Science.gov

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. Further consideration of Advanced Clinical Solutions Word Choice: comparison to the Recognition Memory Test-words and classification accuracy in a clinical sample.

    PubMed

    Davis, Jeremy J

    2014-01-01

    Word Choice (WC), a test in the Advanced Clinical Solutions package for Wechsler measures, was examined in two studies. The first study compared WC to the Recognition Memory Test-Words (RMT-W) in a clinical sample (N = 46). WC scores were significantly higher than RMT-W scores overall and in sample subsets grouped by separate validity indicators. In item-level analyses, WC items demonstrated lower frequency, greater imageability, and higher concreteness than RMT-W items. The second study explored WC classification accuracy in a different clinical sample grouped by separate validity indicators into Pass (n = 54), Fail-1 (n = 17), and Fail-2 (n = 8) groups. WC scores were significantly higher in the Pass group (M = 49.1, SD = 1.9) than in the Fail-1 (M = 46.0, SD = 5.3) and Fail-2 (M = 44.1, SD = 4.8) groups. WC demonstrated area under the curve of .81 in classifying Pass and Fail-2 participants. Using the test manual cutoff associated with a 10% false positive rate, sensitivity was 38% and specificity was 96% in Pass and Fail-2 groups with 24% of Fail-1 participants scoring below cutoff. WC may be optimally used in combination with other measures given observed sensitivity. PMID:25372961

  3. Tissue adhesives for meniscus tear repair: an overview of current advances and prospects for future clinical solutions.

    PubMed

    Bochyńska, A I; Hannink, G; Grijpma, D W; Buma, P

    2016-05-01

    Menisci are crucial structures in the knee joint as they play important functions in load transfer, maintaining joint stability and in homeostasis of articular cartilage. Unfortunately, ones of the most frequently occurring knee injuries are meniscal tears. Particularly tears in the avascular zone of the meniscus usually do not heal spontaneously and lead to pain, swelling and locking of the knee joint. Eventually, after a (partial) meniscectomy, they will lead to osteoarthritis. Current treatment modalities to repair tears and by that restore the integrity of the native meniscus still carry their drawbacks and a new robust solution is desired. A strong tissue adhesive could provide such a solution and could potentially improve on sutures, which are the current gold standard. Moreover, a glue could serve as a carrier for biological compounds known to enhance tissue healing. Only few tissue adhesives, e.g., Dermabond(®) and fibrin glue, are already successfully used in clinical practice for other applications, but are not considered suitable for gluing meniscus tissue due to their sub-optimal mechanical properties or toxicity. There is a growing interest and research field focusing on the development of novel polymer-based tissue adhesives, but up to now, there is no material specially designed for the repair of meniscal tears. In this review, we discuss the current clinical gold standard treatment of meniscal tears and present an overview of new developments in this field. Moreover, we discuss the properties of different tissue adhesives for their potential use in meniscal tear repair. Finally, we formulate recommendations regarding the design criteria of material properties and adhesive strength for clinically applicable glues for meniscal tears. PMID:26970767

  4. 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

  5. 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.

  6. Rewards and advancements for clinical pharmacists.

    PubMed

    Goodwin, S Diane; Kane-Gill, Sandra L; Ng, Tien M H; Melroy, Joel T; Hess, Mary M; Tallian, Kimberly; Trujillo, Toby C; Vermeulen, Lee C

    2010-01-01

    The American College of Clinical Pharmacy charged the Clinical Practice Affairs Committee to review and update the College's 1995 White Paper, "Rewards and Advancements for Clinical Pharmacy Practitioners." Because of the limited data on the present state of rewards and advancements for clinical pharmacists, an online survey of "front-line" clinical pharmacists and pharmacy managers was conducted (1126 total respondents, 14% response rate). The resulting White Paper discusses motivators and existing systems of rewards and advancements for clinical pharmacists, as well as perceived barriers to implementation of these systems. Clinical pharmacists reported work-life balance, a challenging position, and opportunities for professional advancement as the most important factors for career success. At the time of the survey, financial rewards appeared not to be a major motivator for clinical pharmacists. Managers underestimated the importance that clinical pharmacists place on work-life balance and favorable work schedules. Although almost two thirds of the clinical pharmacists surveyed had not developed a professional development plan, 84% indicated an interest in career planning. Both clinical pharmacists and managers rated the lack of a clear reward and advancement structure as the most important barrier to effective systems of rewards and advancements. Pharmacy managers and administrators are encouraged to develop effective systems of rewards and advancements for clinical pharmacists that positively impact patient care and the institution's mission; these systems will benefit the clinical pharmacist, the health care institution, and the patient. PMID:20030483

  7. 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.

  8. 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. PMID:24622889

  9. 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

  10. Advances in cardiology: clinical trial update.

    PubMed

    Howe, Andrew J; Shand, James A; Menown, Ian B A

    2011-05-01

    Multiple key cardiology trials have been presented or published over recent months, several with the potential to change clinical practice. In this article, we summarize and place in clinical context new trial findings regarding anticoagulation in the cardiac catheterization laboratory (enoxaparin, fondaparinux and unfractionated heparin), the implications of genetic polymorphisms and functional testing for antiplatelet therapy (clopidogrel and ticagrelor), new oral anticoagulants for use in atrial fibrillation (apixiban and rivaroxaban), optimal pacing strategies and pharmacological agents in heart failure (ivabradine, eplerenone, cardiac resynchronization therapy, telemonitoring and intracoronary bone marrow stem cell infusion). Clinical trials in percutaneous structural intervention (transcatheter aortic valve implantation, MONARC™ mitral annular implant, STARFlex(®) patent foramen ovale device) and advanced percutaneous coronary intervention (everolimus-eluting stents, biodegradable polymer/polymer-free technologies and contemporary use of intravascular ultrasound) are also discussed. PMID:21627472

  11. Advanced clinical insights & practice: ischemic heart disease.

    PubMed

    Benner, Randall W; Zavarella, Matthew S

    2008-03-01

    This issue sees the debut of a new series of continuing education articles. The series, Advanced Clinical Insights & Practice, is designed to provide continuing education to an ever-expanding realm of paramedicine that needs more of it: the critical care transport paramedic. Secondly, and equally important, are the benefits that can be reaped by other certification levels reading this feature. For EMT-Basics and Intermediates, it will provide a great enhancement to your core knowledge, although most of the interventions discussed will be beyond your traditional scope. For paramedics, it will augment both your pathophysiological understanding and clinical assessment/management skills of diseases and injuries discussed. Ultimately though, it is hoped that anyone who reads these articles will become a better clinician. The next article will appear in the July issue. PMID:18814637

  12. Advanced integrated solution for MEMS design

    NASA Astrophysics Data System (ADS)

    Liateni, Karim; Moulinier, David; Affour, Bachar; Boutamine, H.; Karam, Jean Michel; Veychard, D.; Courtois, Bernard; Cao, Ariel D.

    1999-03-01

    This paper presents a fully integrated solution for the development of Micro Electro Mechanical Systems which covers component libraries, design tools and designs methodologies which are used in conjunction with conventional design automation tools. This solutio enables system houses in wireless and optical communications and consumers electronics markets to reduce their internal development costs and significantly accelerate their product development cycles.

  13. Advance directives: principles, problems, and solutions for physicians.

    PubMed

    Hoffman, B F; Humniski, A

    1997-04-01

    Given the passage of recent legislation, the appearance of common-law reports in Canada and the United States, and the practical problems of implementation of advance directives in health care, physicians should understand the principles and issues involved. In this article, the advantages, disadvantages, and practical solutions to the problems are explored. Family physicians, geriatricians, neurologists, and psychiatrists are most likely to be consulted about advance directives in health care. PMID:12382657

  14. 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.

  15. 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

  16. Advanced practice: the clinical nurse specialist.

    PubMed

    Sparacino, P

    1992-01-01

    Historically, the clinically expert nurse who wanted to continue in direct patient care had few career options. That dilemma is changing in response to the recognised need for greater knowledge and clinical expertise in the domain of patient care. The clinical nurse specialist role is an answer to this concern. The clinical nurse specialist practices within a framework of theoretically-based knowledge and combines that knowledge with clinical expertise. The role is also pivotal in the promotion of patient care focused scientific inquiry and in the generation and refinement of nursing theories. Career options are more versatile than for the educator, researcher, or administrator. While the clinical nurse specialist is an essential person in influencing quality care in the traditional practice settings, there are now opportunities with clientele and practice settings which have expanded beyond the conventional boundaries. PMID:1528295

  17. Optical metrology for advanced process control: full module metrology solutions

    NASA Astrophysics Data System (ADS)

    Bozdog, Cornel; Turovets, Igor

    2016-03-01

    Optical metrology is the workhorse metrology in manufacturing and key enabler to patterning process control. Recent advances in device architecture are gradually shifting the need for process control from the lithography module to other patterning processes (etch, trim, clean, LER/LWR treatments, etc..). Complex multi-patterning integration solutions, where the final pattern is the result of multiple process steps require a step-by-step holistic process control and a uniformly accurate holistic metrology solution for pattern transfer for the entire module. For effective process control, more process "knobs" are needed, and a tighter integration of metrology with process architecture.

  18. Recent advances in clinical/molecular andrology.

    PubMed

    Hafez, B

    1998-01-01

    During the last decade there were extensive investigations in clinical and molecular andrology with emphasis on assisted reproduction, micromanipulation techniques of gametes, sperm/egg interaction, male contraception, diabetes mellitus, varicocele, andropause versus menopause, sexual dysfunction, associated hypertension/stress, prostatic carcinoma and molecular parameters of male reproduction. Sperm hyperactivation is a required step in capacitation sequence. Sperm motility is measured by videotape to evaluate the Straight Line Velocity (microm/s) (VSLI). Fertilization/embryonic development results from single sperm transfer (S-MIST) and multiple sperm transfer. Fertilization/embryo development is achieved by injection of immotile sperm into the perivitelline space. To assess sperm viability, a supravital stain suitable for use in combination with immunofluorescent assay, Hoeschst 33258, is used. The dye fluoresces with an intense blue when bound to DNA. To assess sperm plasma membrane integrity, a hypo-osmotic swelling test (HOST) is performed, using fluoresceinated D-mannose enriched albumin (FITC-DMA). The ability of sperm to swell under hypo-osmotic conditions indicates an intact membrane. A human protein, C-peptide, thought to be a useless byproduct of insulin may protect against devastating heart and nerve damage that diabetes causes. Human diabetics may benefit from the substance. Over 15 million Americans have diabetes, in which blood sugar levels rise out of control. There are two types of diabetics: Type I diabetics produce no insulin, the hormone that regulates blood sugar. Type II diabetics are unable to use their insulin properly. Diabetics are at great risk of heart disease and nerve damage, as arteries throughout the body leak and nerve-cell impulses fail. C-peptide is a byproduct of insulin production; it can be produced by the body or synthetically. Production of this protein is not induced by insulin, so diabetics who take insulin do not get C

  19. Advanced clinical practitioner role in the emergency department.

    PubMed

    Fawdon, Helen; Adams, John

    2013-12-18

    The advanced clinical practitioner role in emergency departments in the UK has developed in an ad hoc manner, without a national framework of registration requirements. This article describes the structure adopted by one NHS trust in England to certify the clinical competence of advanced clinical practitioners in emergency departments through the completion of two portfolios, with a third portfolio to record professional development. The portfolios cover history taking, clinical examination, and interpretation of information and basic investigations to enable the practitioner to undertake medical clerking of a patient attending the emergency department. The portfolios contain evidence of learning and observation of practitioners by middle-grade doctors and consultants. PMID:24345153

  20. 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.

  1. 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

  2. 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)

  3. 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.

