according to ISO 14729 for both biocidal and regimen performance against bacteria and fungi. Acanthamoeba efficacy was tested along with ability to retain antimicrobial activity on partial evaporation. In vitro cytotoxicity of NuMPS and OPTI-FREE® RepleniSH® MPS (MPS-3) was assessed based on ISO 10993-5 and United States Pharmacopeia (USP) methods. In addition, a 3 month, double-masked, parallel group clinical trial comparing safety and acceptability with respect to MPS-3 was conducted with 4 silicone hydrogel (SiHy) and FDA Group IV lens types. Results NuMPS showed broad antimicrobial efficacy, including Acanthamoeba, giving a 3–4 log10 reduction in viability after 6 hours contact time. NuMPS also passed ISO 14729 regimens with SiHy and etafilcon lenses for bacteria, fungi and also Acanthamoeba. The cytotoxicity of NuMPS was equivalent or better compared to MPS-3. In the clinical trial, there was no statistically significant between-group difference in corneal staining (p > 0.05). Patients using MPS-3 had more adverse events than patients using NuMPS: 11.8 % (11/93) versus 2.8 % (5/177), respectively, (p < 0.05). There were no differences noted in cleanliness or wearing comfort (p > 0.05). Conclusion Taken together, the results of these studies indicate that the NuMPS is a novel and effective soft contact lens care solution.

  17. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults.

    PubMed

    Sechi, GianPietro; Sechi, Elia; Fois, Chiara; Kumar, Neeraj

    2016-05-01

    B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans. Recently, new clinical settings that predispose individuals to B vitamin deficiency have been highlighted. Moreover, other data indicate a possible pathogenetic role of subclinical chronic B vitamin deficiency in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In light of these findings, this review examines the clinical manifestations of B vitamin deficiency and the effect of B vitamin deficiency on the adult nervous system. The interrelationships of multiple B vitamin deficiencies are emphasized, along with the clinical phenotypes related to B vitamin deficiencies. Recent advances in the clinical determinants and diagnostic clues of B vitamin deficiency, as well as the suggested therapies for B vitamin disorders, are described.

  18. Advances in clinical determinants and neurological manifestations of B vitamin deficiency in adults.

    PubMed

    Sechi, GianPietro; Sechi, Elia; Fois, Chiara; Kumar, Neeraj

    2016-05-01

    B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans. Recently, new clinical settings that predispose individuals to B vitamin deficiency have been highlighted. Moreover, other data indicate a possible pathogenetic role of subclinical chronic B vitamin deficiency in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In light of these findings, this review examines the clinical manifestations of B vitamin deficiency and the effect of B vitamin deficiency on the adult nervous system. The interrelationships of multiple B vitamin deficiencies are emphasized, along with the clinical phenotypes related to B vitamin deficiencies. Recent advances in the clinical determinants and diagnostic clues of B vitamin deficiency, as well as the suggested therapies for B vitamin disorders, are described. PMID:27034475

  19. Regenerative urology clinical trials: an ethical assessment of road blocks and solutions.

    PubMed

    Oerlemans, Anke J M; Feitz, Wouter F J; van Leeuwen, Evert; Dekkers, Wim J M

    2013-02-01

    Tissue engineering--part of regenerative medicine--is a promising technology that could potentially offer elegant solutions to urogenital defects, but so far, it has fallen short of its potential. Within experimental studies for bladder and urethra reconstructions, two clinical applications have been described, but extension of these techniques to the broader urological patient population has not happened so far. In this article, we aim to identify the ethical road blocks in the clinical evaluation of tissue-engineered products under the European Medicines Agency and Food and Drug Administration regulations for pediatric urological conditions and, ultimately, to recommend strategies to overcome them. The use of human tissue-engineered products (HTEPs) to treat children with congenital urogenital defects poses challenges in the clinical testing phase, connected to three features of the application of this treatment in this patient group: (1) those associated with the product, namely, the multifaceted complexity of the HTEP; (2) those connected to the procedure, namely, the lack of a randomized controlled trial (RCT)-tested gold standard to compare the new treatment to and difficulties surrounding standardization of the treatment protocol; and (3) the patient's young age and associated problems concerning possible long-term effects and the informed consent process. Due to these problems, a conventional RCT is not the methodology of choice to evaluate this treatment in this patient group. The unpredictability of HTEPs necessitates stringent and long-term surveillance and registry to ensure the safety of patients treated with these products. PMID:22784023

  20. Breast Cancer Clinical Trials: Past Half Century Moving Forward Advancing Patient Outcomes.

    PubMed

    Kuerer, Henry M; van la Parra, Raquel F D

    2016-10-01

    Clinical trials in breast cancer have contributed immensely to the advancements of modern multimodal breast cancer treatment. Due to improved screening methods and more effective biologic-based tailored systemic therapies, the extent of surgery necessary for local and systemic control of disease is decreasing. Sequential trials for ductal carcinoma in situ (DCIS) have changed the management of this disease and are culminating in randomized active surveillance studies in an effort potentially to prevent overtreatment of low- and intermediate-grade disease. For patients with initial node-positive disease, clipping and marking of the biopsy-proven nodal metastases before the start of neoadjuvant chemotherapy can allow for selective node dissection based on the axillary response. With the current advances in primary systemic therapy, feasibility trials are beginning to investigate the potential of nonoperative therapy for invasive cancers with percutaneously documented pathologic complete response. This article presents a review and update on landmark clinical trials related to DCIS, the extent of axillary surgery in node-positive disease, and the integration of systemic therapy with local therapy. PMID:27364503

  1. Developing clinical competency: Experiences and perceptions of Advanced Midwifery Practitioners in training.

    PubMed

    Gaskell, Lynne; Beaton, Susan

    2015-07-01

    This paper will describe the experiences and perception of a cohort of trainee Advanced Midwifery Practitioners (AMP's) during their training on an MSc in Advanced Practice. The educational philosophy underpinning the master's programme is interprofessional learning linked closely to work based learning and assessment. The focus group explored how the AMP's were developing core competencies within four domains: The links between the university and clinical assessments were instrumental in developing both midwifery and specialised skills required for extending their scope of practice. The changing demographics of their client group facilitated the need to provide safe assessment and management of ladies with complex health and social needs in pregnancy and childbirth; provide specialised clinics and the development of a robust staff training and assessment process. The generic competencies they gained improved collaborative working with their medical colleagues, raising the trainees profile and acceptance of their extended role. In addition to this, development of specialised midwifery skills promoted a high degree of decision making responsibilities within midwifery to facilitate service development and promote evidence based care.

  2. Advances in asthma, allergy and immunology series 2004: basic and clinical immunology.

    PubMed

    Chinen, Javier; Shearer, William T

    2004-08-01

    This review highlights some of the most significant advances in basic and clinical immunology that were published from August 2002 to December 2003, focusing on manuscripts that appeared in the Journal. Articles selected were those considered most relevant to Journal readers. With regard to basic immunology, this report includes articles describing FcepsilonRI expression in mucosal Langerhans cells and type II dendritic cells, mechanisms of TH1 and TH2 regulation, the role of Foxp3 in the development of CD4+CD25+ regulatory T cells, and the increasing importance of Toll receptors in immunity. Articles related to clinical immunology that were selected include the first report of lymphocyte subsets values from a large cohort of normal children; the description of new genetic defects in primary immunodeficiencies; a description of the complications of gene therapy for X-linked severe combined immunodeficiency; a report of 79 patients with hyper-IgM syndrome; a report of the mechanism of action and complications of intravenous immunoglobulin; a report of new approaches for immunotherapy; and an article on advances in HIV infection and management, including a report of defensins, small molecules with anti-HIV properties. Also summarized is an article that studied the immune system during a prolonged stay in the Antarctic, a model for human studies on the effect of environmental conditions similar to space expeditions.

  3. How institutional change and individual researchers helped advance clinical guidelines in American health care.

    PubMed

    Nigam, Amit

    2013-06-01

    Clinical guidelines are important tools for managing health care quality. Research on the origins of guidelines primarily focuses on the institutional causes of their emergence and growth. Individual medical researchers, however, have played important roles. This paper develops knowledge of the role of individual medical researchers in advancing guidelines, and of how researchers' efforts were enabled or constrained by broader institutional changes. Drawing on an analytical case study focused on the role of Kerr White, John Wennberg, and Robert Brook, it shows that guidelines were a product of the interplay between institutional change in the medical field and actions by individual researchers, acting as institutional entrepreneurs. Increased government involvement in the health care field triggered the involvement of a range of new actors in health care. These new organizations created a context that allowed individual researchers to advance guidelines by creating job opportunities, providing research funding, and creating opportunities for researchers to engage with the policy process. Individual researchers availed of this context to both advance their ideas, and to draw new actors into the field. PMID:23631774

  4. Interactive 3-D graphics workstations in stereotaxy: clinical requirements, algorithms, and solutions

    NASA Astrophysics Data System (ADS)

    Ehricke, Hans-Heino; Daiber, Gerhard; Sonntag, Ralf; Strasser, Wolfgang; Lochner, Mathias; Rudi, Lothar S.; Lorenz, Walter J.

    1992-09-01

    In stereotactic treatment planning the spatial relationships between a variety of objects has to be taken into account in order to avoid destruction of vital brain structures and rupture of vasculature. The visualization of these highly complex relations may be supported by 3-D computer graphics methods. In this context the three-dimensional display of the intracranial vascular tree and additional objects, such as neuroanatomy, pathology, stereotactic devices, or isodose surfaces, is of high clinical value. We report an advanced rendering method for a depth-enhanced maximum intensity projection from magnetic resonance angiography (MRA) and a walk-through approach to the analysis of MRA volume data. Furthermore, various methods for a multiple-object 3-D rendering in stereotaxy are discussed. The development of advanced applications in medical imaging can hardly be successful if image acquisition problems are disregarded. We put particular emphasis on the use of conventional MRI and MRA for stereotactic guidance. The problem of MR distortion is discussed and a novel three- dimensional approach to the quantification and correction of the distortion patterns is presented. Our results suggest that the sole use of MR for stereotactic guidance is highly practical. The true three-dimensionality of the acquired datasets opens up new perspectives to stereotactic treatment planning. For the first time it is possible now to integrate all the necessary information into 3-D scenes, thus enabling an interactive 3-D planning.

  5. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  6. The value of clinical electrophysiology in the assessment of the eye and visual system in the era of advanced imaging.

    PubMed

    Whatham, Andrew R; Nguyen, Vincent; Zhu, Yuan; Hennessy, Michael; Kalloniatis, Michael

    2014-03-01

    Electrophysiological techniques allow clinical investigations to include a 'dissection' of the visual system. Using suitable electrophysiological techniques, the 'dissection' allows function to be ascribed to the different photoreceptors (rod and cone photoreceptors), retinal layers, retinal location or the visual pathway up to the visual cortex. Combined with advances in genetics, retinal biochemistry, visual fields and ocular imaging, it is now possible to obtain a better understanding of diseases affecting the retina and visual pathways. This paper reviews core electrophysiological principles that can complement other examination techniques, including advanced ocular imaging, and help the interpretation of other clinical data and thus, refine and guide clinical diagnosis. PMID:23865913

  7. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up.

    PubMed

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-05-18

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  8. Advanced material and approach for metal ions removal from aqueous solutions

    NASA Astrophysics Data System (ADS)

    Turhanen, Petri A.; Vepsäläinen, Jouko J.; Peräniemi, Sirpa

    2015-03-01

    A Novel approach to remove metals from aqueous solutions has been developed. The method is based on a resin free, solid, non-toxic, microcrystalline bisphosphonate material, which has very low solubility in water (59 mg/l to ion free Milli-Q water and 13 mg/l to 3.5% NaCl solution). The material has been produced almost quantitatively on a 1 kg scale (it has been prepared also on a pilot scale, ca. 7 kg) and tested successfully for its ability to collect metal cations from different sources, such as ground water and mining process waters. Not only was this material highly efficient at collecting several metal ions out of solution it also proved to be regenerable and reusable over a number of adsorption/desorption, which is crucial for environmental friendliness. This material has several advantages compared to the currently used approaches, such as no need for any precipitation step.

  9. Overview of technical solutions and assessment of clinical usefulness of capsule endoscopy.

    PubMed

    Koprowski, Robert

    2015-01-01

    The paper presents an overview of endoscopic capsules with particular emphasis on technical aspects. It indicates common problems in capsule endoscopy such as: (1) limited wireless communication (2) the use of capsule endoscopy in the case of partial patency of the gastrointestinal tract, (3) limited imaging area, (4) external capsule control limitations. It also presents the prospects of capsule endoscopy, the most recent technical solutions for biopsy and the mobility of the capsule in the gastrointestinal tract. The paper shows the possibilities of increasing clinical usefulness of capsule endoscopy resulting from technological limitations. Attention has also been paid to the current role of capsule endoscopy in screening tests and the limitations of its effectiveness. The paper includes the author's recommendations concerning the direction of further research and the possibility of enhancing the scope of capsule endoscopy. PMID:26626725

  10. Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials

    PubMed Central

    Shimizu-Motohashi, Yuko; Miyatake, Shouta; Komaki, Hirofumi; Takeda, Shin’ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked progressive degenerative muscle disorder caused by the absence of dystrophin. There is no curative therapy, although innovative therapeutic approaches have been aggressively investigated over recent years. Currently, the international clinical trial registry platform for this disease has been constructed and clinical trials for innovative therapeutic approaches are underway. Among these, exon skipping and read-through of nonsense mutations are in the most advanced stages, with exon skipping theoretically applicable to a larger number of patients. To date, exon skipping that targets exons 51, 44, 45, and 53 is being globally investigated including in USA, EU, and Japan. The latest announcement from Japan was made, demonstrating successful dystrophin production in muscles of patients with DMD after treating with exon 53 skipping antisense oligonucleotides (ASOs). However, the innovative therapeutic approaches have demonstrated limited efficacy. To address this issue in exon skipping, studies to unveil the mechanism underlying gymnotic delivery of ASO uptake in living cells have been conducted in an effort to improve in vivo delivery. Further, establishing the infrastructures to integrate multi-institutional clinical trials are needed to facilitate the development of successful therapies for DMD, which ultimately is applicable to other myopathies and neurodegenerative diseases, including spinal muscular atrophy and motor neuron diseases. PMID:27398133

  11. Center to Advance Palliative Care palliative care clinical care and customer satisfaction metrics consensus recommendations.

    PubMed

    Weissman, David E; Morrison, R Sean; Meier, Diane E

    2010-02-01

    Data collection and analysis are vital for strategic planning, quality improvement, and demonstration of palliative care program impact to hospital administrators, private funders and policymakers. Since 2000, the Center to Advance Palliative Care (CAPC) has provided technical assistance to hospitals, health systems and hospices working to start, sustain, and grow nonhospice palliative care programs. CAPC convened a consensus panel in 2008 to develop recommendations for specific clinical and customer metrics that programs should track. The panel agreed on four key domains of clinical metrics and two domains of customer metrics. Clinical metrics include: daily assessment of physical/psychological/spiritual symptoms by a symptom assessment tool; establishment of patient-centered goals of care; support to patient/family caregivers; and management of transitions across care sites. For customer metrics, consensus was reached on two domains that should be tracked to assess satisfaction: patient/family satisfaction, and referring clinician satisfaction. In an effort to ensure access to reliably high-quality palliative care data throughout the nation, hospital palliative care programs are encouraged to collect and report outcomes for each of the metric domains described here. PMID:19922199

  12. Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials.

    PubMed

    Shimizu-Motohashi, Yuko; Miyatake, Shouta; Komaki, Hirofumi; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked progressive degenerative muscle disorder caused by the absence of dystrophin. There is no curative therapy, although innovative therapeutic approaches have been aggressively investigated over recent years. Currently, the international clinical trial registry platform for this disease has been constructed and clinical trials for innovative therapeutic approaches are underway. Among these, exon skipping and read-through of nonsense mutations are in the most advanced stages, with exon skipping theoretically applicable to a larger number of patients. To date, exon skipping that targets exons 51, 44, 45, and 53 is being globally investigated including in USA, EU, and Japan. The latest announcement from Japan was made, demonstrating successful dystrophin production in muscles of patients with DMD after treating with exon 53 skipping antisense oligonucleotides (ASOs). However, the innovative therapeutic approaches have demonstrated limited efficacy. To address this issue in exon skipping, studies to unveil the mechanism underlying gymnotic delivery of ASO uptake in living cells have been conducted in an effort to improve in vivo delivery. Further, establishing the infrastructures to integrate multi-institutional clinical trials are needed to facilitate the development of successful therapies for DMD, which ultimately is applicable to other myopathies and neurodegenerative diseases, including spinal muscular atrophy and motor neuron diseases.

  13. New clinical advances in immunotherapy for the treatment of solid tumours

    PubMed Central

    Zavala, Valentina A; Kalergis, Alexis M

    2015-01-01

    Advances in understanding the mechanisms of cancer cells for evading the immune system surveillance, including how the immune system modulates the phenotype of tumours, have allowed the development of new therapies that benefit from this complex cellular network to specifically target and destroy cancer cells. Immunotherapy researchers have mainly focused on the discovery of tumour antigens that could confer specificity to immune cells to detect and destroy cancer cells, as well as on the mechanisms leading to an improved activation of effector immune cells. The Food and Drug Administration approval in 2010 of ipilumumab for melanoma treatment and of pembrolizumab in 2014, monoclonal antibodies against T-lymphocyte-associated antigen 4 and programmed cell death 1, respectively, are encouraging examples of how research in this area can successfully translate into clinical use with promising results. Currently, several ongoing clinical trials are in progress testing new anti-cancer therapies based on the enhancement of immune cell activity against tumour antigens. Here we discuss the general concepts related to immunotherapy and the recent application to the treatment of cancer with positive results that support their consideration of clinical application to patients. PMID:25826229

  14. Determination of hydroxyl radical production in aqueous solutions irradiated to clinically significant doses

    SciTech Connect

    Sagone, A.L. Jr.; Democko, C.; Clark, L.; Kartha, M.

    1983-02-01

    Decarboxylation of /sup 14/C-carboxylbenzoic acid in aqueous solutions after low-dose irradiation has been used to determine the relative magnitude of oxidation reactions and estimate the hydroxyl radicals produced. The G CO/sub 2/ values determined from these measurements of 0.4 to 1.0 mM solutions of benzoic acid after x-ray doses of 1000 rads ranged from 0.72 to 0.77, in excellent agreement with values reported by authors using much higher doses of radiation. Superoxide dismutase and catalase, known scavengers of superoxide and hydrogen peroxide, respectively, did not show impairment of the oxidation of benzoic acid. On the other hand, biologically significant concentrations of phenol and mannitol appear to impair the radiation-induced oxidation of benzoic acid, indicating that the process is secondary to a reaction with OH . . We found that serum and glucose, common cell media contents, are potent OH . scavengers. These observations indicate that the oxidation of benzoic acid can be as a reliable method to estimate OH . with radiation doses of clinically significant magnitudes. In addition, these results suggest that the radiation induced by OH . in cell systems can be significantly modified by the type of buffer used.

  15. Advances in nanoscale alloys and intermetallics: low temperature solution chemistry synthesis and application in catalysis.

    PubMed

    Jana, Subhra

    2015-11-21

    Based on the bottom-up chemistry techniques, the size, shape, and composition controlled synthesis of nanoparticles can now be achieved uniformly, which is of great importance to the nanoscience community as well as in modern catalysis research. The low-temperature solution-phase synthesis approach represents one of the most attractive strategies and has been utilized to synthesize nanoscale metals, alloys and intermetallics, including a number of new metastable phases. This perspective will highlight the solution-based nanoparticle synthesis techniques, a low-temperature platform, for the synthesis of size and shape-tunable nanoscale transition metals, alloys, and intermetallics from the literature, keeping a focus on the utility of these nanomaterials in understanding the catalysis. For each solution-based nanoparticle synthesis technique, a comprehensive overview has been given for the reported nanoscale metals, alloys, and intermetallics, followed by critical comments. Finally, their enhanced catalytic activity and durability as novel catalysts have been discussed towards several hydrogenation/dehydrogenation reactions and also for different inorganic to organic reactions. Hence, the captivating advantages of this controllable low-temperature solution chemistry approach have several important implications and together with them this approach provides a promising route to the development of next-generation nanostructured metals, alloys, and intermetallics since they possess fascinating properties as well as outstanding catalytic activity. PMID:26477400

  16. Americium/Lanthanide Separations in Alkaline Solutions for Advanced Nuclear Fuel Cycles

    SciTech Connect

    Goff, George S.; Long, Kristy Marie; Reilly, Sean D.; Jarvinen, Gordon D.; Runde, Wolfgang H.

    2012-06-11

    Project goals: Can used nuclear fuel be partitioned by dissolution in alkaline aqueous solution to give a solution of uranium, neptunium, plutonium, americium and curium and a filterable solid containing nearly all of the lanthanide fission products and certain other fission products? What is the chemistry of Am/Cm/Ln in oxidative carbonate solutions? Can higher oxidation states of Am be stabilized and exploited? Conclusions: Am(VI) is kinetically stable in 0.5-2.0 M carbonate solutions for hours. Aliquat 336 in toluene has been successfully shown to extract U(VI) and Pu(VI) from carbonate solutions. (Stepanov et al 2011). Higher carbonate concentration gives lower D, SF{sub U/Eu} for = 4 in 1 M K{sub 2}CO{sub 3}. Experiments with Am(VI) were unsuccessful due to reduction by the organics. Multiple sources of reducing organics...more optimization. Reduction experiments of Am(VI) in dodecane/octanol/Aliquat 336 show that after 5 minutes of contact, only 30-40% of the Am(VI) has been reduced. Long enough to perform an extraction. Shorter contact times, lower T, and lower Aliquat 336 concentration still did not result in any significant extraction of Am. Anion exchange experiments using a strong base anion exchanger show uptake of U(VI) with minimal uptake of Nd(III). Experiments with Am(VI) indicate Am sorption with a Kd of 9 (10 minute contact) but sorption mechanism is not yet understood. SF{sub U/Nd} for = 7 and SF{sub U/Eu} for = 19 after 24 hours in 1 M K{sub 2}CO{sub 3}.

  17. Clinical accuracy of a continuous glucose monitoring system with an advanced algorithm.

    PubMed

    Bailey, Timothy S; Chang, Anna; Christiansen, Mark

    2015-03-01

    We assessed the performance of a modified Dexcom G4 Platinum system with an advanced algorithm, in comparison with frequent venous samples measured on a laboratory reference (YSI) during a clinic session and in comparison to self-monitored blood glucose (SMBG) during home use. Fifty-one subjects with diabetes were enrolled in a prospective multicenter study. Subjects wore 1 sensor for 7-day use and participated in one 12-hour in-clinic session on day 1, 4, or 7 to collect YSI reference venous glucose every 15 minutes and capillary SMBG test every 30 minutes. Carbohydrate consumption and insulin dosing and timing were manipulated to obtain data in low and high glucose ranges. In comparison with the laboratory reference method (n = 2,263) the system provided a mean and median absolute relative differences (ARD) of 9.0% and 7.0%, respectively. The mean absolute difference for CGM was 6.4 mg/dL when the YSIs were within hypoglycemia ranges (≤ 70 mg/dL). The percentage in the clinically accurate Clarke error grid A zone was 92.4% and in the benign error B zone was 7.1%. Majority of the sensors (73%) had an aggregated MARD in reference to YSI ≤ 10%. The MARD of CGM-SMBG for home use was 11.3%. The study showed that the point and rate accuracy, clinical accuracy, reliability, and consistency over the duration of wear and across glycemic ranges were superior to current commercial real-time CGM systems. The performance of this CGM is reaching that of a self-monitoring blood glucose meter in real use environment. PMID:25370149

  18. Clinical Accuracy of a Continuous Glucose Monitoring System With an Advanced Algorithm

    PubMed Central

    Bailey, Timothy S.; Chang, Anna; Christiansen, Mark

    2014-01-01

    Background: We assessed the performance of a modified Dexcom G4 Platinum system with an advanced algorithm, in comparison with frequent venous samples measured on a laboratory reference (YSI) during a clinic session and in comparison to self-monitored blood glucose (SMBG) during home use. Methods: Fifty-one subjects with diabetes were enrolled in a prospective multicenter study. Subjects wore 1 sensor for 7-day use and participated in one 12-hour in-clinic session on day 1, 4, or 7 to collect YSI reference venous glucose every 15 minutes and capillary SMBG test every 30 minutes. Carbohydrate consumption and insulin dosing and timing were manipulated to obtain data in low and high glucose ranges. Results: In comparison with the laboratory reference method (n = 2,263) the system provided a mean and median absolute relative differences (ARD) of 9.0% and 7.0%, respectively. The mean absolute difference for CGM was 6.4 mg/dL when the YSIs were within hypoglycemia ranges (≤ 70 mg/dL). The percentage in the clinically accurate Clarke error grid A zone was 92.4% and in the benign error B zone was 7.1%. Majority of the sensors (73%) had an aggregated MARD in reference to YSI ≤ 10%. The MARD of CGM-SMBG for home use was 11.3%. Conclusions: The study showed that the point and rate accuracy, clinical accuracy, reliability, and consistency over the duration of wear and across glycemic ranges were superior to current commercial real-time CGM systems. The performance of this CGM is reaching that of a self-monitoring blood glucose meter in real use environment. PMID:25370149

  19. Clinical advances in geriatric psychiatry: a focus on prevention of mood and cognitive disorders

    PubMed Central

    Eyre, Harris; Baune, Bernhard; Lavretsky, Helen

    2015-01-01

    The world’s population is ageing in the 21st century at a rate unprecedented in human history, and this will place substantial pressure on health systems across the world along with concurrent rises in chronic diseases. In particular, rates of cognitive disorders and late-life affective disorders are expected to rise. In correlation with ageing, there are robust predictions suggesting rates of age-related cognitive decline and dementia, and geriatric depression, will rise with serious consequences. Clearly innovative prevention and treatment strategies are needed. Here we reviewed the latest promising clinical advances which hold promise for assisting the prevention and treatment of depression and cognitive decline and dementia. PMID:26300035

  20. Advanced material and approach for metal ions removal from aqueous solutions

    PubMed Central

    Turhanen, Petri A.; Vepsäläinen, Jouko J.; Peräniemi, Sirpa

    2015-01-01

    A Novel approach to remove metals from aqueous solutions has been developed. The method is based on a resin free, solid, non-toxic, microcrystalline bisphosphonate material, which has very low solubility in water (59 mg/l to ion free Milli-Q water and 13 mg/l to 3.5% NaCl solution). The material has been produced almost quantitatively on a 1 kg scale (it has been prepared also on a pilot scale, ca. 7 kg) and tested successfully for its ability to collect metal cations from different sources, such as ground water and mining process waters. Not only was this material highly efficient at collecting several metal ions out of solution it also proved to be regenerable and reusable over a number of adsorption/desorption, which is crucial for environmental friendliness. This material has several advantages compared to the currently used approaches, such as no need for any precipitation step. PMID:25758924

  1. Persistent Uroplakin Expression in Advanced Urothelial Carcinomas: Implications in Urothelial Tumor Progression and Clinical Outcome

    PubMed Central

    Huang, Hong-Ying; Shariat, Shahrokh F.; Sun, Tung-Tien; Lepor, Herbert; Shapiro, Ellen; Hsieh, Jer-Tsong; Ashfaq, Raheela; Lotan, Yair; Wu, Xue-Ru

    2007-01-01

    As the terminal differentiation products of human urothelium, uroplakins (UPs) would be expected to diminish during urothelial tumorigenesis. Surprisingly, recent studies found UPs to be retained even by well-advanced urothelial carcinomas, suggesting that the loss of UPs does not strictly parallel urothelial transformation. Little is known, however, about whether the status of UPs is associated with a particular pathological parameter, tumor’s biological behavior or patient outcome. Here we assessed UP expression by immunohistochemistry on tissue arrays from 285 patients with bladder urothelial carcinomas or non-tumor conditions. UPs were expressed in all 9 normal urothelial specimens, 63/74 (85%) patients with non-muscle-invasive urothelial carcinomas on transurethral resection, 104/202 (51.5%) patients who underwent radical cystectomy for advanced urothelial carcinomas, and 33/50 (66%) lymph node metastases. Normally associated with urothelial apical surface, UPs were localized aberrantly in tumors, including micro-luminal, basal-laminal, cytoplasmic or uniform patterns. In non-muscle-invasive diseases, there was no association between UP expression and disease recurrence, progression or mortality. In contrast, in invasive diseases, absent UP expression was significantly associated with advanced pathologic stage, lymph node metastases, disease recurrence and bladder cancer-specific mortality (p=0.042, p=0.035, p=0.023 and p=0.022, respectively) in univariate analyses. Furthermore, UP status was independent of key cell-cycle regulators, including p53, pRb, p27 and cyclin D1, thus excluding a functional link between these two groups of proteins. Our data demonstrate for the first time that persistent UP expression is associated with a favorable clinical outcome and that UPs may be used as adjunct markers for predicting the prognoses of patients with invasive and metastatic bladder carcinomas. Our results also suggest that UP-positive and –negative carcinomas

  2. In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

    PubMed Central

    Almeida-Porada, Graça; Atala, Anthony; Porada, Christopher D

    2016-01-01

    Recent advances in high-throughput molecular testing have made it possible to diagnose most genetic disorders relatively early in gestation with minimal risk to the fetus. These advances should soon allow widespread prenatal screening for the majority of human genetic diseases, opening the door to the possibility of treatment/correction prior to birth. In addition to the obvious psychological and financial benefits of curing a disease in utero, and thereby enabling the birth of a healthy infant, there are multiple biological advantages unique to fetal development, which provide compelling rationale for performing potentially curative treatments, such as stem cell transplantation or gene therapy, prior to birth. Herein, we briefly review the fields of in utero transplantation (IUTx) and in utero gene therapy and discuss the biological hurdles that have thus far restricted success of IUTx to patients with immunodeficiencies. We then highlight several recent experimental breakthroughs in immunology, hematopoietic/marrow ontogeny, and in utero cell delivery, which have collectively provided means of overcoming these barriers, thus setting the stage for clinical application of these highly promising therapies in the near future. PMID:27069953

  3. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer

    PubMed Central

    Du, Meijun; Dittmar, Rachel L.; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R.; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L.; Huang, Chiang-Ching; Wang, Liang

    2015-01-01

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer. PMID:25915538

  4. Secured Advanced Federated Environment (SAFE): A NASA Solution for Secure Cross-Organization Collaboration

    NASA Technical Reports Server (NTRS)

    Chow, Edward; Spence, Matthew Chew; Pell, Barney; Stewart, Helen; Korsmeyer, David; Liu, Joseph; Chang, Hsin-Ping; Viernes, Conan; Gogorth, Andre

    2003-01-01

    This paper discusses the challenges and security issues inherent in building complex cross-organizational collaborative projects and software systems within NASA. By applying the design principles of compartmentalization, organizational hierarchy and inter-organizational federation, the Secured Advanced Federated Environment (SAFE) is laying the foundation for a collaborative virtual infrastructure for the NASA community. A key element of SAFE is the Micro Security Domain (MSD) concept, which balances the need to collaborate and the need to enforce enterprise and local security rules. With the SAFE approach, security is an integral component of enterprise software and network design, not an afterthought.

  5. Advanced Subcritical Assistance Radioisotope Thermoelectric Generator: An Imperative Solution for the Future of NASA Exploration

    NASA Astrophysics Data System (ADS)

    Arias, F. J.

    A new generation of radioisotope thermoelectrical generator is proposed for very long space exploration missions. The Advanced Subcritical Assistance Radioisotope Thermoelectric Generator (ASA-RTG) amplify the power from natural decay of pu-238 by a small subcritical multiplication produced from the small neutron background generated from (α, n) reactions between the α particles from Pu-238 and beryllium, lithium or other low-Z isotope, extracting the maximum advantage and performance from the precious α disintegration, and then of the very scarce pu-238. The process is self controlled by the natural decay of Pu-238 with the progressive reduction of the power output (RTG) and additionally and simultaneously compensate by the natural decay of a neutronic poisson which increase simultaneously the subcritical multiplication resulting in a contrary effect, i.e., causing an increase in the power. ASA-RTG is not in conflict with previous RTG, and could fit within the type of Radioisotope Thermoelectric Generator developed for NASA space missions as the Multi-Mission Radioisotope Thermoelectric Generator (MMRTG) and the Advanced Stirling Radioisotope Generator (ASRG).

  6. Technology Solutions Case Study: Advanced Boiler Load Monitoring Controls, Chicago, Illinois

    SciTech Connect

    2014-09-01

    Most of Chicago’s older multifamily housing stock is heated by centrally metered steam or hydronic systems. The cost of heat is typically absorbed into the owner’s operating cost and is then passed to tenants. Central boilers typically have long service lifetimes; the incentive for retrofit system efficiency upgrades is greater than equipment replacement for the efficiency-minded owner. System improvements as the “low-hanging fruit” are familiar, from improved pipe insulation to aftermarket controls such as outdoor temperature reset (OTR) or lead/lag controllers for sites with multiple boilers. Beyond these initial system efficiency upgrades are an emerging class of Advanced Load Monitoring (ALM) aftermarket controllers that dynamically respond to the boiler load, with claims of 10% to 30% of fuel savings over a heating season. In this project, the Building America team Partnership for Advanced Residential Retrofit (PARR) installed and monitored an ALM aftermarket controller, the M2G from Greffen Systems, at two Chicago area multifamily buildings with existing OTR control. Results show that energy savings depend on the degree to which boilers are oversized for their load, represented by cycling rates. Also, savings vary over the heating season with cycling rates, with greater savings observed in shoulder months. Over the monitoring period, oversized boilers at one site showed reductions in cycling and energy consumption in line with prior laboratory studies, while less oversized boilers at another site showed muted savings.

  7. Expression and Clinical Significance of Cytokeratin-19 and Thymidine Kinase-1 in Advanced Gastrointestinal Cancer

    PubMed Central

    Du, Ying-Ying; Zhang, Qiu-Jun; Sun, Guo-Ping

    2016-01-01

    Background: As the clinical value of cytokeratin-19 (CK19) and thymidine kinase-1 (TK1) in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease. Methods: A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK19 was detected using quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival (OS) time. Results: Positive CK19 mRNA expression was detected in 74 (43.3%) of the 171 patients and positive TK1 expression was detected in 66 (68.8%) of the 96 patients. Furthermore, of the 96 patients, 36 (37.5%) were positive for both TK1 protein and CK19 mRNA, 30 (31.3%) were negative for TK1 protein, and 15 (15.6%) were negative for TK1 protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK19 mRNA expression had significantly shorter OS times than those who were negative for it (median OS 7.7 vs. 9.7 months, respectively; P = 0.02). Moreover, patients who were positive for CK19 mRNA and TK1 protein expression had shorter OS times (median OS 6.1 months) than those who were positive for CK19 mRNA and negative for TK1 protein expression (median OS 9.1 months; P = 0.028). Positive CK19 mRNA expression was significantly associated with shorter OS in the univariate analysis (P = 0.027). Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression (P = 0.024) was an independent predictor for OS in gastrointestinal cancer patients. Conclusions: Our results suggest that positive expression of CK19 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CK19 and TK1

  8. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis

    PubMed Central

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-01-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70 000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. PMID:26903594

  9. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis.

    PubMed

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-05-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70,000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. PMID:26903594

  10. Myositis registries and biorepositories: powerful tools to advance clinical, epidemiologic and pathogenic research

    PubMed Central

    Rider, Lisa G.; Dankó, Katalin; Miller, Frederick W.

    2016-01-01

    Purpose of review Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers’ collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes. Recent findings We have identified 46 myositis research registries, including many with biorepositories, which have been developed for a wide variety of purposes and have resulted in great advances in understanding the range of phenotypes, clinical presentations, risk factors, pathogenic mechanisms, outcome assessment, therapeutic responses, and prognoses. These are now available for collaborative use to undertake additional studies. Two myositis patient registries have been developed for research, and myositis patient support groups maintain demographic registries with large numbers of patients available to be contacted for potential research participation. Summary Investigator-initiated myositis research registries and biorepositories have proven extremely useful in understanding many aspects of these rare and diverse autoimmune diseases. These registries and biorepositories, in addition to those developed by myositis patient support groups, deserve continued support to maintain the momentum in this field as they offer major opportunities to improve understanding of the pathogenesis and treatment of these diseases in cost-effective ways. PMID:25225838

  11. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis.

    PubMed

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-05-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70,000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF.

  12. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    NASA Astrophysics Data System (ADS)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  13. Current clinical advances and future perspectives in the psychiatry/mental health field of Latin America.

    PubMed

    Cía, Alfredo H; Rojas, Rodrigo Córdoba; Adad, Miguel Abib

    2010-01-01

    The history of Mental Health in Latin America is relatively young. It dates back to the mid nineteenth century and widely developed during the twentieth century, with formidable scientific, social, political, and ethical challenges. Latin American psychiatry has contributed in the fields of epidemiology, phenomenology, social psychiatry, psychiatric and epistemological research, and clinical genetics as well. More recent advances can also be seen in clinical psychotherapy and psychopharmacology. Now, there is a formal and informal recognition of various areas of expertise, such as children and adolescents, addictions, anxiety disorders, among others. However, we need to solve the health problems resulting from mental illnesses as well as the disorders related to the social, environmental, political, and economic factors of a continent marked by the precariousness of underdevelopment, which have a high impact on population health. Therefore, considering and trying to minimize the impact of those factors, contributing to the destigmatization of mental illnesses and their consequences, together with the growing number of non-governmental organizations (NGOs), human rights defenders, public figures, etc., and collaborating in building a society that guarantees the right to mental health and adequate treatment and rehabilitation are part of our present challenges in Latin America.

  14. Current technological advances in magnetic resonance with critical impact for clinical diagnosis and therapy.

    PubMed

    Runge, Val M

    2013-12-01

    The last 5 years of technological advances with major impact on clinical magnetic resonance (MR) are discussed, with greater emphasis on those that are most recent. These developments have already had a critical positive effect on clinical diagnosis and therapy and presage continued rapid improvements for the next 5 years. This review begins with a discussion of 2 topics that encompass the breadth of MR, in terms of anatomic applications, contrast media, and MR angiography. Subsequently, innovations are discussed by anatomic category, picking the areas with the greatest development, starting with the brain, moving forward to the liver and kidney, and concluding with the musculoskeletal system, breast, and prostate. Two final topics are then considered, which will likely, with time, become independent major fields in their own right, interventional MR and MR positron emission tomography (PET).The next decade will bring a new generation of MR contrast media, with research focused on substantial improvements (>100-fold) in relaxivity (contrast effect), thus providing greater efficacy, safety, and tissue targeting. Magnetic resonance angiography will see major advances because of the use of compressed sensing, in terms of spatial and temporal resolution, with movement away from nondynamic imaging. The breadth of available techniques and tissue contrast has greatly expanded in brain imaging, benefiting both from the introduction of new basic categories of imaging techniques, such as readout-segmented echo planar imaging and 3D fast spin echo imaging with variable flip angles, and from new refinements specific to anatomic areas, such as double inversion recovery and MP2RAGE. Liver imaging has benefited from the development of techniques to easily and rapidly assess lipid, and will see, overall, a marked improvement in the next 5 years from new techniques on the verge of clinical introduction, such as controlled aliasing in parallel imaging results in higher acceleration

  15. The Interplay of Al and Mg Speciation in Advanced Mg Battery Electrolyte Solutions.

    PubMed

    See, Kimberly A; Chapman, Karena W; Zhu, Lingyang; Wiaderek, Kamila M; Borkiewicz, Olaf J; Barile, Christopher J; Chupas, Peter J; Gewirth, Andrew A

    2016-01-13

    Mg batteries are an attractive alternative to Li-based energy storage due to the possibility of higher volumetric capacities with the added advantage of using sustainable materials. A promising emerging electrolyte for Mg batteries is the magnesium aluminum chloride complex (MACC) which shows high Mg electrodeposition and stripping efficiencies and relatively high anodic stabilities. As prepared, MACC is inactive with respect to Mg deposition; however, efficient Mg electrodeposition can be achieved following an electrolytic conditioning process. Through the use of Raman spectroscopy, surface enhanced Raman spectroscopy, (27)Al and (35)Cl nuclear magnetic resonance spectroscopy, and pair distribution function analysis, we explore the active vs inactive complexes in the MACC electrolyte and demonstrate the codependence of Al and Mg speciation. These techniques report on significant changes occurring in the bulk speciation of the conditioned electrolyte relative to the as-prepared solution. Analysis shows that the active Mg complex in conditioned MACC is very likely the [Mg2(μ-Cl)3·6THF](+) complex that is observed in the solid state structure. Additionally, conditioning creates free Cl(-) in the electrolyte solution, and we suggest the free Cl(-) adsorbs at the electrode surface to enhance Mg electrodeposition.