  4. Integrative clinical genomics of advanced prostate cancer.

    PubMed

    Robinson, Dan; Van Allen, Eliezer M; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim; Bradley, Robert K; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P; Hussain, Maha; Feng, Felix Y; Tomlins, Scott A; Cooney, Kathleen A; Smith, David C; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E; Morris, Michael J; Solomon, Stephen B; Durack, Jeremy C; Reuter, Victor E; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T; Bowden, Michaela; Balk, Stephen P; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y; Mostaghel, Elahe A; Cheng, Heather H; Mulcahy, Hyojeong; True, Lawrence D; Plymate, Stephen R; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Perez-Lopez, Raquel; Demichelis, Francesca; Robinson, Brian D; Schiffman, Marc; Nanus, David M; Tagawa, Scott T; Sigaras, Alexandros; Eng, Kenneth W; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I; Scher, Howard I; Pienta, Kenneth J; Kantoff, Philip; de Bono, Johann S; Rubin, Mark A; Nelson, Peter S; Garraway, Levi A; Sawyers, Charles L; Chinnaiyan, Arul M

    2015-05-21

    Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF. Moreover, aberrations of BRCA2, BRCA1, and ATM were observed at substantially higher frequencies (19.3% overall) compared to those in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration, including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides clinically actionable information that could impact treatment decisions for these affected individuals. PMID:26000489

  5. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  6. 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

  7. 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

  8. 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

  9. 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

  10. Dyslexia: advances in clinical and imaging studies.

    PubMed

    Koeda, Tatsuya; Seki, Ayumi; Uchiyama, Hitoshi; Sadato, Norihiro

    2011-03-01

    The aim of this report is to describe the characteristics of Japanese dyslexia, and to demonstrate several of our studies about the extraction of these characteristic and their neurophysiological and neuroimaging abnormalities, as well as advanced studies of phonological awareness and the underlying neural substrate. Based on these results, we have proposed a 2-step approach for remedial education (e-learning web site: http://www.dyslexia-koeda.jp/). The first step is decoding, which decreases reading errors, and the second is vocabulary learning, which improves reading fluency. This 2-step approach is designed to serve first grade children. In addition, we propose the RTI (response to intervention) model as a desirable system for remedial education. PMID:21146943

  11. 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. PMID:26952724

  12. 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

  13. 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

  14. Advances in myelofibrosis: a clinical case approach.

    PubMed

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

    2013-10-01

    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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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…

  20. 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

  1. Introducing advanced clinical reasoning to an adult learning disability service.

    PubMed

    Stansfield, Jois; Matthews, Alison

    2014-03-01

    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 in the service were offered training in the approach. Staff completed pre-course questionnaires, immediate post-course evaluations of the training and questionnaires a year after initial training. Semi-structured interviews took place with three team managers a year after the training. Staff and team managers reported that the training had a positive impact on their practice. All respondents demonstrated confidence in the use of the advanced clinical reasoning terminology and a clear understanding of the nature of duty of care and clinical risk. Enhanced knowledge about caseloads and greater confidence in managing episodes of care were reported by staff and team managers to have resulted in a more efficient and effective service. PMID:24288213

  2. 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

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

    PubMed Central

    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. PMID:25788767

  4. 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

  5. Clinical utility of ramucirumab in advanced gastric cancer

    PubMed Central

    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. PMID:26451083

  6. Clinical Research Environment in India: Challenges and Proposed Solutions

    PubMed Central

    Burt, Tal; Sharma, Pooja; Dhillon, Savita; Manchanda, Mukul; Mittal, Sanjay; Trehan, Naresh

    2015-01-01

    India has compelling need and keen aspirations for indigenous clinical research. Notwithstanding this need and previously reported growth the expected expansion of Indian clinical research has not materialized. We reviewed the scientific literature, lay press reports, and ClinicalTrials.gov data for information and commentary on projections, progress, and impediments associated with clinical trials in India. We also propose targeted solutions to identified challenges. The Indian clinical trial sector grew by (+) 20.3% CAGR (compound annual growth rate) between 2005 and 2010 and contracted by (-) 14.6% CAGR between 2010 and 2013. Phase-1 trials grew by (+) 43.5% CAGR from 2005–2013, phase-2 trials grew by (+) 19.8% CAGR from 2005–2009 and contracted by (-) 12.6% CAGR from 2009–2013, and phase-3 trials grew by (+) 13.0% CAGR from 2005–2010 and contracted by (-) 28.8% CAGR from 2010–2013. This was associated with a slowing of the regulatory approval process, increased media coverage and activist engagement, and accelerated development of regulatory guidelines and recuperative initiatives. We propose the following as potential targets for restorative interventions: Regulatory overhaul (leadership and enforcement of regulations, resolution of ambiguity in regulations, staffing, training, guidelines, and ethical principles [e.g., compensation]).Education and training of research professionals, clinicians, and regulators.Public awareness and empowerment. After a peak in 2009-2010, the clinical research sector in India appears to be experiencing a contraction. There are indications of challenges in regulatory enforcement of guidelines; training of clinical research professionals; and awareness, participation, partnership, and the general image amongst the non-professional media and public. Preventative and corrective principles and interventions are outlined with the goal of realizing the clinical research potential in India. PMID:25590017

  7. 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

  8. 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 ...

  9. 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 ... very emotional." Should You Be Interested in a Clinical Trial People volunteer to take part in clinical ...

  10. 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

  11. 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

  12. Advances in Probes and Methods for Clinical EPR Oximetry

    PubMed Central

    Hou, Huagang; Khan, Nadeem; Jarvis, Lesley A.; Chen, Eunice Y.; Williams, Benjamin B.; Kuppusamy, Periannan

    2015-01-01

    EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings. PMID:24729217

  13. 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

  14. Recent advances of kinesin motor inhibitors and their clinical progress.

    PubMed

    Voultsiadou, Antiopi; Sarli, Vasiliki

    2011-09-01

    Antimitotic chemotherapy remains the most effective approach to treat a variety of human neoplasms. Since the discovery of tubulin-targeting agents, vinca alkaloids and the taxanes including paclitaxel and docetaxel are used clinically to treat several solid tumors of the head and neck, breast, lung, ovary, and bladder. Despite the preclinical and clinical success of tubulin-targeting agents, the ability of tumors to develop an acquired resistance to drugs used for treatment and neurotoxicity severely limited their long-term effectiveness to cancer cure. Lately, advances in antimitotic treatments led to the identification of novel mitosis-specific agents that are expected to show higher selectivity and less cytotoxicity compared to known antimitotics. This review focuses on the progress of kinesin motor inhibitors that target proteins that function predominantly in mitosis. PMID:21682672

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. [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. PMID:21404582

  1. Advances in designs for Alzheimer’s disease clinical trials

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development. PMID:23383393

  2. Advances and applications of molecular cloning in clinical microbiology.

    PubMed

    Sharma, Kamal; Mishra, Ajay Kumar; Mehraj, Vikram; Duraisamy, Ganesh Selvaraj

    2014-10-01

    Molecular cloning is based on isolation of a DNA sequence of interest to obtain multiple copies of it in vitro. Application of this technique has become an increasingly important tool in clinical microbiology due to its simplicity, cost effectiveness, rapidity, and reliability. This review entails the recent advances in molecular cloning and its application in the clinical microbiology in the context of polymicrobial infections, recombinant antigens, recombinant vaccines, diagnostic probes, antimicrobial peptides, and recombinant cytokines. Culture-based methods in polymicrobial infection have many limitation, which has been overcome by cloning techniques and provide gold standard technique. Recombinant antigens produced by cloning technique are now being used for screening of HIV, HCV, HBV, CMV, Treponema pallidum, and other clinical infectious agents. Recombinant vaccines for hepatitis B, cholera, influenza A, and other diseases also use recombinant antigens which have replaced the use of live vaccines and thus reduce the risk for adverse effects. Gene probes developed by gene cloning have many applications including in early diagnosis of hereditary diseases, forensic investigations, and routine diagnosis. Industrial application of this technology produces new antibiotics in the form of antimicrobial peptides and recombinant cytokines that can be used as therapeutic agents. PMID:25023463

  3. Advanced control concepts. [trim solution for space shuttle

    NASA Technical Reports Server (NTRS)

    Hutton, M. F.; Friedland, B.

    1973-01-01

    The selection of a trim solution that provides the space shuttle with the highest level of performance and dynamic control in the presense of wind disturbances and bias torques due to misalignment of rocket engines is described. It was determined that engine gimballing is insufficient to provide control to trim the vehicle for headwind and sidewind disturbances, and that it is necessary to use aerodynamic surfaces in conjunction with engine gimballing to achieve trim. The algebraic equations for computing the trim solution were derived from the differential equations describing the motion of the vehicle by substituting the desired trim conditions. The general problem of showing how the trim equations are derived from the equations of motion and the mathematical forms of the performance criterion is discussed in detail, along with the general equations for studying the dynamic response of the trim solution.

  4. Major clinical research advances in gynecologic cancer in 2014

    PubMed Central

    Lee, Kyung-Hun; Kim, Kidong; Kang, Sokbom

    2015-01-01

    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. Advances in nanomedicine towards clinical application in oncology and immunology.

    PubMed

    Herreros, Eduardo; Morales, Sebastián; Cortés, Cristian; Cabaña, Mauricio; Peñaloza, Juan P; Jara, Lilian; Geraldo, Daniela; Otero, Carolina; Fernández-Ramires, Ricardo

    2014-01-01

    Recent advances in nanotechnology and nanobiotechnology have contributed to the development of nanomaterials, able to be used as drug carriers, probes, targets or cytostatic drugs by itself. Nanomedicine is now the leading area in nanotechnology where a large number and types of nanoparticles (NPs) has been developed and several are already in the clinical practice. Chemotherapy is one of the most widely used strategies to treat cancer. Most chemotherapeutic agents have poor solubility, low bioavailability, and are formulated with toxic solvents. NPs have been designed to overcome the lack of specificity of chemotherapeutic agents as well to improve circulation time in blood, taking advantages on tumor cells characteristics. In immunology, recent advances regarding the activation of the innate immune system artificially enhanced by NPs functionalized with immune-stimulators open a new window as novel methods in vaccines. Also, viruses and virus-like particles (VLPs) engineered to stimulate immune response against their similar virus or as molecular platforms for the presentation of foreign epitopes have been described. In this review we focused in the use of different types of NPs in oncology and immunology, pinpointing the main novelties regarding their development and use of nanotechnology in a broad array of applications, ranging from tumor diagnostics, immune-modulation up to cancer therapeutics. PMID:25213311

  6. Advances in thyroid cancer treatment: latest evidence and clinical potential

    PubMed Central

    Alonso-Gordoa, T.; Díez, J.J.; Durán, M.

    2015-01-01

    Advanced thyroid carcinoma is an infrequent tumor entity with limited treatment possibilities until recently. The extraordinary improvement in the comprehension of genetic and molecular alterations involving the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositide 3-kinase/Akt/mammalian target of rapamycin signaling and interacting pathways that are involved in tumor survival, proliferation, differentiation, motility and angiogenesis have been the rationale for the development of new effective targeted therapies. Data coming from phase II clinical trials have confirmed the efficacy of those targeted agents against receptors in cell membrane and cytoplasmic molecules. Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma. Further analysis for an optimal approach has been conducted according to mutational profile and tumor subtypes. However, consistent results are still awaited and the research for adequate prognostic and predictive biomarkers is ongoing. The following report offers a comprehensive review from the rationale to the basis of targeted agents in the treatment of thyroid carcinoma. In addition, current and future therapeutic developments by the inhibition of further molecular targets are discussed in this setting. PMID:25553081

  7. 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. PMID:26915478

  8. 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…

  9. 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

  10. Clinical implications of hepatitis B virus mutations: recent advances.

    PubMed

    Lazarevic, Ivana

    2014-06-28

    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

  11. 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

  12. 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. PMID:25521851

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

    PubMed

    Codony-Servat, Jordi; Rosell, Rafael

    2015-12-01

    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

  14. 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

  15. 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…

  16. 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

  17. 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.

  18. Implementation of an advanced clinical and administrative hospital information system.

    PubMed

    Vegoda, P R; Dyro, J F

    1986-01-01

    Over the last six years since University Hospital opened, the University Hospital Information System (UHIS) has continued to evolve to what is today an advanced administrative and clinical information system. At University Hospital UHIS is the way of conducting business. A wide range of patient care applications are operational including Patient Registration, ADT for Inpatient/Outpatient/Emergency Room visits, Advanced Order Entry/Result Reporting, Medical Records, Lab Automated Data Acquisition/Quality Control, Pharmacy, Radiology, Dietary, Respiratory Therapy, ECG, EEG, Cardiology, Physical/Occupational Therapy and Nursing. These systems and numerous financial systems have been installed in a highly tuned, efficient computer system. All applications are real-time, on-line, and data base oriented. Each system is provided with multiple data security levels, forward file recovery, and dynamic transaction backout of in-flight tasks. Sensitive medical information is safeguarded by job function passwords, identification codes, need-to-know master screens and terminal keylocks. University Hospital has an IBM 3083 CPU with five 3380 disk drives, four dual density tape drives, and a 3705 network controller. The network of 300 terminals and 100 printers is connected to the computer center by an RF broadband cable. The software is configured around the IBM/MVS operating system using CICS as the telecommunication monitor, IMS as the data base management system and PCS/ADS as the application enabling tool. The most extensive clinical system added to UHIS is the Physiological Monitoring/Patient Data Management System with serves 92 critical care beds. In keeping with the Hospital's philosophy of integrated computing, the PMS/PDMS with its network of minicomputers was linked to the UHIS system. In a pilot program, remote access to UHIS through the IBM personal computer has been implemented in several physician offices in the local community, further extending the communications

  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. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  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 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

  9. 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

  10. Advances in Quantitative UV-Visible Spectroscopy for Clinical and Pre-clinical Application in Cancer

    PubMed Central

    Brown, J. Quincy; Vishwanath, Karthik; Palmer, Gregory M.; Ramanujam, Nirmala

    2009-01-01

    Summary Methods of optical spectroscopy which provide quantitative, physically or physiologically meaningful measures of tissue properties are an attractive tool for the study, diagnosis, prognosis, and treatment of various cancers. Recent development of methodologies to convert measured reflectance and fluorescence spectra from tissue to cancer-relevant parameters such as vascular volume, oxygenation, extracellular matrix extent, metabolic redox states, and cellular proliferation have significantly advanced the field of tissue optical spectroscopy. The number of publications reporting quantitative tissue spectroscopy results in the UV-visible wavelength range has increased sharply in the last 3 years, and includes new and emerging studies which correlate optically-measured parameters with independent measures such as immunohistochemistry, which should aid in increased clinical acceptance of these technologies. PMID:19268567

  11. Hospital clinical career advancement programs: comparing perceptions of nurse participants and nonparticipants.

    PubMed

    Thornhill, S K

    1994-09-01

    The study reported in this article describes nurse participants and nonparticipants in hospital clinical career advancement programs (clinical ladders) and compares perceptions in relation to program intrinsic outcomes, needs, and criteria for level advancement. A stratified random sample consisted of 120 participants and 480 nonparticipants drawn from 1,769 clinical nurses employed full time at five regional general hospitals. The findings suggest that nurses' demographic characteristics do not influence program participation status and that clinical advancement programs have limited impact upon job enrichment designed to recruit and retain clinical nurses providing direct patient care. Program participants (106; 88.3 percent) differed significantly at the .05 level from nonparticipants (385; 80.2 percent) on each factor area measuring perceptions of clinical advancement programs. PMID:10136982

  12. Team Preceptorship Model: A Solution for Students' Clinical Experience

    PubMed Central

    Cooper Brathwaite, Angela; Lemonde, Manon

    2011-01-01

    There is a shortage of registered nurses in developed countries, and this shortage is due to the aging nursing workforce, demand for healthcare services, and shortage of nursing professors to teach students. In order to increase the number of clinical placements for nursing students, the authors developed and implemented a collaborative preceptorship model between a Canadian University and Public Health Department to facilitate the clinical experiences of Bachelor of Science of Nursing (BScN) students. This paper describes the Team Preceptorship Model which guided the clinical experience of nine students and 14 preceptors. It also highlights the model's evaluation, strengths, and limitations. PMID:21994893

  13. Multiple Endocrine Neoplasia, Type 1: Imaging Solutions to Clinical Questions.

    PubMed

    Knaus, Christopher M; Patronas, Nicholas J; Papadakis, Georgios Z; Short, Tyler K; Smirniotopoulos, James G

    2016-01-01

    The common clinical presentations of multiple endocrine neoplasia, type 1 (MEN1) often lead to predictable clinical questions that can be answered with imaging. From pituitary adenomas to parathyroid adenoms and pancreaticoduodenal neuroendocrine tumors, the multiple faces of MEN1 require an understanding of the basic disease characteristics and an understanding of multiple imaging modalities. We attempt to provide the reader with a basic understanding of the common clinical questions raised by patients with MEN1 and how radiologists can provide critical management information. PMID:26547632

  14. 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

  15. Clinical practice: new challenges for the advanced practice nurse.

    PubMed

    Bartel, J C; Buturusis, B

    2000-12-01

    This report describes the challenges for advanced practice nurses (APNs) relative to supply and demand issues. The article also includes opportunities with the Balanced Budget Act, physician acceptance of Advanced Practice Nurses, and expanding practice opportunities. The challenges include the nursing shortage (both in nursing students and faculty), the aging of the nursing workforce, and a lag in nursing salaries; increased demand for nursing based on aging baby boomers, increasing patient acuity and technology, and new arenas for practice. The Balanced Budget Act of 1997 provided new opportunities for advanced practice nurses, including enhanced autonomy to provide services and bill independently of physicians. With these changes come new opportunities for advanced practice nurse entrepreneurs in the areas of independent practice, including opportunities to positively impact the health of families and communities in alignment with the Federal government's vision for "Healthy People 2010." As physician acceptance of advanced practice nurses continues to grow and in light of the changes in medical practice and education (residency reduction), opportunities to expand collaborative practice arrangements also exist. APNs are best suited to make the most of these changes. One example of an opportunity for independent practice, a Community Wellness Center, is developed as an entrepreneurial venture benefiting both the APN and the health of a community. Who better than registered nurses (RNs), especially those practicing at the advanced level, can ensure that these opportunities and challenges are addressed in an ethical manner and focused on the needs and health of the community? PMID:12029667

  16. 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

  17. 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)

  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. The advancing clinical impact of molecular imaging in CVD.

    PubMed

    Osborn, Eric A; Jaffer, Farouc A

    2013-12-01

    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 (positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging), as well as 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

  20. Clinical and Experimental Advances in Regeneration of Spinal Cord Injury

    PubMed Central

    Hyun, Jung Keun; Kim, Hae-Won

    2010-01-01

    Spinal cord injury (SCI) is one of the major disabilities dealt with in clinical rehabilitation settings and is multifactorial in that the patients suffer from motor and sensory impairments as well as many other complications throughout their lifetimes. Many clinical trials have been documented during the last two decades to restore damaged spinal cords. However, only a few pharmacological therapies used in clinical settings which still have only limited effects on the regeneration, recovery speed, or retraining of the spinal cord. In this paper, we will introduce recent clinical trials, which performed pharmacological treatments and cell transplantations for patients with SCI, and evaluate recent in vivo studies for the regeneration of injured spinal cord, including stem-cell transplantation, application of neurotrophic factors and suppressor of inhibiting factors, development of biomaterial scaffolds and delivery systems, rehabilitation, and the combinations of these therapies to evaluate what can be appropriately applied in the future to the patients with SCI. PMID:21350645

  1. Advances in clinical applications of cardiovascular magnetic resonance imaging

    PubMed Central

    Bandettini, W P; Arai, A E

    2008-01-01

    Cardiovascular magnetic resonance (CMR) is an evolving technology with growing indications within the clinical cardiology setting. This review article summarises the current clinical applications of CMR. The focus is on the use of CMR in the diagnosis of coronary artery disease with summaries of validation literature in CMR viability, myocardial perfusion, and dobutamine CMR. Practical uses of CMR in non-coronary diseases are also discussed. PMID:18208827

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Advances in data exchange for the clinical laboratory.

    PubMed

    Dolin, R H

    1999-06-01

    The focus of the article is on the nuts and bolts of those standards relevant to the exchange of data between a clinical laboratory and an electronic health record. These include: Health Level 7 (HL7), Logical Observation Identifier Names and Codes (LOINC), Systematized Nomenclature of Human and Veterinary Medicine (SNOMED), and, most recently, the Extensible Markup Language (XML). PMID:10421962

  9. 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. PMID:24678750

  10. 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

  11. 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…

  12. Rafsanjan AIDS clinic 1996-2005: problems faced and solutions found.

    PubMed

    Shekholeslami, N Z; Rezaeian, M

    2009-01-01

    In response to the growing number of the HIV-positive patients in the Islamic Republic of Iran, the Iranian Ministry of Health and Education established several special clinics in all Iranian provinces to provide treatment and care to HIV-positive patients. The Rafsanjan AIDS Clinic is one such clinic that was set up in 1996. Running such a clinic is not without difficulties, given the nature of the infection and the stigmas associated with it. In this brief report we discuss some of the problems faced at our clinic and the solutions found to overcome them. PMID:20187558

  13. Online, directed journaling in community health advanced practice nursing clinical education.

    PubMed

    Daroszewski, Ellen Beth; Kinser, Anita G; Lloyd, Susan L

    2004-04-01

    The sharing of experiences in advanced practice nursing clinical courses allows for application of core principals to different facets of practice, with the potential to promote discussions beyond the course objectives, create opportunities for mentoring, foster critical thinking, and facilitate change and socialization into advanced practice. A pilot test of online, directed journaling, an innovative sharing and reflection strategy, was incorporated in a two-quarter community health advanced practice nursing clinical course in an attempt to enhance clinical learning. Six female graduate nursing students completed the journaling. A 10-item evaluation measure demonstrated that the online journaling strategy was highly effective and valuable for the students. An assessment of the journaling entries found multiple examples of discussion, mentoring, critical thinking, and socialization. Innovative online strategies should become the standard for sharing in advanced practice nursing education. PMID:15098912

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

    PubMed

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

    2010-12-01

    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

  15. Opioid-induced constipation: advances and clinical guidance.

    PubMed

    Nelson, Alfred D; Camilleri, Michael

    2016-03-01

    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

  16. Enteroviral encephalitis in children: clinical features, pathophysiology, and treatment advances

    PubMed Central

    Jain, Shikha; Patel, Bhupeswari; Bhatt, Girish Chandra

    2014-01-01

    Enteroviruses (EVs) have emerged as one of the important etiological agents as a causative organism for encephalitis, especially in children and adults. After the first report of EV encephalitis cases in 1950s, there have been increasing reports of regular outbreaks of EV encephalitis worldwide. Enteroviruses are RNA viruses of the family Picornaviridae that consists of more than 100 serotypes, which are characterized by a single positive-strand genomic RNA. The clinical features are pleomorphic and can be accompanied by mucocutaneous manifestations or isolated encephalitis only. The incidence of encephalitis in EV infection is reported to be about 3% and is associated with high mortality and morbidity. A number of newer therapeutic agents have been used in EV encephalitis with variable results. This review will focus on clinical features, pathophysiology, and newer treatment modality in EV encephalitis. PMID:25175874

  17. 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

  18. 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

  19. 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

  20. Clinical results of proton beam therapy for advanced neuroblastoma

    PubMed Central

    2013-01-01

    Purpose To evaluate the efficacy of proton beam therapy (PBT) for pediatric patients with advanced neuroblastoma. Methods PBT was conducted at 21 sites in 14 patients with neuroblastoma from 1984 to 2010. Most patients were difficult to treat with photon radiotherapy. Two and 6 patients were classified into stages 3 and 4, respectively, and 6 patients had recurrent disease. Seven of the 8 patients who received PBT as the initial treatment were classified as the high risk group. Twelve patients had gross residual disease before PBT and 2 had undergone intraoperative radiotherapy before PBT. Five patients received PBT for multiple sites, including remote metastases. Photon radiotherapy was used in combination with PBT for 3 patients. The PBT doses ranged from 19.8 to 45.5 GyE (median: 30.6 GyE). Results Seven patients are alive with no evidence of disease, 1 is alive with disease progression, and 6 died due to the tumor. Recurrence in the treatment field was not observed and the 3-year locoregional control rate was 82%. Severe acute radiotoxicity was not observed, but 1 patient had narrowing of the aorta and asymptomatic vertebral compression fracture at 28 years after PBT, and hair loss was prolonged in one patient. Conclusion PBT may be a better alternative to photon radiotherapy for children with advanced neuroblastoma, and may be conducted safely for patients with neuroblastoma that is difficult to manage using photon beams. PMID:23758770