  16. Nonsurgical treatment of moderate and advanced periimplantitis lesions: a controlled clinical study.

    PubMed

    Schwarz, Frank; Bieling, Katrin; Bonsmann, Martin; Latz, Thilo; Becker, Jürgen

    2006-12-01

    The aim of this controlled, parallel design clinical study was to evaluate the effectiveness of an Er:YAG (erbium-doped:yttrium, aluminum, and garnet) laser for nonsurgical treatment of periimplantitis lesions. Twenty patients, each of whom displayed at least one implant with (a) moderate and (b) advanced periimplantitis (n=40 implants; IMZ, ITI, Spline Twist, ZL-Duraplant, Camlog), were randomly instrumented nonsurgically using either (1) an Er:YAG laser (100 mJ/pulse, 10 Hz) device (LAS) or (2) mechanical debridement using plastic curettes and antiseptic therapy with chlorhexidine digluconate (0.2%) (C). The following clinical parameters were measured at baseline, 3, 6, and 12 months after treatment: plaque index, bleeding on probing (BOP), probing depth, gingival recession, and clinical attachment level (CAL). Mean BOP improved significantly in both groups at 3, 6, and 12 months (a- lesions: P<0.001 and b- lesions: P<0.01, respectively). After 3 and 6 months, the mean reduction of BOP was significantly higher in the LAS group when compared to the C group (a- and b- lesions: P<0.01 and P<0.05, respectively). At 3 and 6 months, both groups revealed significant CAL gains at a- and b- lesions (P<0.01, respectively). In both groups, however, the mean CAL at a- and b- lesions was not significantly different from the respective baseline values at 12 months (P>0.05, respectively). Although treatment of periimplantitis lesions with LAS resulted in a significantly higher BOP reduction than C, its effectiveness seemed to be limited to a period of 6 months, particularly at b- lesions.

  17. Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

    PubMed Central

    Ohlow, Marc-Alexander; Chen, Ting-Hui; Schmidt, Andreas; Saenger, Joerg; Lauer, Bernward

    2015-01-01

    Background Endomyocardial biopsy (EMB) is an important tool when patients with inflammatoric cardiomyopathy (DCMi) are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB (Group 1 ≥ 70 years, n = 85; Group 3 < 70 years; n = 418) were compared to patients of the same age group without evidence of DCMi on EMB (Group 2 ≥ 70 years, n = 45; Group 4 < 70 years; n = 147). Results Among 24,275 patients treated at our institution during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 (2.1%) patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ± 2.8 years, mean ejection fraction was 38% ± 14%. On presentation, signs of hemodynamic compromise (NYHA functional class III/IV, low cardiac output/index, and low cardiac power index) were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B19 (PVB) was frequently encountered in both age groups (Group 1: 69.4% vs. Group 2: 59.6%); detection of more than one viral genome was more frequent in Group 1 (21.2% vs. 11.2%; P = 0.02) whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients ≥ 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed. PMID:26788036

  18. Advanced Solution Methods for Microkinetic Models of Catalytic Reactions: A Methanol Synthesis Case Study

    SciTech Connect

    Rubert-Nason, Patricia; Mavrikakis, Manos; Maravelias, Christos T.; Grabow, Lars C.; Biegler, Lorenz T.

    2014-04-01

    Microkinetic models, combined with experimentally measured reaction rates and orders, play a key role in elucidating detailed reaction mechanisms in heterogeneous catalysis and have typically been solved as systems of ordinary differential equations. In this work, we demonstrate a new approach to fitting those models to experimental data. For the specific example treated here, by reformulating a typical microkinetic model for a continuous stirred tank reactor to a system of nonlinear equations, we achieved a 1000-fold increase in solution speed. The reduced computational cost allows a more systematic search of the parameter space, leading to better fits to the available experimental data. We applied this approach to the problem of methanol synthesis by CO/CO2 hydrogenation over a supported-Cu catalyst, an important catalytic reaction with a large industrial interest and potential for large-scale CO2 chemical fixation.

  19. Challenges, Solutions, and Quality Metrics of Personal Genome Assembly in Advancing Precision Medicine

    PubMed Central

    Xiao, Wenming; Wu, Leihong; Yavas, Gokhan; Simonyan, Vahan; Ning, Baitang; Hong, Huixiao

    2016-01-01

    Even though each of us shares more than 99% of the DNA sequences in our genome, there are millions of sequence codes or structure in small regions that differ between individuals, giving us different characteristics of appearance or responsiveness to medical treatments. Currently, genetic variants in diseased tissues, such as tumors, are uncovered by exploring the differences between the reference genome and the sequences detected in the diseased tissue. However, the public reference genome was derived with the DNA from multiple individuals. As a result of this, the reference genome is incomplete and may misrepresent the sequence variants of the general population. The more reliable solution is to compare sequences of diseased tissue with its own genome sequence derived from tissue in a normal state. As the price to sequence the human genome has dropped dramatically to around $1000, it shows a promising future of documenting the personal genome for every individual. However, de novo assembly of individual genomes at an affordable cost is still challenging. Thus, till now, only a few human genomes have been fully assembled. In this review, we introduce the history of human genome sequencing and the evolution of sequencing platforms, from Sanger sequencing to emerging “third generation sequencing” technologies. We present the currently available de novo assembly and post-assembly software packages for human genome assembly and their requirements for computational infrastructures. We recommend that a combined hybrid assembly with long and short reads would be a promising way to generate good quality human genome assemblies and specify parameters for the quality assessment of assembly outcomes. We provide a perspective view of the benefit of using personal genomes as references and suggestions for obtaining a quality personal genome. Finally, we discuss the usage of the personal genome in aiding vaccine design and development, monitoring host immune

  20. Automatically high accurate and efficient photomask defects management solution for advanced lithography manufacture

    NASA Astrophysics Data System (ADS)

    Zhu, Jun; Chen, Lijun; Ma, Lantao; Li, Dejian; Jiang, Wei; Pan, Lihong; Shen, Huiting; Jia, Hongmin; Hsiang, Chingyun; Cheng, Guojie; Ling, Li; Chen, Shijie; Wang, Jun; Liao, Wenkui; Zhang, Gary

    2014-04-01

    Defect review is a time consuming job. Human error makes result inconsistent. The defects located on don't care area would not hurt the yield and no need to review them such as defects on dark area. However, critical area defects can impact yield dramatically and need more attention to review them such as defects on clear area. With decrease in integrated circuit dimensions, mask defects are always thousands detected during inspection even more. Traditional manual or simple classification approaches are unable to meet efficient and accuracy requirement. This paper focuses on automatic defect management and classification solution using image output of Lasertec inspection equipment and Anchor pattern centric image process technology. The number of mask defect found during an inspection is always in the range of thousands or even more. This system can handle large number defects with quick and accurate defect classification result. Our experiment includes Die to Die and Single Die modes. The classification accuracy can reach 87.4% and 93.3%. No critical or printable defects are missing in our test cases. The missing classification defects are 0.25% and 0.24% in Die to Die mode and Single Die mode. This kind of missing rate is encouraging and acceptable to apply on production line. The result can be output and reloaded back to inspection machine to have further review. This step helps users to validate some unsure defects with clear and magnification images when captured images can't provide enough information to make judgment. This system effectively reduces expensive inline defect review time. As a fully inline automated defect management solution, the system could be compatible with current inspection approach and integrated with optical simulation even scoring function and guide wafer level defect inspection.

  1. Conference report: Clinical and Pharmaceutical Solutions through analysis (CPSA USA 2013): connecting patients and subject numbers through analysis.

    PubMed

    Needham, Shane; Premkumar, Noel; Weng, Naidong; Lee, Mike

    2014-02-01

    The 16th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis (CPSA) 7-10 October 2013, Sheraton Bucks County Hotel, Langhorne, PA, USA. The 2013 CPSA brought together the various US FDA regulated analytical fields affecting a 'patient' for the first time - bioanalysts supporting IND and NDAs, clinical diagnostic and pathology laboratory personnel, and clinical researchers that provide insights into new biomarkers. Although the regulatory requirements are different for each of the above disciplines, the unique analytical perspectives that affect the patient were shared - and the goal of the 2013 CPSA - 'Connecting Patients and Subject Numbers Through Analysis' was achieved.

  2. Conference report: Clinical and Pharmaceutical Solutions through analysis (CPSA USA 2013): connecting patients and subject numbers through analysis.

    PubMed

    Needham, Shane; Premkumar, Noel; Weng, Naidong; Lee, Mike

    2014-02-01

    The 16th Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis (CPSA) 7-10 October 2013, Sheraton Bucks County Hotel, Langhorne, PA, USA. The 2013 CPSA brought together the various US FDA regulated analytical fields affecting a 'patient' for the first time - bioanalysts supporting IND and NDAs, clinical diagnostic and pathology laboratory personnel, and clinical researchers that provide insights into new biomarkers. Although the regulatory requirements are different for each of the above disciplines, the unique analytical perspectives that affect the patient were shared - and the goal of the 2013 CPSA - 'Connecting Patients and Subject Numbers Through Analysis' was achieved. PMID:24471949

  3. Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic

    PubMed Central

    Dev, Rony; Hui, David; Chisholm, Gary; Delgado-Guay, Marvin; Dalal, Shalini; Del Fabbro, Egidio; Bruera, Eduardo

    2015-01-01

    Background Elevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients. Aims The aim of this study was to compare the velocity of weight loss, symptom burden (fatigue, insomnia, anxiety, and anorexia—combined score as measured by the Edmonton Symptom Assessment Score), high-sensitivity C-reactive protein, and survival among cancer patients referred to a cachexia clinic with hypermetabolism, elevated REE > 110% of predicted, with normal REE. Methods A retrospective analysis of 60 advanced cancer patients evaluated in a cachexia clinic for either >5% weight loss or anorexia who underwent indirect calorimetry to measure REE. Patients were dichotomized to either elevated or normal REE. Descriptive statistics were generated, and a two-sample Student's t-tests were used to compare the outcomes between the groups. Kaplan–Meier and Cox regression methodology were used to examine the survival times between groups. Results Thirty-seven patients (62%) were men, 41 (68%) were White, 59 (98%) solid tumours, predominantly 23 gastrointestinal cancers (38%), with a median age of 60 (95% confidence interval 57.0–62.9). Thirty-five patients (58%) were hypermetabolic. Non-Caucasian patients were more likely to have high REE [odds ratio = 6.17 (1.56, 24.8), P = 0.01]. No statistical difference regarding age, cancer type, gender, active treatment with chemotherapy, and/or radiation between hypermetabolic and normal REE was noted. The velocity of weight loss over a 3 month period (−8.5 kg vs. −7.2 kg, P = 0.68), C-reactive protein (37.3 vs. 55.6 mg/L, P = 0.70), symptom burden (4.2 vs. 4.5, P = 0.54), and survival (288 vs. 276 days, P = 0.68) was not significantly different between high vs. normal REE, respectively. Conclusion Hypermetabolism is common in cancer patients with weight loss and noted to be more frequent in non-Caucasian patients. No association among velocity of weight loss

  4. Advanced MCCI Modelling Based on Stringent Coupling of Thermal Hydraulics and Real Solution Thermochemistry in COSACO

    SciTech Connect

    Nie, M.; Fischer, M.; Lohnert, G.

    2002-07-01

    The development of the MCCI code COSACO specifically addresses the ex-vessel MCCI phase of the core melt retention concept of the EPR. The general philosophy behind COSACO is a rigorous representation of thermochemical phenomena related to the MCCI. In particular, the code incorporates a real solution database to predict the simultaneous formation of solid and liquid phases as well as chemical reactions for a significant number melt constituents. This offers a great flexibility in terms of application to MCCIs involving reactor materials and to tests conducted with simulant melts. The approach to model heat transfer in oxidic melt pools is based on the phase segregation hypothesis. Besides a brief description of the principal models incorporated in COSACO, this paper highlights specific thermochemical effects that arose as part of post-test calculations of the tests MACE M3b and MACE M4 with this new code version. Particular attention is drawn to the effect of melt ejections on the pool temperature as well as to the evolution of solid volumetric fraction and of melt front progression during the MCCI. Finally, the application to a representative EPR specific sequence indicates that the principal objectives of the MCCI in the reactor pit can be safely fulfilled. (authors)

  5. Unequal Burden of Disease, Unequal Participation in Clinical Trials: Solutions from African American and Latino Community Members

    ERIC Educational Resources Information Center

    Ford, Marvella E.; Siminoff, Laura A.; Pickelsimer, Elisabeth; Mainous, Arch G.; Smith, Daniel W.; Diaz, Vanessa A.; Soderstrom, Lea H.; Jefferson, Melanie S.; Tilley, Barbara C.

    2013-01-01

    African Americans and Latinos are underrepresented in clinical trials. The purpose of this study was to elicit solutions to participation barriers from African Americans and Latinos. Fifty-seven adults (32 African Americans, 25 Latinos) ages 50 years and older participated. The Institute of Medicine's "Unequal Treatment" conceptual framework was…

  6. Primary ciliary dyskinesia. Recent advances in diagnostics, genetics, and characterization of clinical disease.

    PubMed

    Knowles, Michael R; Daniels, Leigh Anne; Davis, Stephanie D; Zariwala, Maimoona A; Leigh, Margaret W

    2013-10-15

    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6-8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD.

  7. Advances in the management of multiple sclerosis spasticity: experiences from recent studies and everyday clinical practice.

    PubMed

    Pozzilli, Carlo

    2013-12-01

    cases of somnolence and dizziness. Under everyday clinical practice conditions, Sativex at a mean daily dose of <7 sprays/day, was shown to relieve spasticity in about 70% of patients previously resistant to treatment. Clear improvements were also noted in associated symptoms such as sleep disturbances, bladder problems, loss of mobility and cramps. In large observational studies, >80% of patients reported no adverse events with the use of Sativex and interim data from safety registries in the UK and Spain indicate a low risk for serious adverse drug reactions. Follow-up studies in Sativex responders support continued benefit without the need to increase doses for at least 1 year. Sativex appears to be a promising solution for a meaningful proportion of patients with MS-related spasticity who have inadequate response to current antispasticity medications. PMID:24289844

  8. Advanced repair solution of clear defects on HTPSM by using nanomachining tool

    NASA Astrophysics Data System (ADS)

    Lee, Hyemi; Kim, Munsik; Jung, Hoyong; Kim, Sangpyo; Yim, Donggyu

    2015-10-01

    As the mask specifications become tighter for low k1 lithography, more aggressive repair accuracy is required below sub 20nm tech. node. To meet tight defect specifications, many maskshops select effective repair tools according to defect types. Normally, pattern defects are repaired by the e-beam repair tool and soft defects such as particles are repaired by the nanomachining tool. It is difficult for an e-beam repair tool to remove particle defects because it uses chemical reaction between gas and electron, and a nanomachining tool, which uses physical reaction between a nano-tip and defects, cannot be applied for repairing clear defects. Generally, film deposition process is widely used for repairing clear defects. However, the deposited film has weak cleaning durability, so it is easily removed by accumulated cleaning process. Although the deposited film is strongly attached on MoSiN(or Qz) film, the adhesive strength between deposited Cr film and MoSiN(or Qz) film becomes weaker and weaker by the accumulated energy when masks are exposed in a scanner tool due to the different coefficient of thermal expansion of each materials. Therefore, whenever a re-pellicle process is needed to a mask, all deposited repair points have to be confirmed whether those deposition film are damaged or not. And if a deposition point is damaged, repair process is needed again. This process causes longer and more complex process. In this paper, the basic theory and the principle are introduced to recover clear defects by using nanomachining tool, and the evaluated results are reviewed at dense line (L/S) patterns and contact hole (C/H) patterns. Also, the results using a nanomachining were compared with those using an e-beam repair tool, including the cleaning durability evaluated by the accumulated cleaning process. Besides, we discuss the phase shift issue and the solution about the image placement error caused by phase error.

  9. Advances in islet cell biology: from stem cell differentiation to clinical transplantation: conference report.

    PubMed

    Kandeel, Fouad; Smith, Craig V; Todorov, Ivan; Mullen, Yoko

    2003-10-01

    The 3rd Annual Rachmiel Levine Symposium entitled "Advances in Islet Cell Biology-From Stem Cell Differentiation to Clinical Transplantation" was organized by the Department of Diabetes, Endocrinology and Metabolism at the City of Hope National Medical Center, with the support of the Southern California Islet Cell Resources Center, American Diabetes Association-David Shapiro Research Fund, Ross Foundation, the National Center for Research Resources (NCRR), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. The symposium was held at the Hilton Anaheim Hotel in Anaheim, CA, in October 2002, and was attended by nearly 400 participants from 23 countries and 30 U.S. states. The symposium consisted of 11 sessions focusing on 3 areas: (1) pancreas and islet cell differentiation and islet generation, (2) beta cell biology and insulin synthesis and/or secretion, and (3) pancreatic islet transplantation in patients with type I diabetes. Thirty-nine world experts lectured on the most current information in each field. Fifty-three abstracts were selected for presentation and discussed at the poster session. The first author of each of the top 10 posters received a Young Investigator Travel Award provided by the National Center for Research Resources and the Southern California Islet Cell Resources Center. The symposium also offered special Meet the Professor sessions, which gave the attendees an opportunity to closely interact with the participating speakers of the day.

  10. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

    PubMed

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-14

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  11. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer

    PubMed Central

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  12. Targeted radionuclide and fluorescence dual-modality imaging of cancer: preclinical advances and clinical translation.

    PubMed

    Lütje, S; Rijpkema, M; Helfrich, W; Oyen, W J G; Boerman, O C

    2014-12-01

    In oncology, sensitive and reliable detection tumor tissue is crucial to prevent recurrences and to improve surgical outcome. Currently, extensive research is focused on the use of radionuclides as well as fluorophores to provide real-time guidance during surgery to aid the surgeon in the identification of malignant tissue. Particularly, dual-modality approaches combining radionuclide and near-infrared fluorescence (NIRF) imaging have shown promising results in preclinical studies. Radionuclide imaging allows sensitive intra-operative localization of tumor lesions using a gamma probe, whereas NIRF imaging allows more accurate real-time tumor delineation. Consequently, both radionuclide and NIRF imaging might complement each other, and dual-modality image-guided surgery may overcome limitations of the currently used single-modality imaging techniques. In this review, a comprehensive overview on recent preclinical advances in tumor-targeted radionuclide and fluorescence dual-modality imaging is provided. Subsequently, the clinical applicability of dual-modality image-guided surgery is discussed.

  13. Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management.

    PubMed

    McDermott, Amelia; Jacks, Jennifer; Kessler, Marcus; Emanuel, Peter D; Gao, Ling

    2015-02-01

    The disease spectrum currently known as the proteasome-associated autoinflammatory syndromes (PRAAS) was first described in 1939 in patients who presented with recurrent fevers beginning in infancy or early childhood, which were accompanied by nodular erythema, a pernio-like rash, and joint contractures. Since then, several syndromes, such as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome, Nakajo-Nishimura syndrome (NNS), joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP) syndrome, and Japanese autoinflammatory syndrome with lipodystrophy (JASL), have been used to categorize patients with diseases within the same spectrum. Recently, independent studies have identified mutations in the human proteasome subunit β type 8 (PSMB8) gene, which result in a sustained inflammatory response in all syndromes. Further functional studies not only suggest a causative role of PSMB8 mutations but also imply that they represent one disease spectrum, referred to as PRAAS. In this paper, we review the clinical presentations and laboratory findings of PRAAS, as well as the most recent advances in pathogeneses, diagnosis, and treatment options for patients with diseases in this spectrum. PMID:25521013

  14. Recurrent and pathological gene fusions in breast cancer: current advances in genomic discovery and clinical implications.

    PubMed

    Veeraraghavan, Jamunarani; Ma, Jiacheng; Hu, Yiheng; Wang, Xiao-Song

    2016-07-01

    Gene fusions have long been considered principally as the oncogenic events of hematologic malignancies, but have recently gained wide attention in solid tumors due to several milestone discoveries and the advancement of deep sequencing technologies. With the progress in deep sequencing studies of breast cancer transcriptomes and genomes, the discovery of recurrent and pathological gene fusions in breast cancer is on the focus. Recently, driven by new deep sequencing studies, several recurrent or pathological gene fusions have been identified in breast cancer, including ESR1-CCDC170, SEC16A-NOTCH1, SEC22B-NOTCH2, and ESR1-YAP1 etc. More important, most of these gene fusions are preferentially identified in the more aggressive breast cancers, such as luminal B, basal-like, or endocrine-resistant breast cancer, suggesting recurrent gene fusions as additional key driver events in these tumors other than the known drivers such as the estrogen receptor. In this paper, we have comprehensively summarized the newly identified recurrent or pathological gene fusion events in breast cancer, reviewed the contributions of new genomic and deep sequencing technologies to new fusion discovery and the integrative bioinformatics tools to analyze these data, highlighted the biological relevance and clinical implications of these fusion discoveries, and discussed future directions of gene fusion research in breast cancer. PMID:27372070

  15. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

    PubMed

    Sangro, B; Mazzolini, G; Ruiz, M; Ruiz, J; Quiroga, J; Herrero, I; Qian, C; Benito, A; Larrache, J; Olagüe, C; Boan, J; Peñuelas, I; Sádaba, B; Prieto, J

    2010-12-01

    The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹⁰ to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient. PMID:20689572

  16. AALIM: a cardiac clinical decision support system powered by advanced multi-modal analytics.

    PubMed

    Amir, Arnon; Beymer, David; Grace, Julia; Greenspan, Hayit; Gruhl, Daniel; Hobbs, Allen; Pohl, Kilian; Syeda-Mahmood, Tanveer; Terdiman, Joseph; Wang, Fei

    2010-01-01

    Modern Electronic Medical Record (EMR) systems often integrate large amounts of data from multiple disparate sources. To do so, EMR systems must align the data to create consistency between these sources. The data should also be presented in a manner that allows a clinician to quickly understand the complete condition and history of a patient's health. We develop the AALIM system to address these issues using advanced multimodal analytics. First, it extracts and computes multiple features and cues from the patient records and medical tests. This additional metadata facilitates more accurate alignment of the various modalities, enables consistency check and empowers a clear, concise presentation of the patient's complete health information. The system further provides a multimodal search for similar cases within the EMR system, and derives related conditions and drugs information from them. We applied our approach to cardiac data from a major medical care organization and found that it produced results with sufficient quality to assist the clinician making appropriate clinical decisions.

  17. New advanced surface modification technique: titanium oxide ceramic surface implants: long-term clinical results

    NASA Astrophysics Data System (ADS)

    Szabo, Gyorgy; Kovacs, Lajos; Barabas, Jozsef; Nemeth, Zsolt; Maironna, Carlo

    2001-11-01

    The purpose of this paper is to discuss the background to advanced surface modification technologies and to present a new technique, involving the formation of a titanium oxide ceramic coating, with relatively long-term results of its clinical utilization. Three general techniques are used to modify surfaces: the addition or removal of material and the change of material already present. Surface properties can also be changed without the addition or removal of material, through the laser or electron beam thermal treatment. The new technique outlined in this paper relates to the production of a corrosion-resistant 2000-2500 A thick, ceramic oxide layer with a coherent crystalline structure on the surface of titanium implants. The layer is grown electrochemically from the bulk of the metal and is modified by heat treatment. Such oxide ceramic-coated implants have a number of advantageous properties relative to implants covered with various other coatings: a higher external hardness, a greater force of adherence between the titanium and the oxide ceramic coating, a virtually perfect insulation between the organism and the metal (no possibility of metal allergy), etc. The coated implants were subjected to various physical, chemical, electronmicroscopic, etc. tests for a qualitative characterization. Finally, these implants (plates, screws for maxillofacial osteosynthesis and dental root implants) were applied in surgical practice for a period of 10 years. Tests and the experience acquired demonstrated the good properties of the titanium oxide ceramic-coated implants.

  18. Clinical management of advanced gastric cancer: The role of new molecular drugs

    PubMed Central

    De Vita, Ferdinando; Di Martino, Natale; Fabozzi, Alessio; Laterza, Maria Maddalena; Ventriglia, Jole; Savastano, Beatrice; Petrillo, Angelica; Gambardella, Valentina; Sforza, Vincenzo; Marano, Luigi; Auricchio, Annamaria; Galizia, Gennaro; Ciardiello, Fortunato; Orditura, Michele

    2014-01-01

    Gastric cancer is the fourth most common malignant neoplasm and the second leading cause of death for cancer in Western countries with more than 20000 new cases yearly diagnosed in the United States. Surgery represents the main approach for this disease but, notwithstanding the advances in surgical techniques, we observed a minimal improvement in terms of overall survival with a significant increasing of relapsing disease rates. Despite the development of new drugs has significantly improved the effectiveness of chemotherapy, the prognosis of patients with unresectable or metastatic gastric adenocarcinoma remains poor. Recently, several molecular target agents have been investigated; in particular, trastuzumab represents the first target molecule showing improvements in overall survival in human epithelial growth factor 2-positive gastric cancer patients. New molecules targeting vascular epithelial growth factor, mammalian target of rapamycin, and anti hepatocyte growth factor-c-Met pathway are also under investigation, with interesting results. Anyway, it seems necessary to select more accurately the population to treat with new agents by the identification of new biomarkers in order to optimize the results. In this paper we review the actual “scenario” of targeted treatments, also focusing on the new agents in development for gastric cancer and gastro-esophageal carcinoma, discussing their efficacy and potential applications in clinical practice. PMID:25356019

  19. Free Levels of Selected Organic Solutes and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Results from the Retained Organic Solutes and Clinical Outcomes (ROSCO) Investigators

    PubMed Central

    Shafi, Tariq; Meyer, Timothy W.; Hostetter, Thomas H.; Melamed, Michal L.; Parekh, Rulan S.; Hwang, Seungyoung; Banerjee, Tanushree; Coresh, Josef; Powe, Neil R.

    2015-01-01

    Background and Objectives Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney — p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine — with outcomes in hemodialysis patients. Design, Setting, Participants and Measurements We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/VUREA. Results Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17–2.25; p=0.004) and first cardiovascular event (1.60; 1.23–2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18–1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05–3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12–2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses. Conclusions Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients. PMID:25938230

  20. Advancing clinical decision support using lessons from outside of healthcare: an interdisciplinary systematic review

    PubMed Central

    2012-01-01

    Background Greater use of computerized decision support (DS) systems could address continuing safety and quality problems in healthcare, but the healthcare field has struggled to implement DS technology. This study surveys DS experience across multiple non-healthcare disciplines for new insights that are generalizable to healthcare provider decisions. In particular, it sought design principles and lessons learned from the other disciplines that could inform efforts to accelerate the adoption of clinical decision support (CDS). Methods Our systematic review drew broadly from non-healthcare databases in the basic sciences, social sciences, humanities, engineering, business, and defense: PsychINFO, BusinessSource Premier, Social Sciences Abstracts, Web of Science, and Defense Technical Information Center. Because our interest was in DS that could apply to clinical decisions, we selected articles that (1) provided a review, overview, discussion of lessons learned, or an evaluation of design or implementation aspects of DS within a non-healthcare discipline and (2) involved an element of human judgment at the individual level, as opposed to decisions that can be fully automated or that are made at the organizational level. Results Clinical decisions share some similarities with decisions made by military commanders, business managers, and other leaders: they involve assessing new situations and choosing courses of action with major consequences, under time pressure, and with incomplete information. We identified seven high-level DS system design features from the non-healthcare literature that could be applied to CDS: providing broad, system-level perspectives; customizing interfaces to specific users and roles; making the DS reasoning transparent; presenting data effectively; generating multiple scenarios covering disparate outcomes (e.g., effective; effective with side effects; ineffective); allowing for contingent adaptations; and facilitating collaboration. The

  1. Processing of solid solution, mixed uranium/refractory metal carbides for advanced space nuclear power and propulsion systems

    NASA Astrophysics Data System (ADS)

    Knight, Travis Warren

    Nuclear thermal propulsion (NTP) and space nuclear power are two enabling technologies for the manned exploration of space and the development of research outposts in space and on other planets such as Mars. Advanced carbide nuclear fuels have been proposed for application in space nuclear power and propulsion systems. This study examined the processing technologies and optimal parameters necessary to fabricate samples of single phase, solid solution, mixed uranium/refractory metal carbides. In particular, the pseudo-ternary carbide, UC-ZrC-NbC, system was examined with uranium metal mole fractions of 5% and 10% and corresponding uranium densities of 0.8 to 1.8 gU/cc. Efforts were directed to those methods that could produce simple geometry fuel elements or wafers such as those used to fabricate a Square Lattice Honeycomb (SLHC) fuel element and reactor core. Methods of cold uniaxial pressing, sintering by induction heating, and hot pressing by self-resistance heating were investigated. Solid solution, high density (low porosity) samples greater than 95% TD were processed by cold pressing at 150 MPa and sintering above 2600 K for times longer than 90 min. Some impurity oxide phases were noted in some samples attributed to residual gases in the furnace during processing. Also, some samples noted secondary phases of carbon and UC2 due to some hyperstoichiometric powder mixtures having carbon-to-metal ratios greater than one. In all, 33 mixed carbide samples were processed and analyzed with half bearing uranium as ternary carbides of UC-ZrC-NbC. Scanning electron microscopy, x-ray diffraction, and density measurements were used to characterize samples. Samples were processed from powders of the refractory mono-carbides and UC/UC 2 or from powders of uranium hydride (UH3), graphite, and refractory metal carbides to produce hypostoichiometric mixed carbides. Samples processed from the constituent carbide powders and sintered at temperatures above the melting point of UC

  2. Advances in umbilical cord blood stem cell expansion and clinical translation.

    PubMed

    Pineault, Nicolas; Abu-Khader, Ahmad

    2015-07-01

    Umbilical cord blood (CB) is a rich source of hematopoietic stem cells (HSCs) with important applications in allogeneic stem cell transplantation. However, the low numbers of hematopoietic stem and progenitor cells (HSPCs) in banked units remain a major limitation. Protocols developed for HSPC expansion ex vivo or to improve HSPC homing to the marrow represent solutions to overcome this shortcoming. In recent decades, wide arrays of functionally divergent approaches were developed for the amplification of HSPCs. These include optimization of cytokine cocktails, coculture systems, small molecules, and delivery systems for HSPC-expansion genes. Herein, we review past and current strategies, focusing on studies that characterize the contribution of expanded CB HSPC to short- and long-term engraftment in transplantation models or in clinical trials. Also discussed are homing effectors used to promote engraftment. In summary, these studies underscore that early-acting cytokines alone can expand HSPC with short-term engraftment activity, but that robust expansion of HSPCs with long-term engraftment necessitates the synergistic action of multiple HSC-expansion agonists. In support of this, early clinical trials based on cytokine-driven HSPC-expansion protocols delivered disappointing results, whereas recent trials based on the synergistic action of cytokines and HSPC-expansion agonists reported significant improvements in engraftment and therapeutic outcomes. Conversely, molecules that enhance homing of HSPC may represent a complementary approach to improve and perhaps accelerate engraftment. Optimization of the next generation of HSPC-expansion and priming strategies should support a paradigm shift in CB transplantation in which smaller, better matched units may preferentially be used.

  3. A simple versatile solution for collecting multidimensional clinical data based on the CakePHP web application framework.

    PubMed

    Biermann, Martin

    2014-04-01

    Clinical trials aiming for regulatory approval of a therapeutic agent must be conducted according to Good Clinical Practice (GCP). Clinical Data Management Systems (CDMS) are specialized software solutions geared toward GCP-trials. They are however less suited for data management in small non-GCP research projects. For use in researcher-initiated non-GCP studies, we developed a client-server database application based on the public domain CakePHP framework. The underlying MySQL database uses a simple data model based on only five data tables. The graphical user interface can be run in any web browser inside the hospital network. Data are validated upon entry. Data contained in external database systems can be imported interactively. Data are automatically anonymized on import, and the key lists identifying the subjects being logged to a restricted part of the database. Data analysis is performed by separate statistics and analysis software connecting to the database via a generic Open Database Connectivity (ODBC) interface. Since its first pilot implementation in 2011, the solution has been applied to seven different clinical research projects covering different clinical problems in different organ systems such as cancer of the thyroid and the prostate glands. This paper shows how the adoption of a generic web application framework is a feasible, flexible, low-cost, and user-friendly way of managing multidimensional research data in researcher-initiated non-GCP clinical projects.

  4. Differential Reinforcement of Alternative Behavior Increases Resistance to Extinction: Clinical Demonstration, Animal Modeling, and Clinical Test of One Solution

    ERIC Educational Resources Information Center

    Mace, F. Charles; McComas, Jennifer J.; Mauro, Benjamin C.; Progar, Patrick R.; Taylor, Bridget; Ervin, Ruth; Zangrillo, Amanda N.

    2010-01-01

    Basic research with pigeons on behavioral momentum suggests that differential reinforcement of alternative behavior (DRA) can increase the resistance of target behavior to change. This finding suggests that clinical applications of DRA may inadvertently increase the persistence of target behavior even as it decreases its frequency. We conducted…

  5. Unequal Burden of Disease, Unequal Participation in Clinical Trials: Solutions from African American and Latino Community Members

    PubMed Central

    Ford, Marvella E.; Siminoff, Laura A.; Pickelsimer, Elisabeth; Mainous, Arch G.; Smith, Daniel W.; Diaz, Vanessa A.; Soderstrom, Lea H.; Jefferson, Melanie S.; Tilley, Barbara C.

    2013-01-01

    African Americans and Latinos are underrepresented in clinical trials. The purpose of this study was to elicit solutions to participation barriers from African Americans and Latinos. Fifty-seven adults (32 African Americans, 25 Latinos) ages 50 years and older participated. The Institute of Medicine's Unequal Treatment conceptual framework was used. Six racially/ethnically homogenous focus groups were conducted at five sites in three counties. Themes within groups and cross-cutting themes were identified. The NVIVO program was used for data classification. The data were reviewed for final coding and consensus. Shared solutions included addressing costs, recruiting in community contexts, conducting community and individualized patient education, and sharing patient safety information. Participants were unanimously in favor of clinical trials navigation recruitment interventions. Solutions specific to African Americans included diversifying research teams, recognizing past research abuses, and increasing community trust. Solutions specific to Latinos included providing low-literacy materials, providing Spanish-speaking clinicians and advocates, and clarifying that immigration status would neither be documented nor prevent participation. Solutions from African Americans and Latinos reflect their cultural backgrounds and historical experiences. The results suggest the importance of developing a tailored, barriers-focused navigation intervention to improve participation among diverse racial and ethnic populations. PMID:23539894

  6. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    PubMed Central

    Li, Kaichun; Li, Jin

    2016-01-01

    Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

  7. "Electro-clinical syndromes" with onset in paediatric age: the highlights of the clinical-EEG, genetic and therapeutic advances

    PubMed Central

    2011-01-01

    The genetic causes underlying epilepsy remain largely unknown, and the impact of available genetic data on the nosology of epilepsy is still limited. Thus, at present, classification of epileptic disorders should be mainly based on electroclinical features. Electro-clinical syndrome is a term used to identify a group of clinical entities showing a cluster of electro-clinical characteristics, with signs and symptoms that together define a distinctive, recognizable, clinical disorder. These often become the focus of treatment trials as well as of genetic, neuropsychological, and neuroimaging investigations. They are distinctive disorders identifiable on the basis of a typical age onset, specific EEG characteristics, seizure types, and often other features which, when taken together, permit a specific diagnosis which, in turn, often has implications for treatment, management, and prognosis. Each electro-clinical syndrome can be classified according to age at onset, cognitive and developmental antecedents and consequences, motor and sensory examinations, EEG features, provoking or triggering factors, and patterns of seizure occurrence with respect to sleep. Therefore, according to the age at onset, here we review the more frequently observed paediatric electro-clinical syndrome from their clinical-EEG, genetic and therapeutic point of views. PMID:22182677

  8. Psychological masquerade embedded in a cluster of related clinical errors: Real practice, real solutions, and their scientific underpinnings.

    PubMed

    Spengler, Paul M; Miller, Deborah J; Spengler, Elliot S

    2016-09-01

    In this paper, we discuss the need for medical rule outs in over 50% of diagnoses and the risk for mental health practitioners to engage in a clinical judgment error called psychological masquerade (Taylor, 2007). We use the specific example of thyroid dysfunction as a relevant rule out when a client presents with symptoms consistent with an affective disorder. A real clinical example is provided and discussed to illustrate how the first author invoked psychological masquerade resulting in clinical decision-making errors during the treatment of a mother participating in family therapy. Solutions for this specific case and more generally for psychological masquerade are provided and discussed in the context of theory and research on mental health clinical decision-making. (PsycINFO Database Record PMID:27631863

  9. Advances with the Chinese anthelminthic drug tribendimidine in clinical trials and laboratory investigations.

    PubMed

    Xiao, Shu-Hua; Utzinger, Jürg; Tanner, Marcel; Keiser, Jennifer; Xue, Jian

    2013-05-01

    The anthelminthic drug tribendimidine has been approved by Chinese authorities for human use in 2004, and a first comprehensive review was published in Acta Tropica in 2005. Here, we summarise further advances made through additional clinical trials and laboratory investigations. Two phase IV trials have been conducted in the People's Republic of China, the first one enrolling 1292 adolescents and adults aged 15-70 years and the second one conducted with 899 children aged 4-14 years who were infected with one or multiple species of soil-transmitted helminths. Oral tribendimidine (single 400mg enteric-coated tablet given to adolescents/adults and 200mg to children) showed high cure rates against Ascaris lumbricoides (90.1-95.0%) and moderate-to-high cure rates against hookworm (82.0-88.4%). Another trial done in school-aged children using a rigorous diagnostic approach found a cure rate against hookworm of 76.5%. A single oral dose of tribendimidine showed only low cure rates against Trichuris trichiura (23.9-36.8%) confirming previous results. Tribendimidine administered to children infected with Enterobius vermicularis (two doses of 200mg each on consecutive days) resulted in a high cure rate (97.1%). Importantly, a series of randomised, exploratory trials revealed that tribendimidine shows interesting activity against the liver flukes Opisthorchis viverrini and Clonorchis sinensis, the tapeworm Taenia spp. and the threadworm Strongyloides stercoralis with respective cure rates of 70.0%, 40.0%, 53.3% and 36.4%. Pharmacokinetic studies in healthy Chinese volunteers indicated that after oral administration of tribendimidine, no parent drug was detected in plasma, but its primary metabolite, p-(1-dimethylamino ethylimino) aniline (aminoamidine, deacylated amidantel) (dADT), was found in plasma. dADT is then further metabolised to acetylated dADT (AdADT). dADT exhibits activity against several species of hookworm and C. sinensis in experimental studies, similar to

  10. Rapid hyperfractionated radiotherapy. Clinical results in 178 advanced squamous cell carcinomas of the head and neck

    SciTech Connect

    Nguyen, T.D.; Demange, L.; Froissart, D.; Panis, X.; Loirette, M.