  1. 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

  2. Using evidence-based practice for managing clinical outcomes in advanced practice nursing.

    PubMed

    Glanville, I; Schirm, V; Wineman, N M

    2000-10-01

    Preparation of advanced practice nurses to assume leadership positions for clinical decision making requires that traditional ways of solving clinical problems be augmented with information from relevant, research-derived evidence. In this article, the authors describe how one graduate program prepares advanced practice nurses to use the best scientific evidence with clinical expertise to influence patient outcomes. The assignments that students complete in their program provide examples of evidence-based practice that apply quality improvement principles and science-based nursing interventions to create best practices. PMID:11008434

  3. Clinical utility of nivolumab in the treatment of advanced melanoma

    PubMed Central

    Asmar, Ramsey; Yang, Jessica; Carvajal, Richard D

    2016-01-01

    Melanomas are highly immunogenic tumors that evade the immune system by exploiting innate checkpoint pathways, rendering effector T-cells anergic. The immunotherapeutic approach of checkpoint inhibition can restore and invigorate endogenous antitumor T-cell responses and has become an important treatment option for patients with advanced melanoma. The CTLA-4 inhibitor ipilimumab and the PD-1 inhibitors nivolumab and pembrolizumab have been shown to induce durable responses and improve overall survival in metastatic, refractory melanoma. Optimization and validation of pretreatment biomarkers to predict response to these agents is a crucial area of ongoing research. Combination immunotherapy has recently demonstrated superior response rates compared to monotherapy; further investigation is needed to refine combinatorial strategies. PMID:27013881

  4. 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. PMID:23346316

  5. 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

  6. Major clinical research advances in gynecologic cancer in 2012

    PubMed Central

    Suh, Dong Hoon; 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. PMID:23346316

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

    PubMed

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

    2006-01-01

    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

  8. Recent Advances in Clinical Glycoproteomics of Immunoglobulins (Igs).

    PubMed

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

    2016-07-01

    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

  9. [Dapoxetine for premature ejaculation: Advances in clinical studies].

    PubMed

    Zhou, Ting-you; Li, Yan-feng

    2015-10-01

    Premature ejaculation (PE) is a most common sexual dysfunction, for which dapoxetine, a novel selective serotonin (5-HT) re-uptake inhibitor (SSRI), is the only licensed oral medicine at present. With the advantages of fast absorption, rapid action, on-demand medication, and short half-life time, dapoxetine has been proved by clinical trials to be effective in prolonging the intravaginal ejaculation latency time (IELT) and improving the overall condition of PE patients in various areas and populations. Compared with the traditional SSRIs, dapoxetine has a better safety and tolerability. The most frequently reported dapoxetine-related adverse events include nausea, diarrhea, headache and dizziness, but with very few severe or serious cases. PMID:26665685

  10. 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

  11. Translating Advances in Cardiogenetics Into Effective Clinical Practice

    PubMed Central

    Silverstein, Louise Bordeaux; Stolerman, Marina; Hidayatallah, Nadia; McDonald, Thomas; Walsh, Christine A.; Paljevic, Esma; Cohen, Lilian L.; Marion, Robert W.; Wasserman, David; Dolan, Siobhan M.

    2015-01-01

    In this article we describe a qualitative research study in which we explored individuals’ subjective experiences of both genetic testing and cardiogenetic disorders. Using a grounded theory approach, we coded and analyzed interview and focus group transcripts from 50 participants. We found that just under half of the participants who received their diagnosis during the study reported difficulty understanding information about both the purpose of genetic testing and their cardiac disease. A high level of anxiety about genetic testing and cardiac symptoms exacerbated individuals’ cognitive confusion. Participants reported both positive and negative interactions with the medical community, depending on health care professionals’ knowledge of cardiogenetic disorders. Overall, participants expressed a range of attitudes—positive, negative, and ambivalent—toward genetic testing. We conclude with a discussion of the barriers to achieving effective clinical care for genetic conditions and offer suggestions for improving collaborative decision making between physicians and patients. PMID:25114027

  12. Shotgun proteomics of bacterial pathogens: advances, challenges and clinical implications.

    PubMed

    Semanjski, Maja; Macek, Boris

    2016-02-01

    Mass spectrometry-based proteomics is increasingly used in analysis of bacterial pathogens. Simple experimental set-ups based on high accuracy mass spectrometry and powerful biochemical and bioinformatics tools are capable of reliably quantifying levels of several thousand bacterial proteins in a single experiment, reaching the analytical capacity to completely map whole proteomes. Here the authors present the state-of-the-art in bacterial pathogen proteomics and discuss challenges that the field is facing, especially in analysis of low abundant, modified proteins from organisms that are difficult to culture. Constant improvements in speed and sensitivity of mass spectrometers, as well as in bioinformatic and biochemical workflows will soon allow for comprehensive analysis of regulatory mechanisms of pathogenicity and enable routine application of proteomics in the clinical setting. PMID:26653908

  13. 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

  14. 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

  15. Advances in basic and clinical immunology in 2006.

    PubMed

    Chinen, Javier; Shearer, William T

    2007-08-01

    This article reviews the progress in the field of basic and clinical immunology in 2006, focusing on the articles published in the Journal. The role of Toll-like receptors in the immune response was explored in detail in several articles. The knowledge gained in these investigations is being used to develop strategies that enhance the immunogenicity of vaccines to prevent infectious diseases and to have an immunomodulatory effect on allergic diseases. Other components of the innate immunity reported on were the recognition of allergens with lipid-derived motifs by CD1d-restricted T cells and the role of dendritic cells in the development of an allergic response. More than 120 primary immunodeficiencies were defined at a molecular level, and biological agents such as TNF-alpha antagonists and IFN-alpha were shown to have therapeutic use. New anti-HIV drugs that block cell entry were proven to be effective, thus offering alternative therapies to respond to the development of multidrug-resistant HIV strains. The modern understanding of immunologic concepts is helping to elucidate the mechanisms of defense against viruses, bacteria, and parasites; as a result, strategies to improve management and prevention continue to emerge. PMID:17590425

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

    PubMed Central

    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. PMID:7950025

  17. 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.

  18. 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.

  19. Recent advances in methods for numerical solution of O.D.E. initial value problems

    NASA Technical Reports Server (NTRS)

    Bui, T. D.; Oppenheim, A. K.; Pratt, D. T.

    1984-01-01

    In the mathematical modeling of physical systems, it is often necessary to solve an initial value problem (IVP), consisting of a system of ordinary differential equations (ODE). A typical program produces approximate solutions at certain mesh points. Almost all existing codes try to control the local truncation error, while the user is really interested in controlling the true or global error. The present investigation provides a review of recent advances regarding the solution of the IVP, giving particular attention to stiff systems. Stiff phenomena are customarily defined in terms of the eigenvalues of the Jacobian. There are, however, some difficulties connected with this approach. It is pointed out that an estimate of the Lipschitz constant proves to be a very practical way to determine the stiffness of a problem.

  20. 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. PMID:21119850

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

    PubMed Central

    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 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. PMID:21119850

  2. 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

  3. Effects of bicarbonate/lactate solution on peritoneal advanced glycosylation end-product accumulation.

    PubMed

    Park, M S; Kim, J K; Holmes, C; Weiss, M F

    2000-01-01

    Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague-Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However

  4. 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

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

    PubMed

    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

  6. 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

  7. 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

  8. 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.

  9. Benefits planning for advanced clinical information systems implementation at Allina hospitals and clinics.

    PubMed

    Thompson, Douglas Ivan; Henry, Sharon; Lockwood, Linda; Anderson, Brian; Atkinson, Susan

    2005-01-01

    Allina Hospitals and Clinics is implementing an enterprise-wide information system with inpatient and ambulatory clinical documentation and orders, clinical decision support, and revenue cycle applications. Allina has adopted a rigorous approach to planning for and realizing the expected clinical and financial benefits from this investment. Allina's strategies include: Forming a benefits realization team with formal responsibility for analysis, education, facilitation, and measurement; Studying system design to consider requirements for benefits realization; Integrating cultural, organizational and process change plans with system implementation plans; Measuring benefits using a measurement framework that matches organizational reporting, enables multi-level sequential analysis and adjusts for bias in quantifying benefits; Assigning accountability for achieving benefits by matching every benefit with an individual and an operational group; system executives, hospital executives, and department managers are held accountable for benefits within their scope of responsibility, and expected financial benefits are part of their yearly budgets. This article describes Allina's approach for benefits planning, contrasting it with the typical provider's approach to benefits realization. It argues that this approach may greatly increase the likelihood of realizing the value of investments in integrated clinical and business IT PMID:15682677

  10. 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

  11. 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

  12. 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

  13. Lost in Translation: The Unintended Consequences of Advance Directive Law on Clinical Care

    PubMed Central

    Castillo, Lesley S.; Williams, Brie A.; Hooper, Sarah M.; Sabatino, Charles P.; Weithorn, Lois A.; Sudore, Rebecca L.

    2011-01-01

    Background Advance directive law may compromise the clinical effectiveness of advance directives. Purpose To identify unintended legal consequences of advance directive law that may prevent patients from communicating end-of-life preferences. Data Sources Advance directive legal statutes for all 50 U.S. states and the District of Columbia and English-language searches of LexisNexis, Westlaw, and MEDLINE from 1966 to August 2010. Study Selection Two independent reviewers selected 51 advance directive statutes and 20 articles. Three independent legal reviewers selected 105 legal proceedings. Data Extraction Two reviewers independently assessed data sources and used critical content analysis to determine legal barriers to the clinical effectiveness of advance directives. Disagreements were resolved by consensus. Data Synthesis Legal and content-related barriers included poor readability (that is, laws in all states were written above a 12th-grade reading level), health care agent or surrogate restrictions (for example, 40 states did not include same-sex or domestic partners as default surrogates), and execution requirements needed to make forms legally valid (for example, 35 states did not allow oral advance directives, and 48 states required witness signatures, a notary public, or both). Vulnerable populations most likely to be affected by these barriers included patients with limited literacy, limited English proficiency, or both who cannot read or execute advance directives; same-sex or domestic partners who may be without legally valid and trusted surrogates; and unbefriended, institutionalized, or homeless patients who may be without witnesses and suitable surrogates. Limitation Only appellate-level legal cases were available, which may have excluded relevant cases. Conclusion Unintended negative consequences of advance directive legal restrictions may prevent all patients, and particularly vulnerable patients, from making and communicating their end

  14. 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

  15. The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification

    PubMed Central

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

    2016-01-01

    Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC–MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC–MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC–MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives. PMID:26581546

  16. 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.

  17. The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification.

    PubMed

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

    2016-01-01

    Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC-MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC-MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC-MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives. PMID:26581546

  18. 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

  19. Military medical advances resulting from the conflict in Korea, Part II: Historic clinical accomplishments.

    PubMed

    Baker, Michael S

    2012-04-01

    Throughout the recorded history of civilization, there has been armed conflict. Warfare has been associated with advances in care for the wounded. Many of these advances when shown effective on the battlefield become incorporated into civilian health care. It is a laboratory where there is unfortunately much clinical material and presents opportunity for the creative, curious, and innovative. This article reviews the medical advances that resulted from the Korean War. There were notable advances in neurosurgery, vascular surgery, and plastic surgery. Tools from prior wars were rediscovered, dusted off, and used to stop combat losses from psychiatric trauma. A treatment was developed for cleft lip by a plastic surgeon, thus giving hope to young lives. War is a disruptive, destructive, and harrowing experience--but can lead to improvements in care for the wounded and these developments can improve the lives of people everywhere. PMID:22594134

  20. Advances in numerical solutions to integral equations in liquid state theory

    NASA Astrophysics Data System (ADS)

    Howard, Jesse J.

    Solvent effects play a vital role in the accurate description of the free energy profile for solution phase chemical and structural processes. The inclusion of solvent effects in any meaningful theoretical model however, has proven to be a formidable task. Generally, methods involving Poisson-Boltzmann (PB) theory and molecular dynamic (MD) simulations are used, but they either fail to accurately describe the solvent effects or require an exhaustive computation effort to overcome sampling problems. An alternative to these methods are the integral equations (IEs) of liquid state theory which have become more widely applicable due to recent advancements in the theory of interaction site fluids and the numerical methods to solve the equations. In this work a new numerical method is developed based on a Newton-type scheme coupled with Picard/MDIIS routines. To extend the range of these numerical methods to large-scale data systems, the size of the Jacobian is reduced using basis functions, and the Newton steps are calculated using a GMRes solver. The method is then applied to calculate solutions to the 3D reference interaction site model (RISM) IEs of statistical mechanics, which are derived from first principles, for a solute model of a pair of parallel graphene plates at various separations in pure water. The 3D IEs are then extended to electrostatic models using an exact treatment of the long-range Coulomb interactions for negatively charged walls and DNA duplexes in aqueous electrolyte solutions to calculate the density profiles and solution thermodynamics. It is found that the 3D-IEs provide a qualitative description of the density distributions of the solvent species when compared to MD results, but at a much reduced computational effort in comparison to MD simulations. The thermodynamics of the solvated systems are also qualitatively reproduced by the IE results. The findings of this work show the IEs to be a valuable tool for the study and prediction of

  1. Development of a solution adaptive unstructured scheme for quasi-3D inviscid flows through advanced turbomachinery cascades

    NASA Technical Reports Server (NTRS)

    Usab, William J., Jr.; Jiang, Yi-Tsann

    1991-01-01

    The objective of the present research is to develop a general solution adaptive scheme for the accurate prediction of inviscid quasi-three-dimensional flow in advanced compressor and turbine designs. The adaptive solution scheme combines an explicit finite-volume time-marching scheme for unstructured triangular meshes and an advancing front triangular mesh scheme with a remeshing procedure for adapting the mesh as the solution evolves. The unstructured flow solver has been tested on a series of two-dimensional airfoil configurations including a three-element analytic test case presented here. Mesh adapted quasi-three-dimensional Euler solutions are presented for three spanwise stations of the NASA rotor 67 transonic fan. Computed solutions are compared with available experimental data.

  2. 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

  3. Contribution of Tumoral and Host Solute Carriers to Clinical Drug Response

    PubMed Central

    Sprowl, Jason A; Mikkelsen, Torben S; Giovinazzo, Hugh; Sparreboom, Alex

    2012-01-01

    Members of the solute carrier family of transporters are responsible for the cellular uptake of a broad range of endogenous compounds and xenobiotics in multiple tissues. Several of these solute carriers are known to be expressed in cancer cells or cancer cell lines, and decreased cellular uptake of drugs potentially contributes to the development of resistance. As result, the expression levels of these proteins in humans have important consequences for an individual’s susceptibility to certain drug-induced side effects, interactions, and treatment efficacy. In this review article, we provide an update of this rapidly emerging field, with specific emphasis on the direct contribution of solute carriers to anticancer drug uptake in tumors, the role of these carriers in regulation of anticancer drug disposition, and recent advances in attempts to evaluate these proteins as therapeutic targets. PMID:22459901

  4. Fourier-domain optical coherence tomography: recent advances toward clinical utility

    PubMed Central

    Bouma, Brett E; Yun, Seok-Hyun; Vakoc, Benjamin J; Suter, Melissa J; Tearney, Guillermo J

    2009-01-01

    With the advent of Fourier-domain techniques, optical coherence tomography (OCT) has advanced from high-resolution ‘point’ imaging over small fields-of-view to comprehensive microscopic imaging over three-dimensional volumes that are comparable to the dimensions of luminal internal organs. This advance has required the development of new lasers, improved spectrometers, minimally invasive catheters and endoscopes, and novel optical and signal processing strategies. In recent cardiovascular, ophthalmic, and gastrointestinal clinical studies, the capabilities of Fourier-domain OCT have enabled a new paradigm for diagnostic screening of large tissue areas, which addresses the shortcomings of existing technologies and focal biopsy. PMID:19264475

  5. 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

  6. Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

    PubMed Central

    Becker, Silke; Jayaram, Hari; Limb, G. Astrid

    2012-01-01

    Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. Stem cell-based therapies offer hope for these patients at risk of or suffering from blindness due to the deterioration of the neural retina. Various sources of stem cells are currently being investigated, ranging from human embryonic stem cells to adult-derived induced pluripotent stem cells as well as human Müller stem cells, with the first clinical trials to investigate the safety and tolerability of human embryonic stem cell-derived retinal pigment epithelium cells having recently commenced. This review aims to summarize the latest advances in the development of stem cell strategies for the replacement of retinal neurons and their supportive cells, the retinal pigment epithelium (RPE) affected by retinal degenerative conditions. Particular emphasis will be given to the advances in stem cell transplantation and the challenges associated with their translation into clinical practice. PMID:24710533

  7. 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

  8. Invest in your data: how clinical mobility solutions liberate data and drive cost savings.

    PubMed

    Luo, Si

    2016-02-01

    Smart point-of-care mobile solutions integrate with a health system's existing communications and IT infrastructure to achieve the following benefits: Unify data management and communication functions using a single device. Improve accuracy of data collection, medication administration, and blood collection through scanning and cross-matching. Facilitate data accessibility from electronic health records and clinical protocols. Enable better care-team communication while safeguarding personal health information. Increase accuracy and efficiency, thereby improving performance and satisfaction scores. PMID:26999979

  9. 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

  10. The Use of Computers for Clinical Care: A Case Series of Advanced U.S. Sites

    PubMed Central

    Doolan, David F.; Bates, David W.; James, Brent C.

    2003-01-01

    Objective: To describe advanced clinical information systems in the context in which they have been implemented and are being used. Design: Case series of five U.S. hospitals, including inpatient, ambulatory and emergency units. Descriptive study with data collected from interviews, observations, and document analysis. Measurements: The use of computerized results, notes, orders, and event monitors and the type of decision support; data capture mechanisms and data form; impact on clinician satisfaction and clinical processes and outcomes; and the organizational factors associated with successful implementation. Results: All sites have implemented a wide range of clinical information systems with extensive decision support. The systems had been well accepted by clinicians and have improved clinical processes. Successful implementation required leadership and long-term commitment, a focus on improving clinical processes, and gaining clinician involvement and maintaining productivity. Conclusion: Despite differences in approach there are many similarities between sites in the clinical information systems in use and the factors important to successful implementation. The experience of these sites may provide a valuable guide for others who are yet to start, or are just beginning, the implementation of clinical information systems. PMID:12509360

  11. Advances and Challenges in Liquid Chromatography-Mass Spectrometry-Based Proteomics Profiling for Clinical Applications

    SciTech Connect

    Qian, Weijun; Jacobs, Jon M.; Liu, Tao; Camp, David G.; Smith, Richard D.

    2006-08-01

    The advances in proteomic technologies provide tremendous opportunities for applying these technologies in biomarker-related clinical applications; however, the unique characteristics of human biofluids such as high dynamic range in protein abundances and extreme complexity of human proteomes present tremendous challenges for current analytical technologies. In this review, we focus on summarizing the recent advances in LC-MS based proteomic profiling and its applications in clinical proteomics as well as the major challenges for implementing these technologies for more effective biomarker discovery. Over the last few years, tremendous efforts have been directed towards the development of more effective approaches for characterizing the human plasma/serum and other biofluid proteomes. The developments in immunodepletion and various fractionation approaches in combination with much improved LC-MS platforms have enabled the profiling of the plasma proteome with much greater dynamic range of coverage, allowing many proteins at low ng/mL levels being confidently identified. Despite the significant advances and efforts, the dynamic range of measurements or extent of proteome coverage, the confidence of peptide/protein identification, the accuracy of quantitation, the throughput of analysis, and the robustness of the present instrumentation are still among the major challenges for implementation of a proteomic profiling platform suitable for efficient clinical applications.

  12. 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.

  13. 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

  14. Biology of advanced uveal melanoma and next steps for clinical therapeutics.

    PubMed

    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

    2015-03-01

    Uveal melanoma is the most common intraocular malignancy although 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-yr 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 the Melanoma Research Foundation's ocular melanoma initiative, 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 immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed. PMID:25113308

  15. 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

  16. 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

  17. 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. PMID:26431849

  18. 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. PMID:26222136

  19. Outcomes of patients with advanced cancer and KRAS mutations in phase I clinical trials

    PubMed Central

    Said, Rabih; Ye, Yang; Falchook, Gerald Steven; Janku, Filip; Naing, Aung; Zinner, Ralph; Blumenschein, George R.; Fu, Siqing; Hong, David S.; Piha-Paul, Sarina Anne; Wheler, Jennifer J.; Kurzrock, Razelle; Palmer, Gary A.; Aldape, Kenneth; Hess, Kenneth R.; Tsimberidou, Apostolia Maria

    2014-01-01

    Background KRAS mutation is common in human cancer. We assessed the clinical factors, including type of KRAS mutation and treatment, of patients with advanced cancer and tumor KRAS mutations and their association with treatment outcomes. Methods Patients referred to the Phase I Clinic for treatment who underwent testing for KRAS mutations were analyzed. Results Of 1,781 patients, 365 (21%) had a KRAS mutation. The G12D mutation was the most common mutation (29%). PIK3CA mutations were found in 24% and 10% of patients with and without KRAS mutations (p<0.0001). Of 223 patients with a KRAS mutation who were evaluable for response, 56 were treated with a MEK inhibitor-containing therapy and 167 with other therapies. The clinical benefit (partial response and stable disease lasting ≥ 6 months) rates were 23% and 9%, respectively, for the MEK inhibitor versus other therapies (p=0.005). The median progression-free survival (PFS) was 3.3 and 2.2 months, respectively (p=0.09). The respective median overall survival was 8.4 and 7.0 months (p=0.38). Of 66 patients with a KRAS mutation and additional alterations, higher rates of clinical benefit (p=0.04), PFS (p=0.045), and overall survival (p=0.02) were noted in patients treated with MEK inhibitor-containing therapy (n=9) compared to those treated with targeted therapy matched to the additional alterations (n=24) or other therapy (n=33). Conclusions MEK inhibitors in patients with KRAS-mutated advanced cancer were associated with higher clinical benefit rates compared to other therapies. Therapeutic strategies that include MEK inhibitors or novel agents combined with other targeted therapies or chemotherapy need further investigation. PMID:25313136

  20. Introductory and Advanced Pharmacy Practice Experiences Within Campus-based Influenza Clinics

    PubMed Central

    Johnson, Eric J.; Hagemann, Tracy M.

    2013-01-01

    Objective. To describe the development, implementation, and assessment of an introductory and an advanced pharmacy practice experience (IPPE and APPE) integrated within campus-based influenza clinics. Design. The influenza clinics were designed to incorporate the learning objectives for the IPPE and APPE, and included preparatory sessions, online learning, and direct patient interactions tailored to the appropriate education level of the learner. Assessment. The clinics provided influenza vaccinations to 2,292 and 2,877 individuals in 2010 and 2011, respectively. The clinics allowed for experiential education of 39 students earning a total of 467 IPPE and APPE hours in 2010 and 58 students earning a total of 656 IPPE and APPE hours in 2011. Third-year students were assessed before and after completing the IPPE, and improvement was seen in knowledge and self-ratings of perceptions and attitudes toward administering immunizations. Conclusions. Integrating pharmacy practice experiences within campus-based influenza clinics was an effective way to provide students with direct patient care experience and preventive health services knowledge. PMID:23610479

  1. 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

  2. From Unmet Clinical Need to Entrepreneurship: Taking Your Informatics Solution to Market

    PubMed Central

    Bowles, Kathryn H.; Heil, Eric

    2015-01-01

    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

  3. [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

  4. 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. PMID:23746659

  5. 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

  6. Evaluation of computed tomographic enterography with an orally administered lactulose solution in clinically normal dogs.