    1985-07-01

    The authors present a series of 178 patients with Stage III or IV squamous cell carcinoma of the head and neck treated by rapid irradiation using multiple and small fractions per day. An initial group of 91 patients (G1) received a total dose of 72 Gy in 80 sessions and 10 days, according to the following split course schedule: J1 to J5, 36 Gy in 40 sessions, eight daily fractions of .9 Gy separated by 2 hours; J6 to J20, rest period; J21 to J25, same as in J1 except that the spinal cord was shielded. This protocol was altered for the following 87 patients (G2) by lessening the total dose to 60 to 66 Gy and the number of fractions to 60. The rest period was lengthened to 4 weeks. All patients but five completed the whole program and the minimal follow-up period was 24 months. At the end of irradiation, 121 patients achieved a total remission, but local recurrences occurred in 56%. Moreover, acute intolerance was considered as severe in 34% of G1 patients, and included extensive mucosal necrosis and bleeding. Although this rate was significantly reduced in G2 patients, late complications were observed in 20 of the 25 survivors, and included trismus, cervical sclerosis, and recurrent laryngeal edema. The crude survival rate is 13% at 2 years. Although this study was not randomized, this particular type of accelerated and hyperfractionated combination of irradiation did not really improve the clinical results in advanced carcinoma of the head and neck. Other schedules and probably other tumors, less extended, should be tested.

  11. GMP facilities for manufacturing of advanced therapy medicinal products for clinical trials: an overview for clinical researchers.

    PubMed

    Alici, Evren; Blomberg, Pontus

    2010-12-01

    To be able to produce advanced therapy medicinal products, compliance with regulatory standards while maintaining flexibility is mandatory. For this purpose, careful planning is vital in the design or upgrade of a facility. Similarly, extensive foresight is elemental to anticipate upcoming needs and requirements. Failing this may lead to the facility's in-ability to meet the demands. In this chapter we aimed to outline the current issues with regards to the European Union Directives (EUD) and the proposal for Advanced Therapies, which are of importance to cellular and gene therapy facilities in Europe. This chapter is an attempt to elucidate what the minimum requirements for GMP facilities for cell and gene therapy products are and what is considered necessary to comply with the regulations in Europe.

  12. Next-generation sequencing in patients with advanced cancer: are we ready for widespread clinical use? A single institute's experience.

    PubMed

    Grenader, Tal; Tauber, Rachel; Shavit, Linda

    2016-10-01

    The next-generation sequencing (NGS) assay targeting cancer-relevant genes has been adopted widely for use in patients with advanced cancer. The primary aim of this study was to assess the clinical utility of commercially available NGS. We retrospectively collected demographic and clinicopathologic data, recommended therapy, and clinical outcomes of 30 patients with a variety of advanced solid tumors referred to Foundation Medicine NGS. The initial pathologic examination was performed at the pathology department of the referring hospital. The comprehensive clinical NSG assay was performed on paraffin-embedded tumor samples using the Clinical Laboratory Improvement Amendments-certified FoundationOne platform. The median number of genomic alterations was 3 (0-19). The median number of therapies with potential benefit was 2 (0-8). In 12 cases, a comprehensive clinical NGS assay did not indicate any therapy with potential benefit according to the genomic profile. Ten of the 30 patients received treatments recommended by genomic profile results. In six of the 10 cases, disease progressed within 2 months and four patients died within 3 months of treatment initiation. Three of the 30 patients benefited from a comprehensive clinical NGS assay and the subsequent recommended therapy. The median PFS was 12 weeks (95% confidence interval 10-57) in patients treated with molecularly targeted agents chosen on the basis of tumor genomic profiling versus 48 weeks (95% confidence interval 8-38) in the control group treated with physician choice therapy (P=0.12). Our study suggests that NGS can detect additional treatment targets in individual patients, but prospective medical research and appropriate clinical guidelines for proper clinical use are vital. PMID:27384593

  13. [Adequacy of clinical interventions in patients with advanced and complex disease. Proposal of a decision making algorithm].

    PubMed

    Ameneiros-Lago, E; Carballada-Rico, C; Garrido-Sanjuán, J A; García Martínez, A

    2015-01-01

    Decision making in the patient with chronic advanced disease is especially complex. Health professionals are obliged to prevent avoidable suffering and not to add any more damage to that of the disease itself. The adequacy of the clinical interventions consists of only offering those diagnostic and therapeutic procedures appropriate to the clinical situation of the patient and to perform only those allowed by the patient or representative. In this article, the use of an algorithm is proposed that should serve to help health professionals in this decision making process.

  14. Randomized Pilot Clinical Trial of Tofacitinib Solution for Plaque Psoriasis: Challenges of the Intra-Subject Study Design.

    PubMed

    Ports, William C; Feldman, Steven R; Gupta, Pankaj; Tan, Huaming; Johnson, Theodore R; Bissonnette, Robert

    2015-08-01

    Intra-subject, left-right, randomized, controlled study designs are often used for proof-of-concept studies in dermatology. This design was used to evaluate the safety and efficacy of a topical solution of tofacitinib (NCT00678561), a small-molecule Janus kinase inhibitor under investigation for the topical and oral treatment of patients with chronic plaque psoriasis. Eighty-one patients, each with matched left and right target plaques, were randomized to 2%, 0.2%, or 0.02% tofacitinib or vehicle solution once or twice daily. Patients treated one plaque as per their randomization group (2%, 0.2%, 0.02% tofacitinib, or vehicle solution), and used vehicle to treat the contralateral plaque for 4 weeks. Except during clinic visits, study drug applications were performed unsupervised outside the clinical trial site. Intra-subject, vehicle-adjusted mean percent change from baseline in Target Plaque Severity Score at week 4 (primary efficacy endpoint) was not significantly different from baseline for any treatment group (P values of 0.28-0.68). However, skin biopsy analyses detected tofacitinib in both tofacitinib- and vehicle-treated plaques of some patients, suggesting cross-contamination or solution misapplication. Lack of efficacy with tofacitinib relative to vehicle may be due to the intra-subject study design with unsupervised applications. These findings have potential implications for future intra-subject studies of topical treatments.

  15. Residency training in advance care planning: can it be done in the outpatient clinic?

    PubMed

    Alderman, Jeffrey S; Nair, Baishali; Fox, Mark D

    2008-01-01

    Resident physicians are expected to assist their outpatients to understand and complete advance directives, but their efficacy in doing so remains uncertain. After receiving educational training, internal medicine residents identified at-risk patients and solicited them about advance directives. Residents completed pretest and posttest questionnaires that assessed their knowledge, skills, attitude, and comfort with advance directives. Patients were also surveyed about their attitudes regarding advance directives. Ten internal medicine residents and 88 patients participated. Residents' self-assessed knowledge rose from 6.0 to 9.2 on a 10-point Likert scale. Skills using advance directives increased from 4.0 to 7.9, attitudes improved from 6.0 to 8.4, and comfort rose from 5.4 to 8.9. Eighty-four percent of patients expressed interest in completing advance directives, and 16% actually completed documents. An educational intervention improved knowledge, skills, attitudes, and comfort with advance directives among internal medicine residents practicing in the outpatient setting. Meanwhile, patients demonstrated a strong interest in completing advance directives.

  16. Validation of an advanced practice physiotherapy model of care in an orthopaedic outpatient clinic

    PubMed Central

    2013-01-01

    Background In Canada, new models of orthopaedic care involving advanced practice physiotherapists (APP) are being implemented. In these new models, aimed at improving the efficiency of care for patients with musculoskeletal disorders, APPs diagnose, triage and conservatively treat patients. Formal validation of the efficiency and appropriateness of these emerging models is scarce. The purpose of this study is to assess the diagnostic agreement of an APP compared to orthopaedic surgeons as well as to assess treatment concordance, healthcare resource use, and patient satisfaction in this new model. Methods 120 patients presenting for an initial consult for hip or knee complaints in an outpatient orthopaedic hospital clinic in Montreal, Canada, were independently assessed by an APP and by one of three participating orthopaedic surgeons. Each health care provider independently diagnosed the patients and provided triage recommendations (conservative or surgical management). Proportion of raw agreement and Cohen’s kappa were used to assess inter-rater agreement for diagnosis, triage, treatment recommendations and imaging tests ordered. Chi-Square tests were done in order to compare the type of conservative treatment recommendations made by the APP and the surgeons and Student t-tests to compare patient satisfaction between the two types of care. Results The majority of patients assessed were female (54%), mean age was 54.1 years and 91% consulted for a knee complaint. The raw agreement proportion for diagnosis was 88% and diagnostic inter-rater agreement was very high (κ=0.86; 95% CI: 0.80-0.93). The triage recommendations (conservative or surgical management) raw agreement proportion was found to be 88% and inter-rater agreement for triage recommendation was high (κ=0.77; 95% CI: 0.65-0.88). No differences were found between providers with respect to imaging tests ordered (p≥0.05). In terms of conservative treatment recommendations made, the APP gave significantly

  17. Dementia and Robotics: People with Advancing Dementia and Their Carers Driving an Exploration into an Engineering Solution to Maintaining Safe Exercise Regimes.

    PubMed

    Cooper, Carol; Penders, Jacques; Procter, Paula M

    2016-01-01

    The merging of the human world and the information technology world is advancing at a pace, even for those with dementia there are many useful smart 'phone applications including reminders, family pictures display, GPS functions and video communications. This paper will report upon initial collaborative work developing a robotic solution to engaging individuals with advancing dementia in safe exercise regimes. The research team has been driven by the needs of people with advancing dementia and their carers through a focus group methodology, the format, discussions and outcomes of these groups will be reported. The plans for the next stage of the research will be outlined including the continuing collaboration with advancing dementia and their carers. PMID:27332260

  18. The "Commitment Model" for Clinical Ethics Consultations: Society's Involvement in the Solution of Individual Cases.

    PubMed

    Fournier, Véronique; Spranzi, Marta; Foureur, Nicolas; Brunet, Laurence

    2015-01-01

    Several approaches to clinical ethics consultation (CEC) exist in medical practice and are widely discussed in the clinical ethics literature; different models of CECs are classified according to their methods, goals, and consultant's attitude. Although the "facilitation" model has been endorsed by the American Society for Bioethics and Humanities (ASBH) and is described in an influential manual, alternative approaches, such as advocacy, moral expertise, mediation, and engagement are practiced and defended in the clinical ethics field. Our Clinical Ethics Center in Paris was founded in 2002 in the wake of the Patients' Rights Act, and to date it is the largest center that provides consultation services in France. In this article we shall describe and defend our own approach to clinical ethics consultation, which we call the "Commitment Model," in comparison with other existing models. Indeed commitment implies, among other meanings, continuity through time, a series of coherent actions, and the realization of important social goals. By drawing on a recent consultation case, we shall describe the main steps of our consultation procedure: interviews with major stakeholders, including patients and proxies; case conferences; and follow up. We shall show why we have chosen the term "commitment" to represent our approach at three different but interrelated levels: commitment towards patients, within the case conference group, and towards society as a whole.

  19. The "Commitment Model" for Clinical Ethics Consultations: Society's Involvement in the Solution of Individual Cases.

    PubMed

    Fournier, Véronique; Spranzi, Marta; Foureur, Nicolas; Brunet, Laurence

    2015-01-01

    Several approaches to clinical ethics consultation (CEC) exist in medical practice and are widely discussed in the clinical ethics literature; different models of CECs are classified according to their methods, goals, and consultant's attitude. Although the "facilitation" model has been endorsed by the American Society for Bioethics and Humanities (ASBH) and is described in an influential manual, alternative approaches, such as advocacy, moral expertise, mediation, and engagement are practiced and defended in the clinical ethics field. Our Clinical Ethics Center in Paris was founded in 2002 in the wake of the Patients' Rights Act, and to date it is the largest center that provides consultation services in France. In this article we shall describe and defend our own approach to clinical ethics consultation, which we call the "Commitment Model," in comparison with other existing models. Indeed commitment implies, among other meanings, continuity through time, a series of coherent actions, and the realization of important social goals. By drawing on a recent consultation case, we shall describe the main steps of our consultation procedure: interviews with major stakeholders, including patients and proxies; case conferences; and follow up. We shall show why we have chosen the term "commitment" to represent our approach at three different but interrelated levels: commitment towards patients, within the case conference group, and towards society as a whole. PMID:26752382

  20. A regulatory perspective of clinical trial applications for biological products with particular emphasis on Advanced Therapy Medicinal Products (ATMPs).

    PubMed

    Jones, David R; McBlane, James W; McNaughton, Graham; Rajakumaraswamy, Nishanthan; Wydenbach, Kirsty

    2013-08-01

    The safety of trial subjects is the tenet that guides the regulatory assessment of a Clinical Trial Authorization application and applies equally to trials involving small molecules and those with biological/biotechnological products, including Advanced Therapy Medicinal Products. The objective of a regulator is to ensure that the potential risk faced by a trial subject is outweighed by the potential benefit to them from taking part in the trial. The focus of the application review is to assess whether risks have been identified and appropriate steps taken to alleviate these as much as possible. Other factors are also taken into account during a review, such as regulatory requirements, and emerging non-clinical and clinical data from other trials on the same or similar products. This paper examines the regulatory review process of a Clinical Trial Authorization application from the perspectives of Quality, Non-Clinical and Clinical Regulatory Assessors at the Medicines and Healthcare products Regulatory Agency. It should be noted that each perspective has highlighted specific issues from their individual competence and that these can be different between the disciplines.

  1. High pressure jet injection of viscous solutions for endoscopic submucosal dissection (ESD): first clinical experience

    PubMed Central

    Pioche, Mathieu; Lépilliez, Vincent; Déprez, Pierre; Giovannini, Marc; Caillol, Fabrice; Piessevaux, Hubert; Rivory, Jérôme; Guillaud, Olivier; Ciocîrlan, Mihai; Salmon, Damien; Lienhart, Isabelle; Lafon, Cyril; Saurin, Jean-Christophe; Ponchon, Thierry

    2015-01-01

    Background: Long lasting elevation is a key factor during endoscopic submucosal dissection (ESD) and can be obtained by water jet injection of saline solution or by viscous macromolecular solutions. In a previous animal study, we assessed the Nestis Enki II system to combine jet injection and viscous solutions. In the present work, we used this combination in humans in different sites of the digestive tract. Methods: We retrospectively report all of the consecutive ESD procedures performed with jet injection of viscous solutions in four centers. Information was collected about the lesion, the procedure, the histological result, and the outcomes for the patient. Results: In total, 45 resections were completed by six operators: five experts and one beginner with only one previous experience in human ESD. Lesions were located in the esophagus (10), the stomach (11), the duodenum (1), the colon (1) and the rectum (22). Average maximal lesion diameter was 4.8 cm (SD 2.4, range 2 – 11 cm), average lesion surface area was 19.8 cm2 (SD 17.7, range 2.2 – 72 cm2), and average duration of procedure was 79.9 min (SD 50.3 min, range 19 – 225 min). ESD could be conducted while the endoscope was retroflexed at its maximum in 26 cases. Four adverse events were observed: two diminutive perforations and two delayed bleeding occurrences treated conservatively. The R0 resection rate was 91.1 %. The catheter was obstructed in six occurrences of bleeding. Conclusion: Endoscopic submucosal dissection using high pressure injection of viscous macromolecular solutions is safe and effective in different parts of the digestive tract. It does not impede working with the endoscope in the maximal retroflexed position. PMID:26356488

  2. Offshore Medical Schools Are Buying Clinical Clerkships in U.S. Hospitals: The Problem and Potential Solutions.

    PubMed

    Halperin, Edward C; Goldberg, Robert B

    2016-05-01

    U.S. medical education faces a threat from for-profit Caribbean medical schools which purchase clinical rotation slots for their students at U.S. hospitals. These offshore schools are monetizing a system that was previously characterized as a duty-the duty of the current generation of physicians to educate their successors. Offshore schools purchase clinical rotation slots using funds largely derived from federally subsidized student loans. This leads to pressure on U.S. schools to pay for clinical clerkships and is forcing some of them to find new clinical training sites.For-profit Caribbean schools largely escape the type of scrutiny that U.S. schools face from U.S. national accreditation organizations. They also enroll large classes of students with lower undergraduate GPAs and Medical College Admission Test scores than those of students at U.S. medical schools; their students take and pass Step 1 of the United States Medical Licensing Examination at a substantially lower rate than that of U.S. medical students; and their students match for residencies at a fraction of the rate of U.S. medical school graduates.Among the potential solutions proposed by the authors are passing laws to hold for-profit Caribbean schools to standards for board passage rates, placing restrictions on federal student loans, monitoring attrition rates, and denying offshore schools access to U.S. clinical training sites unless they meet accreditation standards equivalent to those of U.S. medical schools.

  3. Advances in clinical NK cell studies: Donor selection, manufacturing and quality control

    PubMed Central

    Koehl, U.; Kalberer, C.; Spanholtz, J.; Lee, D. A.; Miller, J. S.; Cooley, S.; Lowdell, M.; Uharek, L.; Klingemann, H.; Curti, A.; Leung, W.; Alici, E.

    2016-01-01

    ABSTRACT Natural killer (NK) cells are increasingly used in clinical studies in order to treat patients with various malignancies. The following review summarizes platform lectures and 2013–2015 consortium meetings on manufacturing and clinical use of NK cells in Europe and United States. A broad overview of recent pre-clinical and clinical results in NK cell therapies is provided based on unstimulated, cytokine-activated, as well as genetically engineered NK cells using chimeric antigen receptors (CAR). Differences in donor selection, manufacturing and quality control of NK cells for cancer immunotherapies are described and basic recommendations are outlined for harmonization in future NK cell studies. PMID:27141397

  4. The INTEGRATE project: Delivering solutions for efficient multi-centric clinical research and trials.

    PubMed

    Kondylakis, Haridimos; Claerhout, Brecht; Keyur, Mehta; Koumakis, Lefteris; van Leeuwen, Jasper; Marias, Kostas; Perez-Rey, David; De Schepper, Kristof; Tsiknakis, Manolis; Bucur, Anca

    2016-08-01

    The objective of the INTEGRATE project (http://www.fp7-integrate.eu/) that has recently concluded successfully was the development of innovative biomedical applications focused on streamlining the execution of clinical research, on enabling multidisciplinary collaboration, on management and large-scale sharing of multi-level heterogeneous datasets, and on the development of new methodologies and of predictive multi-scale models in cancer. In this paper, we present the way the INTEGRATE consortium has approached important challenges such as the integration of multi-scale biomedical data in the context of post-genomic clinical trials, the development of predictive models and the implementation of tools to facilitate the efficient execution of postgenomic multi-centric clinical trials in breast cancer. Furthermore, we provide a number of key "lessons learned" during the process and give directions for further future research and development. PMID:27224847

  5. The INTEGRATE project: Delivering solutions for efficient multi-centric clinical research and trials.

    PubMed

    Kondylakis, Haridimos; Claerhout, Brecht; Keyur, Mehta; Koumakis, Lefteris; van Leeuwen, Jasper; Marias, Kostas; Perez-Rey, David; De Schepper, Kristof; Tsiknakis, Manolis; Bucur, Anca

    2016-08-01

    The objective of the INTEGRATE project (http://www.fp7-integrate.eu/) that has recently concluded successfully was the development of innovative biomedical applications focused on streamlining the execution of clinical research, on enabling multidisciplinary collaboration, on management and large-scale sharing of multi-level heterogeneous datasets, and on the development of new methodologies and of predictive multi-scale models in cancer. In this paper, we present the way the INTEGRATE consortium has approached important challenges such as the integration of multi-scale biomedical data in the context of post-genomic clinical trials, the development of predictive models and the implementation of tools to facilitate the efficient execution of postgenomic multi-centric clinical trials in breast cancer. Furthermore, we provide a number of key "lessons learned" during the process and give directions for further future research and development.

  6. [Diagnosis of dementia in non-western elderly migrants in memory clinics: obstacles and solutions].

    PubMed

    Goudsmit, M; Parlevliet, J L; van Campen, J P C M; Schmand, B

    2011-10-01

    In the next decade the number of non-western elderly immigrants will double in the Netherlands. Because of specific risk factors (hypertension, diabetes), the number of elderly immigrants with dementia will probably increase. Memory clinics are not well prepared for these patients, because health professionals lack knowledge about important obstacles in intercultural dementia diagnostics. They should consider language barriers, cultural differences, low level of education and illiteracy, as well as ignorance about dementia, shame and special care expectations of patients and their families. We give recommendations to improve communication, (neuropsychological) testing and counseling in clinical practice. PMID:22470986

  7. The relational clinical database: a possible solution to the star wars in registry systems.

    PubMed

    Michels, D K; Zamieroski, M

    1990-12-01

    In summary, having data from other service areas available in a relational clinical database could resolve many of the problems existing in today's registry systems. Uniting sophisticated information systems into a centralized database system could definitely be a corporate asset in managing the bottom line.

  8. Topical 5-fluorouracil solution in the treatment of warts--clinical experience and percutaneous absorption.

    PubMed

    Senff, H; Reinel, D; Matthies, C; Witts, D

    1988-03-01

    Disseminated warts in six patients were pre-treated with topical 5-fluorouracil solution three times daily for 5 consecutive days. Curettage was then carried out under local anaesthesia. During pre-treatment less than 0.1% of the dose applied was absorbed through the skin. The warts had not reappeared in 5 of the 6 patients at follow-up 1 year later.

  9. Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

    PubMed Central

    Nguyen, Chinh; Barker, Bridget Marie; Hoover, Susan; Nix, David E.; Ampel, Neil M.; Frelinger, Jeffrey A.; Orbach, Marc J.

    2013-01-01

    SUMMARY Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii. This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine. PMID:23824371

  10. [A device for mandibular advancement in respiratory disorders of sleep. Clinical study].

    PubMed

    Bacon, W; Tschill, P; Sforza, E; Krieger, J

    2000-12-01

    This study describes the technical steps for the making of a mandibular advancement device for sleep disordered patients (apnea index < 10). In a second part of the study, a group of 21 patients with sleep disordered breathing treated successfully with a mandibular advancement device is compared to a homologous control group. The experimental group showed cephalometric characteristics approaching those seen in patients with sleep apnea syndrome. The mandibular advancement device moved the mandibule forward (SNB angle increases by 1.7 degrees) and downward (mandibular plane angle increases by 3 degrees, which can be related to the 7.4 mm anterior vertical height increase). The hyoid bone adopted a more distant position from the cervical vertebrae. Important individual variations were seen among the patients for the optimal repositioning of the mandible.

  11. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness.

    PubMed

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R

    2016-09-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  12. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    PubMed Central

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  13. Advances in stent technologies and their effect on clinical efficacy and safety

    PubMed Central

    Nikam, Navin; Steinberg, Toby B; Steinberg, Daniel H

    2014-01-01

    The introduction of intracoronary stents represented a major advance in interventional cardiology. While bare metal stents set the benchmark for improved safety over angioplasty, intimal hyperplasia and subsequent restenosis were important limitations. First-generation drug-eluting stents demonstrated significant improvements in efficacy, but not necessarily safety, and further technologic developments have focused on optimizing both. Current advances and understanding in stent design continue to improve on these concepts. This review summarizes past and present technology with particular emphasis on the principles underlying the efficacy and safety of drug-eluting stents, and offers a glimpse into the next generations of stents aimed at treating symptomatic coronary artery disease. PMID:24940085

  14. Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: part III – convergence toward clinical trials

    PubMed Central

    2013-01-01

    Rapid scientific and technological advances have allowed for a more detailed understanding of the relevance of intestinal microbiota, and the entire body-wide microbiome, to human health and well-being. Rodent studies have provided suggestive evidence that probiotics (e.g. lactobacillus and bifidobacteria) can influence behavior. More importantly, emerging clinical studies indicate that the administration of beneficial microbes, via supplementation and/or fecal microbial transplant (FMT), can influence end-points related to mood state (glycemic control, oxidative status, uremic toxins), brain function (functional magnetic resonance imaging fMRI), and mental outlook (depression, anxiety). However, despite the advances in the area of gastro-biological psychiatry, it becomes clear that there remains an urgent need to explore the value of beneficial microbes in controlled clinical investigations. With the history explored in this series, it is fair to ask if we are now on the cusp of major clinical breakthroughs, or are we merely in the quicksand of Autointoxication II? PMID:23497650

  15. An external portable device for adaptive deep brain stimulation (aDBS) clinical research in advanced Parkinson's Disease.

    PubMed

    Arlotti, Mattia; Rossi, Lorenzo; Rosa, Manuela; Marceglia, Sara; Priori, Alberto

    2016-05-01

    Compared to conventional deep brain stimulation (DBS) for patients with Parkinson's Disease (PD), the newer approach of adaptive DBS (aDBS), regulating stimulation on the basis of the patient's clinical state, promises to achieve better clinical outcomes, avoid adverse-effects and save time for tuning parameters. A remaining challenge before aDBS comes into practical use is to prove its feasibility and its effectiveness in larger groups of patients and in more ecological conditions. We developed an external portable aDBS system prototype designed for clinical testing in freely-moving PD patients with externalized DBS electrodes. From a single-channel bipolar artifact-free recording, it analyses local field potentials (LFPs), during ongoing DBS for tuning stimulation parameters, independent from the specific feedback algorithm implemented. We validated the aDBS system in vitro, by testing both its sensing and closed-loop stimulation capabilities, and then tested it in vivo, focusing on the sensing capabilities. By applying the aDBS system prototype in a patient with PD, we provided evidence that it can track levodopa and DBS-induced LFP spectral power changes among different patient's clinical states. Our system, intended for testing LFP-based feedback strategies for aDBS, should help understanding how and whether aDBS therapy works in PD and indicating future technical and clinical advances. PMID:27029510

  16. The Role of Technical Advances in the Adoption and Integration of Patient-Reported Outcomes in Clinical Care

    PubMed Central

    Jensen, Roxanne E.; Rothrock, Nan E.; DeWitt, Esi Morgan; Spiegel, Brennan; Tucker, Carole A.; Crane, Heidi M.; Forrest, Christopher B.; Patrick, Donald L.; Fredericksen, Rob; Shulman, Lisa M.; Cella, David; Crane, Paul K.

    2016-01-01

    Background Patient-reported outcomes (PROs) are gaining recognition as key measures for improving the quality of patient care in clinical care settings. Three factors have made the implementation of PROs in clinical care more feasible: increased use of modern measurement methods in PRO design and validation, rapid progression of technology (e.g., touch screen tablets, Internet accessibility, and electronic health records (EHRs)), and greater demand for measurement and monitoring of PROs by regulators, payers, accreditors, and professional organizations. As electronic PRO collection and reporting capabilities have improved, the challenges of collecting PRO data have changed. Objectives To update information on PRO adoption considerations in clinical care, highlighting electronic and technical advances with respect to measure selection, clinical workflow, data infrastructure, and outcomes reporting. Methods Five practical case studies across diverse healthcare settings and patient populations are used to explore how implementation barriers were addressed to promote the successful integration of PRO collection into the clinical workflow. The case studies address selecting and reporting of relevant content, workflow integration, pre-visit screening, effective evaluation, and EHR integration. Conclusions These case studies exemplify elements of well-designed electronic systems, including response automation, tailoring of item selection and reporting algorithms, flexibility of collection location, and integration with patient health care data elements. They also highlight emerging logistical barriers in this area, such as the need for specialized technological and methodological expertise, and design limitations of current electronic data capture systems. PMID:25588135

  17. Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.

    PubMed

    Friedman, Kenneth; Resnick, Murray B; Safran, Howard

    2015-10-01

    The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic alterations in genes commonly mutated in cancer. However, several unexpected genomic alterations were discovered in certain cancers with potential therapeutic intervention. Most cancers contained "actionable" genomic alterations despite being of advanced stage. Our experience demonstrates that application of NGS in the clinical setting contributes both to increasing the therapeutic armamentarium as well as our understanding of tumor biology.

  18. Infusing Swanson's Theory of caring into an advanced practice nursing model for an infectious diseases anal dysplasia clinic.

    PubMed

    Ahern, Richard L; Corless, Inge B; Davis, Sheila M; Kwong, Jeffrey J

    2011-01-01

    The incidence of anal cancer is increasing among HIV-infected men and women. The process of screening for anal dysplasia and the management of abnormal findings are currently and most often based on a medical model. The needs of these patients, however, go well beyond medical care. A more comprehensive and holistic approach to health care is, therefore, required. Given the scope of practice of advanced practice nurses who are involved in the diagnosis and treatment of patients with anal dysplasia, it is appropriate for them to assume leadership roles in addressing the needs of these patients. This article describes the application of a theory of caring to create an advanced practice nursing model of care for HIV-infected men and women in infectious diseases anal dysplasia clinics. PMID:22035527

  19. PROBLEM OF COMPLEX EIGENSYSTEMS INTHE SEMIANALYTICAL SOLUTION FOR ADVANCEMENT OF TIME IN SOLUTE TRANSPORT SIMULATIONS: A NEW METHOD USING REAL ARITHMETIC.

    USGS Publications Warehouse

    Umari, Amjad M. J.; Gorelick, Steven M.

    1986-01-01

    In the numerical modeling of groundwater solute transport, explicit solutions may be obtained for the concentration field at any future time without computing concentrations at intermediate times. The spatial variables are discretized and time is left continuous inthe governing differnetial equation. These semianalytical solutions have been presented in the literature and involve the eigensystem of a coefficient matrix. This eigensystem may be complex (i. e. , have imaginary components) due to the asymmetry created by the advection term in the governing advection-dispersionequation. It is shown here that the error due to ignoring the imaginary components of complex eigenvalues is large for small dispersivity values. A new algorithm that represents the complex eigensystem by converting it to a real eigensystem is presented. The method requires only real arithmetic.

  20. A Clinical Assessment Tool for Advanced Theory of Mind Performance in 5 to 12 Year Olds

    ERIC Educational Resources Information Center

    O'Hare, Anne E.; Bremner, Lynne; Nash, Marysia; Happe, Francesca; Pettigrew, Luisa M.

    2009-01-01

    One hundred forty typically developing 5- to 12-year-old children were assessed with a test of advanced theory of mind employing Happe's strange stories. There was no significant difference in performance between boys and girls. The stories discriminated performance across the different ages with the lowest performance being in the younger…

  1. Clinical applications of recent molecular advances in urologic malignancies: no longer chasing a "mirage"?

    PubMed

    Netto, George J

    2013-05-01

    As our understanding of the molecular events leading to the development and progression of genitourologic malignancies, new markers of detection, prognostication, and therapy prediction can be exploited in the management of these prevalent tumors. The current review discusses the recent advances in prostate, bladder, renal, and testicular neoplasms that are pertinent to the anatomic pathologist. PMID:23574774

  2. Advances In Infection Surveillance and Clinical Decision Support With Fuzzy Sets and Fuzzy Logic.

    PubMed

    Koller, Walter; de Bruin, Jeroen S; Rappelsberger, Andrea; Adlassnig, Klaus-Peter

    2015-01-01

    By the use of extended intelligent information technology tools for fully automated healthcare-associated infection (HAI) surveillance, clinicians can be informed and alerted about the emergence of infection-related conditions in their patients. Moni--a system for monitoring nosocomial infections in intensive care units for adult and neonatal patients--employs knowledge bases that were written with extensive use of fuzzy sets and fuzzy logic, allowing the inherent un-sharpness of clinical terms and the inherent uncertainty of clinical conclusions to be a part of Moni's output. Thus, linguistic as well as propositional uncertainty became a part of Moni, which can now report retrospectively on HAIs according to traditional crisp HAI surveillance definitions, as well as support clinical bedside work by more complex crisp and fuzzy alerts and reminders. This improved approach can bridge the gap between classical retrospective surveillance of HAIs and ongoing prospective clinical-decision-oriented HAI support.

  3. Mogamulizumab for the treatment of cutaneous T-cell lymphoma: recent advances and clinical potential

    PubMed Central

    Duvic, Madeleine; Evans, Mark; Wang, Casey

    2016-01-01

    Mogamulizumab (KW-0761) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets CC chemokine receptor 4 (CCR4). It has shown promising therapeutic potential in phase I and II clinical trials and is currently being investigated for efficacy in treating cutaneous T-cell lymphoma (CTCL). We review the mechanism of action of mogamulizumab and its role in treating CTCL. We also discuss the results of major clinical trials. PMID:27247757

  4. SU-E-T-588: Characterization and Clinical Validation of the Varian Pivotal™ Treatment Solution for Prone Breast Care

    SciTech Connect

    Dewyngaert, K; Jozsef, G; Formenti, S

    2014-06-01

    Purpose: To report on the clinical validation of the Varian Pivotal™ Treatment Solution for Prone Breast Care: a platform for prone breast radiation therapy. Methods: Patients treated using Breast Conserving Radiation Therapy may benefit from treatment in the prone position with the breast tissue falling freely away from the body. This geometry allows the breast tissue to be treated while avoiding the lung and heart tissue. Eighteen patients simulated and treated using the Varian Medical Systems Pivotal™ Treatment Solution for Prone Breast Care were monitored over the course of treatment for positioning integrity and reproducibility. As this carbon-fiber platform actually replaces a portion of the couch top, indexing is inherent to its design. Patients were positioned on the couch and aligned using fiducial markers and lateral SSD to the breast fiducial point. The daily couch coordinates then serves as indicators for positioning variability with this system. Results: The variations in couch vertical, longitudinal and lateral positions were centered on a mean value of zero with standard deviations of 0.44cm, 0.75cm and 0.79cm respectively. Other factors explored were variations in distance of mid-sternum to table edge and patient rotation into the opening. The median rotation of the chest wall was found to be 11.5 degrees at CT-Simulation with a median distance of 2.5cm from midsternum to support opening. Patient rotation was not associated with either breast size or distance from edge of platform. Conclusion: The Pivotal™ Treatment solution consists of a couch top that replaces the standard top and as such is open from beneath without obstruction. This is a distinction from all other solutions which rely on a platform positioned above and indexed to the treatment couch. We found the reproducibility to be consistent with our historical measures while offering benefits of an integrated solution as stated above. supported by Professional Services Agreeement with

  5. Utilization of advanced metal-ceramic technology: clinical and laboratory procedures for a lower-fusing porcelain.

    PubMed

    McLaren, E A

    1998-09-01

    Metal-ceramic restorations remain the most widely accepted type of indirect restorative modality, and have been applied successfully for years. Recent advances in material science have resulted in the development of a new class of metal-ceramic materials that have been termed lower-fusing ceramics. Following proper procedures for preparation and metal framework design, these metal-ceramic porcelains achieve the aesthetics normally demonstrated by conventional all-ceramic restorations. This article provides an overview of the clinical and laboratory processes utilizing these materials and is illustrated by two case presentations.

  6. SU-E-P-03: The Australian Clinical Dosimetry Service, a Bespoke National Solution

    SciTech Connect

    Williams, I; Lye, J; Alves, A; Lehmann, J; Kenny, J; Dunn, L; Kron, T

    2015-06-15

    Purpose: The Australian Clinical Dosimetry Service, (ACDS) was a pilot program to enable the Australian Government to determine whether a locally designed audit program was suitable for mitigating dosimetric error risk to radiotherapy patients within Australia. The outcomes from four years of operations will be presented and discussed with a focus why and how the pilot requirements were met. The consequnces of success will be considered, the lessons learnt from the pilot program and how they are impacting the future ACDS design, operation and engagement with stakeholders. Methods: The ACDS was designed over 2010/11 by experts drawn from the three professions in consultation with the national Department of Health. The list of outcomes required over a three year pilot was expressed in a Memorandum of Understanding, (MoU) between Health and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) which hosted the ACDS. Results: The ACDS has achieved all the MoU requirements. This paper describes how the staff within the ACDS engaged with the professional clinical workforce and provided a successful and functioning audit service. It identifies the strengths and weaknesses within the MoU and the ACDS structure and how the ACDS resolved a number of conflicting issues. It identifies the successes within the ACDS and how these were achieved. It provides details to assist and advise those seeking to design or modify national or regional auditing programs. Finally the paper reviews potential futures for the ACDS. Conclusion: The raw number of audits and outcomes indicate that the ACDS has met the MoU auditing requirements. The reasons for the ACDS’ success are highly dependent on: attracting quality staff who can respond with agility to changing situations, a high level of communication with the professional community, a high level of engagement by the community and an interested and engaged Federal Department. The Australian Clinical Dosimetry Service is a

  7. Translational research platforms integrating clinical and omics data: a review of publicly available solutions

    PubMed Central

    Canuel, Vincent; Avillach, Paul; Degoulet, Patrice; Burgun, Anita

    2015-01-01

    The rise of personalized medicine and the availability of high-throughput molecular analyses in the context of clinical care have increased the need for adequate tools for translational researchers to manage and explore these data. We reviewed the biomedical literature for translational platforms allowing the management and exploration of clinical and omics data, and identified seven platforms: BRISK, caTRIP, cBio Cancer Portal, G-DOC, iCOD, iDASH and tranSMART. We analyzed these platforms along seven major axes. (1) The community axis regrouped information regarding initiators and funders of the project, as well as availability status and references. (2) We regrouped under the information content axis the nature of the clinical and omics data handled by each system. (3) The privacy management environment axis encompassed functionalities allowing control over data privacy. (4) In the analysis support axis, we detailed the analytical and statistical tools provided by the platforms. We also explored (5) interoperability support and (6) system requirements. The final axis (7) platform support listed the availability of documentation and installation procedures. A large heterogeneity was observed in regard to the capability to manage phenotype information in addition to omics data, their security and interoperability features. The analytical and visualization features strongly depend on the considered platform. Similarly, the availability of the systems is variable. This review aims at providing the reader with the background to choose the platform best suited to their needs. To conclude, we discuss the desiderata for optimal translational research platforms, in terms of privacy, interoperability and technical features. PMID:24608524

  8. The Genotype-Tissue Expression (GTEx) Project: Linking Clinical Data with Molecular Analysis to Advance Personalized Medicine

    PubMed Central

    Keen, Judy C.; Moore, Helen M.

    2015-01-01

    Evaluation of how genetic mutations or variability can directly affect phenotypic outcomes, the development of disease, or determination of a tailored treatment protocol is fundamental to advancing personalized medicine. To understand how a genotype affects gene expression and specific phenotypic traits, as well as the correlative and causative associations between such, the Genotype-Tissue Expression (GTEx) Project was initiated The GTEx collection of biospecimens and associated clinical data links extensive clinical data with genotype and gene expression data to provide a wealth of data and resources to study the underlying genetics of normal physiology. These data will help inform personalized medicine through the identification of normal variation that does not contribute to disease. Additionally, these data can lead to insights into how gene variation affects pharmacodynamics and individualized responses to therapy. PMID:25809799

  9. Almanac 2011: cardiomyopathies. The national society journals present selected research that has driven recent advances in clinical cardiology.

    PubMed

    Elliott, Perry M; Mohiddin, Saidi A

    2012-01-01

    As we approach the end of 2011 it is clear that the next few years are going to be dominated by the application of new high throughput genetic screening techniques, capable of screening the entire exome or indeed genome. Understanding the data generated by these techniques will require new and equally sophisticated analysis of large and complex datasets, using a systems biology approach with deeper phenotyping and advanced modelling techniques that have the flexibility for continuous update, refinement with discovery of new knowledge. Exciting new developments that may also transform cardiomyopathy research include those of infrastructure and organisation (multi-centre collaborations) and spin-offs from the field of regenerative medicine research. For clinical researchers that translate this information to the clinic the focus will however remain the same; namely improvement of quality and quantity of life.