    PubMed

    Keh, Seoyeon; Sohn, Jungmin; Choi, Mihyun; Lee, Namsoon; Jang, Jaeyoung; Kim, Hyunwook; Chang, Dongwoo; Choi, Mincheol; Yoon, Junghee

    2016-04-01

    OBJECTIVE To determine optimal techniques for CT enterography in clinically normal dogs and to evaluate luminal distention after oral administration of lactulose solution as a contrast agent. ANIMALS 15 healthy dogs. PROCEDURES CT was performed in a control group (2 dogs that underwent CT to evaluate metastasis and 5 other dogs). In a bolus administration group (5 dogs from the control group), lactulose solution (1.34 g/mL) was administered (60 mL/kg) rapidly via gastric tube to anesthetized dogs, and CT was performed every 10 minutes for 1 hour. In a continuous administration group of 8 other dogs, lactulose solution (60 mL/kg) was administered slowly via nasoesophageal tube over a period of 45 minutes. Then, 15 minutes after anesthetic induction, CT was performed every 10 minutes for 1 hour. Luminal distention of the small intestines was evaluated qualitatively by use of a 3-point scale. RESULTS All small intestinal segments had poor luminal distention in the control group. The terminal ileum had poor luminal distention for the bolus administration group. Nearly all segments had good luminal distention for the continuous administration group with mild adverse effects. Luminal distention scores from 0 to 20 minutes after lactulose administration were significantly higher than scores from 30 to 60 minutes. Interobserver reproducibility was high for all intestinal segments. CONCLUSIONS AND CLINICAL RELEVANCE CT performed between 0 and 20 minutes after continuous administration of lactulose solution (60 mL/kg) may reveal adequate luminal distention for examination of small intestinal segments in dogs. PMID:27027835

  7. Evidence-based use of electronic clinical tracking systems in advanced practice registered nurse education: an integrative review.

    PubMed

    Branstetter, M Laurie; Smith, Lynette S; Brooks, Andrea F

    2014-07-01

    Over the past decade, the federal government has mandated healthcare providers to incorporate electronic health records into practice by 2015. This technological update in healthcare documentation has generated a need for advanced practice RN programs to incorporate information technology into education. The National Organization of Nurse Practitioner Faculties created core competencies to guide program standards for advanced practice RN education. One core competency is Technology and Information Literacy. Educational programs are moving toward the utilization of electronic clinical tracking systems to capture students' clinical encounter data. The purpose of this integrative review was to evaluate current research on advanced practice RN students' documentation of clinical encounters utilizing electronic clinical tracking systems to meet advanced practice RN curriculum outcome goals in information technology as defined by the National Organization of Nurse Practitioner Faculties. The state of the science depicts student' and faculty attitudes, preferences, opinions, and data collections of students' clinical encounters. Although electronic clinical tracking systems were utilized to track students' clinical encounters, these systems have not been evaluated for meeting information technology core competency standards. Educational programs are utilizing electronic clinical tracking systems with limited evidence-based literature evaluating the ability of these systems to meet the core competencies in advanced practice RN programs. PMID:24814999

  8. Circulating Chromogranin A as A Marker for Monitoring Clinical Response in Advanced Gastroenteropancreatic Neuroendocrine Tumors

    PubMed Central

    Li, Na; Li, Yanyan; Lu, Ming; Li, Zhongwu; Lu, Zhihao; Li, Jie; Shen, Lin

    2016-01-01

    Chromogranin A (CgA), present in the chromaffin granules of neuroendocrine cells, is a useful biomarker for the diagnosis of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This study was conducted to investigate the potential role of circulating CgA in monitoring clinical response in Chinese patients with advanced GEP-NETs. Eighty patients with advanced GEP-NETs treated in Peking University Cancer Hospital from September 2011 to May 2014 and 65 healthy individuals were included in this study. Serum CgA levels were analyzed for relationship with patient’s baseline characteristics and clinical outcome. Median CgA levels were significantly higher in patients with advanced GEP-NETs than in healthy individuals (93.8 ng/mL vs. 37.1 ng/mL; P<0.01), as well as significantly higher in patients with carcinoid syndrome or liver metastasis than in those without carcinoid syndrome (298.8 ng/mL vs. 82.9 ng/mL; P = 0.011) or liver metastasis (137.0 ng/mL vs. 64.4 ng/mL; P = 0.023). A CgA cutoff value of 46.2 ng/mL was used in this study with a sensitivity of 78.8% and specificity of 73.8%. Patients with CgA levels higher than 46.2 ng/mL had a worse prognosis than patients with CgA levels lower than 46.2 ng/mL (P = 0.045). Notably, a weak correlation was observed between changes in serum CgA levels and clinical response to the IP regimen as well as SSAs. Our data also indicate that serum CgA could be a useful indicator of patient prognosis though there is more research required in order to validate such claims. PMID:27159453

  9. An infrastructure for cooperation and communication in an advanced clinical information system.

    PubMed Central

    Kuhn, K.; Reichert, M.; Nathe, M.; Beuter, T.; Dadam, P.

    1994-01-01

    In a research project, organizational and technological requirements for an advanced clinical information system have been analysed, and a concept has been developed. From the application's perspective, medical personnel is more actively relieved from routine tasks by support of organizational tasks and by coordination of distributed activities. Program development is supported by a concept of simple and complex services with well-defined interfaces, and by the use of activity templates, i.e. pre-modeled activities describing possible sequences of services. The concept is based on an open systems approach, with a reliable and secure communication infrastructure. In addition, monitoring facilities are provided. PMID:7949982

  10. 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

  11. 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

  12. Joint modeling of progression-free survival and death in advanced cancer clinical trials.

    PubMed

    Dejardin, David; Lesaffre, Emmanuel; Verbeke, Geert

    2010-07-20

    Progression-related endpoints (such as time to progression or progression-free survival) and time to death are common endpoints in cancer clinical trials. It is of interest to study the link between progression-related endpoints and time to death (e.g. to evaluate the degree of surrogacy). However, current methods ignore some aspects of the definitions of progression-related endpoints. We review those definitions and investigate their impact on modeling the joint distribution. Further, we propose a multi-state model in which the association between the endpoints is modeled through a frailty term. We also argue that interval-censoring needs to be taken into account to more closely match the latent disease evolution. The joint distribution and an expression for Kendall's tau are derived. The model is applied to data from a clinical trial in advanced metastatic ovarian cancer. PMID:20572123

  13. Tracking Patient Encounters and Clinical Skills to Determine Competency in Ambulatory Care Advanced Pharmacy Practice Experiences

    PubMed Central

    Pereira, Chrystian R.; Harris, Ila M.; Moon, Jean Y.; Westberg, Sarah M.; Kolar, Claire

    2016-01-01

    Objective. To determine if the amount of exposure to patient encounters and clinical skills correlates to student clinical competency on ambulatory care advanced pharmacy practice experiences (APPEs). Design. Students in ambulatory care APPEs tracked the number of patients encountered by medical condition and the number of patient care skills performed. At the end of the APPE, preceptors evaluated students’ competency for each medical condition and skill, referencing the Dreyfus model for skill acquisition. Assessment. Data was collected from September 2012 through August 2014. Forty-six responses from a student tracking tool were matched to preceptor ratings. Students rated as competent saw more patients and performed more skills overall. Preceptors noted minimal impact on workload. Conclusions. Increased exposure to patient encounters and skills performed had a positive association with higher Dreyfus stage, which may represent a starting point in the conversation for more thoughtful design of ambulatory care APPEs. PMID:26941440

  14. Clinical studies in the second line setting of advanced pancreatic cancer: are we making any progress?

    PubMed

    Ramfidis, Vassilios S; Strimpakos, Alexios S; Syrigos, Kostas N; Saif, Muhammad W

    2012-07-01

    Despite the enormous advances in clinical research in oncology, the prognosis of pancreatic carcinoma remains poor. The therapeutic options in this type of cancer are very limited, with modest results at present. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting trials on the second line treatment of pancreatic cancer were presented. The first study (Abstract #4017) with a phase II design suggested that maintenance therapy with sunitinib, after a complete course of standard first line treatment, was feasible and effective while the second phase I/II study (Abstract #4034) evaluated the role of trabedersen, an agent that inhibits TGF-β2 expression. Finally, the efficacy and toxicity of lapatinib combined with either FOLFOX (Abstract #e14533) or capecitabine (Abstract #e14569) were examined in the second line setting of pancreatic cancer. PMID:22797389

  15. Rational Combination of Immunotherapies with Clinical Efficacy in Mice with Advanced Cancer.

    PubMed

    Bransi, Ali; Salgado, Oscar Camilo; Beffinger, Michal; Milo, Karim; Silina, Karina; Yagita, Hideo; Becher, Burkhard; Knuth, Alexander; van den Broek, Maries

    2015-11-01

    In the context of cancer, naïve T cells are insufficiently primed and become progressively dysfunctional. Boosting antitumor responses by blocking PD-1 or CTLA-4 results in durable clinical responses only in a limited proportion of cancer patients, suggesting that other pathways must be targeted to improve clinical efficacy. Our preclinical study in TRAMP mice comparing 14 different immune interventions identified anti-CD40 + IL2/anti-IL2 complexes + IL12Fc as a uniquely efficacious treatment that prevents tolerance induction, promotes priming of sustained, protective tumor-specific CD8(+) T cells, and cures late-stage cancer when given together with adoptively transferred tumor-specific T cells. We propose that improving signals 2 (costimulation) and 3 (cytokines) together with fresh tumor-specific, rather than boosting of dysfunctional preexisting memory, T cells represents a potent therapy for advanced cancer. PMID:26141620

  16. Preliminary data from an advanced dementia consult service: integrating research, education, and clinical expertise.

    PubMed

    Catic, Angela G; Berg, Andrea I; Moran, Julie A; Knopp, Julie R; Givens, Jane L; Kiely, Dan K; Quinlan, Nicky; Mitchell, Susan L

    2013-11-01

    Hospitalized individuals with advanced dementia often receive care that is of limited clinical benefit and inconsistent with preferences. An advanced dementia consultation service was designed, and a pre and post pilot study was conducted in a Boston hospital to evaluate it. Geriatricians and a palliative care nurse practitioner conducted consultations, which consisted of structured consultation, counseling and provision of an information booklet to the family, and postdischarge follow-up with the family and primary care providers. Individuals aged 65 and older with advanced dementia who were admitted were identified, and consultations were solicited using pop-ups programmed into the computerized provider order entry (POE) system. In the initial 3-month period, 24 subjects received usual care. In the subsequent 3-month period, consultations were provided to five subjects for whom they were requested. Data were obtained from the electronic medical record and proxy interviews (admission, 1 month after discharge). Mean age of the combined sample (N = 29) was 85.4, 58.6% were from nursing homes, and 86.2% of their proxies stated that comfort was the goal of care. Nonetheless, their hospitalizations were characterized by high rates of intravenous antibiotics (86.2%), more than five venipunctures (44.8%), and radiological examinations (96.6%). Acknowledging the small sample size, there were trends toward better outcomes in the intervention group, including greater proxy knowledge of the disease, better communication between proxies and providers, more advance care planning, lower rehospitalization 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 after discharge. PMID:24219202

  17. A Pharmacotherapy Capstone Course to Advance Pharmacy Students’ Clinical Documentation Skills

    PubMed Central

    Ahmed, Ghada F.

    2012-01-01

    Objective. To implement and assess the effectiveness of a capstone pharmacotherapy course designed to integrate in-class curriculum using patient cases and drug-information questions. The course was intended to improve third-year doctor of pharmacy (PharmD) students' clinical documentation skills in preparation for beginning advanced pharmacy practice experiences (APPEs). Design. This 2-credit, semester-long course consisted of 6 patient cases and 12 drug-information questions posted electronically on an Internet-based medical chart, a public health presentation, a knowledge examination, and an objective standardized performance assessment. In class, students engaged in active-learning exercises and clinical problem-solving. Students worked outside of class in small groups to retrieve and discuss assigned articles and review medication information in preparation for in-class discussions. Assessment. A rubric was used to assess the patient cases and questions that students completed and submitted individually. Data for 4 consecutive course offerings (n=622) were then analyzed. A significant improvement was found in the “misplaced” but not the “missing” documentation ratings for both assessment and plan notes in the final assessment compared with baseline. In course evaluations, the majority of students agreed that the course integrated material across the curriculum (97%) and improved their clinical writing skills (80.5%). Conclusion. A capstone pharmacy course was successful in integrating and reviewing much of the material covered across the PharmD curriculum and in improving students’ clinical documentation skills. PMID:23049106

  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. 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. PMID:25892367

  20. [Clinical study of Peptide-cocktail vaccination with tegafur-uracil/leucovorin for advanced colorectal cancer].

    PubMed

    Sugiura, Fumiaki; Inoue, Keisuke; Okuno, Kiyotaka; Sukegawa, Yasushi

    2012-11-01

    cDNA microarray technology coupled with laser microdissection has been used to identify human leukocyte antigen(HLA)-A24-restricted epitope peptides as potential targets for cancer vaccination in colorectal cancer patients. These antigenic peptides were derived from 2 different testis cancer antigens, ring finger protein 43(RNF43) and translocase of outer mitochondrial membrane 34(TOMM34). We conducted a clinical trial of vaccines against colorectal cancer specific peptides(RNF43 and TOMM34) with tegafur-uracil/Leucovorin( UFT/LV) for the treatment of advanced or recurrent colorectal cancer. The vaccinations were well tolerated without any adverse events. The highest long-term survival was observed in the group showing cytolytic T-lymphocyte (CTL) responses against both RNF43 and TOMM34, followed by the group showing CTL responses against only RNF43 or only TOMM34. A new study has been planned in order to obtain more immunological responses, and we have started a clinical trial of vaccines against multiple peptides[RNF43, TOMM34, forkhead box protein M1(FOXM1), maternal embryonic leucine zipper kinase(MELK), holliday junction recognition protein(HJURP), vascular endothelial growth factor receptor (VEGFR)1, and VEGFR2]by using UFT/LV for the treatment of advanced or recurrent colorectal cancer. PMID:23267878

  1. 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

  2. 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.

  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. 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.

  5. 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

  6. Advance directives outside the USA: are they the best solution everywhere?

    PubMed

    Sanchez-Gonzalez, M A

    1997-09-01

    This article evaluates the potential role of advance directives outside of their original North American context. In order to do this, the article first analyses the historical process which has promoted advance directives in recent years. Next, it brings to light certain presuppositions which have given them force: atomistic individualism, contractualism, consumerism and entrepreneurialism, pluralism, proceduralism, and "American moralism." The article next studies certain European cultural peculiarities which could affect advance directives: the importance of virtue versus rights, stoicism versus consumerist utilitarianism, rationalism verus empiricism, statism versus citizens' initiative, and justice versus autonomy. The article concludes by recognising that autonomy has a transcultural value, although it must be balanced with other principles. Advance Directives can have a function in certain cases. But it does not seem adequate to delegate to advance directives more and more medical decisions, and to make them more binding everyday. It is indispensable to develop other decision-making criteria. PMID:9271918

  7. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage.

    PubMed

    Mastellos, Dimitrios C; Reis, Edimara S; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D

    2016-10-01

    Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192

  8. 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

  9. 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

  10. Differences in difficulty adjudicating clinical events in patients with advanced HIV disease.

    PubMed

    Eisenbud, R; Assmann, S F; Kalish, L A; van Der Horst, C; Collier, A C

    2001-09-01

    Adjudication of clinical events is often used as a quality assurance method in clinical research. During the design of the Viral Activation Transfusion Study (a clinical trial in patients with advanced HIV disease), a set of study endpoints was defined (primarily AIDS-defining conditions), criteria for confirmation of each event type were developed, and an adjudication procedure was established. The adjudication process included 1) an initial review of documentation of each event by two independent reviewers, 2) the opportunity to request additional information, 3) a second review either of additional documentation or of cases in which there was disagreement on first review, and 4) the consultation of a third reviewer if there was still disagreement. Overall, of 288 reported endpoints, 30% required additional documentation or more than one review, and 16% were not confirmed at the end of the adjudication process. However, these percentages varied widely over different types of events. For example, of 30 reported nonophthalmalogic cytomegalovirus events, 37% required additional documentation and 40% were not confirmed. In contrast, every one of 17 reported Pneumocystis cariini pneumonias were confirmed with no requirement for additional documentation. The results can be used to help design endpoint documentation and adjudication procedures for other studies, thereby improving data quality and reducing costs. PMID:11579276

  11. An advanced low-fluorine solution route for fabrication of high-performance YBCO superconducting films

    NASA Astrophysics Data System (ADS)

    Chen, Yuanqing; Wu, Chuanbao; Zhao, Gaoyang; You, Caiyin

    2012-06-01

    We have developed a new low-fluorine solution consisting of non-fluorine (F-free) barium and copper salts, and fluorine-containing yttrium trifluoroacetate. Using this new low-fluorine solution, the BaCO3 phase was avoided in the pyrolyzed precursor films. Instead, CuO, Y and Ba fluorides (YF3 and BaF2) were formed in the precursor films pyrolyzed at 450 °C, which was the same as when an All-TFA solution (prepared using Y, Ba, Cu trifluoroacetates as precursors) or other fluorine-reduced solutions were used. This new kind of low-fluorine solution has only 23% of the fluorine content in an All-TFA solution, and the fluorine content was lower than any other fluorine-reduced solution. Thus, rapid production of YBa2Cu3O7-x (YBCO) films can be easily realized. Using a heating rate of 10 °C min-1 in the pyrolysis process, a high critical current density (Jc) of 5 MA cm-2 (at 77 K, 0 T) was obtained in YBCO films fabricated on LaAlO3 (LAO) single crystal substrates from the new starting solution.

  12. Overall survival should be the primary endpoint in clinical trials for advanced non-small-cell lung cancer

    PubMed Central

    Cheema, P.K.; Burkes, R.L.

    2013-01-01

    An article in a recent edition of Current Oncology explored the validation of progression-free survival (pfs) as an endpoint in clinical trials of antineoplastic agents for metastatic colorectal cancer, metastatic renal cell carcinoma, and ovarian cancer. The support for pfs as a surrogate endpoint for overall survival (os) was elucidated. As with the aforementioned tumour types, advanced non-small-cell lung cancer (nsclc) has seen a rise in active agents since the year 2000. Those agents range from improved cytotoxics such as pemetrexed, to targeted therapies such as tyrosine kinase inhibitors of the epidermal growth factor receptor and agents that target the EML4–ALK gene mutation. More recently, it has also become apparent that histology plays an important role in the response to and outcomes of treatment. With the therapeutic options for patients with advanced nsclc increasing, concerns are being raised that the efficacy of drugs measured by os may be diluted in clinical trials, thereby underestimating their true clinical benefit. That possibility, together with the need to have efficacious drugs available to patients earlier, has resulted in the search for a surrogate to the os endpoint in advanced nsclc. The present article follows up the recent article on pfs as a surrogate. Although advances in identifying pfs as a valid surrogate endpoint for os have been made in other tumour types, in advanced nsclc, such surrogacy has not been formally validated. Until it has, os should remain the primary endpoint of clinical trials in advanced nsclc. PMID:23559882

  13. 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

  14. Evaluation of the Antimicrobial Activity of a Super Oxidized Solution in Clinical Isolates.

    PubMed

    Velazquez-Meza, María Elena; Hernández-Salgado, Margarita; Sánchez-Alemán, Miguel Angel

    2015-08-01

    This study evaluated the antimicrobial activity of Estericide(®) QX (super oxidized solution) in 524 bacterial clinical isolates causing nosocomial infections. The minimum inhibitory concentration (MIC) was determined by the serial broth microdilution method. The bacterial viability of the isolates and control strains was tested. The bactericidal effect of the disinfectant was determined according to the European Standards (EN) Test Methods-1040 guidelines. Assay of stability in Estericide QX after 1 year of storage was performed. The microdilution assays showed that the isolates were inhibited at concentrations of 10-40 parts per million (ppm). For gram-positive bacteria, the MIC values 20 and 40 ppm were more predominant (95%), whereas for gram-negative bacteria, the MIC values 10 and 20 ppm had the highest percentage (91.7%). The difference between the two groups was statistically significant (p<0.001). The results of the assay of bactericidal activity showed that all tested bacteria (99.999%) were killed within 30 sec of contact time. The stability test showed that Estericide QX maintained its disinfectant action over time. In conclusion, the results of the present study showed that the super oxidized solution of Estericide QX provides a high antibacterial activity on both gram-positive and gram-negative bacteria. Based on these results and under the conditions of the present study, we believe that Estericide QX can be used efficiently against multiresistant nosocomial bacteria, providing an opportunity for new disinfection alternatives. PMID:26083738

  15. Facing the challenges and building solutions in clinical psychiatric nursing in Iran: a qualitative study.

    PubMed

    Zarea, Kourosh; Nikbakht-Nasrabadi, Alireza; Abbaszadeh, Abbas; Mohammadpour, Ali

    2012-10-01

    Psychiatric nurses play an important role in the process of caring for mentally ill patients and are continually faced with the numerous challenges and complex issues related to this field. This study aimed to understand the perspectives of psychiatric nurses regarding the issues they face while providing care and examine the possible solutions for improvement of inpatient care in clinical settings. The study adopted a qualitative approach that utilized a content analysis of audio taped, semi-structured interviews that had been conducted with 24 nurses. Two main themes emerged from the data. The first, Challenges in Providing Care within Psychiatric Wards, had the following subthemes: Politics and Rules of Organization, Safety and Security Issues, Uncertainty about the Role, Lack of Trained Staff, and Sociocultural Issues. The second theme, Solutions for Improving Psychiatric Care, had the subthemes of Empowerment across four domains: Psychiatric Nurses, Mentally Ill Patients and their Families, The Psychiatric Mental Health System, and the Cultural Context. The results indicated that if nurses are expected to provide optimal nursing care within a psychiatric ward, then there is a need for a stable and responsible organizational structure, skilled psychiatric nurses, and community-based care along with an anti-stigma program. PMID:23017047

  16. Circulating tumor cells: advances in isolation and analysis, and challenges for clinical applications

    PubMed Central

    Harouaka, Ramdane; Kang, Zhigang; Zheng, Siyang; Cao, Liang

    2013-01-01

    Circulating tumor cells (CTCs) are rare cancer cells released from tumors into the bloodstream that are thought to have a key role in cancer metastasis. The presence of CTCs has been associated with worse prognosis in several major cancer types, including breast, prostate and colorectal cancer. There is considerable interest in CTC research and technologies for their potential use as cancer biomarkers that may enhance cancer diagnosis and prognosis, facilitate drug development, and improve the treatment of cancer patients. This review provides an update on recent progress in CTC isolation and molecular characterization technologies. Furthermore, the review covers significant advances and limitations in the clinical applications of CTC-based assays for cancer prognosis, response to anti-cancer therapies, and exploratory studies in biomarkers predictive of sensitivity and resistance to cancer therapies. PMID:24134902

  17. The cellular origin for malignant glioma and prospects for clinical advancements

    PubMed Central

    Zong, Hui; Verhaak, Roel GW; Canoll, Peter

    2012-01-01

    Glioma remains incurable despite great advancements in medicine. Targeting the cell of origin for gliomas could bring great hope for patients. However, as a collection of diverse diseases, each subtype of glioma could derive from a distinct cell of origin. To resolve such a complex problem, one must use multiple research approaches to gain deep insights. Here we review current evidence regarding the cell of origin from clinical observations, whole-genome molecular pathology and glioma animal models. We conclude that neural stem cells, glial progenitors (including oligodendrocyte progenitor cells) and astrocytes could all serve as cells of origin for gliomas, and that cells incurring initial mutations (cells of mutation) might not transform, while their progeny cells could instead transform and act as cells of origin. Further studies with multidisciplinary approaches are needed to link each subtype to a particular cell of origin, and to develop effective therapies that target the signaling network within these cells. PMID:22616703

  18. 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

  19. Toward cardiovascular MRI at 7 T: clinical needs, technical solutions and research promises

    PubMed Central

    Sodickson, Daniel K.; Krombach, Gabriele A.; Schulz-Menger, Jeanette

    2010-01-01

    Objective To consider potential clinical needs, technical solutions and research promises of ultrahigh-field strength cardiovascular MR (CMR). Methods A literature review is given, surveying advantages and disadvantages of CMR at ultrahigh fields (UHF). Key concepts, emerging technologies, practical considerations and applications of UHF CMR are provided. Examples of UHF CMR imaging strategies and their added value are demonstrated, including the numerous unsolved problems. A concluding section explores future directions in UHF CMR. Results UHF CMR can be regarded as one of the most challenging MRI applications. Image quality achievable at UHF is not always exclusively defined by signal-to-noise considerations. Some of the inherent advantages of UHF MRI are offset by practical challenges. But UHF CMR can boast advantages over its kindred lower field counterparts by trading the traits of high magnetic fields for increased temporal and/or spatial resolution. Conclusions CMR at ultrahigh-field strengths is a powerful motivator, since speed and signal may be invested to overcome the fundamental constraints that continue to hamper traditional CMR. If practical challenges can be overcome, UHF CMR will help to open the door to new approaches for basic science and clinical research. PMID:20676653

  20. 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.