  10. Almanac 2011: cardiomyopathies. The national society journals present selected research that has driven recent advances in clinical cardiology.

    PubMed

    Elliott, Perry M; Mohiddin, Saidi A

    2012-03-01

    As we approach the end of 2011 it is clear that the next few years are going to be dominated by the application of new high throughput genetic screening techniques, capable of screening the entire exome or indeed genome. Understanding the data generated by these techniques will require new and equally sophisticated analysis of large and complex datasets, using a systems biology approach with deeper phenotyping and advanced modelling techniques that have the flexibility for continuous update, refinement with discovery of new knowledge. Exciting new developments that may also transform cardiomyopathy research include those of infrastructure and organisation (multi-centre collaborations) and spin-offs from the field of regenerative medicine research. For clinical researchers that translate this information to the clinic the focus will however remain the same; namely improvement of quality and quantity of life.

  11. Almanac 2011: cardiomyopathies. The national society journals present selected research that has driven recent advances in clinical cardiology.

    PubMed

    M Elliott, Perry; A Mohiddin, Saidi

    2011-12-01

    As we approach the end of 2011 it is clear that the next few years are going to be dominated by the application of new high throughput genetic screening techniques, capable of screening the entire exome or indeed genome. Understanding the data generated by these techniques will require new and equally sophisticated analysis of large and complex datasets, using a systems biology approach with deeper phenotyping and advanced modelling techniques that have the flexibility for continuous update, refinement with discovery of new knowledge. Exciting new developments that may also transform cardiomyopathy research include those of infrastructure and organisation (multi-centre collaborations) and spin-offs from the field of regenerative medicine research. For clinical researchers that translate this information to the clinic the focus will however remain the same; namely improvement of quality and quantity of life.

  12. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation.

    PubMed

    Rincon, Melvin Y; VandenDriessche, Thierry; Chuah, Marinee K

    2015-10-01

    Gene therapy is a promising modality for the treatment of inherited and acquired cardiovascular diseases. The identification of the molecular pathways involved in the pathophysiology of heart failure and other associated cardiac diseases led to encouraging preclinical gene therapy studies in small and large animal models. However, the initial clinical results yielded only modest or no improvement in clinical endpoints. The presence of neutralizing antibodies and cellular immune responses directed against the viral vector and/or the gene-modified cells, the insufficient gene expression levels, and the limited gene transduction efficiencies accounted for the overall limited clinical improvements. Nevertheless, further improvements of the gene delivery technology and a better understanding of the underlying biology fostered renewed interest in gene therapy for heart failure. In particular, improved vectors based on emerging cardiotropic serotypes of the adeno-associated viral vector (AAV) are particularly well suited to coax expression of therapeutic genes in the heart. This led to new clinical trials based on the delivery of the sarcoplasmic reticulum Ca(2+)-ATPase protein (SERCA2a). Though the first clinical results were encouraging, a recent Phase IIb trial did not confirm the beneficial clinical outcomes that were initially reported. New approaches based on S100A1 and adenylate cyclase 6 are also being considered for clinical applications. Emerging paradigms based on the use of miRNA regulation or CRISPR/Cas9-based genome engineering open new therapeutic perspectives for treating cardiovascular diseases by gene therapy. Nevertheless, the continuous improvement of cardiac gene delivery is needed to allow the use of safer and more effective vector doses, ultimately bringing gene therapy for heart failure one step closer to reality.

  13. Regeneration of tissues of the oral complex: current clinical trends and research advances.

    PubMed

    Nguyen, Thomas T; Mui, Brennan; Mehrabzadeh, Mahsa; Chea, Yannie; Chaudhry, Zoya; Chaudhry, Kamran; Tran, Simon D

    2013-01-01

    Regenerative therapy in oral health care is limited by both the body's natural capacity for regeneration and the materials and methods currently available. Research on various aspects of regenerative therapy, such as tissue engineering and stem cell and gene therapy, has produced promising results. Compelling advances, ranging from the discovery and characterization of stem cell populations in oral tissue to the engineering and transplantation of whole tooth structures, could result in exciting new treatment methods for clinicians in the near future. In this review, we discuss the limitations of natural healing and regeneration of various tissues of the oral complex, including teeth, periodontium and salivary glands, and summarize current treatment methods for tissue damage as well as research advances in oral tissue regeneration.

  14. Optimal restoration of dental esthetics and function with advanced implant-supported prostheses: a clinical report.

    PubMed

    Meulen, Peter van der; Linden, Wynand van der; Eeden, Ronnie van

    2012-07-01

    For more than 25 years, computer-aided design and computer-aided manufacturing (CAD/CAM) technology has been used in implant restorative dentistry. Today this technology offers a means of milling titanium frameworks that fit dental implants accurately. This report presents a restoratively driven protocol employing advanced implant restorative and surgical techniques. Treatment of a patient with advanced periodontitis with extensive loss of hard and soft tissues is presented. After extraction of the patient's remaining hopeless teeth, dental implants were placed, along with interim, fixed-margin abutments and abutment protection caps. Two days later, acrylic resin fixed-interim prostheses restored the patient's esthetics and partial masticatory function. After implant osseointegration, maxillary, and mandibular frameworks for definitive prostheses were milled from Ti alloy, using one specific CAD/CAM technology. The benefits of this technology are also discussed.

  15. Extrapyramidal features in advanced Down's syndrome: clinical evaluation and family history.

    PubMed Central

    Vieregge, P; Ziemens, G; Freudenberg, M; Piosinski, A; Muysers, A; Schulze, B

    1991-01-01

    Extrapyramidal, frontal release, and other neurological signs were studied in 54 demented and non-demented patients with Down's syndrome (DS). Fourteen patients were demented and five showed extrapyramidal signs, mainly of the rigid-hypokinetic spectrum and similar to Parkinsonian features in advanced Alzheimer's disease (AD). None of the non-demented patients had Parkinsonian signs. The mean age of the demented DS patients with extrapyramidal signs was significantly higher than that of the patients without. Frontal release signs were present in demented and non-demented patients. A questionnaire showed no increase in either the proportion of early- or senile-onset dementia or Parkinsonism among first- and second-degree relatives of DS patients. Parkinsonian signs appear to be present at a lower frequency in DS than in advanced AD. A speculative hypothesis about a gene dosage effect of Cu/Zn-superoxide dismutase in preventing toxic radical formation in the substantia nigra of DS patients is presented. PMID:1826326

  16. Recent Advances in Molecular Biology of Thyroid Cancer and Their Clinical Implications

    PubMed Central

    Xing, Mingzhao

    2009-01-01

    Synopsis Thyroid cancer is the most common endocrine malignancy with a rapid rising incidence in recent years. Novel efficient management strategies are increasingly needed for this cancer. Remarkable advances have occurred in recent years in understanding the molecular biology of thyroid cancer. This is reflected in several major biological areas of thyroid cancer, including the molecular alterations for the loss of radioiodine avidity of thyroid cancer, the pathogenic role of the MAP kinase and PI3K/Akt pathways and their related genetic alterations, and the aberrant methylation of functionally important genes in thyroid tumorigenesis and pathogenesis. These exciting advances in molecular biology of thyroid cancer provide unprecedented opportunities for the development of molecular-based novel diagnostic, prognostic, and therapeutic strategies for this cancer. PMID:19040974

  17. Barrett’s Esophagus and Cancer Risk: How Research Advances Can Impact Clinical Practice

    PubMed Central

    di Pietro, Massimiliano; Alzoubaidi, Durayd; Fitzgerald, Rebecca C.

    2014-01-01

    Barrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), whose incidence has increased sharply in the last 4 decades. The annual conversion rate of BE to cancer is significant, but small. The identification of patients at a higher risk of cancer therefore poses a clinical conundrum. Currently, endoscopic surveillance is recommended in BE patients, with the aim of diagnosing either dysplasia or cancer at early stages, both of which are curable with minimally invasive endoscopic techniques. There is a large variation in clinical practice for endoscopic surveillance, and dysplasia as a marker of increased risk is affected by sampling error and high interobserver variability. Screening programs have not yet been formally accepted, mainly due to the economic burden that would be generated by upper gastrointestinal endoscopy. Screening programs have not yet been formally accepted, mainly due to the economic burden that would be generated by widespread indication to upper gastrointestinal endoscopy. In fact, it is currently difficult to formulate an accurate algorithm to confidently target the population at risk, based on the known clinical risk factors for BE and EAC. This review will focus on the clinical and molecular factors that are involved in the development of BE and its conversion to cancer and on how increased knowledge in these areas can improve the clinical management of the disease. PMID:25071900

  18. Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers

    PubMed Central

    Jhaveri, Komal; Taldone, Tony; Modi, Shanu; Chiosis, Gabriela

    2011-01-01

    Hsp90 is an ATP dependent molecular chaperone protein which integrates multiple oncogenic pathways. As such, Hsp90 inhibition is a promising anti-cancer strategy. Several inhibitors that act on Hsp90 by binding to its N-terminal ATP pocket have entered clinical evaluation. Robust pre-clinical data suggested anti-tumor activity in multiple cancer types. Clinically, encouraging results have been demonstrated in melanoma, acute myeloid leukemia, castrate refractory prostate cancer, non-small cell lung carcinoma and multiple myeloma. In breast cancer, proof-of-concept was demonstrated by first generation Hsp90 inhibitors in combination with trastuzumab mainly in human epidermal growth factor receptor 2 (HER2) + metastatic breast cancer. There are a multitude of second generation Hsp90 inhibitors currently under investigation. To date, however, there is no FDA approved Hsp90 inhibitor nor standardized assay to ascertain Hsp90 inhibition. This review summarizes the current status of both first and second generation Hsp90 inhibitors based on their chemical classification and stage of clinical development. It also discusses the pharmacodynamic assays currently implemented in clinic as well as other novel strategies aimed at enhancing the effectiveness of Hsp90 inhibitors. Ultimately, these efforts will aid in maximizing the full potential of this class of agents. PMID:22062686

  19. Registered nurses' constructed meaning of concepts of solution and their use in clinical practice

    NASA Astrophysics Data System (ADS)

    Wilkes, Lesley M.; Batts, Judith E.

    1991-12-01

    Since the introduction of nursing into tertiary institutions in Australia in 1975, there has been increasing interest in the teaching of physical science to nurses. Various courses in physical science for nurse students have been developed. They vary in length and content but there is agreement that concepts taught should be closely related to nursing applications. The choice of relevant concepts tends to be made by individual curriculum developers. This paper reports an examination of the use of physical science concepts and their relevance from the perspective of registered nurses practising in general ward areas. Inherent in this study is the premise that for registered nurses to have ideas of the physical science underlying their practice they must have constructed meaning first for these concepts. Specific chemical concepts related to solutions are discussed in these terms.

  20. Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection

    PubMed Central

    Yu, Steven S; Quinn, David I; Dorff, Tanya B

    2016-01-01

    Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib’s designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC. PMID:27713636

  1. Industry Perspectives on Advanced Inverters for U.S. Solar Photovoltaic Systems. Grid Benefits, Deployment Challenges, and Emerging Solutions

    SciTech Connect

    Reiter, Emerson; Ardani, Kristen; Margolis, Robert; Edge, Ryan

    2015-09-01

    To clarify current utility strategies and other considerations related to advanced inverter deployment, we interviewed 20 representatives from 11 leading organizations closely involved with advanced inverter pilot testing, protocols, and implementation. Included were representatives from seven utilities, a regional transmission operator, an inverter manufacturer, a leading solar developer, and a consortium for grid codes and standards. Interview data represent geographically the advanced inverter activities identified in SEPA's prior survey results--most interviewed utilities serve California, Arizona, and Hawaii, though we also interviewed others from the Northeast, Mid-Atlantic, and Southeast.

  2. Bench to bedside: integrating advances in basic science into daily clinical practice.

    PubMed

    McGoldrick, Rory B; Hui, Kenneth; Chang, James

    2014-08-01

    This article focuses on the initial steps of commercial development of a patentable scientific discovery from an academic center through to marketing a clinical product. The basics of partnering with a technology transfer office (TTO) and the complex process of patenting are addressed, followed by a discussion on marketing and licensing the patent to a company in addition to starting a company. Finally, the authors address the basic principles of obtaining clearance from the Food and Drugs Administration, production in a good manufacturing practice (GMP) facility, and bringing the product to clinical trial.

  3. Bench to bedside: integrating advances in basic science into daily clinical practice.

    PubMed

    McGoldrick, Rory B; Hui, Kenneth; Chang, James

    2014-08-01

    This article focuses on the initial steps of commercial development of a patentable scientific discovery from an academic center through to marketing a clinical product. The basics of partnering with a technology transfer office (TTO) and the complex process of patenting are addressed, followed by a discussion on marketing and licensing the patent to a company in addition to starting a company. Finally, the authors address the basic principles of obtaining clearance from the Food and Drugs Administration, production in a good manufacturing practice (GMP) facility, and bringing the product to clinical trial. PMID:25066849

  4. Peritoneal dialysis solutions low in glucose degradation products--evidence for clinical benefits.

    PubMed

    Tomo, Tadashi

    2008-06-01

    In Japan, two types of new peritoneal dialysis fluid (PDF) are ordinarily used: two-chambered PDF, and icodextrin PDF. Two-chambered PDF has several biocompatible characteristics, one being low glucose degradation products (GDPs). Of the several GDPs in PDF, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is thought to be strongly associated with the cytotoxicity of standard PDF. Using a PDF low in GDPs may reduce exposure of the peritoneum to 3,4-DGE, helping to preserve peritoneal function in PD patients. Additionally, use of a PDF low in GDPs may reduce plasma levels of advanced glycosylation end-products in PD patients, a change that may help to preserve vascular function in PD patients. Peritoneal rest for 24 hours after exposure to a PDF with low GDPs improves the activity of human peritoneal mesothelial cells. As compared with the use of standard PDF, the use of low-GDP PDF in combination therapy (peritoneal dialysis plus hemodialysis) may more effectively preserve peritoneal function. The new PDF low in GDPs has biocompatible characteristics relative to peritoneum and system that may help to preserve peritoneal function or reduce complications such as atherosclerosis or dialysis-related amyloidosis in dialysis patients.

  5. Data Science Solution to Event Prediction in Outsourced Clinical Trial Models.

    PubMed

    Dalevi, Daniel; Lovick, Susan; Mann, Helen; Metcalfe, Paul D; Spencer, Stuart; Hollis, Sally; Ruau, David

    2015-01-01

    Late phase clinical trials are regularly outsourced to a Contract Research Organisation (CRO) while the risk and accountability remain within the sponsor company. Many statistical tasks are delivered by the CRO and later revalidated by the sponsor. Here, we report a technological approach to standardised event prediction. We have built a dynamic web application around an R-package with the aim of delivering reliable event predictions, simplifying communication and increasing trust between the CRO and the in-house statisticians via transparency. Short learning curve, interactivity, reproducibility and data diagnostics are key here. The current implementation is motivated by time-to-event prediction in oncology. We demonstrate a clear benefit of standardisation for both parties. The tool can be used for exploration, communication, sensitivity analysis and generating standard reports. At this point we wish to present this tool and share some of the insights we have gained during the development. PMID:26262364

  6. Data Science Solution to Event Prediction in Outsourced Clinical Trial Models.

    PubMed

    Dalevi, Daniel; Lovick, Susan; Mann, Helen; Metcalfe, Paul D; Spencer, Stuart; Hollis, Sally; Ruau, David

    2015-01-01

    Late phase clinical trials are regularly outsourced to a Contract Research Organisation (CRO) while the risk and accountability remain within the sponsor company. Many statistical tasks are delivered by the CRO and later revalidated by the sponsor. Here, we report a technological approach to standardised event prediction. We have built a dynamic web application around an R-package with the aim of delivering reliable event predictions, simplifying communication and increasing trust between the CRO and the in-house statisticians via transparency. Short learning curve, interactivity, reproducibility and data diagnostics are key here. The current implementation is motivated by time-to-event prediction in oncology. We demonstrate a clear benefit of standardisation for both parties. The tool can be used for exploration, communication, sensitivity analysis and generating standard reports. At this point we wish to present this tool and share some of the insights we have gained during the development.

  7. The committee for advanced therapies' of the European Medicines Agency reflection paper on management of clinical risks deriving from insertional mutagenesis.

    PubMed

    Aiuti, Alessandro; Cossu, Giulio; de Felipe, Pablo; Galli, Maria Cristina; Narayanan, Gopalan; Renner, Matthias; Stahlbom, Axel; Schneider, Christian K; Voltz-Girolt, Caroline

    2013-06-01

    In the European Union, the Committee for Advanced Therapies of the European Medicines Agency takes the lead in the scientific assessment for marketing authorization applications for advanced therapy medicinal products, which include gene therapy medicinal products, somatic cell therapy medicinal products, and tissue-engineered products. The Committee for Advanced Therapies also takes the lead in defining the scientific framework for the quality, nonclinical and clinical development of such products. This reflection paper represents the Committee's current thinking on management of clinical risks deriving from insertional mutagenesis. A multidisciplinary approach to insertional mutagenesis is provided. This reflection paper has been adopted by the committee in its April 2013 meeting.

  8. Long-term follow-up of patients with advanced ovarian cancer treated in randomised clinical trials.

    PubMed Central

    Warwick, J.; Kehoe, S.; Earl, H.; Luesley, D.; Redman, C.; Chan, K. K.

    1995-01-01

    The data from two prospective randomised phase III trials that were initiated by the West Midlands Ovarian Cancer Study Group (WMOCSG) in 1981 and 1986, recruiting 167 and 195 patients respectively, have been pooled and the survival patterns of the 362 patients treated for advanced epithelial ovarian cancer within clinical trials in the West Midlands over the 10 year period (1981-91) have been explored. All patients had histologically proven epithelial ovarian cancer and all had residual disease after primary surgery, with the majority having stage III/IV disease. The primary treatment for all patients was debulking surgery followed by platinum-based chemotherapy. Eligible patients were further randomised to undergo a second debulking operation. The main end point, survival, was assessed using Kaplan-Meier curves and the log-rank test. A Cox proportional hazards model identified performance status (P = 0.002), residual disease (P = 0.005) and albumin level (P = 0.04) as independent prognostic factors. A multivariate model to predict survival curves for patients with the best and worst prognoses was developed with predicted 5 year survival of 30% and 3% for those in the best and worst prognostic groups respectively. The identification of clinical interventions to improve outcome is an urgent matter since the prognosis for patients with advanced ovarian cancer remains poor. PMID:8519669

  9. African American Participation in Oncology Clinical Trials--Focus on Prostate Cancer: Implications, Barriers, and Potential Solutions.

    PubMed

    Ahaghotu, Chiledum; Tyler, Robert; Sartor, Oliver

    2016-04-01

    In the United States, the incidence and mortality rates of many cancers, especially prostate cancer, are disproportionately high among African American men compared with Caucasian men. Recently, mortality rates for prostate cancer have declined more rapidly in African American versus Caucasian men, but prostate cancer is still the most common cancer and the second leading cause of cancer deaths in African American men in the United States. Compared with Caucasian men, prostate cancer occurs at younger ages, has a higher stage at diagnosis, and is more likely to progress after definitive treatments in African American men. Reasons for racial discrepancies in cancer are multifactorial and potentially include socioeconomic, cultural, nutritional, and biologic elements. In addition to improving access to novel therapies, clinical trial participation is essential to adequately establish the risks and benefits of treatments in African American populations. Considering the disproportionately high mortality rates noted in these groups, our understanding of the natural history and responses to therapies is limited. This review will explore African American underrepresentation in clinical trials with a focus on prostate cancer, and potentially effective strategies to engage African American communities in prostate cancer research. Solutions targeting physicians, investigators, the community, and health care systems are identified. Improvement of African American participation in prostate cancer clinical trials will benefit all stakeholders. PMID:26786562

  10. Advances in the Molecular Analysis of Soft Tissue Tumors and Clinical Implications

    PubMed Central

    Marino-Enriquez, Adrian

    2016-01-01

    SYNOPSIS The emergence of high-throughput molecular technologies has accelerated the discovery of novel diagnostic, prognostic and predictive molecular markers. Clinical implementation of these technologies is expected to transform the practice of surgical pathology. In soft tissue tumor pathology, accurate interpretation of comprehensive genomic data provides useful diagnostic and prognostic information, and informs therapeutic decisions. Most clinical molecular data will be likely generated by high-throughput genomic technologies, and reporting clinically actionable somatic mutations will be part of the routine pathology workflow, informing patient management and treatment. The purpose of this review is to introduce recently developed molecular technologies and to briefly discuss their potential for clinical implementation, focusing on various applications to the evaluation of soft tissue tumors. A special emphasis is made on practical diagnostic uses relevant to the surgical pathologist, with illustrative examples of how these technologies have helped characterize and diagnose soft tissue lesions. The concept of genomically-informed therapies will be mentioned, as an essential motivation to implement molecular tests to identify targetable molecular alterations in sarcoma. PMID:26297069

  11. Potential impact of advanced clinical information technology on cancer care in 2015.

    PubMed

    Sittig, Dean F

    2006-08-01

    New clinical information technologies now sporadically available will soon be in routine clinical use, bringing many changes to all phases of the cancer care continuum. For example, new technologies such as: (1) The next generation Internet; (2) Real-time clinical decision support systems; (3) Off-line, population-based systems; (4) Large, integrated, individual patient-level phenotypic and genotypic databases with intelligent data mining capabilities; (5) Wireless, invasive and non-invasive physiologic monitoring devices; (6) Natural Language Processing (NLP) systems; and (7) Mathematical models of complex biological systems all have the potential to impact significantly the provision of cancer care throughout its continuum. While new information management and communication techniques and technologies will reduce many of the inefficiencies and inaccuracies of our present systems, there will be an equal, and potentially far more dangerous, set of unintended consequences. Informatics investigators, cancer specialists, and health system administrators must focus on the study of what is working and what is not, as well as, on development and testing of the new clinical information management and communication technologies, if we are to be ready for the future. PMID:16783609

  12. Potential impact of advanced clinical information technology on healthcare in 2015.

    PubMed

    Sittig, Dean F

    2004-01-01

    Clinical information technologies now sporadically available will soon be in routine clinical use, bringing many changes to healthcare. For example, 1) The next generation Internet; 2) Real-time clinical decision support systems; 3) Off-line, population-based systems; 4) Large, integrated, individual patient-level phenotypic and genotypic databases with intelligent data mining capabilities; 5) Wireless, invasive and non-invasive physiologic monitoring devices; 6) Natural Language Processing (NLP) systems; and 7) Mathematical models of complex biological systems have the potential to impact significantly the future healthcare delivery system. While new information management and communication techniques and technologies will reduce many of the inefficiencies and inaccuracies of our present systems, there will be an equal, and potentially far more dangerous, set of unintended consequences. Informatics investigators and health system administrators must focus on the study of what is working and what is not, as well as, on development and testing of the new clinical information management and communication technologies, if we are to be ready for the future. PMID:15361041

  13. Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data.

    PubMed

    Ferré, Marc; Caignard, Angélique; Milea, Dan; Leruez, Stéphanie; Cassereau, Julien; Chevrollier, Arnaud; Amati-Bonneau, Patrizia; Verny, Christophe; Bonneau, Dominique; Procaccio, Vincent; Reynier, Pascal

    2015-01-01

    Autosomal-dominant optic atrophy (ADOA) is the most common inherited optic neuropathy, due to mutations in the optic atrophy 1 gene (OPA1) in about 60%-80% of cases. At present, the clinical heterogeneity of patients carrying OPA1 variants renders genotype-phenotype correlations difficulty. Since 2005, when we published the first locus-specific database (LSDB) dedicated to OPA1, a large amount of new clinical and genetic knowledge has emerged, prompting us to update this database. We have used the Leiden Open-Source Variation Database to develop a clinico-biological database, aiming to add clinical phenotypes related to OPA1 variants. As a first step, we validated this new database by registering several patients previously reported in the literature, as well as new patients from our own institution. Contributors may now make online submissions of clinical and molecular descriptions of phenotypes due to OPA1 variants, including detailed ophthalmological and neurological data, with due respect to patient anonymity. The updated OPA1 LSDB (http://opa1.mitodyn.org/) should prove useful for molecular diagnoses, large-scale variant statistics, and genotype-phenotype correlations in ADOA studies.

  14. Recent clinical and pathophysiological advances in non-functioning pituitary adenomas.

    PubMed

    Korbonits, Márta; Carlsen, Eivind

    2009-04-01

    Pituitary adenomas are being recognized and diagnosed with increasing frequency. One of the most common forms of pituitary lesion is the clinically non-functioning pituitary adenoma (NFPA), which is often diagnosed incidentally. The vast majority of pituitary adenomas are sporadic, but familial adenomas can occur in the multiple pituitary adenoma type 1 syndrome, in Carney complex or in familial isolated pituitary adenoma. Distinguishing NFPA from prolactinomas can occasionally cause a differential diagnostic problem due to the 'stalk effect'. NFPA often show hormone synthesis on tissue immunostaining without causing clinical symptoms. Most often these are silent gonadotroph adenomas, with silent corticotroph or somatotroph adenomas occurring less frequently. It is unclear why these silent adenomas do not release hormones at a clinically recognizable level, although it is probable that there is a continuum between fully functional and completely silent adenomas. Another intriguing feature of NFPAs is the lack of clinical response to somatostatin analogues, despite the presence of somatostatin receptors and an often good response in the in vitro setting. Temozolomide has been successfully used for the treatment of a few aggressive pituitary adenomas, and the response to this drug could be influenced by the expression of the DNA repair enzyme O-6-methylguanine DNA methyltransferase. The early diagnosis, prediction of long-term outcome and treatment of NFPAs remain a challenge for endocrinologists. PMID:19407508

  15. Efficacy of mandibular advancement device in the treatment of obstructive sleep apnea syndrome: A randomized controlled crossover clinical trial

    PubMed Central

    Crovetto-Martínez, Rafael; Alkhraisat, Mohammad-Hamdan; Crovetto, Miguel; Municio, Antonio; Kutz, Ramón; Aizpuru, Felipe; Miranda, Erika; Anitua, Eduardo

    2015-01-01

    Background Evaluation of the efficacy and safety of a mandibular advancement device (MAD) (KlearwayTM) in the treatment of mild-to-moderate obstructive sleep apnea and chronic roncopathy. Material and Methods A randomized, placebo-controlled, double blinded, and crossover clinical trial was conducted. Placebo device (PD) defined as a splint in the centric occlusion that did not induce a mandibular advancement served as a control. The mandible was advanced to the maximum tolerable distance or to a minimum of 65% of the maximum protrusion. After each sequence of treatment, patients were assessed by questionnaires, conventional polysomnography, and objective measurement of snoring at the patient’s own home. Results Forty two patients participated in the study and 38 completed the study. Patients mean age was 46 ±9 years and the 79% were males. The mean mandibular advancement was 8.6 ±2.8 mm. Patients used the MAD and the PD for 6.4 +2.4 hours and 6.2 +2.0 hours, respectively. Secondary effects (mostly mild) occurred in the 85.7% and the 86.8% of the users of MAD and PD, respectively. The MAD induced a decrease in the apnea-hypopnea index (AHI) from 15.3 +10.2 to 11.9 +15.5. The 50% reduction in the AHI was achieved in the 46.2% and the 18.4% of the patients treated with MAD and PD, respectively. The use of the MAD induced a reduction in the AHI by 3.4 +15.9 while the PD induced an increase by 10.6 +26.1. The subjective evaluation of the roncopathy indicated an improvement by the MAD and an increase in the perceptive quality of sleep. However, the objective evaluation of the roncopathy did not show significant improvements. Conclusions The use of MAD is efficient to reduce the AHI and improve subjectively the roncopathy. MAD could be considered in the treatment of mild-to-moderate OSA and chronic roncopathy. Key words:Obstructive sleep apnea (OSA), mandibular advance device, treatment, efficacy, clinical assay. PMID:26241460

  16. Introduction to special section of the Journal of Family Psychology, advances in mixed methods in family psychology: integrative and applied solutions for family science.

    PubMed

    Weisner, Thomas S; Fiese, Barbara H

    2011-12-01

    Mixed methods in family psychology refer to the systematic integration of qualitative and quantitative techniques to represent family processes and settings. Over the past decade, significant advances have been made in study design, analytic strategies, and technological support (such as software) that allow for the integration of quantitative and qualitative methods and for making appropriate inferences from mixed methods. This special section of the Journal of Family Psychology illustrates how mixed methods may be used to advance knowledge in family science through identifying important cultural differences in family structure, beliefs, and practices, and revealing patterns of family relationships to generate new measurement paradigms and inform clinical practice. Guidance is offered to advance mixed methods research in family psychology through sound principles of peer review.

  17. Determination of minimal clinically important change in early and advanced Parkinson's disease.

    PubMed

    Hauser, Robert A; Auinger, Peggy

    2011-04-01

    Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies.

  18. Advanced Multi-Axis Spine Testing: Clinical Relevance and Research Recommendations

    PubMed Central

    Holsgrove, Timothy P.; Nayak, Nikhil R.; Welch, William C.

    2015-01-01

    Back pain and spinal degeneration affect a large proportion of the general population. The economic burden of spinal degeneration is significant, and the treatment of spinal degeneration represents a large proportion of healthcare costs. However, spinal surgery does not always provide improved clinical outcomes compared to non-surgical alternatives, and modern interventions, such as total disc replacement, may not offer clinically relevant improvements over more established procedures. Although psychological and socioeconomic factors play an important role in the development and response to back pain, the variation in clinical success is also related to the complexity of the spine, and the multi-faceted manner by which spinal degeneration often occurs. The successful surgical treatment of degenerative spinal conditions requires collaboration between surgeons, engineers, and scientists in order to provide a multi-disciplinary approach to managing the complete condition. In this review, we provide relevant background from both the clinical and the basic research perspectives, which is synthesized into several examples and recommendations for consideration in increasing translational research between communities with the goal of providing improved knowledge and care. Current clinical imaging, and multi-axis testing machines, offer great promise for future research by combining invivo kinematics and loading with in-vitro testing in six degrees of freedom to offer more accurate predictions of the performance of new spinal instrumentation. Upon synthesis of the literature, it is recommended that in-vitro tests strive to recreate as many aspects of the in-vivo environment as possible, and that a physiological preload is a critical factor in assessing spinal biomechanics in the laboratory. A greater link between surgical procedures, and the outcomes in all three anatomical planes should be considered in both the in-vivo and in-vitro settings, to provide data relevant to

  19. Argus T® versus Advance® Sling for postprostatectomy urinary incontinence: A randomized clinical trial

    PubMed Central

    Lima, João Paulo Cunha; Pompeo, Antonio Carlos Lima; Bezerra, Carlos Alberto

    2016-01-01

    ABSTRACT Objective To compare the results of two slings, Argus T® and Advance®, for the treatment of postprostatectomy urinary incontinence (PPUI). Material and Methods: From December 2010 to December 2011, 22 patients with PPUI were randomized as follows: 11 (mean age 62.09(±5.30)) underwent treatment with Advance® and 11 (mean age 62.55(±8.54)) with Argus T®. All patients were evaluated preoperatively with urodynamic testing, quality of life questionnaire (ICIQ-SF), voiding diary and 24-hour pad test. Exclusion criteria were: neurological diseases, severe detrusor overactivity and urethral stenosis. Evaluation was performed at 6, 12 and 18 months after the surgery. After implantation of the Argus T® sling, patients who experienced urine leakage equal to or greater than the initial volume underwent adjustment of the sling tension. Results were statistically analyzed using the Fisher’s test, Kolmogorov-Smirnov test, Friedman’s non-parametric test or the Mann-Whitney test. Results Significant improvement of the 24-hour pad test was observed with the Argus T® sling (p=0.038) , With regard to the other parameters, there was no significant difference between the two groups. Removal of the Argus T® device due to perineal pain was performed in one patient (9%). Despite non uniform results, both devices were considered useful to improve quality of life (ICIQ-SF): Argus T® (p=0.018) and Advance® (p=0.017). Conclusions Better results were observed in the 24h pad test and in levels of satisfaction with the Argus T® device. Both slings contributed to improve quality of life (ICIQ-SF), with acceptable side effects. PMID:27286117

  20. Clinical benefits of combined chemotherapy with S-1, oxaliplatin, and docetaxel in advanced gastric cancer patients with palliative surgery

    PubMed Central

    Liu, Yan; Feng, Ye; Gao, Yongjian; Hou, Ruizhi

    2016-01-01

    Background and aim Advanced gastric cancer accounts for a substantial portion of cancer-related mortality worldwide. Surgical intervention is the curative therapeutic approach, but patients with advanced gastric cancer are not eligible for the radical resection. The present work aimed to investigate the efficacy and safety of palliative surgery combined with S-1, oxaliplatin, and docetaxel chemotherapy in the treatment of patients with advanced gastric cancer. Method A total of 20 patients who underwent palliative resection of gastric cancer in China–Japan Union Hospital of Jilin University from 2010 to 2011 were evaluated. Days 20–30 postoperative, these patients started to receive chemotherapy of S-1 (40 mg/m2, oral intake twice a day) and intravenous infusion of oxaliplatin (135 mg/m2) and docetaxel (75 mg/m2). After three cycles of chemotherapy (21 days/cycle), patients were evaluated, and only those who responded toward the treatment continued to receive six to eight cycles of the treatment and were included in end point evaluation. Patients’ survival time and adverse reactions observed along the treatment were compared with those treated with FOLFOX. Results Out of 20 patients evaluated, there was one case of complete response, nine cases of partial response, six cases of stable disease, and four cases of progressive disease. The total efficacy (complete response + partial response) and clinical benefit rates were 50% and 80%, respectively. Of importance, the treatment achieved a significantly longer survival time compared to FOLFOX, despite the fact that both regimens shared common adverse reactions. The adverse reactions were gastrointestinal reaction, reduction in white blood cells, and peripheral neurotoxicity. All of them were mild, having no impact on the treatment. Conclusion Combination therapy of S-1, oxaliplatin, and docetaxel improves the survival of gastric cancer patients treated with palliative resection, with adverse reactions being

  1. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances.

    PubMed

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

    While the majority of children and adolescents with newly diagnosed childhood acute lymphoblastic leukemia (ALL) will be cured, as many as 20 % of patients will experience relapse. On current treatment regimens, the intensity of upfront treatment is stratified based upon prognostic factors with the aim of improving cure rates (for those at the highest risk of relapse) and minimizing treatment-related morbidity (for lower-risk patients). Here we review advances in the understanding of prognostic factors and their application. We also highlight novel treatment approaches aimed at improving outcomes in childhood ALL.

  2. HIV infection and AIDS: new biology, therapeutic advances, and clinical implications. Introduction.

    PubMed

    Miles, S A

    1997-01-01

    Recent advances in our understanding of the pathogenesis of human immunodeficiency virus (HIV) disease and the important role that viral load plays in the initial selection of antiretroviral therapy significantly alters our management of this disease. Guidelines from the British HIV Association, International AIDS Society-USA, and United States Public Health Service panels regarding the selection of appropriate antiretroviral therapy, and from the Centers for Disease Control and Prevention on prophylaxis for opportunistic infections, have recently been published. Despite tremendous advances in treating the disease and its related complications, a comprehensive, long-term disease management plan that includes recognition of patient concerns about quality of life is lacking. New approaches to managing HIV disease must now include strategies that address patient concerns about fatigue, gastrointestinal distress, malnutrition, and weight loss. Patients must become more involved in decisions about selection of specific drugs and drug regimens and must be consulted about their expectations and needs. We have made significant strides in the treatment of HIV disease. We can readily reduce the viral burden to virtually undetectable levels, and we must continue to develop even more potent and tolerable treatment regimens. We can make patients live longer. Helping patients live better quality lives deserves further study. PMID:9389309

  3. [Clinical evaluation of M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy for advanced urothelial cancer].

    PubMed

    Mikami, K; Nakagawa, S; Takada, H; Ebisui, K; Sugimoto, K; Watanabe, H; Maegawa, M; Nakao, M

    1994-04-01

    M-VAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy was performed on 27 patients with advanced urothelial cancer. The patients included 20 with bladder cancer, 4 with upper urinary tract cancer and 3 with both lesions. Complete response (CR) was observed in 2 (7.4 +/- 9.9%) patients and partial response (PR) in 10 (37.0 +/- 18.2%) patients after the treatment, i.e., the overall objective response rate was 44.4 +/- 18.7%. The rate of relapse or recurrence in the patients with CR and PR was 100% and 90.0%, respectively. The mean duration of the response was 18.5 +/- 13.4 months and 10.7 +/- 10.9 months for CR and PR, respectively. The overall survival rate after one year was 30.2%. Bone marrow suppression was the most serious side effect. The white blood cell count became below 1,000/microliters in 10 patients (36.7%). Among them, 4 patients suffered from sepsis. In conclusion, M-VAC chemotherapy was effective for induction therapy against advanced urothelial cancer, although the effective duration was short. Further maintenance therapy should be established.

  4. Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center.

    PubMed

    Gallo, Marco; Michelon, Federica; Castiglione, Anna; Felicetti, Francesco; Viansone, Alessandro Adriano; Nervo, Alice; Zichi, Clizia; Ciccone, Giovannino; Piovesan, Alessandro; Arvat, Emanuela

    2015-08-01

    Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC.

  5. Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center.

    PubMed

    Gallo, Marco; Michelon, Federica; Castiglione, Anna; Felicetti, Francesco; Viansone, Alessandro Adriano; Nervo, Alice; Zichi, Clizia; Ciccone, Giovannino; Piovesan, Alessandro; Arvat, Emanuela

    2015-08-01

    Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC. PMID:25414068

  6. Novel Systemic Therapies in Advanced Liposarcoma: A Review of Recent Clinical Trial Results

    PubMed Central

    Tseng, William W.; Somaiah, Neeta; Lazar, Alexander J.; Lev, Dina C.; Pollock, Raphael E.

    2013-01-01

    Liposarcoma is one of the most common adult soft tissue sarcomas an consists of three histologic subtypes (well and dedifferentiated, myxoid/round cell, and pleomorphic). Surgery is the mainstay of treatment for localized disease; however for unresectable or metastatic disease, effective treatment options are currently limited. In the past decade, a better understanding of the distinct genetic and molecular aberrations for each of the three histologic subtypes has led to the development of several novel systemic therapies. Data from phase I and early phase II clinical trials have been reported. Despite challenges with conducting clinical trials in liposarcoma, preliminary results for several of these novel, biology-driven therapies are encouraging. PMID:24216990

  7. Applying knowledge-anchored hypothesis discovery methods to advance clinical and translational research: the OAMiner project

    PubMed Central

    Jackson, Rebecca D; Best, Thomas M; Borlawsky, Tara B; Lai, Albert M; James, Stephen; Gurcan, Metin N

    2012-01-01

    The conduct of clinical and translational research regularly involves the use of a variety of heterogeneous and large-scale data resources. Scalable methods for the integrative analysis of such resources, particularly when attempting to leverage computable domain knowledge in order to generate actionable hypotheses in a high-throughput manner, remain an open area of research. In this report, we describe both a generalizable design pattern for such integrative knowledge-anchored hypothesis discovery operations and our experience in applying that design pattern in the experimental context of a set of driving research questions related to the publicly available Osteoarthritis Initiative data repository. We believe that this ‘test bed’ project and the lessons learned during its execution are both generalizable and representative of common clinical and translational research paradigms. PMID:22647689

  8. Plant-based vaccines for animals and humans: recent advances in technology and clinical trials.

    PubMed

    Takeyama, Natsumi; Kiyono, Hiroshi; Yuki, Yoshikazu

    2015-09-01

    It has been about 30 years since the first plant engineering technology was established. Although the concept of plant-based pharmaceuticals or vaccines motivates us to develop practicable commercial products using plant engineering, there are some difficulties in reaching the final goal: to manufacture an approved product. At present, the only plant-made vaccine approved by the United States Department of Agriculture is a Newcastle disease vaccine for poultry that is produced in suspension-cultured tobacco cells. The progress toward commercialization of plant-based vaccines takes much effort and time, but several candidate vaccines for use in humans and animals are in clinical trials. This review discusses plant engineering technologies and regulations relevant to the development of plant-based vaccines and provides an overview of human and animal vaccines currently under clinical trials.

  9. Plant-based vaccines for animals and humans: recent advances in technology and clinical trials

    PubMed Central

    Takeyama, Natsumi; Kiyono, Hiroshi; Yuki, Yoshikazu

    2015-01-01

    It has been about 30 years since the first plant engineering technology was established. Although the concept of plant-based pharmaceuticals or vaccines motivates us to develop practicable commercial products using plant engineering, there are some difficulties in reaching the final goal: to manufacture an approved product. At present, the only plant-made vaccine approved by the United States Department of Agriculture is a Newcastle disease vaccine for poultry that is produced in suspension-cultured tobacco cells. The progress toward commercialization of plant-based vaccines takes much effort and time, but several candidate vaccines for use in humans and animals are in clinical trials. This review discusses plant engineering technologies and regulations relevant to the development of plant-based vaccines and provides an overview of human and animal vaccines currently under clinical trials. PMID:26668752

  10. Recent Advances in Dipeptidyl-Peptidase-4 Inhibition Therapy: Lessons from the Bench and Clinical Trials

    PubMed Central

    Zhong, Jixin; Gong, Quan; Goud, Aditya; Srinivasamaharaj, Srividya; Rajagopalan, Sanjay

    2015-01-01

    DPP4 inhibitors (DPP4i) are a class of newly developed antidiabetic drugs which preserve incretin hormones and promote postprandial insulin secretion. Although the cardiovascular effect of DPP4 inhibition has been substantially studied, the exact role of DPP4 in cardiovascular disease especially in humans remains elusive. Previous small studies and meta-analyses have suggested a benefit in both surrogate outcomes and cardiovascular events for these agents. However, there was growing evidence in recent years questioning the cardioprotective effect of DPP4i. Further, a signal of heart failure hospitalization in a recent large scale clinical trial SAVOR-TIMI 53 has called into question the safety of these agents and their utility in the treatment of cardiovascular disease. In this review, we will revisit the physiologic function of DPP4 and discuss its role in cardiometabolic disease based on recent experimental and clinical studies. PMID:26075284

  11. CELL THERAPY FOR INTERVERTEBRAL DISC REPAIR: ADVANCING CELL THERAPY FROM BENCH TO CLINICS

    PubMed Central

    Benneker, L.M.; Andersson, G.; Iatridis, J.C.; Sakai, D.; Härtl, R.; Ito, K.; Grad, S.

    2016-01-01

    Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encourageing results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium “Where Science meets Clinics”, sponsored by the AO Foundation and held in Davos, Switzerland, from September 5–7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imageing methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neurogenesis. Discogenic pain, originating from “black discs” or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in outline order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects. PMID:24802611

  12. Clinical evaluation of the effect of platelet rich plasma on the coronally advanced flap root coverage procedure

    PubMed Central

    Biradar, Sharashchandra Madhavarao; Satyanarayan, Ashok; Kulkarni, Arun J; Patti, Basavaraj; Mysore, Sunil K; Patil, Ambika

    2015-01-01

    Background: Coronally advanced flap (CAF) has been shown to effectively treat gingival recession. Platelet rich plasma (PRP), containing autologous growth factors, has been shown to promote soft tissue healing. The aim of this clinical study was to determine whether the addition of an autologous PRP to a CAF when compared to a CAF alone would improve the clinical outcome for treatment of multiple gingival recessions. Materials and Methods: Thirty patients with Miller's class I and class II buccal recession defect were randomly assigned to control (CAF alone) or test (CAF with PRP) groups. Recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), width of keratinized tissue, wound healing index, percentage of root coverage was assessed. Patients were followed at 2, 4, 12 and 16 weeks post-surgery. Statistical analysis for intra and inter group comparisons was done using Wilcoxon sign rank and Wilcoxon rank sum tests respectively. P < 0.05 denoted statistical significance. Results: The differences between the test and control groups were not significant with respect to all the clinical variables. The RD at 16 weeks was significantly reduced from 2.88 ± 0.69 to 0.76 ± 0.24 mm in control group (P < 0.05) and from 2.95 ± 0.43 to 0.76 ± 0.35 mm in the test group (P < 0.05). The mean percentage of root coverage was 73.1 ± 7.3 in the control group and 75.0 ± 8.3 in test group (P < 0.05). The CAL gain was 3.17 ± 0.84 mm within the control group and 3.17 ± 0.79 mm within test group. Conclusion: Within the limitations of this study, PRP with CAF can provide an early healing of soft tissues, but does not provide clinically measurable improvement in the final therapeutics outcome in CAF. PMID:26604962

  13. The Connecticut Cardiovascular Consortium: a unique, state-wide research collaboration to advance clinical outcomes in patients with heart disease.

    PubMed

    Boden, W E; McKay, R G; Cabin, H S; Radford, M J; Krumholz, H M; Zaret, B L; Garner, L; Bull, M B; Fisherkeller, M; Kosinski, E J; Krauthamer, M J; Maljanian, R; McDowell, A V; Sands, M J; Schwartz, K V; Seltzer, J P; Hager, J D

    2001-10-01

    The establishment of "best clinical practices" founded upon evidence-based medicine has become an increasingly important priority. Frequently, management guidelines are derived from published research data and disseminated among practitioners to help optimize patient care. The ultimate clinical impact of these guidelines in the "real world," however, is often clouded by an incomplete assessment of patient outcomes throughout the continuum of health-care delivery models. In order to address this gap in clinical outcome assessment, we propose to establish the Connecticut Cardiovascular Consortium. The Consortium will consist of a collaborative partnership among all 31 Connecticut hospitals working in concert with Connecticut Office of Health Care Access (OHCA). The primary objective of the Consortium will be to assess, compare, and optimize clinical outcomes among Connecticut residents with cardiovascular disease. As an initial goal for the Consortium, we further propose to undertake a prospective, observational study of Connecticut residents who present with ST Segment Elevation Acute Myocardial Infarction (STEMI). Recent advances in pharmacologic and mechanical reperfusion for STEMI have resulted in a need to define the optimal use of these therapies in the community at large. The primary purpose of this study will be to determine the relative merits of different treatment patterns for STEMI with regard to the use of fibrinolytic therapy and percutaneous coronary intervention (PCI). Particular emphasis will be placed on assessing the relative benefits of urgent mechanical revascularization performed at the state's seven tertiary facilities with PCI capability compared to all other treatment modalities. Successful completion of this unique collaborative endeavor is expected to have significant impact on improved patient care and on current health-care policy for medical resource allocation. Moreover, continued collaboration of health-care providers within the

  14. Developing treatment and control conditions in a clinical trial of massage therapy for advanced cancer.

    PubMed

    Smith, Marlaine; Kutner, Jean; Hemphill, Linnea; Yamashita, Traci; Felton, Susanne

    2007-01-01

    The purpose of this article is to describe the challenges faced by a research team in developing treatment and control conditions in a study of the efficacy of massage therapy for advanced cancer. Five design considerations were addressed related to developing a massage therapy protocol: (1) dosage, that is, the number, spacing and length of treatments; (2) type of massage therapy; (3) degree to which the protocol for the treatment is standardized; (4) qualifications of the persons providing the treatment; and (5) conditions under which the treatment is provided. Five criteria for structuring the control condition of the study are elaborated: (1) equivalency of contact; (2) similarity of form; (3) minimum adverse or negative effects; (4) expectancy of therapeutic benefit; and (5) minimum therapeutic benefit.

  15. In vitro fertilization (IVF): a review of 3 decades of clinical innovation and technological advancement

    PubMed Central

    Wang, Jeff; Sauer, Mark V

    2006-01-01

    In vitro fertilization, popularly referred to as IVF, has captured the attention of the public since its sensational introduction in 1978. Today assisted reproductive technology is available throughout most of the civilized world, and the practice is largely different from that used during the early days. Refinements in laboratory technology and clinical practice have allowed IVF to evolve into a medical procedure that is efficient, safe, readily accessible, and relatively affordable. More than 2 million IVF children have been born to date, and it is likely that continued enhancements will widen its appeal and applicability. PMID:18360648

  16. [Advances in the research of clinical features and treatment of ammonia burns].

    PubMed

    Wu, Guosheng; Xiao, Shichu; Sun, Yu; Ji, Shizhao; Xia, Zhaofan

    2015-02-01

    Ammonia is commonly used in industry and agriculture. It is also one of the most frequently accidentally spilled chemicals. Exposure to ammonia can cause severe cutaneous burn or freezing injury, ocular injury, and inhalation injury, among them inhalation injury is the most lethal one. Although the diagnosis and treatment of ammonia burns have been improved, the long-term prognosis is not satisfactory. In this article, we reviewed the literature concerning ammonia burns, in order to summarize the clinical features and treatment of such injury.

  17. In vitro fertilization (IVF): a review of 3 decades of clinical innovation and technological advancement.

    PubMed

    Wang, Jeff; Sauer, Mark V

    2006-12-01

    In vitro fertilization, popularly referred to as IVF, has captured the attention of the public since its sensational introduction in 1978. Today assisted reproductive technology is available throughout most of the civilized world, and the practice is largely different from that used during the early days. Refinements in laboratory technology and clinical practice have allowed IVF to evolve into a medical procedure that is efficient, safe, readily accessible, and relatively affordable. More than 2 million IVF children have been born to date, and it is likely that continued enhancements will widen its appeal and applicability.

  18. The advancement of human pluripotent stem cell-derived therapies into the clinic.

    PubMed

    Thies, R Scott; Murry, Charles E

    2015-09-15

    Human pluripotent stem cells (hPSCs) offer many potential applications for drug screening and 'disease in a dish' assay capabilities. However, a more ambitious goal is to develop cell therapeutics using hPSCs to generate and replace somatic cells that are lost as a result of disease or injury. This Spotlight article will describe the state of progress of some of the hPSC-derived therapeutics that offer the most promise for clinical use. Lessons from developmental biology have been instrumental in identifying signaling molecules that can guide these differentiation processes in vitro, and will be described in the context of these cell therapy programs.

  19. Technical Advances of the Recombinant Antibody Microarray Technology Platform for Clinical Immunoproteomics

    PubMed Central

    Delfani, Payam; Dexlin Mellby, Linda; Nordström, Malin; Holmér, Andreas; Ohlsson, Mattias; Borrebaeck, Carl A. K.; Wingren, Christer

    2016-01-01

    In the quest for deciphering disease-associated biomarkers, high-performing tools for multiplexed protein expression profiling of crude clinical samples will be crucial. Affinity proteomics, mainly represented by antibody-based microarrays, have during recent years been established as a proteomic tool providing unique opportunities for parallelized protein expression profiling. But despite the progress, several main technical features and assay procedures remains to be (fully) resolved. Among these issues, the handling of protein microarray data, i.e. the biostatistics parts, is one of the key features to solve. In this study, we have therefore further optimized, validated, and standardized our in-house designed recombinant antibody microarray technology platform. To this end, we addressed the main remaining technical issues (e.g. antibody quality, array production, sample labelling, and selected assay conditions) and most importantly key biostatistics subjects (e.g. array data pre-processing and biomarker panel condensation). This represents one of the first antibody array studies in which these key biostatistics subjects have been studied in detail. Here, we thus present the next generation of the recombinant antibody microarray technology platform designed for clinical immunoproteomics. PMID:27414037

  20. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice.

    PubMed

    Markoski, Melissa Medeiros

    2016-01-01

    Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals. PMID:27379197

  1. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice

    PubMed Central

    2016-01-01

    Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals. PMID:27379197

  2. Technical Advances of the Recombinant Antibody Microarray Technology Platform for Clinical Immunoproteomics.

    PubMed

    Delfani, Payam; Dexlin Mellby, Linda; Nordström, Malin; Holmér, Andreas; Ohlsson, Mattias; Borrebaeck, Carl A K; Wingren, Christer

    2016-01-01

    In the quest for deciphering disease-associated biomarkers, high-performing tools for multiplexed protein expression profiling of crude clinical samples will be crucial. Affinity proteomics, mainly represented by antibody-based microarrays, have during recent years been established as a proteomic tool providing unique opportunities for parallelized protein expression profiling. But despite the progress, several main technical features and assay procedures remains to be (fully) resolved. Among these issues, the handling of protein microarray data, i.e. the biostatistics parts, is one of the key features to solve. In this study, we have therefore further optimized, validated, and standardized our in-house designed recombinant antibody microarray technology platform. To this end, we addressed the main remaining technical issues (e.g. antibody quality, array production, sample labelling, and selected assay conditions) and most importantly key biostatistics subjects (e.g. array data pre-processing and biomarker panel condensation). This represents one of the first antibody array studies in which these key biostatistics subjects have been studied in detail. Here, we thus present the next generation of the recombinant antibody microarray technology platform designed for clinical immunoproteomics.

  3. Nuclear magnetic resonance based metabolomics and liver diseases: Recent advances and future clinical applications.

    PubMed

    Amathieu, Roland; Triba, Mohamed Nawfal; Goossens, Corentine; Bouchemal, Nadia; Nahon, Pierre; Savarin, Philippe; Le Moyec, Laurence

    2016-01-01

    Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. It is an "omics" technique that is situated downstream of genomics, transcriptomics and proteomics. Metabolomics is recognized as a promising technique in the field of systems biology for the evaluation of global metabolic changes. During the last decade, metabolomics approaches have become widely used in the study of liver diseases for the detection of early biomarkers and altered metabolic pathways. It is a powerful technique to improve our pathophysiological knowledge of various liver diseases. It can be a useful tool to help clinicians in the diagnostic process especially to distinguish malignant and non-malignant liver disease as well as to determine the etiology or severity of the liver disease. It can also assess therapeutic response or predict drug induced liver injury. Nevertheless, the usefulness of metabolomics is often not understood by clinicians, especially the concept of metabolomics profiling or fingerprinting. In the present work, after a concise description of the different techniques and processes used in metabolomics, we will review the main research on this subject by focusing specifically on in vitro proton nuclear magnetic resonance spectroscopy based metabolomics approaches in human studies. We will first consider the clinical point of view enlighten physicians on this new approach and emphasis its future use in clinical "routine".

  4. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice.

    PubMed

    Markoski, Melissa Medeiros

    2016-01-01

    Today, several veterinary diseases may be treated with the administration of stem cells. This is possible because these cells present a high therapeutic potential and may be injected as autologous or allogenic, freshly isolated, or previously cultured. The literature supports that the process is safe and brings considerable benefits to animal health. Knowledge about how adult stem cells modulate the molecular signals to activate cell homing has also been increasingly determined, evidencing the mechanisms which enable cells to repair and regenerate injured tissues. Preclinical studies were designed for many animal models and they have contributed to the translation to the human clinic. This review shows the most commonly used stem cell types, with emphasis on mesenchymal stem cells and their mechanistic potential to repair, as well as the experimental protocols, studied diseases, and species with the highest amount of studies and applications. The relationship between stem cell protocols utilized on clinics, molecular mechanisms, and the physiological responses may offer subsidies to new studies and therefore improve the therapeutic outcome for both humans and animals.

  5. Clinical development of nintedanib for advanced non-small-cell lung cancer

    PubMed Central

    Takeda, Masayuki; Okamoto, Isamu; Nakagawa, Kazuhiko

    2015-01-01

    Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. Several angiogenesis inhibitors have been developed as potential therapies for non-small-cell lung cancer (NSCLC). Nintedanib is a small-molecule tyrosine kinase inhibitor that targets receptors for vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor as well as RET (rearranged during transfection) and Flt3. When administered as monotherapy, nintedanib was well tolerated at doses up to 250 mg or 200 mg twice daily in European and Japanese patients, respectively, with liver toxicity featuring prominently among dose-limiting toxicities in both populations. A recent Phase III trial demonstrated that treatment with the combination of nintedanib and docetaxel resulted in a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with docetaxel alone in predefined NSCLC patients with adenocarcinoma tumor histology. Although the incidence of elevated alanine aminotransferase or aspartate aminotransferase as well as of diarrhea was higher in patients treated with nintedanib plus docetaxel, most of these adverse events were manageable with supportive treatment or dose reduction. The results of completed and ongoing clinical trials of nintedanib monotherapy and combination therapy for the treatment of NSCLC are summarized in this study. PMID:26622180

  6. Advanced 3-D analysis, client-server systems, and cloud computing—Integration of cardiovascular imaging data into clinical workflows of transcatheter aortic valve replacement

    PubMed Central

    Zimmermann, Mathis; Falkner, Juergen

    2013-01-01

    Degenerative aortic stenosis is highly prevalent in the aging populations of industrialized countries and is associated with poor prognosis. Surgical valve replacement has been the only established treatment with documented improvement of long-term outcome. However, many of the older patients with aortic stenosis (AS) are high-risk or ineligible for surgery. For these patients, transcatheter aortic valve replacement (TAVR) has emerged as a treatment alternative. The TAVR procedure is characterized by a lack of visualization of the operative field. Therefore, pre- and intra-procedural imaging is critical for patient selection, pre-procedural planning, and intra-operative decision-making. Incremental to conventional angiography and 2-D echocardiography, multidetector computed tomography (CT) has assumed an important role before TAVR. The analysis of 3-D CT data requires extensive post-processing during direct interaction with the dataset, using advance analysis software. Organization and storage of the data according to complex clinical workflows and sharing of image information have become a critical part of these novel treatment approaches. Optimally, the data are integrated into a comprehensive image data file accessible to multiple groups of practitioners across the hospital. This creates new challenges for data management requiring a complex IT infrastructure, spanning across multiple locations, but is increasingly achieved with client-server solutions and private cloud technology. This article describes the challenges and opportunities created by the increased amount of patient-specific imaging data in the context of TAVR. PMID:24282750

  7. The Clinical Effectiveness of Intralesional Injection of 2% Zinc Sulfate Solution in the Treatment of Common Warts

    PubMed Central

    Mohamed, Essam-elden Mohamed; Tawfik, Khaled Mohamed; Mahmoud, Asmaa Moneir

    2016-01-01

    Objective. To investigate the clinical efficacy and safety of intralesional injection of 2% zinc sulfate solution in the treatment of common warts. Patients and Methods. One hundred and twenty patients (78 females and 42 males) aged 5–55 years with 225 common warts participated in this prospective monocentric randomized study. All lesions were treated with intralesional injection of 2% zinc sulfate. Results. From 225 warts injected, 135 warts (60%) cured from the first session, 51 warts (22.67%) cured from the second session, and 12 warts (5.33%) cured from the third session. There is no significant relation between improvement and patient's ages, duration, or number of warts (P > 0.05). All patients complained from pain during injection, and all treated lesions showed redness, tenderness, and swelling in the first 3 days after injection. Late complications were postinflammatory hyperpigmentation in 90 patients (75%), scaring in 9 patients (7.5%), and ulceration in 3 patients (2.5%). Recurrence occurred in 3 lesions (1.33%). Conclusion. The clinical data indicate that intralesional injection of 2% zinc sulfate is an effective maneuver in the treatment of common warts; however, its associated complications limit its use. PMID:27123361

  8. Medical management of the traumatic consequences of civil unrest incidents: causation, clinical approaches, needs and advanced planning criteria.

    PubMed

    Ballantyne, Bryan

    2006-01-01

    toxicity or introduce additional local and/or systemic toxicity. By the very circumstances of civil unrest incidents, injuries are inevitable, particularly when emotions are heightened and police and security forces have to resort to various chemical and/or physical means of control. Trauma may include slight to severe physical and/or chemical injuries, psychological problems and occasional deaths. Hospitals should be prepared for a wide range of casualties, and the fact that those seeking help will constitute a heterogeneous group, including wide age range, male, female, and individuals with pre-existing ill health. A major civil unrest incident necessitates that the local receiving hospital should be prepared and equipped for decontamination and triage processes. It is necessary to reassure patients who have been exposed to sensory irritants that the signs and symptoms are rapidly reversible, and do not result in long-term sequelae. With respect to chemical exposures, detailed evaluation should be given to possible ocular, cutaneous, respiratory and gastrointestinal effects. Also, exposure to chemosensory irritants results in transient increases in blood pressure, bradycardia and increased intraocular pressure. This indicates that those with cardiovascular diseases and glaucoma may be at increased risk for the development of complications. This article details the pharmacological, toxicological and clinical effects of chemicals used in civil disturbance control and discusses the management of contaminated individuals. Additionally, the potential for adverse effects from delivery systems and other physical restraint procedures is summarised. Due to the emergency and specialised circumstances and conditions of a civil unrest incident, there is a clear need for advanced planning by healthcare institutions in the event that such an incident occurs in their catchment area. This should include ensuring a good information base, preparations for medical and support staff

  9. Proteomic strategies in the search for novel pancreatic cancer biomarkers and drug targets: recent advances and clinical impact.

    PubMed

    Coleman, Orla; Henry, Michael; McVey, Gerard; Clynes, Martin; Moriarty, Michael; Meleady, Paula

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers; despite a low incidence rate it is the fourth leading cause of cancer-related death in the world. Improvement of the diagnosis, prognosis and treatment remains the main focus of pancreatic cancer research. Rapid developments in proteomic technologies has improved our understanding of the pancreatic cancer proteome. Here, the authors summarise the recent proteomic strategies undertaken in the search for: novel biomarkers for early diagnosis, pancreatic cancer-specific proteins which may be used for novel targeted therapies and proteins which may be useful for monitoring disease progression post-therapy. Recent advances and findings discussed here provide great promise of having a significant clinical impact and improving the outcome of patients with this malignancy. PMID:26985644

  10. Clinical assessment following tibial tuberosity advancement in 28 stifles at 6 months and 1 year after surgery.

    PubMed

    MacDonald, Tamara L; Allen, David A; Monteith, Gabrielle J

    2013-03-01

    This prospective study evaluated the effect of tibial tuberosity advancement (TTA) on lameness, thigh circumference, range of motion (ROM), and radiographic osteoarthritis (OA) scores at 6 wk, 6 mo, and 1 y after surgery in 24 client-owned dogs with cranial cruciate ligament (CrCL) deficiency. Complications associated with TTA were also assessed. A significant improvement in lameness score and thigh circumference was observed in CrCL deficient limbs that received TTA, but no significant overall change in range of motion occurred in the affected limbs over the course of the study. Post-operative complications were identified in 33.3% of the dogs. This study demonstrates that TTA results in significant clinical improvement in patients up to 1 y after surgery. However, 21% of the dogs had post-operative recurrent lameness.

  11. [Sequential Chemoradiotherapy for Advanced Head and Neck Cancer: A Clinical Study with 33 Cases].

    PubMed

    Takahashi, Katsumasa; Nakajima, Kyoko; Murata, Takaaki; Shino, Masato; Nikkuni, Osamu; Toyoda, Minoru; Takayasu, Yukihiro; Chikamatsu, Kazuaki

    2016-05-01

    A total of 33 patients with advanced head and neck cancer (AHNC) treated with sequential chemoradiotherapy (SCRT) were retrospectively evaluated at Gunma University Hospital between 2009 and 2011. The regimen of SCRT was docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy (ICT), accompanied by docetaxel and cisplatin-based concurrent chemoradiotherapy (CCRT), and oral administration of TS-1 after that. The response rate was 61%, the 3-year overall survival rate was 42%, the non-tumor-bearing survival rate was 27%, and the tumor-bearing survival rate was 15%. Fourteen of 33 patients were tumor-free, and their 3-year overall survival rate was surprisingly 86%. On the other hand, 3-year overall survival rate in the remaining 19 patients was significantly low. To select good response cases for ICT was important. In such cases, TPF should be applied repeatedly, which achieved a 61% response rate even in AHNC. A long-term TS-1 oral medication suppressed cancer regrowth and contributed to long-term survival. PMID:27459819

  12. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  13. A novel dentifrice technology for advanced oral health protection: A review of technical and clinical data.

    PubMed

    Baig, Arif; He, Tao

    2005-09-01

    Throughout the world, dentifrices have played a key role in the practice of good oral hygiene and promotion of better oral health. In addition to providing general dental cleaning, toothpastes also have served as an excellent vehicle for the introduction of new agents that deliver therapeutic and cosmetic benefits. Key examples of using dentifrices to provide added benefits include the introduction in 1955 of the first fluoridated toothpaste clinically proven to fight caries (Crest Cavity Protection) and the launch of the first tartar-control dentifrice (Crest Tartar Control) in the mid-1980s. To continue expanding the health and esthetic benefits offered by a single dentifrice, a multitude of agents have been investigated over the past 3 decades. The focus of these investigations has been in the multibenefit segment, the most widely used among US consumers.

  14. [Abnormal of tear lipid layer and recent advances in clinical study of dry eye].

    PubMed

    Xiao, Xin-Ye; Liu, Zu-Guo

    2012-03-01

    Dry eye is a common disease in the ophthalmological clinic, which is related to the dysfunction of tear film. The tear film is composed of lipid layer, aqueous layer and mucin layer (or lipid layer, aqueous/mucin layer). The lipid of the outmost layer derived from Meibomian gland and distributed on the tear film after blinking can decrease the evaporation and stabilize the tear film. The thickness, quality, and distribution of lipid layer are impaired in many dry eye patients, hence restoring the physiological function of lipid layer may be crucial for the treatment of this kind of dry eye. The lipid artificial tears manifest great effects on increasing lipid layer thickness, stabilizing tear film, improving Meibomian gland dysfunction, and promoting tear film distribution.

  15. Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems.

    PubMed

    Vaquero, Juan José; Kinahan, Paul

    2015-01-01

    Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges.

  16. Recent advances of liquid chromatography-(tandem) mass spectrometry in clinical and forensic toxicology - An update.

    PubMed

    Remane, Daniela; Wissenbach, Dirk K; Peters, Frank T

    2016-09-01

    Liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) is a well-established and widely used technique in clinical and forensic toxicology as well as doping control especially for quantitative analysis. In recent years, many applications for so-called multi-target screening and/or quantification of drugs, poisons, and or their metabolites in biological matrices have been developed. Such methods have proven particularly useful for analysis of so-called new psychoactive substances that have appeared on recreational drug markets throughout the world. Moreover, the evolvement of high resolution MS techniques and the development of data-independent detection modes have opened new possibilities for applications of LC-(MS/MS) in systematic toxicological screening analysis in the so called general unknown setting. The present paper will provide an overview and discuss these recent developments focusing on the literature published after 2010.

  17. Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems.

    PubMed

    Vaquero, Juan José; Kinahan, Paul

    2015-01-01

    Positron emission tomography (PET) imaging is based on detecting two time-coincident high-energy photons from the emission of a positron-emitting radioisotope. The physics of the emission, and the detection of the coincident photons, give PET imaging unique capabilities for both very high sensitivity and accurate estimation of the in vivo concentration of the radiotracer. PET imaging has been widely adopted as an important clinical modality for oncological, cardiovascular, and neurological applications. PET imaging has also become an important tool in preclinical studies, particularly for investigating murine models of disease and other small-animal models. However, there are several challenges to using PET imaging systems. These include the fundamental trade-offs between resolution and noise, the quantitative accuracy of the measurements, and integration with X-ray computed tomography and magnetic resonance imaging. In this article, we review how researchers and industry are addressing these challenges. PMID:26643024

  18. Recent advances in Gilles de la Tourette syndrome: implications for clinical practice and future research.

    PubMed

    Leckman, J F; Cohen, D J

    1983-01-01

    The clinical presentation and natural history of Gilles de la Tourette syndrome (TS) are reviewed. The waxing and waning of symptoms, the rostrocaudal progression of areas of motor involvement, complex stereotypies, and the familial aggregation of TS and chronic multiple tics are suggestions of underlying neurochemical disturbance; whereas attentional problems, impulsivity and obsessive-compulsive behaviors create interesting links with other disorders. The most robust metabolic findings are the lowered CSF HVA in many TS patients, and the positive response of symptoms to dopamine blockers and clonidine particularly, which would be consistent with dopamine receptor hypersensitivity and possible noradrenergic-dopaminergic interactions in TS. However, no definitive account of patho-physiology or genetic contributions to the disorder is yet available.

  19. Recent advances of liquid chromatography-(tandem) mass spectrometry in clinical and forensic toxicology - An update.

    PubMed

    Remane, Daniela; Wissenbach, Dirk K; Peters, Frank T

    2016-09-01

    Liquid chromatography (LC) coupled to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) is a well-established and widely used technique in clinical and forensic toxicology as well as doping control especially for quantitative analysis. In recent years, many applications for so-called multi-target screening and/or quantification of drugs, poisons, and or their metabolites in biological matrices have been developed. Such methods have proven particularly useful for analysis of so-called new psychoactive substances that have appeared on recreational drug markets throughout the world. Moreover, the evolvement of high resolution MS techniques and the development of data-independent detection modes have opened new possibilities for applications of LC-(MS/MS) in systematic toxicological screening analysis in the so called general unknown setting. The present paper will provide an overview and discuss these recent developments focusing on the literature published after 2010. PMID:27452180

  20. Advances in recent patent and clinical trial drug development for Alzheimer’s disease

    PubMed Central

    Liu, Haibin; Wang, Lirong; Su, Weiwei; Xie, Xiang-Qun

    2015-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease, involving a large number of genes, proteins and their complex interactions. Currently, no effective therapeutic agents are available to either stop or reverse the progression of this disease, likely due to its polygenic nature. The complicated pathophysiology of AD remains unresolved. Although it has been hypothesized that the amyloid β cascade and the hyper-phosphorylated tau protein may be primarily involved, other mechanisms, such as oxidative stress, deficiency of central cholinergic neurotransmitter, mitochondrial dysfunction and inflammation have also been implicated. The main focus of this review is to document current therapeutic agents in clinical trials and patented candidate compounds under development based on their main mechanisms of action. It also discusses the relationship between the recent understanding of key targets and the development of potential therapeutic agents for the treatment of AD. PMID:25291315

  1. Stress and coping research. Methodological challenges, theoretical advances, and clinical applications.

    PubMed

    Somerfield, M R; McCrae, R R

    2000-06-01

    Coping is among the most widely studied topics in contemporary psychology. However, the explosion of interest in coping has yielded little and the field is in crisis. This section offers a survey of the state of the art in theory and research on stress and adaptational processes. The four core articles in the section take up, respectively, problems in research design, the neglect of unconscious reactions to stress, the selection of adaptational outcomes, and the link between research on adaptational processes and clinical practice. The final article by Richard S. Lazarus offers a commentary. The present introduction provides the historical backdrop for the section. Then, after a brief overview of research on adaptational processes, the authors summarize the scope and yield of coping research and preview the four core articles in the section. The strengths and limits of individual coping efforts and the need for realistic expectations and redoubled efforts are discussed.

  2. Copper-64 radiopharmaceuticals for PET imaging of cancer: advances in preclinical and clinical research.

    PubMed

    Anderson, Carolyn J; Ferdani, Riccardo

    2009-08-01

    Copper-64 (T(1/2) = 12.7 hours; beta(+), 0.653 MeV [17.8 %]; beta(-), 0.579 MeV [38.4 %]) has decay characteristics that allow for positron emission tomography (PET) imaging and targeted radiotherapy of cancer. The well-established coordination chemistry of copper allows for its reaction with a wide variety of chelator systems that can potentially be linked to peptides and other biologically relevant small molecules, antibodies, proteins, and nanoparticles. The 12.7-hours half-life of 64Cu provides the flexibility to image both smaller molecules and larger, slower clearing proteins and nanoparticles. In a practical sense, the radionuclide or the 64Cu-radiopharmaceuticals can be easily shipped for PET imaging studies at sites remote to the production facility. Due to the versatility of 64Cu, there has been an abundance of novel research in this area over the past 20 years, primarily in the area of PET imaging, but also for the targeted radiotherapy of cancer. The biologic activity of the hypoxia imaging agent, 60/64Cu-ATSM, has been described in great detail in animal models and in clinical PET studies. An investigational new drug application for 64Cu-ATSM was recently approved by the U.S. Food and Drug Administration (FDA) in the United States, paving the way for a multicenter trial to validate the utility of this agent, with the hopeful result being FDA approval for routine clinical use. This article discusses state-of-the-art cancer imaging with 64Cu radiopharmaceuticals, including 64Cu-ATSM for imaging hypoxia, 64Cu-labeled peptides for tumor-receptor targeting, (64)Cu-labeled monoclonal antibodies for targeting tumor antigens, and 64Cu-labeled nanoparticles for cancer targeting. The emphasis of this article will be on the new scientific discoveries involving (64)Cu radiopharmaceuticals, as well as the translation of these into human studies.

  3. Opioid requirement, opioid receptor expression, and clinical outcomes in patients with advanced prostate cancer

    PubMed Central

    Zylla, Dylan; Gourley, Brett L.; Vang, Derek; Jackson, Scott; Boatman, Sonja; Lindgren, Bruce; Kuskowski, Michael A.; Le, Chap; Gupta, Kalpna; Gupta, Pankaj

    2013-01-01

    Background Preclinical studies show that opioids stimulate angiogenesis and tumor progression through the mu opioid receptor (MOR). Although MOR is over-expressed in several human malignancies, the effect of chronic opioid requirement on cancer progression or survival has not been examined in humans. Methods We performed a retrospective analysis on 113 patients identified in the Minneapolis VA Tumor Registry (test cohort) and 480 patients from the national VA Central Cancer Registry (validation cohort) diagnosed with stage IV prostate cancer between 1995 and 2010, to examine whether MOR expression or opioid requirement is associated with disease progression and survival. All opioids were converted to oral morphine equivalents (OME) for comparison. Laser scanning confocal microscopy was used to analyze MOR-immunoreactivity in prostate cancer biopsies. The effects of variables on outcomes were analyzed in univariable and multivariable models. Results In patients with metastatic prostate cancer, MOR expression and opioid requirement were independently associated with inferior progression-free survival (PFS) (HR 1.65, 1.33–2.07; p<0.001 and HR 1.08, 1.03–1.13; p<0.001, respectively) and overall survival (OS; HR 1.55, 1.20–1.99; p<0.001 and HR 1.05, 1.00–1.10; p=0.031, respectively). The validation cohort confirmed that increasing opioid requirement was associated with worse OS (HR 1.005, 1.002–1.008, p=0.001). Conclusion Higher MOR expression and greater opioid requirement are associated with shorter PFS and OS in patients with metastatic prostate cancer. Nevertheless, clinical practice should not be changed until prospective randomized trials show that opioid use is associated with inferior clinical outcomes, and that abrogation of the peripheral activities of opioids ameliorates this effect. PMID:24104703

  4. Natural products are the future of anticancer therapy: Preclinical and clinical advancements of Viscum album phytometabolites.

    PubMed

    Attar, R; Tabassum, S; Fayyaz, S; Ahmad, M S; Nogueira, D R; Yaylim, I; Timirci-Kahraman, O; Kucukhuseyin, O; Cacina, C; Farooqi, A A; Ismail, M

    2015-10-30

    Cancer is a multifaceted and genomically complex disease. Research over the years has gradually provided a near complete resolution of cancer landscape and it is now known that genetic/epigenetic mutations, inactivation of tumor suppressors, Overexpression of oncogenes, spatio-temporally dysregulated intracellular signaling cascades, epithelial to mesenchymal transition (EMT), metastasis and loss of apoptosis are some of the most extensively studied biological mechanisms that underpin cancer development and progression. Increasingly it is being realized that current therapeutic interventions are becoming ineffective because of tumor heterogeneity and rapidly developing resistance against drugs. Considerable biological activities exerted by bioactive ingredients isolated from natural sources have revolutionized the field of natural product chemistry and rapid developments in preclinical studies are encouraging. Viscum album has emerged as a deeply studied natural source with substantial and multifaceted biological activities. In this review we have attempted to provide recent breakthroughs in existing scientific literature with emphasis on targeting of protein network in cancer cells. We partition this review into different sections, highlighting latest information from cell culture studies, preclinical and clinically oriented studies. We summarized how bioactive ingredients of Viscum album modulated extrinsic and intrinsic pathways in cancer cells. However, surprisingly, none of the study reported stimulatory effects on TRAIL receptors. The review provided in-depth analysis of how Viscum album modulated Endoplasmic Reticulum Stress in cancer cells and how bioactive chemicals tactfully targeted cytoskeletal machinery in cancer cells as evidenced by cell culture studies. It is noteworthy that Viscum album has entered into various phases of clinical trials, however, there are still knowledge gaps in our understanding regarding how various bioactive constituents of

  5. Amnion and Chorion Allografts in Combination with Coronally Advanced Flap in the Treatment of Gingival Recession: A Clinical Study

    PubMed Central

    Chakraborthy, Sonali; Sambashivaiah, Savita; Bilchodmath, Shivaprasad

    2015-01-01

    Background Guided tissue regeneration (GTR) based root coverage using different allograft membranes has been utilized to correct gingival recession defects with promising results. Amnion and chorion allograft membranes of alternative origin derived from human placental tissue has been advocated in the treatment of gingival recession. However, chorion membrane has been used in combination with amnion membrane no study has compared these allograft membranes in the treatment of gingival recession. Therefore, the purpose of this study was to clinically evaluate and compare the efficacy of amnion membrane and chorion membrane in combination with coronally advanced flap in the treatment of gingival recessions. Materials and Methods Twelve systemically healthy patients having at least 2 bilateral Miller’s Class I or Class II gingival recession were recruited and coronally advanced flap was performed with amnion membrane or chorion membrane. Clinical parameters such as gingival Index, plaque index, length of the recession, width of the recession, width of keratinized gingiva, relative attachment level were evaluated at baseline, 3 and 6 months post-surgery. Results The mean decrease in length of recession (LR) for Chorion site was 2.00±1.54mm and amnion site was 1.58±1.14mm. The gain in attachment level for amnion site was 2.17±1.53mm and for chorion site was 1.58±1.22mm. The total mean percentage of root coverage was 34% for chorion site and 22% for amnion site. Conclusion Both amnion membrane and chorion membrane has shown to be versatile allograft material to be used in the treatment of root coverage. PMID:26501023

  6. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    SciTech Connect

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-12-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  7. Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

    PubMed Central

    Tey, Jeremy; Choo, Bok Ai; Leong, Cheng Nang; Loy, En Yun; Wong, Lea Choung; Lim, Keith; Lu, Jiade Jay; Koh, Wee Yao

    2014-01-01

    Abstract The purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques. We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity. Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (≤39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (α/β ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia). External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (≤39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing. PMID:25396330

  8. Default options in advance directives: study protocol for a randomised clinical trial

    PubMed Central

    Gabler, Nicole B; Cooney, Elizabeth; Small, Dylan S; Troxel, Andrea B; Arnold, Robert M; White, Douglas B; Angus, Derek C; Loewenstein, George; Volpp, Kevin G; Bryce, Cindy L; Halpern, Scott D

    2016-01-01

    Introduction Although most seriously ill Americans wish to avoid burdensome and aggressive care at the end of life, such care is often provided unless patients or family members specifically request otherwise. Advance directives (ADs) were created to provide opportunities to set limits on aggressive care near life's end. This study tests the hypothesis that redesigning ADs such that comfort-oriented care is provided as the default, rather than requiring patients to actively choose it, will promote better patient-centred outcomes. Methods and analysis This multicentre trial randomises seriously ill adults to receive 1 of 3 different ADs: (1) a traditional AD that requires patients to actively choose their goals of care or preferences for specific interventions (eg, feeding tube insertion) or otherwise have their care guided by their surrogates and the prevailing societal default toward aggressive care; (2) an AD that defaults to life-extending care and receipt of life-sustaining interventions, enabling patients to opt out from such care; or (3) an AD that defaults to comfort care, enabling patients to opt into life-extending care. We seek to enrol 270 patients who return complete, legally valid ADs so as to generate sufficient power to detect differences in the primary outcome of hospital-free days (days alive and not in an acute care facility). Secondary outcomes include hospital and intensive care unit admissions, costs of care, hospice usage, decision conflict and satisfaction, quality of life, concordance of preferences with care received and bereavement outcomes for surrogates of patients who die. Ethics and dissemination This study has been approved by the Institutional Review Boards at all trial centres, and is guided by a data safety and monitoring board and an ethics advisory board. Study results will be disseminated using methods that describe the results in ways that key stakeholders can best understand and implement. Trial registration number NCT02017548

  9. Advancing Clinical Proteomics via Analysis Based on Biological Complexes: A Tale of Five Paradigms.

    PubMed

    Goh, Wilson Wen Bin; Wong, Limsoon

    2016-09-01

    Despite advances in proteomic technologies, idiosyncratic data issues, for example, incomplete coverage and inconsistency, resulting in large data holes, persist. Moreover, because of naïve reliance on statistical testing and its accompanying p values, differential protein signatures identified from such proteomics data have little diagnostic power. Thus, deploying conventional analytics on proteomics data is insufficient for identifying novel drug targets or precise yet sensitive biomarkers. Complex-based analysis is a new analytical approach that has potential to resolve these issues but requires formalization. We categorize complex-based analysis into five method classes or paradigms and propose an even-handed yet comprehensive evaluation rubric based on both simulated and real data. The first four paradigms are well represented in the literature. The fifth and newest paradigm, the network-paired (NP) paradigm, represented by a method called Extremely Small SubNET (ESSNET), dominates in precision-recall and reproducibility, maintains strong performance in small sample sizes, and sensitively detects low-abundance complexes. In contrast, the commonly used over-representation analysis (ORA) and direct-group (DG) test paradigms maintain good overall precision but have severe reproducibility issues. The other two paradigms considered here are the hit-rate and rank-based network analysis paradigms; both of these have good precision-recall and reproducibility, but they do not consider low-abundance complexes. Therefore, given its strong performance, NP/ESSNET may prove to be a useful approach for improving the analytical resolution of proteomics data. Additionally, given its stability, it may also be a powerful new approach toward functional enrichment tests, much like its ORA and DG counterparts.

  10. How to apply modern scientific and technological advances to the practice of clinical gastroenterology in Vietnam.

    PubMed

    Ha, M V

    1997-06-01

    There are some differences between the spectrum of gastroenterological diseases in Vietnam compared with those of more developed countries. These may be due to different living standards, quality of nutrition, and different infection rates of intestinal parasites and hepatotropic viruses. Gastric carcinoma and hepatocellular carcinoma (HCC) are leading malignancies, while colorectal cancer is less frequent. Bile duct stones often have Ascaris eggs in the centre, and they prevail in incidence over gall-bladder stones. The majority of digestive cancers are detected at a very late stage. The Vietnamese Association of Gastroenterology aims to contribute to the development of modern gastroenterology (GE) in Vietnam, to study and apply recent advances in imaging technology, such as fibre-optic diagnostic and therapeutical endoscopy, ultrasonography, laparoscopic surgery etc. and to do further work in molecular biology. For this purpose, besides our self-reliance, we need, and ask for, support and assistance from the Japanese Society of GE (JSGE), the Asian Pacific Association of GE (APAGE) and the Organisation Mondiale de GE (OMEGE). At the same time, we suggest a choice be made among the different technologies, bearing in mind their cost-effectiveness, and to give preference to measures for the primary prevention and early detection of the diseases. Japanese experience in the early detection of gastric cancer and HCC, and in the Percutaneous Ethanol Injection Therapy (PEIT) for treatment of HCC, are highly appreciated. We recommend also a judicious and scientific combination of traditional medicine and modern technology in the research and the struggle against digestive diseases.

  11. Recent advances in bariatric/metabolic surgery: appraisal of clinical evidence

    PubMed Central

    Lee, Wei-Jei; Almulaifi, Abdullah

    2015-01-01

    Abstract Obesity and associated type 2 diabetes mellitus (T2DM) are becoming a serious medical issue worldwide. Bariatric surgery has been shown to be the most effective and durable therapy for the treatment of morbid obese patients. Increasing data indicates bariatric surgery as metabolic surgery is an effective and novel therapy for not well controlled obese T2DM patients. The review of recent developments in bariatric/metabolic surgery covers 4 major fields. 1) Improvement of safety: recent advances in laparoscopic/metabolic surgery has made this minimal invasive surgery more than ten times safer than a decade ago. The safety profile of laparoscopic/metabolic surgery is compatible with that of laparoscopic cholecystectomy now. 2) New bariatric/metabolic surgery: laparoscopic sleeve gastrectomy (LSG) is becoming the leading bariatric surgery because of its simplicity and efficacy. Other new procedures, such as gastric plication, banded plication, single anastomosis (mini) gastric bypass and Duodeno-jejunal bypass with sleeve gastrectomy have all been accepted as treatment modalities for bariatric/metabolic surgery. 3) Mechanism of bariatric/metabolic surgery: Restriction is the most important mechanism for bariatric surgery. Weight regain after bariatric surgery is usually associated with loss of restriction. Recent studies demonstrated that gut hormone, microbiota and bile acid changes after bariatric surgery may play an important role in durable weight loss as well as in T2DM remission. However, weight loss is still the cornerstone of T2DM remission after metabolic surgery. 4) Patient selection: patients who may benefit most from bariatric surgery was found to be patients with insulin resistance. For Asian T2DM patients, the indication of metabolic surgery has been set to those with not well controlled (HbA1c > 7.5%) disease and with their BMI > 27.5 Kg/m2. A novel diabetes surgical score, ABCD score, is a simple system for predicting the success of surgical

  12. Advancing Clinical Proteomics via Analysis Based on Biological Complexes: A Tale of Five Paradigms.

    PubMed

    Goh, Wilson Wen Bin; Wong, Limsoon

    2016-09-01

    Despite advances in proteomic technologies, idiosyncratic data issues, for example, incomplete coverage and inconsistency, resulting in large data holes, persist. Moreover, because of naïve reliance on statistical testing and its accompanying p values, differential protein signatures identified from such proteomics data have little diagnostic power. Thus, deploying conventional analytics on proteomics data is insufficient for identifying novel drug targets or precise yet sensitive biomarkers. Complex-based analysis is a new analytical approach that has potential to resolve these issues but requires formalization. We categorize complex-based analysis into five method classes or paradigms and propose an even-handed yet comprehensive evaluation rubric based on both simulated and real data. The first four paradigms are well represented in the literature. The fifth and newest paradigm, the network-paired (NP) paradigm, represented by a method called Extremely Small SubNET (ESSNET), dominates in precision-recall and reproducibility, maintains strong performance in small sample sizes, and sensitively detects low-abundance complexes. In contrast, the commonly used over-representation analysis (ORA) and direct-group (DG) test paradigms maintain good overall precision but have severe reproducibility issues. The other two paradigms considered here are the hit-rate and rank-based network analysis paradigms; both of these have good precision-recall and reproducibility, but they do not consider low-abundance complexes. Therefore, given its strong performance, NP/ESSNET may prove to be a useful approach for improving the analytical resolution of proteomics data. Additionally, given its stability, it may also be a powerful new approach toward functional enrichment tests, much like its ORA and DG counterparts. PMID:27454466

  13. Advances in the development of tau PET radiotracers and their clinical applications.

    PubMed

    Okamura, Nobuyuki; Harada, Ryuichi; Furukawa, Katsutoshi; Furumoto, Shozo; Tago, Tetsuro; Yanai, Kazuhiko; Arai, Hiroyuki; Kudo, Yukitsuka

    2016-09-01

    Alzheimer's disease and other neurodegenerative dementias belong to the family of tauopathies. These diseases are characterized by the deposition of insoluble tau aggregates possessing an enriched β-sheet structure. In vivo imaging of the tau deposits by positron emission tomography (PET) will facilitate the early and accurate diagnosis of these diseases, tracking of disease progression, assessment of disease severity, and prediction of disease prognosis. Furthermore, this technology is expected to play a vital role in the monitoring of treatment outcomes and in the selection of patients for the therapeutic trials of anti-dementia drugs. Recently, several tau PET tracers have been successfully developed and demonstrated as having high binding affinity and selectivity to tau protein deposits. Recent clinical studies using these tracers have demonstrated significant tracer retention in sites susceptible to tau deposition in Alzheimer's disease, as well as correlations with the disease severity and cognitive impairment in cases with dementia. These tracers, thus, have the potential to effectively diagnose the tauopathies. Further longitudinal assessment will clarify the effect of the tau deposition on the neurodegenerative process and cognitive decline and the interaction of tau with amyloid-β in the human brain.

  14. Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science.

    PubMed

    Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel

    2016-01-01

    One of the prevailing applications of machine learning is the use of predictive modelling in clinical survival analysis. In this work, we present our view of the current situation of computer tools for survival analysis, stressing the need of transferring the latest results in the field of machine learning to biomedical researchers. We propose a web based software for survival analysis called OSA (Online Survival Analysis), which has been developed as an open access and user friendly option to obtain discrete time, predictive survival models at individual level using machine learning techniques, and to perform standard survival analysis. OSA employs an Artificial Neural Network (ANN) based method to produce the predictive survival models. Additionally, the software can easily generate survival and hazard curves with multiple options to personalise the plots, obtain contingency tables from the uploaded data to perform different tests, and fit a Cox regression model from a number of predictor variables. In the Materials and Methods section, we depict the general architecture of the application and introduce the mathematical background of each of the implemented methods. The study concludes with examples of use showing the results obtained with public datasets. PMID:27532883

  15. Corticosteroid-Binding Globulin: A Review of Basic and Clinical Advances.

    PubMed

    Meyer, E J; Nenke, M A; Rankin, W; Lewis, J G; Torpy, D J

    2016-06-01

    Corticosteroid-binding globulin (CBG, transcortin) is the primary cortisol binding protein. It is a non-inhibitory serine protease inhibitor, capable of conformational change from a high cortisol-binding affinity form to a low affinity form upon cleavage of its reactive centre loop by various proteases, such as neutrophil elastase. The burgeoning inflammatory role of CBG applies to acute, severe inflammation where depletion is associated with mortality, and to chronic inflammation where defects in cortisol delivery may perpetuate inflammation. Naturally occurring human mutations influence a wide range of CBG properties and point toward a role in hitherto unexplained chronic musculoskeletal pain and fatigue disorders as well as potentially affecting fertility outcomes including offspring gender. In vitro and knock-out animal models of CBG propose a role for CBG in cortisol transport to the brain, providing a foundation for understanding the human observations in those with CBG mutations and sex differences in stress-related mood and behaviour. Finally, CBG measurement has a practical role in the estimation of free cortisol, useful in clinical circumstances where CBG levels or cortisol binding affinity is reduced. Taken together, novel data suggest a role for cortisol in targeted cortisol delivery, with implications in acute and chronic inflammation, as well as roles in metabolism and neurocognitive function, implying that CBG is a multifaceted component in the mechanisms of hypothalamic-pituitary-adrenal axis related homeostasis.

  16. The Ease of Language Understanding (ELU) model: theoretical, empirical, and clinical advances

    PubMed Central

    Rönnberg, Jerker; Lunner, Thomas; Zekveld, Adriana; Sörqvist, Patrik; Danielsson, Henrik; Lyxell, Björn; Dahlström, Örjan; Signoret, Carine; Stenfelt, Stefan; Pichora-Fuller, M. Kathleen; Rudner, Mary

    2013-01-01

    Working memory is important for online language processing during conversation. We use it to maintain relevant information, to inhibit or ignore irrelevant information, and to attend to conversation selectively. Working memory helps us to keep track of and actively participate in conversation, including taking turns and following the gist. This paper examines the Ease of Language Understanding model (i.e., the ELU model, Rönnberg, 2003; Rönnberg et al., 2008) in light of new behavioral and neural findings concerning the role of working memory capacity (WMC) in uni-modal and bimodal language processing. The new ELU model is a meaning prediction system that depends on phonological and semantic interactions in rapid implicit and slower explicit processing mechanisms that both depend on WMC albeit in different ways. It is based on findings that address the relationship between WMC and (a) early attention processes in listening to speech, (b) signal processing in hearing aids and its effects on short-term memory, (c) inhibition of speech maskers and its effect on episodic long-term memory, (d) the effects of hearing impairment on episodic and semantic long-term memory, and finally, (e) listening effort. New predictions and clinical implications are outlined. Comparisons with other WMC and speech perception models are made. PMID:23874273

  17. The South African form of severe and complicated canine babesiosis: clinical advances 1994-2004.

    PubMed

    Jacobson, Linda S

    2006-05-31

    Babesia (canis) rossi infection is common in dogs in South Africa, and frequently causes severe, life-threatening disease. Acidemia, persistent hyperlactatemia, hemoconcentration, elevated creatinine, cerebral babesiosis, pulmonary edema and pancreatitis are all associated with mortality rates above 30%, compared with overall mortality of 12% in admitted cases. Although half the admitted cases are severely anemic, hemoconcentration is associated with far higher mortality. Cerebral babesiosis is uncommon, but carries a poor prognosis. The pathological mechanism has been suggested to be endothelial cell damage and necrosis, followed by segmental microvascular necrosis with perivascular edema and hemorrhage. Renal involvement in babesiosis resembles the functional renal failure of sepsis. Hypotension is common, and other cardiovascular disturbances have been documented. Cerebellar ataxia, rhabdomyolysis and pancreatitis are recently identified complications. While the previous categorization into "severe" (life-threatening anemia) and "complicated" (complications not directly attributable to anemia) disease has proved useful, the distinction is artificial and probably unnecessary. An updated approach to classification is suggested, aimed at grouping animals by severity and prognosis, and using simple measures, such as clinical collapse and abnormal breathing, as much as possible. Although inflammatory mechanisms are undoubtedly important in the pathophysiology of babesiosis, there can be little doubt that tissue hypoxia plays a major role in the disease process. PMID:16503090

  18. MicroRNAS in endometrial cancer: recent advances and potential clinical applications

    PubMed Central

    Yanokura, Megumi; Banno, Kouji; Iida, Miho; Irie, Haruko; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

    2015-01-01

    Endometrial cancer is a common malignant gynecological tumor, but there are few biomarkers that are useful for early and accurate diagnosis and few treatments other than surgery. However, use of microRNAs (miRNAs) that induces gene downregulation in cells may permit effective and minimally invasive diagnosis and treatment. In endometrial cancer cells, expression levels of miRNAs including miR-185, miR-210 and miR-423 are upregulated and those of miR-let7e, miR-30c and miR-221 are downregulated compared to normal tissues, and these miRNAs are involved in carcinogenesis, invasion and metastasis. miRNAs with expression changes such as miR-181b, miR-324-3p and miR-518b may be used as prognostic biomarkers and transfection of miR-152 may inhibit cancer growth. However, most current studies of miRNAs are at a basic level and further work is needed to establish clinical applications targeting miRNAs. PMID:26535032

  19. Developing advanced clinical skills in the management of breathlessness: evaluation of an educational intervention.

    PubMed

    Froggatt, Katherine; Walford, Carole

    2005-09-01

    The dissemination of knowledge regarding care interventions is often supported through educational initiatives. However, the efficacy of education to make a difference to practice is not always demonstrated. An educational course has been developed and piloted that aimed to educate nurses about skills for the management of breathlessness. The course was developed with, and utilised the expertise of, researchers, practitioners and educators experienced in the management of breathlessness. Twelve clinical nurse specialists, from Scotland and South East England, working in oncology and palliative care, participated in the first course. A longitudinal evaluation was undertaken to consider the impact of the course upon the participants' practice and the care of people who are breathless. Interviews were conducted at two time points and a self-rated familiarity and confidence tool was completed by the participants at three time points. The participants rated themselves as improving their familiarity and confidence with the different aspects of the intervention. Attendance on the course also impacted upon the care of people who were breathless, improving their ability to self-manage their condition. Recommendations for future educational developments of this type are provided. PMID:16112528

  20. Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science

    PubMed Central

    Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel

    2016-01-01

    One of the prevailing applications of machine learning is the use of predictive modelling in clinical survival analysis. In this work, we present our view of the current situation of computer tools for survival analysis, stressing the need of transferring the latest results in the field of machine learning to biomedical researchers. We propose a web based software for survival analysis called OSA (Online Survival Analysis), which has been developed as an open access and user friendly option to obtain discrete time, predictive survival models at individual level using machine learning techniques, and to perform standard survival analysis. OSA employs an Artificial Neural Network (ANN) based method to produce the predictive survival models. Additionally, the software can easily generate survival and hazard curves with multiple options to personalise the plots, obtain contingency tables from the uploaded data to perform different tests, and fit a Cox regression model from a number of predictor variables. In the Materials and Methods section, we depict the general architecture of the application and introduce the mathematical background of each of the implemented methods. The study concludes with examples of use showing the results obtained with public datasets. PMID:27532883

  1. Coronally Advanced Flap with Different Designs in the Treatment of Gingival Recession: A Comparative Controlled Randomized Clinical Trial.

    PubMed

    Zucchelli, Giovanni; Stefanini, M; Ganz, S; Mazzotti, Claudio; Mounssif, Ilham; Marzadori, Matteo

    2016-01-01

    The aim of this parallel double-blind randomized controlled clinical trial was to describe a modified approach using the coronally advanced flap (CAF) with triangular design and to compare its efficacy, in terms of root coverage and esthetics, with a trapezoidal type of CAF. A sample of 50 isolated Miller Class I and II gingival recessions with at least 1 mm of keratinized tissue apical to the defects were treated with CAF. Of these recessions, 25 were randomly treated with trapezoidal CAF (control group) while the other 25 (test group) were treated with a modified triangular CAF. The clinical and esthetic evaluations, made by the patient and an independent periodontist, were performed 3 months, 6 months, and 1 year after the surgery. No statistically significant difference was demonstrated between the two CAF groups in terms of recession reduction, complete root coverage, or 6-month and 1-year patient esthetic scores. Better 3-month patient esthetic evaluations and better periodontist root coverage, color match, and contiguity assessments were reported after triangular CAF. Trapezoidal CAF was associated with greater incidence of keloid formation. Single-type gingival recessions can be successfully covered with both types of CAF. The triangular CAF should be preferred for esthetically demanding patients. PMID:27100801

  2. Phase I clinical and pharmacokinetic study of titanocene dichloride in adults with advanced solid tumors.

    PubMed

    Korfel, A; Scheulen, M E; Schmoll, H J; Gründel, O; Harstrick, A; Knoche, M; Fels, L M; Skorzec, M; Bach, F; Baumgart, J; Sass, G; Seeber, S; Thiel, E; Berdel, W E

    1998-11-01

    This Phase I dose-escalation clinical trial of a lyophilized formulation of titanocene dichloride (MKT4) was conducted to determine the maximum tolerated dose, the dose-limiting toxicity (DLT), and pharmacokinetics of titanium (Ti) after a single i.v. infusion of MKT4. Forty patients with refractory solid malignancies were treated with a total of 78 courses. Using a modified Fibonacci scheme, 15 mg/m2 initial doses of titanocene dichloride were increased in cohorts of three patients up to level 11 (560 mg/m2) if DLT was not observed. The maximum tolerated dose was 315 mg/m2, and nephrotoxicity was DLT. Two minor responses (bladder carcinoma and non-small cell lung cancer) were observed. The pharmacokinetics of plasma Ti were assessed in 14 treatment courses by atomic absorption spectroscopy. The ratio for the area under the curve(0-infinity) in plasma and whole blood was 1.2. The following pharmacokinetic parameters were determined for plasma, as calculated in a two-compartment model: biological half-life t1/2beta in plasma was 22.8+/-11.2 h (xh +/- pseudo-SD), peak plasma concentration cmax approximately 30 microg/ml at a dose of 420 mg/m2, distribution volume Vss= 5.34+/-2.1 L (xa +/- SD), and a total clearance CItotal = 2.58+/-1.23 ml/min (xa +/- SD). There was a linear correlation between the area under the curve(0-infinity) of Ti in plasma and the titanocene dichloride dose administered with a correlation coefficient r2 of 0.8856. Plasma protein binding of Ti was in the 70-80% range. Between 3% and 16% of the total amount of Ti administered were renally excreted during the first 36 h. The recommended dose for Phase II evaluation is 240 mg/m2 given every 3 weeks with i.v. hydration to reduce renal toxicity. PMID:9829732

  3. Clinical development of an advanced intranasal delivery system of azelastine hydrochloride and fluticasone propionate.

    PubMed

    Derendorf, H; Meltzer, E O; Hermann, R; Canonica, G W

    2014-01-01

    There is no shortage of pharmacologic treatments available for the management of allergic rhinitis (AR), but none regularly provide full relief from all symptoms. MP29-02 (Dymista®) is a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP), benefiting from an enhanced formulation and improved device characteristics compared to marketed intranasal corticosteroid (INS) formulations. Results from large, randomized, double-blind, placebo-controlled, head-to-head trials versus first-line therapies, confirmed MP29-02 as the evidence-based drug-of-choice for AR treatment. MP29-02 was twice as effective as AZE or FP for nasal and ocular symptom relief in moderate to severe seasonal AR patients, with superiority documented regardless of season, and in more severe patients. More MP29-02-treated patients experienced clinically relevant responses (i.e., halving of nasal symptom burden and complete/near-to-complete relief) days faster than those on INS or intranasal antihistamine monotherapy. MP29-02's efficacy was sustained long-term versus FP (up to 52 weeks) in chronic rhinitis patients (perennial AR or nonallergic rhinitis), with 7 out of 10 patients first becoming symptom-free following 1 month's treatment with MP29-02, and days faster than with the INS. These results confirm MP29-02's superiority over the historical gold-standard therapy for AR (i.e., INS), and position it now as first-line treatment for moderate to severe AR patients, the majority of whom are uncontrolled on existing medications. PMID:24524103

  4. Clinical Use of the Utrecht Applicator for Combined Intracavitary/Interstitial Brachytherapy Treatment in Locally Advanced Cervical Cancer

    SciTech Connect

    Nomden, Christel N.; Leeuw, Astrid A.C. de; Moerland, Marinus A.; Roesink, Judith M.; Tersteeg, Robbert J.H.A.; Juergenliemk-Schulz, Ina Maria

    2012-03-15

    Purpose: The aims of this study were to investigate the benefit of the Utrecht interstitial CT/MR applicator for combined intracavitary/interstitial (IC/IS) approach, using magnetic resonance imaging-guided brachytherapy, over the intracavitary approach alone in patients with locally advanced cervical cancer and to analyze the clinical use of needles. Methods and Materials: This study includes the first 20 patients treated with the new applicator. Brachytherapy consisted of two pulsed dose rate applications, and the second application was performed with the IC/IS approach. The number of needles, chosen guiding holes through the ovoids, and insertion depths were based on the dose distribution and dosimetric shortcomings of the first application (IC alone). We investigated the dosimetric gain by comparing the clinical interstitial optimized plan (IC/IS{sub clinical}) with an additionally generated optimized plan without needle use (IC{sub study}). Furthermore, we studied the relation of the inserted needles and their source loading patterns with the high-risk clinical target volume (HR-CTV). Results: A total of 54 needles (range, 1-6 per application) were applied with an average depth of 25 mm. The chosen needle positions corresponded with the location of the HR-CTV extensions. The total and individual needle treatment times per application were on average 19% (range, 4-35%) and 7% (range, 2-14%) of the implant treatment time, respectively. The total (external-beam radiotherapy + brachytherapy) D90 HR-CTV for the IC{sub study} and the IC/IS{sub clinical} were on average 79.5 (SD 7.4) Gy{sub {alpha}/{beta}10} and 83.9 (SD 6.7) Gy{sub {alpha}/{beta}10}, respectively, with an average gain of 4.4 (SD 2.3) Gy{sub {alpha}/{beta}10} for the second application. Conclusions: Needle placement was feasible in all patients and resulted in a gain in dose and better coverage of HR-CTV. Defining the location of HR-CTV protrusions and analyzing the associated needles has given us

  5. Linking HIV-positive adolescents to care in 15 different clinics across the United States: Creating solutions to address structural barriers for linkage to care

    PubMed Central

    Philbin, Morgan M.; Tanner, Amanda E.; DuVal, Anna; Ellen, Jonathan; Kapogiannis, Bill; Fortenberry, J. Dennis

    2013-01-01

    Linkage to care is a critical corollary to expanded HIV testing, but many adolescents are not successfully linked to care, in part due to fragmented care systems. Through a collaboration of the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC) and the Adolescent Trials Network (ATN), a linkage to care outreach worker was provided to ATN clinics. Factors related to linkage were explored to better understand how to improve retention rates and health outcomes for HIV-positive adolescents. We conducted 124 interviews with staff at 15 Adolescent Trials Network clinics to better understand linkage to care processes, barriers, and facilitators. Content analysis was conducted focusing on structural barriers to care and potential solutions, specifically at the macro-, meso-, and micro-levels. Macro-level barriers included navigating health insurance policies, transportation to appointments, and ease of collecting and sharing client-level contact information between testing agencies, local health departments and clinics; meso-level barriers included lack of youth friendliness within clinic space and staff, and duplication of linkage services; micro-level barriers included adolescents’ readiness for care and adolescent developmental capacity. Staff initiated solutions included providing transportation for appointments and funding clinic visits and tests with a range of grants and clinic funds while waiting for insurance approval. However, such solutions were often ad hoc and partial, using micro-level solutions to address macro-level barriers. Comprehensive initiatives to improve linkage to care are needed to address barriers to HIV-care for adolescents, whose unique developmental needs make accessing care particularly challenging. Matching the level of structural solution to the level of structural barriers (i.e., macro-level with macro-level), such as creating policy to address needed youth healthcare entitlements versus covering

  6. Advances in preparation of modified activated carbon and its applications in the removal of chromium (VI) from aqueous solutions

    NASA Astrophysics Data System (ADS)

    Deng, Z. L.; Liang, M. N.; Li, H. H.; Zhu, Z. J.

    2016-08-01

    The wastewater in which Cr(VI) is not fully treated has drawn environment researchers’ attention increasingly, due to its environmental pollution and harms to human health. Thus a high efficiency of modified activated carbon (MAC) to remove Cr(VI) has become one of the hot topics among environmental material research. This paper introduces the modification methods from the physical structure features and chemical properties of the activated carbon (AC) surface. At the same time, it briefly analyses the chemical characteristics of Cr(VI) in aqueous solutions, and on the basis of the aforementioned introduces the modification methods of the surface chemical characteristics of AC, such as: oxidation modification, reduction modification, loaded metal modification, and microwave modification. Combining studies on removing Cr(VI) from aqueous solutions by MAC in recent years, this paper anticipates the new trends of preparing MAC and the points in absorption research, offering some suggestions for future studies.

  7. Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique - Skin Autofluorescence.

    PubMed

    Oleniuc, Mihaela; Secara, Irina; Onofriescu, Mihai; Hogas, Simona; Voroneanu, Luminita; Siriopol, Dimitrie; Covic, Adrian

    2011-10-01

    Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors

  8. Clinical and microbial impact of screening kidney allograft preservative solution for bacterial contamination with high-sensitivity methods.

    PubMed

    Bertrand, Dominique; Pallet, Nicolas; Sartorius, Albane; Zahar, Jean Ralph; Soussan, Rebecca Sberro; Lortholary, Olivier; Legendre, Christophe; Mamzer, Marie-France

    2013-08-01

    The clinical and bacteriological consequences of routinely performing highly sensitive bacterial screening of kidney transplant preservation solution (PS) are not known. To evaluate the clinical and microbiological impacts of this strategy, we retrospectively analyzed 200 consecutive kidney allograft recipients from March 2009 to February 2011 for whom PS samples were routinely screened. PS were inoculated into aerobic and anaerobic blood culture bottles, as well as blood agar plates. A rectal swab for extended-spectrum β-lactamase-producing Enterobacteriaceae (EBSL-PE) faecal carriage was also routinely obtained from each patient at admission and every 7 days until hospital discharge. In addition, a standard culture of drain fluid was collected on the day after kidney transplantation. Complete samples and cultures of PS were performed in 165 cases (82.5%), and 62 (37.6%) had positive blood culture results. The most frequent microbial agent isolated was coagulase-negative staphylococci (51.8%). Of these 62 positive samples, only seven (11.3%) were confirmed to contain the same organism by the standard culture method. Drain fluid and PS culture positivity with the same microorganism occurred in only two patients. Of the 62 patients with positive PS cultures, 26 (41.9%) received pre-emptive antibiotic therapy initiated within 48 h post-transplant. During the hospitalization period, patients with a positive PS culture, regardless of whether they received pre-emptive antibiotic therapy, did not exhibit any invasive infections (urinary, blood, peritoneal or wound) related to the microorganisms isolated in the PS. Patients with positive PS cultures who were treated with antibiotic therapy acquired significantly more colonizing ESBL-PE than patients who did not receive antibiotics (53.8% vs. 16.6%; P = 0.01); these patients also developed more clinical infections related to the ESBL-PE (23.1% vs. 5.2%; P < 0.01). The use of antibiotics for patients with positive PS

  9. Part I. 3DPTV: Advances and error analysis. Part II. Extension of Guderley's solution for converging shock waves

    NASA Astrophysics Data System (ADS)

    Ponchaut, Nicolas F.

    This work is divided into two unrelated parts. In the first part, a full three-dimensional particle tracking system was developed and tested. Three images, from three separate CCDs placed at the vertices of an equilateral triangle, permit the three-dimensional location of particles to be determined by triangulation. Particle locations measured at two different times can then be used to create a three-component, three-dimensional velocity field. Key developments are the ability to accurately process overlapping particle images, offset CCDs to significantly improve effective resolution, treatment of dim particle images, and a hybrid particle tracking technique ideal for three-dimensional flows when only two sets of images exist. An in-depth theoretical error analysis was performed, which gives the important sources of error and their effect on the overall system. This error analysis was verified through a series of experiments, and a vortex flow measurement was performed. In the second part, the problem of a cylindrically or spherically imploding and reflecting shock wave in a flow initially at rest was examined. Guderley's strong shock solution around the origin was improved by adding two more terms in the series expansion solution for both the incoming and the reflected shock waves. A series expansion was also constructed for the case where the shock is still very far from the origin. In addition, a program based on the characteristics method was written. Thanks to an appropriate change of variables, the shock motion could be computed from virtually infinity to very close to the reflection point. Comparisons were made between the series expansions, the characteristics program, and the results obtained using an Euler solver. These comparisons showed that the addition of two terms to the Guderley solution significantly increases the accuracy of the series expansion.

  10. The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma

    PubMed Central

    Wild, Aaron T.; Ye, Xiaobu; Ellsworth, Susannah G.; Smith, Jessica A.; Narang, Amol K.; Garg, Tanu; Campian, Jian; Laheru, Daniel A.; Zheng, Lei; Wolfgang, Christopher L.; Tran, Phuoc T.; Grossman, Stuart A.; Herman, Joseph M.

    2014-01-01

    Objectives Lymphopenia is a common consequence of chemoradiation therapy yet is seldom addressed clinically. This study was conducted to determine if patients with locally advanced pancreatic cancer (LAPC) treated with definitive chemoradiation develop significant lymphopenia and if this affects clinical outcomes. Methods A retrospective analysis of patients with LAPC treated with chemoradiation at a single institution from 1997 to 2011 was performed. Total lymphocyte counts (TLCs) were recorded at baseline and then monthly during and after chemoradiation. The correlation between treatment-induced lymphopenia, established prognostic factors, and overall survival was analyzed using univariate Cox regression analysis. Important factors identified by univariate analysis were selected as covariates to construct a multivariate proportional hazards model for survival. Results A total of 101 patients met eligibility criteria. TLCs were normal in 86% before chemoradiation. The mean reduction in TLC per patient was 50.6% (SD, 40.6%) 2 months after starting chemoradiation (P< 0.00001), and 46% had TLC< 500 cells/mm3. Patients with TLC < 500 cells/mm3 2 months after starting chemoradiation had inferior median survival (8.7 vs. 13.3mo, P= 0.03) and PFS (4.9 vs. 9.0mo, P = 0.15). Multivariate analysis revealed TLC< 500 cells/mm3 to be an independent predictor of inferior survival (HR= 2.879, P= 0.001) along with baseline serum albumin (HR= 3.584, P = 0.0002), BUN (HR = 1.060, P= 0.02), platelet count (HR= 1.004, P = 0.005), and radiation planning target volume (HR= 1.003, P= 0.0006). Conclusions Severe treatment-related lymphopenia occurs frequently after chemoradiation for LAPC and is an independent predictor of inferior survival. PMID:23648440

  11. Objective Structured Clinical Examination (OSCE)-based Assessment of the Advanced Trauma Life Support (ATLS) Course in Iran

    PubMed Central

    Abbasi, Hamid Reza; Amini, Mitra; Bolandparvaz, Shahram; Paydar, Shahram; Ali, Jameel; Sefidbakht, Sepideh

    2016-01-01

    Objective: To evaluate the effect of advance trauma life support (ATLS®) training on general surgery residents clinical reasoning skills using the national boards-style objective structured clinical examination (OSCE). Methods: This cross-sectional single-center study was conducted in Shiraz University of Medical Sciences including 51 surgery residents that participated in a mandatory national board style OSCE between May 2014 and May 2015. OSCE scores of two groups of general surgery residents including 23 ATLS® trained and 28 non-ATLS® trained were compared using Mann-Whitney U test. The exam was graded out of 20 points and the passing score was ≥14 including 40% trauma cases. Results: There were 8(15.7%) women and 43(84.3%) men among the participants with mean age of 31.12 ± 2.69 and 33.67 ± 4.39 years in women and men respectively. Overall 7 (87.5%) women and 34 (79.07%) men passed the OSCE. The trauma section OSCE score was significantly higher in the ATLS® trained participants when compared to non-ATLS®(7.79 ± 0.81vs.6.90 ± 1.00; p=0.001). In addition, the total score was also significantly higher in ATLS® trained residents (16.07 ± 1.41 vs. 14.60 ± 1.40; p=0.001). There was no association between gender and ATLS® score (p=0.245) or passing the OSCE (p=0.503). Conclusion: ATLS® training is associated with improved overall OSCE scores of general surgery residents completing the board examinations suggesting a positive transfer of ATLS learned skills to management of simulated surgical patients including trauma cases. PMID:27331063

  12. Evaluation of an Advanced-Practice Physical Therapist in a Specialty Shoulder Clinic: Diagnostic Agreement and Effect on Wait Times

    PubMed Central

    Robarts, Susan; Kennedy, Deborah; McKnight, Cheryl; MacLeod, Anne Marie; Holtby, Richard

    2013-01-01

    ABSTRACT Purpose: To examine the role of an advanced-practice physiotherapist (APP) with respect to (1) agreement with an orthopaedic surgeon on diagnosis and management of patients with shoulder problems; (2) wait times; and (3) satisfaction with care. Methods: This prospective study involved patients with shoulder complaints who were referred to a shoulder specialist in a tertiary care centre. Agreement was examined on seven major diagnostic categories, need for further examination and surgery, and type of surgical procedure. Wait times were compared between the APP- and surgeon-led clinics from referral date to date of initial consultation, date of final diagnostic test, and date of confirmed diagnosis and planned treatment. A modified and validated version of the Visit-Specific Satisfaction Instrument assessed satisfaction in seven domains. Kappa (κ) coefficients and bias- and prevalence-adjusted kappa (PABAK) values were calculated, and strength of agreement was categorized. Wait time and satisfaction data were examined using non-parametric statistics. Results: Agreement on major diagnostic categories varied from 0.68 (good) to 0.96 (excellent). Agreement with respect to indication for surgery was κ=0.75, p<0.001; 95% CI, 0.62–0.88 (good). Wait time for APP assessment was significantly shorter than wait time for surgeon consultation at all time points (p<0.001); the surgeon's wait time was significantly reduced over 3 years. High satisfaction was reported in all components of care received from both health care providers. Conclusions: Using experienced physiotherapists in an extended role reduces wait times without compromising patient clinical management and overall satisfaction. PMID:24381382

  13. The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy

    PubMed Central

    Faloppi, Luca; Del Prete, Michela; Gardini, Andrea Casadei; Santini, Daniele; Silvestris, Nicola; Bianconi, Maristella; Giampieri, Riccardo; Valgiusti, Martina; Brunetti, Oronzo; Bittoni, Alessandro; Andrikou, Kalliopi; Lai, Eleonora; Dessì, Alessandra; Cascinu, Stefano; Scartozzi, Mario

    2016-01-01

    LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37–0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54–1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33–0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27–0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy. PMID:27063994

  14. Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance

    PubMed Central

    Zanger, Ulrich M.; Klein, Kathrin

    2013-01-01

    Cytochrome P450 2B6 (CYP2B6) belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both between individuals and within individuals, owing to non-genetic factors, genetic polymorphisms, inducibility, and irreversible inhibition by many compounds. Drugs metabolized mainly by CYP2B6 include artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine, and methadone. CYP2B6 is one of the most polymorphic CYP genes in humans and variants have been shown to affect transcriptional regulation, splicing, mRNA and protein expression, and catalytic activity. Some variants appear to affect several functional levels simultaneously, thus, combined in haplotypes, leading to complex interactions between substrate-dependent and -independent mechanisms. The most common functionally deficient allele is CYP2B6*6 [Q172H, K262R], which occurs at frequencies of 15 to over 60% in different populations. The allele leads to lower expression in liver due to erroneous splicing. Recent investigations suggest that the amino acid changes contribute complex substrate-dependent effects at the activity level, although data from recombinant systems used by different researchers are not well in agreement with each other. Another important variant, CYP2B6*18 [I328T], occurs predominantly in Africans (4–12%) and does not express functional protein. A large number of uncharacterized variants are currently emerging from different ethnicities in the course of the 1000 Genomes Project. The CYP2B6 polymorphism is clinically relevant for HIV-infected patients treated with the reverse transcriptase inhibitor efavirenz, but it is increasingly being recognized for other drug substrates. This review summarizes recent advances on the functional and clinical significance of CYP2B6 and its genetic polymorphism, with particular emphasis on the comparison of kinetic data obtained with different substrates for variants expressed in different recombinant expression systems. PMID

  15. Genetic Counselors' and Genetic Counseling Students' Attitudes Around the Clinical Doctorate and Other Advanced Educational Options for Genetic Counselors: A Report from the Genetic Counseling Advanced Degree Task Force.

    PubMed

    Nagy, Rebecca; Peay, Holly; Hicks, Melissa; Kloos, Jacqueline; Westman, Rachel; Conway, Laura; Finucane, Brenda; Fitzpatrick, Jennifer; Gordon, Erynn; Ramos, Erica; Sekhon-Warren, Jaspreet; Silver, Josh; Walton, Carol; Reiser, Catherine

    2015-08-01

    Since its establishment over 40 years ago, the genetic counseling profession has grown to an estimated ~4,000 professionals in North America. While the profession has maintained the Master's degree as the entry-level and terminal degree, many other allied health professions have added advanced training pathways, such as the clinical doctorate (ClinD) either as an optional post-professional degree or required entry-level degree. Discussions regarding advanced degrees have also occurred within the genetic counseling profession, dating back to as early as the 1980s. In 2011, the Genetic Counseling Advanced Degree Task Force (GCADTF) was convened to explore the issue again, with the goal of "[engaging] all of the professional leadership organizations in the field of genetic counseling in a decision-making process about whether the profession should move to a Clinical Doctorate". As part of their work, the GCADTF surveyed practicing genetic counselors (n = 4,321) and genetic counseling students (n = 522) in the US and Canada regarding their interest in moving to the ClinD as the entry-level degree. This survey also included questions about other options for advanced training to generate data to inform future discussions around this very important professional issue. Herein, we describe the results of the survey, with particular attention to genetic counselor preferences for additional advanced education/certification opportunities and recommendations for future discussion. PMID:25352337

  16. Advanced Genetic Testing Comes to the Pain Clinic to Make a Diagnosis of Paroxysmal Extreme Pain Disorder

    PubMed Central

    Cannon, Ashley; Guthrie, Kimberly J.

    2016-01-01

    Objective. To describe the use of an advanced genetic testing technique, whole exome sequencing, to diagnose a patient and their family with a SCN9A channelopathy. Setting. Academic tertiary care center. Design. Case report. Case Report. A 61-year-old female with a history of acute facial pain, chronic pain, fibromyalgia, and constipation was found to have a gain of function SCN9A mutation by whole exome sequencing. This mutation resulted in an SCN9A channelopathy that is most consistent with a diagnosis of paroxysmal extreme pain disorder. In addition to the patient being diagnosed, four siblings have a clinical diagnosis of SCN9A channelopathy as they have consistent symptoms and a sister with a known mutation. For treatment, gabapentin was ineffective and carbamazepine was not tolerated. Nontraditional therapies improved symptoms and constipation resolved with pelvic floor retraining with biofeedback. Conclusion. Patients with a personal and family history of chronic pain may benefit from a referral to Medical Genetics. Pelvic floor retraining with biofeedback should be considered for patients with a SCN9A channelopathy and constipation. PMID:27525141

  17. Clinical roundtable monograph: Recent advances in the treatment of mantle cell lymphoma: a post-ASH 2009 discussion.

    PubMed

    Czuczman, Myron S; Leonard, John P; Williams, Michael E

    2010-04-01

    Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma characterized by CD5 expression and a t(11;14) cytogenetic translocation that results in overexpression of the cyclin D1 gene. Currently, there is no standard of care for the treatment of MCL, and patient prognosis is poor. Traditional treatments for MCL rely on conventional chemotherapy agents, including cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The addition of the immunotherapeutic agent rituximab to this regimen (CHOP-R) has helped to improve patient response to treatment. These treatments often provide good initial responses that are difficult to sustain. Therefore, a number of newer agents and combinations have been investigated to produce more durable benefit. Several of these advances were reported at the 51st American Society of Hematology (ASH) Annual Meeting and Exposition, held December 5-8, 2009 in New Orleans, Louisiana. In this clinical roundtable monograph, new strategies in the treatment of MCL are discussed. Some of the drug classes examined here are proteasome inhibitors, inhibitors of the protein mammalian target of rapamycin (mTOR), the unique alkylating agent bendamustine, and immunomodulatory agents. PMID:20539272

  18. Thrombotic microangiopathy: expanding genetic, clinical and therapeutic spectra and the need for worldwide implementation of recent advances.

    PubMed

    Sanchez-Niño, Maria D; Ortiz, Alberto

    2015-12-01

    In this issue of CKJ, four reports address different aspects of a rare condition, thrombotic microangiopathy, including atypical haemolytic uraemic syndrome. For rare diseases, a single case report may provide hypothesis-generating information that may lead to concept-changing research with the potential to influence patient care. The present reports and small series illustrate the following aspects of thrombotic microangiopathy: (i) the role of whole-exome sequencing and of repeating the family history assessment over time in reducing the number of chronic kidney disease patients with non-specific diagnosis (e.g. focal segmental glomerulosclerosis without any further indication as to aetiology or hypertension-attributed kidney disease) and the need for further studies on the potential for type IV collagen mutations to be associated with thrombotic microangiopathy, i.e. the potential for an expanding genetic spectrum; (ii) the expanding clinical spectrum from an acute catastrophic disease to a chronic, mild, stable condition with unknown long-term consequences and uncharted therapeutic approaches; (iii) the expanding therapeutic spectrum, with the successful use of eculizumab to treat thrombotic microangiopathy in the context of overlap autoimmune disease and (iv) the huge worldwide inequalities in the implementation of these and other advances. International collaboration is needed to address these issues and should encompass the wider use of already available registries for this rare disease and the worldwide implementation of current effective, yet expensive, therapies. PMID:26613024

  19. Thrombotic microangiopathy: expanding genetic, clinical and therapeutic spectra and the need for worldwide implementation of recent advances

    PubMed Central

    Sanchez-Niño, Maria D.; Ortiz, Alberto

    2015-01-01

    In this issue of CKJ, four reports address different aspects of a rare condition, thrombotic microangiopathy, including atypical haemolytic uraemic syndrome. For rare diseases, a single case report may provide hypothesis-generating information that may lead to concept-changing research with the potential to influence patient care. The present reports and small series illustrate the following aspects of thrombotic microangiopathy: (i) the role of whole-exome sequencing and of repeating the family history assessment over time in reducing the number of chronic kidney disease patients with non-specific diagnosis (e.g. focal segmental glomerulosclerosis without any further indication as to aetiology or hypertension-attributed kidney disease) and the need for further studies on the potential for type IV collagen mutations to be associated with thrombotic microangiopathy, i.e. the potential for an expanding genetic spectrum; (ii) the expanding clinical spectrum from an acute catastrophic disease to a chronic, mild, stable condition with unknown long-term consequences and uncharted therapeutic approaches; (iii) the expanding therapeutic spectrum, with the successful use of eculizumab to treat thrombotic microangiopathy in the context of overlap autoimmune disease and (iv) the huge worldwide inequalities in the implementation of these and other advances. International collaboration is needed to address these issues and should encompass the wider use of already available registries for this rare disease and the worldwide implementation of current effective, yet expensive, therapies. PMID:26613024

  20. Use of luteinising hormone-releasing hormone agonist (leuprorelin) in advanced post-menopausal breast cancer: clinical and endocrine effects.

    PubMed Central

    Crighton, I. L.; Dowsett, M.; Lal, A.; Man, A.; Smith, I. E.

    1989-01-01

    Fifteen post-menopausal patients with advanced breast cancer were treated with the LH-RH agonist leuprorelin (D-leu6-des-gly10-Gn-RH-ethylamide) given in a dosage of 7.5 mg as a monthly subcutaneous depot injection, to assess the clinical activity and endocrine response to treatment. None of the 15 patients showed an objective response to treatment, although four patients had stable disease for at least 6 months. No toxicity was demonstrated. Endocrine effects after 4 weeks' treatment were as follows: mean levels of serum gonadotrophins fell to 10% of their pretreatment values; there were no significant changes in the levels of prolactin on treatment; there was a significant decrease in the levels of serum testosterone in 12 out of 14 patients; there were no significant changes in the levels of oestradiol, androstenedione and oestrone. The lowering of serum testosterone suggests that androgens in post-menopausal women may be partly produced by the ovaries, stimulated by LH and FSH. This fall in testosterone may explain why some post-menopausal breast cancer patients in other studies have been reported to respond to treatment with LH-RH agonists, as it would decrease the substrate for the peripheral synthesis of oestrogens. PMID:2508735

  1. [Clinical results of combination chemotherapy with cisplatin, vinblastine and bleomycin (pvb) for advanced testicular cancer: evaluation of risk criteria].

    PubMed

    Mikami, K; Nakagawa, S; Sugimoto, K; Nomoto, T; Urano, S; Watanabe, H; Iwamoto, N; Yamazaki, S; Hiratake, Y; Maegawa, M

    1997-08-01

    Between 1982 and 1991, 24 patients with advanced testicular germ cell tumor were treated by combination chemotherapy with cisplatin, vinblastine and bleomycin (PVB). Based on short-term efficacy of the PVB regimen and long-term prognosis in our patients, we evaluated 4 risk criteria proposed by Indiana University, National Cancer Institute (NCI), Memorial Sloan-Kettering Cancer Center (MSKCC) and European Organization for Research and Treatment of Cancer (EORTC). Clinical staging were IIA in 8 patients, IIB in 8, IIIA in 1, IIIB in 5 and IIIC in 2. Metastases included retroperitoneal lymph node in 20 cases (> 5 cm in 10), lung in 6, bone and liver in each 1. Complete response (CR) was obtained in 12 (50%) patients and partial response (PR) in 9 (38%). According to the stage and metastatic site, CR was achieved in 75%, 38% and 38%of the stage IIA, IIB and III tumors, respectively, and in 60% and 50% of retroperitoneal and pulmonary metastases, respectively. However, neither CR nor PR was recognized for live and bone metastases. Prognosis was assessed with a mean followup period of 88.5 months. Although all 12 patients with CR were alive, 4 of the 9 with PR and all patients on whom the drug was ineffective died of cancer. Accuracy in predicting prognosis was 82%, 75%, 74%, and 63% using the MSKCC, Indiana, NCI and EORTC risk criteria, respectively.

  2. Retrospective Analysis of Implant Overdenture Treatment in the Advanced Prosthodontic Clinic at the University of Illinois at Chicago.

    PubMed

    Marinis, Aristotelis; Afshari, Fatemeh S; Yuan, Judy Chia-Chun; Lee, Damian J; Syros, George; Knoernschild, Kent L; Campbell, Stephen D; Sukotjo, Cortino

    2016-02-01

    The aim of the present retrospective study was to evaluate the clinical outcomes of implant-supported overdenture treatment provided by prosthodontic specialty residents. Twenty-three patients with 25 implant-supported overdentures (IODs) participated in the study. Seventy-four implants were placed by periodontic, prosthodontics, or oral and maxillofacial surgery students. All prostheses were fabricated in the advanced prosthodontics clinic at University of Illinois at Chicago. The condition of the peri-implant soft tissue, implants, and prostheses were evaluated. Complications and any maintenance were documented. Patients completed an oral health impact profile-14 and semantic differential scale questionnaires. Statistical analyses were performed using SPSS statistical software. Twenty mandibular and 5 maxillary IODs were evaluated. Ninety-seven percent of the attachments were locators (Zest Anchors) and 3% ball attachments. None of the implants had lost osseointegration, but 14 implants (19%) had developed marginal bone loss in one-third of the implant length or more. Fourteen (19%) implants had developed dehiscence, which ranged from 1 to 4 mm. A variation in the width of the keratinized tissue, gingival, plaque, and calculus index was observed. There was a statistically significant relationship between the presence of plaque and the bleeding on probing on the buccal aspect of implants (P = .012). The incidence of dehiscence was significantly higher on the midfacial when the keratinized tissue was less than 2 mm (P < .0001). The majority of the complications were prosthetic in nature, such as broken denture teeth (74%) and worn or loose matrices (35%). Debris was observed in 19% of the locator abutments, and 36% of the overdentures were not stable in application of anterior force. Patients were compliant with oral hygiene protocols and their chewing ability was high (mean = 8.0). The overall experience was pleasant (mean = 7.5); the treatment provided good

  3. UV-Visible Spectrooelectrochemistry of the Reduction Products of Anthraquinone in Dimethylformamide Solutions: An Advanced Undergraduate Experiment

    NASA Astrophysics Data System (ADS)

    Babaei, Ali; Connor, Paul A.; McQuillan, A. James; Umapathy, Siva

    1997-10-01

    The redox properties of anthraquinone (AQ) may be used to model the behaviour of quinones in biological systems. AQ undergoes two successive one-electron reductions in aprotic solvents to form a stable radical anion (AQ.-) and a stable dianion (AQ2-) but this behaviour is altered in the presence of a proton donor. This advanced undergraduate experiment shows how cyclic voltammetry, digital simulations of cyclic voltammograms, and UV-visible spectroelectrochemistry may be used to examine the reduction behaviour of AQ in dimethylformamide (DMF), both in the absence and presence of benzoic acid. The cyclic voltammetry of AQ in DMF shows two reversible one-electron reductions. This allows the UV-visible spectra of AQ.- and of AQ2- to be determined using an optically transparent thin layer electrode (OTTLE) cell. AQH- may also be detected in the spectra if there are proton impurities. When benzoic acid is added to the DMF, the cyclic voltammograms are markedly altered with almost all the reduction occurring near the AQ/AQ.- potential and the corresponding oxidation at rather more positive potentials. The UV-visible spectroelectrochemistry shows AQH2 as the stable reduction product under these conditions while digital simulations of the cyclic voltammograms support a mechanism involving protonation of AQ.- followed by AQH. disproportionation.

  4. The Effect of Preoperative Oral Carbohydrate or Oral Rehydration Solution on Postoperative Quality of Recovery: A Randomized, Controlled Clinical Trial

    PubMed Central

    Asakura, Ayako; Mihara, Takahiro; Goto, Takahisa

    2015-01-01

    Background Numerous studies have demonstrated the beneficial effects of preoperative administration of oral carbohydrate (CHO) or oral rehydration solution (ORS). However, the effects of preoperative CHO or ORS on postoperative quality of recovery after anesthesia remain unclear. Consequently, the purpose of the current study was to evaluate the effect of preoperative CHO or ORS on patient recovery, using the Quality of Recovery 40 questionnaire (QoR-40). Methods This prospective, randomized, controlled clinical trial included American Society of Anesthesiologists (ASA) physical status 1 and 2 adult patients, who were scheduled to undergo a surgical procedure of body surface. Subjects were randomized to one of the three groups: 1) preoperative CHO group, 2) preoperative ORS group, and 3) control group. The primary outcome was the global QoR-40 administered 24 h after surgery. Intraoperative use of vasopressor, intraoperative body temperature changes, and postoperative nausea and vomiting (PONV) were also evaluated. Results We studied 134 subjects. The median [interquartile range (IQR)] global QoR-40 scores 24 h after the surgery were 187 [177–197], 186 [171–200], and 184 [171–198] for the CHO, ORS, and control groups, respectively (p = 0.916). No significant differences existed between the groups regarding intraoperative vasopressor use during the surgery (p = 0.475). Conclusions Results of the current study indicated that the preoperative administration of either CHO or ORS did not improve the quality of recovery in patients undergoing minimally invasive body surface surgery. Trial Registration www.umin.ac.jp UMIN000009388 https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000011029&language=E PMID:26317629

  5. Effectiveness and safety of first-generation protease inhibitors in clinical practice: Hepatitis C virus patients with advanced fibrosis

    PubMed Central

    Salmerón, Javier; Vinaixa, Carmen; Berenguer, Rubén; Pascasio, Juan Manuel; Sánchez Ruano, Juan José; Serra, Miguel Ángel; Gila, Ana; Diago, Moisés; Romero-Gómez, Manuel; Navarro, José María; Testillano, Milagros; Fernández, Conrado; Espinosa, Dolores; Carmona, Isabel; Pons, José Antonio; Jorquera, Francisco; Rodriguez, Francisco Javier; Pérez, Ramón; Montero, José Luis; Granados, Rafael; Fernández, Miguel; Martín, Ana Belén; Muñoz de Rueda, Paloma; Quiles, Rosa

    2015-01-01

    AIM: To evaluates the effectiveness and safety of the first generation, NS3/4A protease inhibitors (PIs) in clinical practice against chronic C virus, especially in patients with advanced fibrosis. METHODS: Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1, treatment-naïve (TN) or treatment-experienced (TE), who underwent triple therapy with the first generation NS3/4A protease inhibitors, boceprevir (BOC) and telaprevir (TVR), in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up. RESULTS: One thousand and fifty seven patients were included, 405 (38%) were treated with BOC and 652 (62%) with TVR. Of this total, 30% (n = 319) were TN and the remaining were TE: 28% (n = 298) relapsers, 12% (n = 123) partial responders (PR), 25% (n = 260) null-responders (NR) and for 5% (n = 57) with prior response unknown. The rate of sustained virologic response (SVR) by intention-to-treatment (ITT) was greater in those treated with TVR (65%) than in those treated with BOC (52%) (P < 0.0001), whereas by modified intention-to-treatment (mITT) no were found significant differences. By degree of fibrosis, 56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients, both TN and TE. In the analysis by groups, the TN patients treated with TVR by ITT showed a higher SVR (P = 0.005). However, by mITT there were no significant differences between BOC and TVR. In the multivariate analysis by mITT, the significant SVR factors were relapsers, IL28B CC and non-F4; the type of treatment (BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients, treated with BOC (46%) or with TVR (45%). 28% of the patients interrupted the treatment

  6. The electronic patient records solution.

    PubMed

    Braunstein, M L

    1993-07-01

    Automation has been the solution for many business problems, yet few home care agencies have extended computerization beyond the traditional billing and financial functions to the clinical nursing process. Excessive nursing time spent in documentation is arguably the single biggest business problem facing the industry. Why haven't computers been accepted by home care clinicians? How could new advances in technology create virtually paperless home care nursing?

  7. Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced heart failure.

    PubMed

    Greenberg, B; Butler, J; Felker, G M; Ponikowski, P; Voors, A A; Pogoda, J M; Provost, R; Guerrero, J; Hajjar, R J; Zsebo, K M

    2016-03-01

    Adeno-associated virus serotype 1 (AAV1) has many advantages as a gene therapy vector, but the presence of pre-existing neutralizing antibodies (NAbs) is an important limitation. This study was designed to determine: (1) characteristics of AAV NAbs in human subjects, (2) prevalence of AAV1 NAbs in heart failure patients and (3) utility of aggressive immunosuppressive therapy in reducing NAb seroconversion in an animal model. NAb titers were assessed in a cohort of heart failure patients and in patients screened for a clinical trial of gene therapy with AAV1 carrying the sarcoplasmic reticulum calcium ATPase gene (AAV1/SERCA2a). AAV1 NAbs were found in 59.5% of 1552 heart failure patients. NAb prevalence increased with age (P=0.001) and varied geographically. The pattern of NAb titers suggested that exposure is against AAV2, with AAV1 NAb seropositivity due to crossreactivity. The effects of immunosuppression on NAb formation were tested in mini-pigs treated with immunosuppressant therapy before, during and after a single AAV1/SERCA2a infusion. Aggressive immunosuppression did not prevent formation of AAV1 NAbs. We conclude that immunosuppression is unlikely to be a viable solution for repeat AAV1 dosing. Strategies to reduce NAbs in heart failure patients are needed to increase eligibility for gene transfer using AAV vectors.

  8. Novel frequency domain techniques and advances in Finite Difference Time domain (FDTD) method for efficient solution of multiscale electromagnetic problems

    NASA Astrophysics Data System (ADS)

    Panayappan, Kadappan

    With the advent of sub-micron technologies and increasing awareness of Electromagnetic Interference and Compatibility (EMI/EMC) issues, designers are often interested in full- wave solutions of complete systems, taking to account a variety of environments in which the system operates. However, attempts to do this substantially increase the complexities involved in computing full-wave solutions, especially when the problems involve multi- scale geometries with very fine features. For such problems, even the well-established numerical methods, such as the time domain technique FDTD and the frequency domain methods FEM and MoM, are often challenged to the limits of their capabilities. In an attempt to address such challenges, three novel techniques have been introduced in this work, namely Dipole Moment (DM) Approach, Recursive Update in Frequency Domain (RUFD) and New Finite Difference Time Domain ( vFDTD). Furthermore, the efficacy of the above techniques has been illustrated, via several examples, and the results obtained by proposed techniques have been compared with other existing numerical methods for the purpose of validation. The DM method is a new physics-based approach for formulating MoM problems, which is based on the use of dipole moments (DMs), as opposed to the conventional Green's functions. The absence of the Green's functions, as well as those of the vector and scalar potentials, helps to eliminate two of the key sources of difficulties in the conventional MoM formulation, namely the singularity and low-frequency problems. Specifically, we show that there are no singularities that we need to be concerned with in the DM formulation; hence, this obviates the need for special techniques for integrating these singularities. Yet another salutary feature of the DM approach is its ability to handle thin and lossy structures, or whether they are metallic, dielectric-type, or even combinations thereof. We have found that the DM formulation can handle these

  9. ILSI Health and Environmental Sciences Institute (HESI), global leader in advancing translational science to create science-based solutions for a sustainable, healthier world.

    PubMed

    Takei, Ayako

    2015-01-01

    The Health and Environmental Sciences Institute (HESI) is a non-profit scientific research organization based in Washington, D.C., U.S.A. HESI was established in 1989 as a global branch of the International Life Sciences Institute (ILSI) to provide an international forum to advance the understanding of scientific issues related to human health, toxicology, risk assessment and the environment. For the last 25 years, HESI has been the global leader to advance application of new science and technologies in the areas of human health, toxicology, risk assessment and environment. The core principle of "tripartite approach" and the multi-sector operational model have successfully supported HESI's scientific programs to create science-based solutions for a sustainable and healthier world. HESI's achievements include the dataset to guide the selection of appropriate supporting assays for carcinogenicity testing, a new testing framework for agricultural chemicals with enhanced efficacy, predictivity, and reduced animal usage, novel biomarkers of nephrotoxicity which provide data on the location of timing of drug effects in the kidney allowing for enhanced drug development, etc.

  10. Advanced microscopy solutions for monitoring the kinetics and dynamics of drug-DNA targeting in living cells.

    PubMed

    Errington, R J; Ameer-Beg, S M; Vojnovic, B; Patterson, L H; Zloh, M; Smith, P J

    2005-01-01

    Many anticancer drugs require interaction with DNA or chromatin components of tumor cells to achieve therapeutic activity. Quantification and exploration of drug targeting dynamics can be highly informative in the rational development of new therapies and in the drug discovery pipeline. The problems faced include the potential infrequency and transient nature of critical events, the influence of micropharmacokinetics on the drug-target equilibria, the dependence on preserving cell function to demonstrate dynamic processes in situ, the need to map events in functional cells and the confounding effects of cell-to-cell heterogeneity. We demonstrate technological solutions in which we have integrated two-photon laser scanning microscopy (TPLSM) to track drug delivery in subcellular compartments, with the mapping of sites of critical molecular interactions. We address key design concepts for the development of modular tools used to uncover the complexity of drug targeting in single cells. First, we describe the combination of two-photon excitation with fluorescence lifetime imaging microscopy (FLIM) to map the nuclear docking of the anticancer drug topotecan (TPT) at a subset of DNA sites in nuclear structures of live breast tumor cells. Secondly, we demonstrate how we incorporate the smart design of a two-photon 'dark' DNA binding probe, such as DRAQ5, as a well-defined quenching probe to uncover sites of drug interaction. Finally, we discuss the future perspectives on introducing these modular kinetic assays in the high-content screening arena and the interlinking of the consequences of drug-target interactions with cellular stress responses.

  11. [The role of bacterial contamination of milking utensils and disinfecting solutions as a possible cause of clinical mastitis in dairy cows].

    PubMed

    Hässig, M; Sigrist, S M; Corti, S; Giezendanner, N; Stephan, R

    2011-06-01

    Various instruments and utensils used during milking as well as teat dip solutions were examined for contamination with coagulase-negative staphylococci (CNS). The goal of this study was to investigate the relationship between contaminated fomites and udder infection in dairy cows. A total of 344 cows from ten dairy farms with the highest rate of clinical mastitis among the farms serviced by the Ambulatory Clinic of the University of Zurich were included in the study. Each farm was visited five times. All lactating cows, with the exception of those undergoing antibiotic treatment, were examined immediately before milking using the California Mastitis Test (CMT). A milk sample was collected from positive quarters. Items used to clean the udder, which included wood wool, paper towels and disinfecting towels as well as the milker's hands and the teat dip cup were swabbed for bacteriological examination. Water samples, samples of teat dip and cleaning solutions were also collected and cultured. Our results demonstrate that cleaning and disinfecting solutions have the potential to transmit udder pathogens and cause clinical mastitis. The most common CNS isolated from quarter samples were S. saprophyticus, S. sciuri and S. chromogenes, and the most common CNS isolated from utensils, cleaning and disinfecting solutions were S. fleuretii, S. vitulus, S. equorum, S. sciuri, S. haemolyticus, S. succinus and S. saprophyticus. PMID:21638262

  12. [Clinical pilot study to evaluate the efficacy of a preservative-free hypertonic ophthalmic solution for patients with symptomatic corneal edema].

    PubMed

    Rouland, J-F

    2015-11-01

    This exploratory clinical trial aims to assess the effect on visual acuity and central corneal thickness of an unpreserved hypertonic ophthalmic solution containing sodium chloride (5%) and sodium hyaluronate, in patients with chronic corneal edema caused by endothelial disease reducing their visual acuity. Twenty patients were enrolled and treated with the hypertonic solution (1 to 2 drops per eye, 4 times a day over 28 days). Progression of visual acuity (ETDRS score) and corneal thickness (ultrasonic pachymetry) was measured from baseline (without treatment) through the treatment period (Day 7 and Day 28). The analyses were performed on 18 patients (Full Analysis Set [FAS] population). The causes of corneal edema were Fuchs endothelial dystrophy in 10 cases and post-cataract surgery endothelial decompensation in 8 patients. The mean visual acuity values for the FAS population compared between baseline (Day-7) and one week of treatment (Day+7) show a significant 5-point VA improvement (P<0.001 paired Wilcoxon test). For corneal thickness, there was also a significant decrease (P=0.033 paired Wilcoxon test). Functional improvement was observed at 28 days of instillation. No adverse events were recorded during the clinical study. In conclusion, the unpreserved hyperosmolar solution containing sodium chloride and sodium hyaluronate significantly improved ETDRS visual acuity after one week of use. In this clinical trial, the solution also showed excellent tolerability results.

  13. Advanced-practice pharmacists: practice characteristics and reimbursement of pharmacists certified for collaborative clinical practice in New Mexico and North Carolina.

    PubMed

    Murawski, Matthew; Villa, Kristin R; Dole, Ernest J; Ives, Timothy J; Tinker, Dale; Colucci, Vincent J; Perdiew, Jeffrey

    2011-12-15

    PURPOSE The results of a survey assessing the practice settings, clinical activities, and reimbursement experiences of pharmacists with advanced-practice designations are reported. METHODS A questionnaire was sent to all certified Pharmacist Clinicians in New Mexico and all Clinical Pharmacist Practitioners in North Carolina (a total of 189 pharmacists at the time of the survey in late 2008) to elicit information on practice settings, billing and reimbursement methods, collaborative drug therapy management (CDTM) protocols, and other issues. RESULTS Of the 189 targeted pharmacists, 64 (34%) responded to the survey. On average, the reported interval from pharmacist licensure to certification as an advanced practitioner was 11 years. The majority of survey participants were practicing in community or institutional settings, most often hospital clinics or physician offices. About two thirds of the respondents indicated that their employer handled the billing of their services using standard evaluation and management codes, with estimated total monthly billings averaging $6500. At the time of the survey, about 80% of the respondents were engaged in a CDTM protocol. The survey results suggest that pharmacists with advanced-practice designations are perceived favorably by patients and physicians and their services are in high demand, but more than one third of respondents indicated a need to justify their advanced-practice positions to administrators. CONCLUSION Pharmacists with advanced-practice designations are providing clinical services in various settings under collaborative practice arrangements that include prescribing privileges. Despite growing patient and physician acceptance, reimbursement challenges continue to be a barrier to wider use of CDTM programs.

  14. Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

    PubMed

    Noronha, Vanita; Prabhash, Kumar; Joshi, Amit; Patil, Vijay Maruti; Talole, Sanjay; Nakti, Dipti; Sahu, Arvind; Shah, Srushti; Ghosh-Laskar, Sarbani; Patil, Prachi S; Mehta, Shaesta A; Jambhekar, Nirmala; Mahajan, Abhishek; Purandare, Nilendu

    2016-01-01

    There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.]. PMID:27053347

  15. Advances in Tryptophan Hydroxylase-2 Gene Expression Regulation: New Insights into Serotonin-Stress Interaction and Clinical Implications

    PubMed Central

    Chen, Guo-Lin; Miller, Gregory M.

    2013-01-01

    Serotonin (5-HT) modulates the stress response by interacting with the hormonal hypothalamic-pituitary-adrenal (HPA) axis and neuronal sympathetic nervous system (SNS). Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT biosynthesis, and the recent identification of a second, neuron-specific TPH isoform (TPH2) opened up a new area of research. While TPH2 genetic variance has been linked to numerous behavioral traits and disorders, findings on TPH2 gene expression have not only reinforced, but also provided new insights into, the long-recognized but not yet fully understood 5-HT-stress interaction. In this review, we summarize advances in TPH2 expression regulation and its relevance to the stress response and clinical implications. Particularly, based on findings on rhesus monkey TPH2 genetics and other relevant literature, we propose that: 1) upon activation of adrenal cortisol secretion, the cortisol surge induces TPH2 expression and de novo 5-HT synthesis; 2) the induced 5-HT in turn inhibits cortisol secretion by modulating the adrenal sensitivity to ACTH via the suprachiasmatic nuclei (SCN)-SNS-adrenal system, such that it contributes to the feedback inhibition of cortisol production; 3) basal TPH2 expression or 5-HT synthesis, as well as early-life experience, influence basal cortisol primarily via the hormonal HPA axis; and 4) 5′- and 3′-regulatory polymorphisms of TPH2 may differentially influence the stress response, presumably due to their differential roles in gene expression regulation. Our increasing knowledge of TPH2 expression regulation not only helps us better understand the 5-HT-stress interaction and the pathophysiology of neuropsychiatric disorders, but also provides new strategies for the treatment of stress-associated diseases. PMID:22241550

  16. Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

    PubMed

    Noronha, Vanita; Prabhash, Kumar; Joshi, Amit; Patil, Vijay Maruti; Talole, Sanjay; Nakti, Dipti; Sahu, Arvind; Shah, Srushti; Ghosh-Laskar, Sarbani; Patil, Prachi S; Mehta, Shaesta A; Jambhekar, Nirmala; Mahajan, Abhishek; Purandare, Nilendu

    2016-01-01

    There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.].

  17. Effect of cleansing the birth canal with antiseptic solution on maternal and newborn morbidity and mortality in Malawi: clinical trial.

    PubMed Central

    Taha, T. E.; Biggar, R. J.; Broadhead, R. L.; Mtimavalye, L. A.; Justesen, A. B.; Liomba, G. N.; Chiphangwi, J. D.; Miotti, P. G.

    1997-01-01

    OBJECTIVE: To determine if cleansing the birth canal with an antiseptic at delivery reduces infections in mothers and babies postnatally. DESIGN: Clinical trial; two months of no intervention were followed by three months of intervention and a final month of no intervention. SETTING: Queen Elizabeth Central Hospital (tertiary care urban hospital), Blantyre, Malawi. SUBJECTS: A total of 6965 women giving birth in a six month period and their 7160 babies. INTERVENTION: Manual wipe of the maternal birth canal with a 0.25% chlorhexidine solution at every vaginal examination before delivery. Babies born during the intervention were also wiped with chlorhexidine. MAIN OUTCOME MEASURES: Effects of the intervention on neonatal and maternal morbidity and mortality. RESULTS: 3635 women giving birth to 3743 babies were enrolled in the intervention phase and 3330 women giving birth to 3417 babies were enrolled in the non-intervention phase. There were no adverse reactions related to the intervention among the mothers or their children. Among infants born in the intervention phase, overall neonatal admissions were reduced (634/3743 (16.9%) v 661/3417 (19.3%), P < 0.01), as were admissions for neonatal sepsis (7.8 v 17.9 per 1000 live births, P < 0.0002), overall neonatal mortality (28.6 v 36.9 per 1000 live births, P < 0.06), and mortality due to infectious causes (2.4 v 7.3 per 1000 live births, P < 0.005). Among mothers receiving the intervention, admissions related to delivery were reduced (29.4 v 40.2 per 1000 deliveries, P < 0.02), as were admissions due to postpartum infections (1.7 v 5.1 per 1000 deliveries, P = 0.02) and duration of hospitalisation (Wilcoxon P = 0.008). CONCLUSIONS: Cleansing the birth canal with chlorhexidine reduced early neonatal and maternal postpartum infectious problems. The safety, simplicity, and low cost of the procedure suggest that it should be considered as standard care to lower infant and maternal morbidity and mortality. PMID:9253269

  18. A generalized analytic solution to the win ratio to analyze a composite endpoint considering the clinical importance order among components.

    PubMed

    Dong, Gaohong; Li, Di; Ballerstedt, Steffen; Vandemeulebroecke, Marc

    2016-09-01

    A composite endpoint consists of multiple endpoints combined in one outcome. It is frequently used as the primary endpoint in randomized clinical trials. There are two main disadvantages associated with the use of composite endpoints: a) in conventional analyses, all components are treated equally important; and b) in time-to-event analyses, the first event considered may not be the most important component. Recently Pocock et al. (2012) introduced the win ratio method to address these disadvantages. This method has two alternative approaches: the matched pair approach and the unmatched pair approach. In the unmatched pair approach, the confidence interval is constructed based on bootstrap resampling, and the hypothesis testing is based on the non-parametric method by Finkelstein and Schoenfeld (1999). Luo et al. (2015) developed a close-form variance estimator of the win ratio for the unmatched pair approach, based on a composite endpoint with two components and a specific algorithm determining winners, losers and ties. We extend the unmatched pair approach to provide a generalized analytical solution to both hypothesis testing and confidence interval construction for the win ratio, based on its logarithmic asymptotic distribution. This asymptotic distribution is derived via U-statistics following Wei and Johnson (1985). We perform simulations assessing the confidence intervals constructed based on our approach versus those per the bootstrap resampling and per Luo et al. We have also applied our approach to a liver transplant Phase III study. This application and the simulation studies show that the win ratio can be a better statistical measure than the odds ratio when the importance order among components matters; and the method per our approach and that by Luo et al., although derived based on large sample theory, are not limited to a large sample, but are also good for relatively small sample sizes. Different from Pocock et al. and Luo et al., our approach is a

  19. A generalized analytic solution to the win ratio to analyze a composite endpoint considering the clinical importance order among components.

    PubMed

    Dong, Gaohong; Li, Di; Ballerstedt, Steffen; Vandemeulebroecke, Marc

    2016-09-01

    A composite endpoint consists of multiple endpoints combined in one outcome. It is frequently used as the primary endpoint in randomized clinical trials. There are two main disadvantages associated with the use of composite endpoints: a) in conventional analyses, all components are treated equally important; and b) in time-to-event analyses, the first event considered may not be the most important component. Recently Pocock et al. (2012) introduced the win ratio method to address these disadvantages. This method has two alternative approaches: the matched pair approach and the unmatched pair approach. In the unmatched pair approach, the confidence interval is constructed based on bootstrap resampling, and the hypothesis testing is based on the non-parametric method by Finkelstein and Schoenfeld (1999). Luo et al. (2015) developed a close-form variance estimator of the win ratio for the unmatched pair approach, based on a composite endpoint with two components and a specific algorithm determining winners, losers and ties. We extend the unmatched pair approach to provide a generalized analytical solution to both hypothesis testing and confidence interval construction for the win ratio, based on its logarithmic asymptotic distribution. This asymptotic distribution is derived via U-statistics following Wei and Johnson (1985). We perform simulations assessing the confidence intervals constructed based on our approach versus those per the bootstrap resampling and per Luo et al. We have also applied our approach to a liver transplant Phase III study. This application and the simulation studies show that the win ratio can be a better statistical measure than the odds ratio when the importance order among components matters; and the method per our approach and that by Luo et al., although derived based on large sample theory, are not limited to a large sample, but are also good for relatively small sample sizes. Different from Pocock et al. and Luo et al., our approach is a

  20. Partnerships in translation: advancing research and clinical care. The 14th Annual HMO Research Network Conference, April 13-16, 2008, Minneapolis, Minnesota.

    PubMed

    Greenlee, Robert T; Coleman, Laura A; Nelson, Andrew F; Selby, Joseph V

    2008-12-01

    The Health Maintenance Organization Research Network held its annual meeting in Minneapolis in April of 2008, with more than 300 investigators, research staff, clinical leaders, and academic partners gathering in conjunction with the conference theme 'Partnerships in Translation: Advancing Research and Clinical Care.' This article provides some background on the network, its research activities, and the annual conference. Also featured is an article by Coleman and colleagues summarizing the conference's first plenary session, where operational leaders of health care organizations discussed the optimization of health care through research. This issue of Clinical Medicine & Research also includes a selection of scientific abstracts presented at the meeting on a wide range of clinical and population health topics.

  1. Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique - Skin Autofluorescence.

    PubMed

    Oleniuc, Mihaela; Secara, Irina; Onofriescu, Mihai; Hogas, Simona; Voroneanu, Luminita; Siriopol, Dimitrie; Covic, Adrian

    2011-10-01

    Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors

  2. Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies

    SciTech Connect

    Williams, Jason M.; Rani, Sudheer D.; Li, Xia; Whisenant, Jennifer G.; Abramson, Richard G.; Arlinghaus, Lori R.; Lee, Tzu-Cheng; MacDonald, Lawrence R.; Partridge, Savannah C.; Kang, Hakmook; Linden, Hannah M.; Kinahan, Paul E.; Yankeelov, Thomas E.

    2015-07-15

    Purpose: Previous studies have demonstrated how imaging of the breast with patients lying prone using a supportive positioning device markedly facilitates longitudinal and/or multimodal image registration. In this contribution, the authors’ primary objective was to determine if there are differences in the standardized uptake value (SUV) derived from [{sup 18}F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in breast tumors imaged in the standard supine position and in the prone position using a specialized positioning device. Methods: A custom positioning device was constructed to allow for breast scanning in the prone position. Rigid and nonrigid phantom studies evaluated differences in prone and supine PET. Clinical studies comprised 18F-FDG-PET of 34 patients with locally advanced breast cancer imaged in the prone position (with the custom support) followed by imaging in the supine position (without the support). Mean and maximum values (SUV{sub peak} and SUV{sub max}, respectively) were obtained from tumor regions-of-interest for both positions. Prone and supine SUV were linearly corrected to account for the differences in 18F-FDG uptake time. Correlation, Bland–Altman, and nonparametric analyses were performed on uptake time-corrected and uncorrected data. Results: SUV from the rigid PET breast phantom imaged in the prone position with the support device was 1.9% lower than without the support device. In the nonrigid PET breast phantom, prone SUV with the support device was 5.0% lower than supine SUV without the support device. In patients, the median (range) difference in uptake time between prone and supine scans was 16.4 min (13.4–30.9 min), which was significantly—but not completely—reduced by the linear correction method. SUV{sub peak} and SUV{sub max} from prone versus supine scans were highly correlated, with concordance correlation coefficients of 0.91 and 0.90, respectively. Prone SUV{sub peak} and SUV{sub max} were

  3. Clinical and Pharmaceutical Solutions through Analysis (CPSA BRASIL 2015): on the way to innovation - pharmaceutical/analytical technology, regulation and knowledge management.

    PubMed

    Needham, Shane; Yates, Nathan; Barrientos, Rafael; Steel, Martin; Lee, Mike

    2015-12-01

    Clinical and Pharmaceutical Solutions through Analysis, São Paulo, Brazil, 3-5 August 2015 The 2nd Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis was held on 3-5 August 2015 at Club Transatlântico, São Paulo, Brazil. This annual meeting began in 2014 and was the first industry-led event in Brazil to focus on the specific needs of industry researchers while bringing together technology and regulators. The goal of CPSA is to provide an in-depth review of innovative technology and industry practices through open discussion of industry-related issues and needs. Education and specialized training are the foundation of all CPSA events. As the industry has evolved so has CPSA. The CPSA annual meeting thrived with high quality scientific content, open interaction from industry opinion leaders and a collegial environment.

  4. Clinical and Pharmaceutical Solutions through Analysis (CPSA BRASIL 2015): on the way to innovation - pharmaceutical/analytical technology, regulation and knowledge management.

    PubMed

    Needham, Shane; Yates, Nathan; Barrientos, Rafael; Steel, Martin; Lee, Mike

    2015-12-01

    Clinical and Pharmaceutical Solutions through Analysis, São Paulo, Brazil, 3-5 August 2015 The 2nd Annual Symposium on Clinical and Pharmaceutical Solutions through Analysis was held on 3-5 August 2015 at Club Transatlântico, São Paulo, Brazil. This annual meeting began in 2014 and was the first industry-led event in Brazil to focus on the specific needs of industry researchers while bringing together technology and regulators. The goal of CPSA is to provide an in-depth review of innovative technology and industry practices through open discussion of industry-related issues and needs. Education and specialized training are the foundation of all CPSA events. As the industry has evolved so has CPSA. The CPSA annual meeting thrived with high quality scientific content, open interaction from industry opinion leaders and a collegial environment. PMID:26617112

  5. Innovating to enhance clinical data management using non-commercial and open source solutions across a multi-center network supporting inpatient pediatric care and research in Kenya

    PubMed Central

    Tuti, Timothy; Bitok, Michael; Paton, Chris; Makone, Boniface; Malla, Lucas; Muinga, Naomi; Gathara, David; English, Mike

    2015-01-01

    Objective To share approaches and innovations adopted to deliver a relatively inexpensive clinical data management (CDM) framework within a low-income setting that aims to deliver quality pediatric data useful for supporting research, strengthening the information culture and informing improvement efforts in local clinical practice. Materials and methods The authors implemented a CDM framework to support a Clinical Information Network (CIN) using Research Electronic Data Capture (REDCap), a noncommercial software solution designed for rapid development and deployment of electronic data capture tools. It was used for collection of standardized data from case records of multiple hospitals’ pediatric wards. R, an open-source statistical language, was used for data quality enhancement, analysis, and report generation for the hospitals. Results In the first year of CIN, the authors have developed innovative solutions to support the implementation of a secure, rapid pediatric data collection system spanning 14 hospital sites with stringent data quality checks. Data have been collated on over 37 000 admission episodes, with considerable improvement in clinical documentation of admissions observed. Using meta-programming techniques in R, coupled with branching logic, randomization, data lookup, and Application Programming Interface (API) features offered by REDCap, CDM tasks were configured and automated to ensure quality data was delivered for clinical improvement and research use. Conclusion A low-cost clinically focused but geographically dispersed quality CDM (Clinical Data Management) in a long-term, multi-site, and real world context can be achieved and sustained and challenges can be overcome through thoughtful design and implementation of open-source tools for handling data and supporting research. PMID:26063746

  6. [Management and accounting solution required in clinical laboratory department in the hospital and the balanced scorecard (BSC)].

    PubMed

    Takahashi, Toshiro

    2006-11-01

    This is to describe required accounting knowledge and the techniques for the clinical laboratory department management level people to operate their division from the viewpoint of management. Especially, the necessity and the efficacy of the BSC implementation in the clinical laboratory department are being explained.

  7. [Management and accounting solution required in clinical laboratory department in the hospital and the balanced scorecard (BSC)].

    PubMed

    Takahashi, Toshiro

    2006-11-01

    This is to describe required accounting knowledge and the techniques for the clinical laboratory department management level people to operate their division from the viewpoint of management. Especially, the necessity and the efficacy of the BSC implementation in the clinical laboratory department are being explained. PMID:17240833

  8. Use of a new tandem cation/anion exchange system with clinical-scale generators provides high specific volume solutions of technetium-99m and rhenium-188

    SciTech Connect

    Knapp, F.R. Jr.; Beets, A.L.; Mirzadeh, S.; Guhlke, S. |

    1998-03-01

    In this paper the authors describe the first application of a simple and inexpensive post elution tandem cation-anion exchange column system which is based on generator elution with salts of weak acids such as ammonium acetate instead of saline solution to provide very high specific volume solutions of technetium-99m and rhenium-188 from clinical scale molybdenum-99/technetium-99m generator prepared from low specific activity (n,y) molybdenum-99, and tungsten-188/rhenium-188 generators, respectively. Initial passage of the bolus through a strong cation exchange cartridge converts the ammonium acetate to acetic acid which is essentially not ionized at the acidic pH, allowing specific subsequent amine type (QMA SepPak{trademark}) anion exchange cartridge column trapping of the microscopic levels of the pertechnetate or perrhenate. Subsequent elution of the anion cartridge with a small volume (< 1 mL) of saline then provides high specific volume solutions of technetium-99m by concentration of the high eluant volumes obtained by elution of clinical-scale (1 Ci) generators. This new approach also works very effectively to obtain high specific volume solutions of rhenium-188 (> 500 mCi/mL) from the alumina-based tungsten-188/rhenium-188 generator.

  9. Case Study for Integration of an Oncology Clinical Site in a Semantic Interoperability Solution based on HL7 v3 and SNOMED-CT: Data Transformation Needs.

    PubMed

    Ibrahim, Ahmed; Bucur, Anca; Perez-Rey, David; Alonso, Enrique; de Hoog, Matthy; Dekker, Andre; Marshall, M Scott

    2015-01-01

    This paper describes the data transformation pipeline defined to support the integration of a new clinical site in a standards-based semantic interoperability environment. The available datasets combined structured and free-text patient data in Dutch, collected in the context of radiation therapy in several cancer types. Our approach aims at both efficiency and data quality. We combine custom-developed scripts, standard tools and manual validation by clinical and knowledge experts. We identified key challenges emerging from the several sources of heterogeneity in our case study (systems, language, data structure, clinical domain) and implemented solutions that we will further generalize for the integration of new sites. We conclude that the required effort for data transformation is manageable which supports the feasibility of our semantic interoperability solution. The achieved semantic interoperability will be leveraged for the deployment and evaluation at the clinical site of applications enabling secondary use of care data for research. This work has been funded by the European Commission through the INTEGRATE (FP7-ICT-2009-6-270253) and EURECA (FP7-ICT-2011-288048) projects.

  10. Antimicrobial activity of complete denture cleanser solutions based on sodium hypochlorite and Ricinus communis – a randomized clinical study

    PubMed Central

    SALLES, Marcela Moreira; BADARÓ, Maurício Malheiros; de ARRUDA, Carolina Noronha Ferraz; LEITE, Vanessa Maria Fagundes; da SILVA, Cláudia Helena Lovato; WATANABE, Evandro; OLIVEIRA, Viviane de Cássia; PARANHOS, Helena de Freitas Oliveira

    2015-01-01

    ABSTRACT To preserve oral health and to maintain the prosthetic devices, it is important not only to improve the properties of commonly known hygiene products, but also to investigate new materials with antimicrobial action. Objectives This study evaluated the antimicrobial activity of sodium hypochlorite (0.25% and 0.50%) and 10% Ricinus communis’ solutions against specific microorganisms. Material and Methods Sixty four maxillary complete denture wearers were instructed to brush their dentures three times a day and to soak them (20 min/day) in the solutions: SH1: 0.25% sodium hypochlorite; SH2: 0.5% sodium hypochlorite; RC: 10% R. communis oil; and C: 0.85% saline (control). The solutions were used for 7 days in a randomized sequence. Following each period of use, there was a 1-week washout period. Antimicrobial activity was determined by Colony Forming Units (CFU) counts of Streptococcus mutans, Candida spp., and gram-negative microorganisms. For collecting biofilm, the internal surface of maxillary dentures was brushed with saline solution, and biofilm suspension obtained. After dilutions (100 - 10-3), aliquots were seeded in Mitis salivarius, CHROMagar Candida®, and MacConkey agar for detecting S. mutans, Candida spp., or gram-negative microorganisms, respectively. After incubation, colonies were counted, and CFU/mL values were calculated. Then, transformation - log10 (CFU+1) - data were analyzed using the Friedman test (α=0.05). Results showed significant differences between the solutions (p<0.001). Results All three solutions showed antimicrobial activity against S. mutans. Against Candida spp., RC and SH1 solutions showed similar effect while SH2 showed superior activity. SH1 and SH2 solutions showed antimicrobial action against gram-negative microorganisms. The Candida species most frequently isolated was C. albicans, followed by C. tropicalis and C. glabrata. Conclusions The 0.5% sodium hypochlorite solution was the most effective and might be used to

  11. “EXHALE”: exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients

    PubMed Central

    2013-01-01

    Background Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). Methods/Design A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb - IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO2peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). Discussion The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. Trial registration http://ClinicalTrials.gov, NCT01881906 PMID:24124893

  12. [Clinical and morphological characteristics of systemic vasculitides: contribution of professor N.E. Yarygin into the solution of the problem].

    PubMed

    Shilkina, N P; Panchenko, K I

    2016-01-01

    The article deals with the role of Professor N.E. Yarygin in studying the clinical and morphological characteristics of systemic vasculitides and is dedicated to the 70th anniversary of the Yaroslavl State Medical University.

  13. CT-Based Evaluation of Tumor Volume After Intra-Arterial Chemotherapy of Locally Advanced Carcinoma of the Oral Cavity: Comparison with Clinical Remission Rates

    SciTech Connect

    Rohde, Stefan Turowski, Bernd; Berkefeld, Joachim; Kovacs, Adorjan F.

    2007-02-15

    Purpose. To assess the volume of locally advanced tumors of the oral cavity and the oropharynx before and after intra-arterial (i.a.) chemotherapy by means of computed tomography and to compare these data with clinically determined treatment response of the same patient population. Methods. Eighty-eight patients with histologically proven, advanced carcinoma of the oral cavity and/or the oropharynx (local tumor stages T3/4) received neoadjuvant i.a. chemotherapy with cisplatin as part of a multimodal therapeutic regimen, comprising (1) local chemotherapy, (2) surgery, and (3) combined radio-chemotherapy. Three weeks after the intervention, residual disease was evaluated radiologically by measurement of the tumor volume and clinically by inspection and palpation of the primary tumor according to WHO criteria. Results. Comparison of treatment response according to radiological and clinical criteria respectively revealed complete remission in 5% vs. 8% (p < 0.05), partial remission in 30% vs. 31%, stable disease in 61% vs. 58%, and tumor progression in 5% vs. 2%. Conclusion. Radiological volumetry and clinical evaluation found comparable response rates after local chemotherapy. However, in patients with good response after local treatment, volumetric measurement with CT may help to distinguish between partial and complete remission. Thus, radiological tumor volumetry provides precise and differentiated information about tumor response and should be used as an additional tool in treatment monitoring after local chemotherapy.

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-09-01

    The objective of this study was to document and review advances and groundbreaking progress in cardiac and body MR at ultrahigh fields (UHF, B0 ≥ 7.0 T) with the goal to attract talent, clinical adopters, collaborations and resources to the biomedical and diagnostic imaging communities. This review surveys traits, advantages and challenges of cardiac and body MR at 7.0 T. The considerations run the gamut from technical advances to clinical opportunities. Key concepts, emerging technologies, practical considerations, frontier applications and future directions of UHF body and cardiac MR are provided. Examples of UHF cardiac and body imaging strategies are demonstrated. Their added value over the kindred counterparts at lower fields is explored along with an outline of research promises. The achievements of cardiac and body UHF-MR are powerful motivators and enablers, since extra speed, signal and imaging capabilities may be invested to overcome the fundamental constraints that continue to hamper traditional cardiac and body MR applications. If practical obstacles, concomitant physics effects and technical impediments can be overcome in equal measure, sophisticated cardiac and body UHF-MR will help to open the door to new MRI and MRS approaches for basic research and clinical science, with the lessons learned at 7.0 T being transferred into broad clinical use including diagnostics and therapy guiding at lower fields. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25706103

  16. [Comparative evaluation of clinical use of cardioplegic solutions custodiol and konsol in the correction of cardiac valvular diseases].

    PubMed

    Zhidkov, I L; Kozhevnikov, V A; Ivanov, V A; Morozov, Iu A; Andrianova, M Iu; Van, E Iu; Trekova, N A

    2006-01-01

    The efficiency of myocardial protection with cold crystalloid cardioplegia (CC) during operations on the heart under total ischemia and extracorporeal circulation was studied. Two hundred and fifty patients who underwent prosthetic or plastic repair of the aortic and mitral valves or plastic repair of the tricuspid valve were examined. Group 1 comprised 218 patients in whom the myocardium was protected with Konsol solution ("Biofarm "research-and-production enterprise, Russia); Group 2 included 32 patients in whom Custodiol solution ("Dr Franz Kohler Chemia GMBH", Germany). The volume of the Konsol solution required for CC was 400-2000 ml, with the duration of myocardial ischemia (MI) being 75 +/- 33 min; that of the Custodiol was 2000-4000 ml, with the duration of MI being 80 +/- 22 min. The used algorithm of administration of the solutions provided a persistent cardioplegic effect in both groups. After aortic declamping, there was a spontaneous recovery of cardiac performance in 84 and 40% in Groups 1 and 2, respectively. In the reperfusion period (RP), no significant differences were found in the basic hemodynamic parameters (heart rate, blood pressure, and central venous pressure) in both groups. After defect correction, cardiac output equally increased in both groups. The groups did not differ in the rate of inotropic support either. In RP, transient cardiac rhythm and conduction disturbances occurred in 19 and 28% in Groups 1 and 2, respectively.

  17. Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study.

    PubMed

    Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

    2016-01-01

    Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

  18. Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

    PubMed Central

    Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

    2016-01-01

    Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

  19. Solution structure of the variable-type domain of the receptor for advanced glycation end products: new insight into AGE-RAGE interaction.

    PubMed

    Matsumoto, Shigeyuki; Yoshida, Takuya; Murata, Hiroko; Harada, Shusaku; Fujita, Naoko; Nakamura, Shota; Yamamoto, Yasuhiko; Watanabe, Takuo; Yonekura, Hideto; Yamamoto, Hiroshi; Ohkubo, Tadayasu; Kobayashi, Yuji

    2008-11-25

    Diabetes is defined by chronic hyperglycemia due to deficiency in insulin action. It has been found that the amount of advanced glycation end products (AGE) from the Maillard reaction between proteins and sugar molecules increases in blood of diabetic patients and furthermore that AGE binding to their cell surface receptor (RAGE) triggers both macrovascular and microvascular impairments to cause diabetic complications. Due to the clinical significance of the vascular complications, RAGE is currently a focus as an attractive target for drug discovery of candidates which interfere with AGE-RAGE binding to prevent the subsequent intracellular signaling related to pathogenical effects. Here, we determined the three-dimensional structure of the recombinant AGE-binding domain by using multidimensional heteronuclear NMR spectroscopy and showed that the domain assumes a structure similar to those of other immunoglobulin V-type domains. The site-directed mutagenesis studies identified the basic amino acids which play a key role in the AGE binding activities. Our results obtained from this study provide new insight into AGE-RAGE interaction. PMID:19032093

  20. A New Framework and Prototype Solution for Clinical Decision Support and Research in Genomics and Other Data-intensive Fields of Medicine

    PubMed Central

    Evans, James P.; Wilhelmsen, Kirk C.; Berg, Jonathan; Schmitt, Charles P.; Krishnamurthy, Ashok; Fecho, Karamarie; Ahalt, Stanley C.

    2016-01-01

    Introduction: In genomics and other fields, it is now possible to capture and store large amounts of data in electronic medical records (EMRs). However, it is not clear if the routine accumulation of massive amounts of (largely uninterpretable) data will yield any health benefits to patients. Nevertheless, the use of large-scale medical data is likely to grow. To meet emerging challenges and facilitate optimal use of genomic data, our institution initiated a comprehensive planning process that addresses the needs of all stakeholders (e.g., patients, families, healthcare providers, researchers, technical staff, administrators). Our experience with this process and a key genomics research project contributed to the proposed framework. Framework: We propose a two-pronged Genomic Clinical Decision Support System (CDSS) that encompasses the concept of the “Clinical Mendeliome” as a patient-centric list of genomic variants that are clinically actionable and introduces the concept of the “Archival Value Criterion” as a decision-making formalism that approximates the cost-effectiveness of capturing, storing, and curating genome-scale sequencing data. We describe a prototype Genomic CDSS that we developed as a first step toward implementation of the framework. Conclusion: The proposed framework and prototype solution are designed to address the perspectives of stakeholders, stimulate effective clinical use of genomic data, drive genomic research, and meet current and future needs. The framework also can be broadly applied to additional fields, including other ‘-omics’ fields. We advocate for the creation of a Task Force on the Clinical Mendeliome, charged with defining Clinical Mendeliomes and drafting clinical guidelines for their use. PMID:27195307

  1. Transfer and adoption of advanced information technology solutions in resource-poor environments: the case of telemedicine systems adoption in Ethiopia.

    PubMed

    Kifle, Mengistu; Payton, Fay Cobb; Mbarika, Victor; Meso, Peter

    2010-04-01

    The study of the adoption of information technology (IT) by individuals has taken two approaches, one emphasizing rationalistic goal-oriented behavior and the other focusing on poignant forces that influence an individual's reaction to a new IT. These approaches are not necessarily mutually exclusive. Individuals' acceptance and subsequent usage of a new IT is predicated on both. Additionally, the tendency in past studies has been to examine either the rational or the poignant factors in the context of a "resource-rich" environment-one in which there is an abundance of IT, adequate infrastructure, and a high level of acculturation to technology solutions. Consequently, there is a clear need for the examination of these factors in resource-poor environments, where assumptions on technology abundance and technology culturation do not hold. We empirically test a model that explains the intention of physicians in a resource-poor environment (epitomized by rural Ethiopia) to adopt telemedicine systems. This model integrates the rational factors driving goal-oriented behavior with the poignant/emotive factors that are an innate part of each adopter's reaction to the new technology. We use the model to expose salient contextual factors that explain the acceptance behavior of individuals toward complex information and communications technology (ICT) solutions and implications of these on the management of technology transfer initiatives in a resource-poor environment. The model is parsimonious, yet explains 28% of the variance in the intention to adopt telemedicine systems and 58% in perceived ease of use. The theoretical and practical implications of this model are discussed. Namely, Sub-Saharan African, in general, and Ethiopian culture, in particular, plays an integral role in the adoption of ICT solutions. Organizational positions and roles among physicians, clinical professionals, and superiors stand to impact the adoption of telemedicine and other healthcare

  2. Almanac 2013: cardiac arrhythmias and pacing--an editorial overview of selected research that has driven recent advances in clinical cardiology.

    PubMed

    Liew, Reginald

    2014-04-01

    Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management.This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing. PMID:24783482

  3. Almanac 2013: cardiac arrhythmias and pacing--an editorial overview of selected research that has driven recent advances in clinical cardiology.

    PubMed

    Liew, Reginald

    2014-04-01

    Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management.This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.

  4. Update and clinical utility of alcaftadine ophthalmic solution 0.25% in the treatment of allergic conjunctivitis.

    PubMed

    Chigbu, DeGaulle I; Coyne, Alissa M

    2015-01-01

    Allergic disorders of the ocular surface are primarily characterized as IgE- and/or T-lymphocyte-mediated disorders that affect the cornea, conjunctiva, and eyelid. Approximately 40% of individuals in the developed countries have allergic conjunctivitis, and as such, it is the most common form of ocular allergy. Seasonal allergic conjunctivitis is the most prevalent type of allergic conjunctivitis that impacts the quality of life of patients. This article reviews the pharmacology, pharmacodynamics, pharmacokinetics, clinical trials, clinical efficacy, and safety of alcaftadine. Histamine and the pathological mechanism of ocular allergy will be briefly reviewed with the intent of providing a background for the detailed discussion on the clinical utility of alcaftadine in allergic conjunctivitis. The Medline PubMed, Elsevier Science Direct, and Google Scholar databases were used to search for evidence-based literature on histamine and immunopathological mechanism of allergic conjunctivitis, as well as on pharmacology, pharmacodynamics, pharmacokinetics, clinical trials, and clinical efficacy of alcaftadine. The treatment and management goals of allergic conjunctivitis are to prevent or minimize the inflammatory cascade associated with allergic response in the early stages of the pathological mechanism. It is of note that activation of histamine receptors on immune and nonimmune cells are associated with allergen-induced inflammation of the conjunctiva and its associated ocular allergic manifestations, including itching, edema, hyperemia, and tearing. Alcaftadine is an efficacious multiple action antiallergic therapeutic agent with inverse agonist activity on H1, H2, and H4 receptors, as well as anti-inflammatory and mast cell stabilizing effects that could provide therapeutic benefits to patients with allergic conjunctivitis.

  5. Clinical Impact of Education Provision on Determining Advance Care Planning Decisions among End Stage Renal Disease Patients Receiving Regular Hemodialysis in University Malaya Medical Centre

    PubMed Central

    Hing (Wong), Albert; Chin, Loh Ee; Ping, Tan Li; Peng, Ng Kok; Kun, Lim Soo

    2016-01-01

    Introduction: Advance care planning (ACP) is a process of shared decision-making about future health-care plans between patients, health care providers, and family members, should patients becomes incapable of participating in medical treatment decisions. ACP discussions enhance patient's autonomy, focus on patient's values and treatment preferences, and promote patient-centered care. ACP is integrated as part of clinical practice in Singapore and the United States. Aim: To assess the clinical impact of education provision on determining ACP decisions among end-stage renal disease patients on regular hemodialysis at University Malaya Medical Centre (UMMC). To study the knowledge and attitude of patients toward ACP and end-of-life issues. Materials and Methods: Fifty-six patients were recruited from UMMC. About 43 questions pretest survey adapted from Lyon's ACP survey and Moss's cardiopulmonary resuscitation (CPR) attitude survey was given to patients to answer. An educational brochure is then introduced to these patients, and a posttest survey carried out after that. The results were analyzed using SPSS version 22.0. Results: Opinion on ACP, including CPR decisions, showed an upward trend on the importance percentage after the educational brochure exposure, but this was statistically not significant. Seventy-five percent of participants had never heard of ACP before, and only 3.6% had actually prepared a written advanced directive. Conclusion: The ACP educational brochure clinically impacts patients’ preferences and decisions toward end-of-life care; however, this is statistically not significant. Majority of patients have poor knowledge on ACP. This study lays the foundation for execution of future larger scale clinical trials, and ultimately, the incorporation of ACP into clinical practice in Malaysia. PMID:27803566

  6. Evaluation of an advanced process control solution to detect wafer positioning issues within the hot and cold plate modules of a lithography track

    NASA Astrophysics Data System (ADS)

    Guillaume, Olivier; Bouchardy, Marc; Armellin, Louis-Pierre

    2006-03-01

    To run the various steps of the process, multiple robot arm transfers within the Hot and Cold Plate modules which directly influence the critical dimension of the production wafers were performed on the lithography track. Wafer positioning inside these modules was found to be one of the key parameters to obtain the best critical dimensional uniformity across the wafer. With the currently realized track monitoring and conventional Statistical Process Control (SPC), potential process drifts or errors within these modules can only be detected from wafers measured during the post process control of product parameters. To catch all potential non-conformal production wafers directly at the tool, minimize equipment downtime and identify the root cause of maintenance issues, the real-time control of tool and process parameters is required. This paper presents the results of the evaluation of an Advanced Process Control (APC) solution used to detect in real-time mode any wafer positioning issues within the Hot and Cold Plate modules of a lithography track based on the monitoring of the plate temperature profile during wafer processing. After an explanation of the methodology used to collect the data from the tool, an initial phase of analysis of the temperature profile of the different Hot Plate modules was carried out. The monitoring of the temperature range was identified as the key parameter for the detection of wafer positioning issues where the temperature profile depends on the number of resistive heating elements, temperature settings and process conditions of the Hot Plate. The wafer tilt was simulated to compare the temperature profile to standard process conditions and in turn determine the detection capability. For the Cold Plate module, it was necessary to know the time between the end of the hot step and the start of the following cold step in order to detect a real tilt issue.

  7. Using 18F Fluorodeoxyglucose Positron Emission Tomography (FDG PET) to Monitor Clinical Outcomes in Patients Treated with Neoadjuvant Chemo-Radiotherapy for Locally Advanced Pancreatic Cancer

    PubMed Central

    Choi, Minsig; Heilbrun, Lance K.; Venkatramanamoorthy, Raghu; Lawhorn-Crews, Jawana M.; Zalupski, Mark M.; Shields, Anthony F.

    2013-01-01

    BACKGROUND Pancreatic cancer ranks as the fourth leading cause of cancer death in the United States with five year survival ranging from 1-5%. Positron emission tomography (PET) is a metabolic imaging system that is widely used for the initial staging of cancer and detecting residual disease after treatment. There are limited data, however, on the use of this molecular imaging technique to assess early tumor response after treatment in pancreatic cancer. METHODS The objective of the study was to explore the relationship of early treatment response using the 18 F- fluorodeoxyglucose (FDG) PET with surgical outcome and overall survival in patients with locally advanced pancreatic cancer. FDG-PET measurements of maximum standardized uptake value (SUV) and kinetic parameters were compared to the clinical outcome. RESULTS Twenty patients were enrolled in the study evaluating neoadjuvant induction chemotherapy followed by concurrent chemoradiotherapy (chemo-RT) for locally advanced pancreatic cancer. All twenty patients had pre-study PET scans and a total of fifty PET scans were performed. Among patients who were PET responders (≥50% decrease in SUV after cycle 1), 100% (2/2) had complete surgical resection. Only 6% (1/16) had surgical resection in the PET non-responders (<50% decrease). Two patients did not have the second PET scan due to clinical progression or treatment toxicity. Mean survival was 23.2 months for PET responders and 11.3 months for non-responders (p=0.234). Similar differences in survival were also noted when response was measured using Patlak analysis. CONCLUSION FDG-PET can aid in monitoring the clinical outcome of patients with locally advanced pancreatic cancer treated with neoadjuvant chemo-RT. FDG-PET may be used to aid patients who could have complete surgical resection as well as prognosticate patients’ survival. PMID:19806035

  8. Towards Horizon 2020: challenges and advances for clinical mental health research – outcome of an expert survey

    PubMed Central

    van der Feltz-Cornelis, Christina M; van Os, Jim; Knappe, Susanne; Schumann, Gunter; Vieta, Eduard; Wittchen, Hans-Ulrich; Lewis, Shôn W; Elfeddali, Iman; Wahlbeck, Kristian; Linszen, Donald; Obradors-Tarragó, Carla; Haro, Josep Maria

    2014-01-01

    Background The size and increasing burden of disease due to mental disorders in Europe poses substantial challenges to its population and to the health policy of the European Union. This warrants a specific research agenda concerning clinical mental health research as one of the cornerstones of sustainable mental health research and health policy in Europe. The aim of this research was to identify the top priorities needed to address the main challenges in clinical research for mental disorders. Methods The research was conducted as an expert survey and expert panel discussion during a scientific workshop. Results Eighty-nine experts in clinical research and representing most European countries participated in this survey. Identified top priorities were the need for new intervention studies, understanding the diagnostic and therapeutic implications of mechanisms of disease, and research in the field of somatic-psychiatric comorbidity. The “subjectivity gap” between basic neuroscience research and clinical reality for patients with mental disorders is considered the main challenge in psychiatric research, suggesting that a shift in research paradigms is required. Conclusion Innovations in clinical mental health research should bridge the gap between mechanisms underlying novel therapeutic interventions and the patient experience of mental disorder and, if present, somatic comorbidity. Clinical mental health research is relatively underfunded and should receive specific attention in Horizon 2020 funding programs. PMID:25061300

  9. Phase I clinical study with multiple peptide vaccines in combination with tetanus toxoid and GM-CSF in advanced-stage HLA-A*0201-positive melanoma patients.

    PubMed

    Bins, Adriaan; Mallo, Henk; Sein, Johan; van den Bogaard, Colette; Nooijen, Willem; Vyth-Dreese, Florry; Nuijen, Bastiaan; de Gast, Gijsbert C; Haanen, John B A G

    2007-01-01

    Successful induction of functional tumor-specific T cells by peptide vaccination in animal models has resulted in many clinical trials to test this approach in advanced-stage melanoma patients. In this phase I clinical trial, 11 end-stage melanoma patients were vaccinated intradermally with 3 peptides: MART-1(26-35) E27L (ELAGIGILTV), tyrosinase(368-376) N375Q (YMDGTMSQV), and gp100(209-217) T210M (IMQVPFSV), admixed with tetanus toxoid and granulocyte-monocyte colony stimulating factor. The peptide vaccine was well tolerated at all tested doses, and led to grade 1-2 toxicity only. Although all patients did show a rise in antitetanus IgG titers, in only 3 patients peptide-specific CD8 T-cells were induced. In 2 cases, the response was directed against MART-1(26-35) and consisted of 0.2% and 3.3% of the CD8 population; however, in both instances these cells did not produce interferon-gamma on stimulation with the unmodified peptide. The third patient mounted a small (0.1%) response against gp100. In a fourth patient, a nonfunctional tyrosinase-specific response (0.6%) was found that was present before vaccination, but was not affected in size nor in function by the vaccine. None of the 11 patients responded clinically according to response evaluation criteria in solid tumors criteria. Although this study is a small scale phase I clinical trial, the efficacy that was observed was disappointingly low. In accordance with previously published peptide vaccination studies, these results add to the increasing evidence that peptide vaccination in itself is not potent enough as an effective melanoma immunotherapy in advanced-stage patients.

  10. The Role of Communication and Interpersonal Skills in Clinical Ethics Consultation: The Need for a Competency in Advanced Ethics Facilitation.

    PubMed

    Shelton, Wayne; Geppert, Cynthia; Jankowski, Jane

    2016-01-01

    Clinical ethics consultants (CECs) often face some of the most difficult communication and interpersonal challenges that occur in hospitals, involving stressed stakeholders who express, with strong emotions, their preferences and concerns in situations of personal crisis and loss. In this article we will give examples of how much of the important work that ethics consultants perform in addressing clinical ethics conflicts is incompletely conceived and explained in the American Society of Bioethics and Humanities Core Competencies for Healthcare Ethics Consultation and the clinical ethics literature. The work to which we refer is best conceptualized as a specialized type of interviewing, in which the emotional barriers of patients and their families or surrogates can be identified and addressed in light of relevant ethical obligations and values within the context of ethics facilitation.

  11. The Role of Communication and Interpersonal Skills in Clinical Ethics Consultation: The Need for a Competency in Advanced Ethics Facilitation.

    PubMed

    Shelton, Wayne; Geppert, Cynthia; Jankowski, Jane

    2016-01-01

    Clinical ethics consultants (CECs) often face some of the most difficult communication and interpersonal challenges that occur in hospitals, involving stressed stakeholders who express, with strong emotions, their preferences and concerns in situations of personal crisis and loss. In this article we will give examples of how much of the important work that ethics consultants perform in addressing clinical ethics conflicts is incompletely conceived and explained in the American Society of Bioethics and Humanities Core Competencies for Healthcare Ethics Consultation and the clinical ethics literature. The work to which we refer is best conceptualized as a specialized type of interviewing, in which the emotional barriers of patients and their families or surrogates can be identified and addressed in light of relevant ethical obligations and values within the context of ethics facilitation. PMID:27045302

  12. Noteworthy clinical case studies in cancer gene therapy: tumor-targeted Rexin-G advances as an efficacious anti-cancer agent.

    PubMed

    Gordon, Erlinda M; Hall, Frederick L

    2010-06-01

    The advent of pathotropic (disease-seeking) targeting technology has ushered cancer gene therapy across the threshold of history, marking the beginning of a new epoch of medical praxis. For the first time, clinical oncologists can reach beyond the finest of catheters, beyond the reach of the most gifted surgeons, to the very fabric of metastatic disease in an effort to halt the progression and turn the tide of otherwise intractable cancers. The enabling molecular biotechnologies embodied in the leading tumor-targeted agent, Rexin-G, and its timely development as a safe and effective anti-cancer drug - from oncogene discovery and target validation, to molecular engineering of the core nanotechnologies, to the first clinical proofs-of principle, confirmatory trials, expanded access programs, and accelerated regulatory approvals - have been extensively documented in the medical literature. Therefore, this paper represents a final chapter, highlighting a series of noteworthy cases studies in the emergent field of targeted genetic medicine: case studies which, in and of themselves, reveal vital and important aspects of the molecular-genetic bio-pharmacology, advanced clinical protocols, refinement of patient monitoring, expanding treatment options, and strategic medical approaches to patient care that exemplify and thereby extend the established principles of pathotropic targeting and cancer gene therapy to a new generation of clinical practitioners.

  13. Comparative clinical evaluation of coronally advanced flap with or without platelet rich fibrin membrane in the treatment of isolated gingival recession

    PubMed Central

    Thamaraiselvan, Murugan; Elavarasu, Sugumari; Thangakumaran, Suthanthiran; Gadagi, Jayaprakash Sharanabasappa; Arthie, Thangavelu

    2015-01-01

    Aim: The aim of this study was to determine whether the addition of an autologous platelet rich fibrin (PRF) membrane to a coronally advanced flap (CAF) would improve the clinical outcome in terms of root coverage, in the treatment of isolated gingival recession. Materials and Methods: Systemically healthy 20 subjects each with single Miller's class I or II buccal recession defect were randomly assigned to control (CAF) or test (CAF + PRF) group. Clinical outcome was determined by measuring the following clinical parameters such as recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), width of keratinized tissue (WKT), gingival thickness (GTH), plaque index (PI), and gingival index (GI) at baseline, 3rd, and 6th month postsurgery. Results: The root coverage was 65.00 ± 44.47% in the control group and 74.16 ± 28.98% in the test group at 6th month, with no statistically significant difference between them. Similarly, CAL, PD, and WKT between the groups were not statistically significant. Conversely, there was statistically significant increase in GTH in the test group. Conclusion: CAF is a predictable treatment for isolated Miller's class I and II recession defects. The addition of PRF to CAF provided no added advantage in terms of root coverage except for an increase in GTH. PMID:25810596

  14. Multiple Gingival Recession Defects Treated with Coronally Advanced Flap and Either the VISTA Technique Enhanced with GEM 21S or Periosteal Pedicle Graft: A 9-Month Clinical Study.

    PubMed

    Dandu, Shruti Raju; Murthy, K Raja

    2016-01-01

    The objective of this study was to clinically evaluate and compare the efficacy of the vestibular incision subperiosteal tunnel access (VISTA) technique using Bio-Gide (Geistlich) membrane enhanced with GEM 21S (Osteohealth) with periosteal pedicle graft (PPG) using a coronally advanced flap. Multiple gingival recession sites in 15 individuals were randomly assigned either to experimental site A (VISTA) or experimental site B (PPG) in a split-mouth design. The clinical parameters were recorded at baseline and 9 months postoperatively. Repeated measures analysis of variance with post hoc Bonferroni correction and paired t test were used to assess statistical significance (P < .05). Mean recession depth significantly decreased from 4.21 ± 1.08 mm (presurgery) to 0.61 ± 0.92 mm (9 months) with VISTA (87.37 ± 17.78% root coverage) and from 4.17 ± 1.18 mm (presurgery) to 1.16 ± 0.92 mm (9 months) with PPG (71.84 ± 19.25% root coverage). Width of keratinized tissue and clinical attachment gain were significantly higher in the VISTA group compared with the PPG group. Within the limits of the study both VISTA and PPG groups resulted in a significant amount of root coverage. The VISTA technique was less invasive and required minimal time and clinical maneuvering. It also resulted in a superior esthetic outcome. PMID:26901301

  15. Multiple Gingival Recession Defects Treated with Coronally Advanced Flap and Either the VISTA Technique Enhanced with GEM 21S or Periosteal Pedicle Graft: A 9-Month Clinical Study.

    PubMed

    Dandu, Shruti Raju; Murthy, K Raja

    2016-01-01

    The objective of this study was to clinically evaluate and compare the efficacy of the vestibular incision subperiosteal tunnel access (VISTA) technique using Bio-Gide (Geistlich) membrane enhanced with GEM 21S (Osteohealth) with periosteal pedicle graft (PPG) using a coronally advanced flap. Multiple gingival recession sites in 15 individuals were randomly assigned either to experimental site A (VISTA) or experimental site B (PPG) in a split-mouth design. The clinical parameters were recorded at baseline and 9 months postoperatively. Repeated measures analysis of variance with post hoc Bonferroni correction and paired t test were used to assess statistical significance (P < .05). Mean recession depth significantly decreased from 4.21 ± 1.08 mm (presurgery) to 0.61 ± 0.92 mm (9 months) with VISTA (87.37 ± 17.78% root coverage) and from 4.17 ± 1.18 mm (presurgery) to 1.16 ± 0.92 mm (9 months) with PPG (71.84 ± 19.25% root coverage). Width of keratinized tissue and clinical attachment gain were significantly higher in the VISTA group compared with the PPG group. Within the limits of the study both VISTA and PPG groups resulted in a significant amount of root coverage. The VISTA technique was less invasive and required minimal time and clinical maneuvering. It also resulted in a superior esthetic outcome.

  16. From the laboratory to the clinic: How translational studies in animals have lead to clinical advances in boron neutron capture therapy.

    PubMed

    Barth, Rolf F

    2015-12-01

    In this report five examples have been selected to illustrate how studies in experimental animals have lead directly to clinical implementation. These include (1) the use of BSH as a boron delivery agent for BNCT of patients with brain tumors, and more specifically gliomas; (2) the use of BPA as a delivery agent for BNCT for patients with melanomas and (3) its subsequent use for BNCT of patients with gliomas; (4) optimization of the delivery of BPA in patients with gliomas; and finally (5) the combination of BSH and BPA with BNCT alone or together with X-irradiation to treat patients with gliomas.

  17. Regulatory acceptance of animal models of disease to support clinical trials of medicines and advanced therapy medicinal products.

    PubMed

    Cavagnaro, Joy; Silva Lima, Beatriz

    2015-07-15

    The utility of animal models of disease for assessing the safety of novel therapeutic modalities has become an increasingly important topic of discussion as research and development efforts focus on improving the predictive value of animal studies to support accelerated clinical development. Medicines are approved for marketing based upon a determination that their benefits outweigh foreseeable risks in specific indications, specific populations, and at specific dosages and regimens. No medicine is 100% safe. A medicine is less safe if the actual risks are greater than the predicted risks. The purpose of preclinical safety assessment is to understand the potential risks to aid clinical decision-making. Ideally preclinical studies should identify potential adverse effects and design clinical studies that will minimize their occurrence. Most regulatory documents delineate the utilization of conventional "normal" animal species to evaluate the safety risk of new medicines (i.e., new chemical entities and new biological entities). Animal models of human disease are commonly utilized to gain insight into the pathogenesis of disease and to evaluate efficacy but less frequently utilized in preclinical safety assessment. An understanding of the limitations of the animal disease models together with a better understanding of the disease and how toxicity may be impacted by the disease condition should allow for a better prediction of risk in the intended patient population. Importantly, regulatory authorities are becoming more willing to accept and even recommend data from experimental animal disease models that combine efficacy and safety to support clinical development.

  18. Regulatory acceptance of animal models of disease to support clinical trials of medicines and advanced therapy medicinal products.

    PubMed

    Cavagnaro, Joy; Silva Lima, Beatriz

    2015-07-15

    The utility of animal models of disease for assessing the safety of novel therapeutic modalities has become an increasingly important topic of discussion as research and development efforts focus on improving the predictive value of animal studies to support accelerated clinical development. Medicines are approved for marketing based upon a determination that their benefits outweigh foreseeable risks in specific indications, specific populations, and at specific dosages and regimens. No medicine is 100% safe. A medicine is less safe if the actual risks are greater than the predicted risks. The purpose of preclinical safety assessment is to understand the potential risks to aid clinical decision-making. Ideally preclinical studies should identify potential adverse effects and design clinical studies that will minimize their occurrence. Most regulatory documents delineate the utilization of conventional "normal" animal species to evaluate the safety risk of new medicines (i.e., new chemical entities and new biological entities). Animal models of human disease are commonly utilized to gain insight into the pathogenesis of disease and to evaluate efficacy but less frequently utilized in preclinical safety assessment. An understanding of the limitations of the animal disease models together with a better understanding of the disease and how toxicity may be impacted by the disease condition should allow for a better prediction of risk in the intended patient population. Importantly, regulatory authorities are becoming more willing to accept and even recommend data from experimental animal disease models that combine efficacy and safety to support clinical development.