  1. Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer

    PubMed Central

    2014-01-01

    Background The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and only a few standard treatments are available for this condition. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with three peptides derived from cancer-testis antigens. Methods This study was conducted as a phase I trial. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. Three HLA-A*2402 restricted epitope peptides-cell division cycle associated 1 (CDCA1), cadherin 3 (CDH3) and kinesin family member 20A (KIF20A)-were administered subcutaneously, and the adverse events and immune response were assessed. The clinical effects observed were the tumor response, progression-free survival (PFS) and overall survival (OS). Results The three-peptide vaccination was well-tolerated up to a dose of 3 mg per peptide (9 mg total). No grade 3 or 4 adverse events were observed after vaccination. Peptide-specific T cell immune responses were observed in all patients and stable disease was observed in 5 of 9 patients. The median PFS and OS were 3.4 and 9.7 months. The Grade 2 injection site reaction and continuous vaccination after PD judgment appeared to be prognostic of OS. Conclusions Multiple-peptide vaccination was well tolerated and induced peptide-specific T-cell responses. Trial registration This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003229). PMID:24606884

  2. Clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery in advanced ovarian cancer patients

    PubMed Central

    Takada, Toshio; Iitsuka, Chiaki; Nomura, Hidetaka; Abe, Akiko; Taniguchi, Tomoko; Takizawa, Ken

    2015-01-01

    Objective To investigate the clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) patients. Methods We retrospectively reviewed the medical records of 124 advanced EOC patients and analyzed the details of neoadjuvant chemotherapy (NACT), IDS, postoperative treatment, and prognoses. Results Following IDS, 98 patients had no gross residual disease (NGRD), 15 had residual disease sized <1 cm (optimal), and 11 had residual disease sized ≥1 cm (suboptimal). Two-year overall survival (OS) and progression-free survival (PFS) rates were 88.8% and 39.8% in the NGRD group, 40.0% and 13.3% in the optimal group (p<0.001 vs. NGRD for both), and 36.3% and 0% in the suboptimal group, respectively. Five-year OS and 2-year PFS rates were 62% and 56.1% in the lymph node-negative (LN-) group and 26.2% and 24.5% in the lymph node-positive (LN+) group (p=0.0033 and p=0.0024 vs. LN-, respectively). Furthermore, survival in the LN+ group, despite surgical removal of positive nodes, was the same as that in the unknown LN status group, in which lymphadenectomy was not performed (p=0.616 and p=0.895, respectively). Multivariate analysis identified gross residual tumor during IDS (hazard ratio, 3.68; 95% confidence interval, 1.31 to 10.33 vs. NGRD) as the only independent predictor of poor OS. Conclusion NGRD after IDS improved prognosis in advanced EOC patients treated with NACT-IDS. However, while systematic retroperitoneal lymphadenectomy during IDS may predict outcome, it does not confer therapeutic benefits. PMID:26197771

  3. 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

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

    PubMed

    Xia, Shu; Kohli, Manish; 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

    2015-06-30

    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

  5. 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

  6. 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

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

    PubMed

    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

  8. 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.

  9. 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

  10. 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. PMID:20874063

  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. PMID:26903594

  12. Application of Molecular Profiling in Clinical Trials for Advanced Metastatic Cancers

    PubMed Central

    Williams, P. Mickey; Lih, Chih-Jian; Polley, Eric C.; Chen, Alice P.; Rubinstein, Larry V.; Zhao, Yingdong; Simon, Richard M.; Conley, Barbara A.; Doroshow, James H.

    2015-01-01

    There is growing interest in the application of molecular profiling, including sequencing, genotyping, and/or mRNA expression profiling, to the analysis of patient tumors with the objective of applying these data to inform therapeutic choices for patients with advanced cancers. Multiple clinical trials that are attempting to validate this personalized or precision medicine approach are in various stages of development and execution. Although preliminary data from some of these efforts have fueled excitement about the value and utility of these studies, their execution has also provoked many questions about the best way to approach complicating factors such as tumor heterogeneity and the choice of which genetic mutations to target. This commentary highlights some of the challenges confronting the clinical application of molecular tumor profiling and the various trial designs being utilized to address these challenges. Randomized trials that rigorously test patient response to molecularly targeted agents assigned based on the presence of a defined set of mutations in putative cancer-driving pathways are required to address some of the current challenges and to identify patients likely to benefit from this approach. PMID:25663694

  13. Metrology solutions using optical scatterometry for advanced CMOS: III-V and Germanium multi-gate field-effect transistors

    NASA Astrophysics Data System (ADS)

    Chin, Hock-Chun; Liu, Bin; Zhang, Xingui; Ling, Moh-Lung; Yip, Chan-Hoe; Liu, Yongdong; Hu, Jiangtao; Yeo, Yee-Chia

    2013-04-01

    In this work, we report metrology solutions using scatterometry Optical Critical Dimension (OCD) characterization on two advanced CMOS devices: novel n-channel gate-last In0.53Ga0.47As FinFET with self-aligned Molybdenum (Mo) contacts and p-channel Ge FinFET formed on Germanium-on-Insulator (GOI) substrate. Key critical process steps during the fabrication of these advanced transistors were identified for process monitor using scatterometry OCD measurement to improve final yield. Excellent correlation with reference metrology and high measurement precision were achieved by using OCD characterization, confirming scatterometry OCD as a promising metrology technique for next generation device applications. In addition, we also further explore OCD characterization using normal incidence spectroscopic reflectometry (SR), oblique incidence spectroscopic ellipsometry (SE), and combined SR+SE technologies. The combined SR+SE approach was found to provide better precision.

  14. Challenges and Solutions for Clinical Development of New Antibacterial Agents: Results of a Survey among Pharmaceutical Industry Professionals

    PubMed Central

    Wetherington, Jeffrey D.; Schmitt, Nicola; Harbarth, Stephan

    2015-01-01

    As the number of antibacterial medicines in the pipeline remains low, we anonymously surveyed pharmaceutical industry professionals on challenges and solutions for clinical development of these agents. Challenges were reported primarily as financial and regulatory. For multidrug-resistant organisms, there are needs for rapid diagnostic tests, new regulatory guidance, and adaptation of endpoints/trial designs. Regulators and public/private initiatives are addressing these challenges to help ensure that proposed solutions have the support of all involved stakeholders. PMID:25918147

  15. Free Radical Reactions in Aqueous Solutions: Examples from Advanced Oxidation Processes for Wastewater from the Chemistry in Airborne Water Droplets

    NASA Astrophysics Data System (ADS)

    Baird, N. Colin

    1997-07-01

    Inorganic chemistry involving free radicals in aqueous solutions can be important in environmental processes. A common free radical reaction in aqueous solution is electron transfer, especially to the hydroxyl radical and to ozone. Hydrogen peroxide and free radicals related to it act as weak acids, so both their neutral and deprotonated forms must be considered in reactions. In Advanced Oxidation Processes, the hydroxyl radical concentration in water is greatly increased by reactions involving ozone and/or ultraviolet light. Irradiation of solid titanium dioxide can also be used to generate the radicals. The hydroxyl radicals are used in the Processes to initiate the oxidation of dissolved organic pollutants. Free radical reactions also play an important role in the chemistry of water droplets suspended in air in clouds and fogs. The radicals arise indirectly from the photoionization of dissolved organic compounds such as aldehydes and from the iron-catalyzed decomposition of dissolved hydrogen peroxide. They oxidize dissolved sulfur dioxide and certain organic compounds.

  16. 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

  17. 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}.

  18. MRI Helps Depict Clinically Undetectable Risk Factors in Advanced Stage Retinoblastomas

    PubMed Central

    Hadjistilianou, Theodora; Cerase, Alfonso; Toti, Paolo; Leonini, Sara; Bracco, Sandra; de Francesco, Sonia; Galimberti, Daniela; Balducci, Donatella; Piu, Pietro; Monti, Lucia; Bellini, Matteo; Caini, Mauro; Rossi, Alessandro

    2015-01-01

    SUMMARY This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas. PMID:25924174

  19. 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

  20. Clinical use of gatifloxacin ophthalmic solution for treatment of bacterial conjunctivitis

    PubMed Central

    Cervantes, Lorenzo J; Mah, Francis S

    2011-01-01

    Bacterial conjunctivitis is a common infectious disease of the eye, characterized by conjunctival hyperemia, eyelid edema, and purulent discharge. Although the prevalence and incidence are not well reported, bacterial conjunctivitis represents one of the most frequent causes of patient visits to both primary care physicians and ophthalmologists. Most cases of nongonococcal and nonchlamydial bacterial conjunctivitis are self-limiting and may resolve without intervention. There is a place for treatment, however, which allows for a shorter time to clinical and microbiological resolution which may decrease the mild morbidity, decrease health care costs of visits and potential complications, return patients back to school or the work force, and limit the potential spread of this communicable infection. Gatifloxacin ophthalmic solution is a broad spectrum 8-methoxyfluroroquinolone bactericidal antibiotic, with good activity against Staphylococcus aureus, Streptococcus species, and Gram-negative pathogens. It also has a relatively good resistance profile, making it a more than adequate choice in the treatment of bacterial conjunctivitis when therapy is warranted. PMID:21573098

  1. Recent advances and clinical application of erythropoietin and erythropoiesis-stimulating agents.

    PubMed

    Tanaka, Tetsuhiro; Nangaku, Masaomi

    2012-05-15

    Erythropoietin (EPO) is an essential glycoprotein that facilitates red blood cell maturation from erythroid progenitors and mediates erythropoiesis. The use of recombinant human EPO (rhEPO) dramatically changed management of anemic patients with chronic kidney disease and improved their quality of life. EPO is mainly produced in the fetal liver and the postnatal kidney, although the molecular determinants for tissue-specific expression are elusive. Meanwhile, recent advances established a role of hypoxia-inducible factors (HIF) in transcriptionally upregulating EPO in hypoxia. Out of three HIF- isoforms, HIF-2 appears to play a central role. Prolyl hydroxylase domain-containing protein (PHD), a key regulator connecting oxygen availability and HIF-α expression, is also involved in hypoxic induction of EPO mRNA and the precise roles of PHD paralogs in erythropoiesis are now beginning to be uncovered. On the other hand, widespread expression of EPO receptors (EPOR) beyond erythroid progenitors led to the discovery of non-hematopoietic, pleiotropic roles of EPO in the brain, the heart and the kidney. The precise signal transduction pathways of pleiotropic EPO remain unclear, but carbamylated EPO, which fails to bind to the canonical EPOR homodimers or transduce the JAK2-STAT5 signaling, conferred organ protection through multimeric receptors composed of EPO-R and the common β subunit (βCR). The clinical benefit of normalization of anemia in pre-dialysis CKD by EPO therapy is controversial and recent large-scale, randomized-controlled trials do not favor normalization of anemia by EPO in improving cardiovascular as well as renal outcomes. The optimal EPO therapy should be determined based on the clinical context of individual patients. PMID:22414872

  2. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

  3. 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

  4. ‘You can’t just hit a button’: an ethnographic study of strategies to repurpose data from advanced clinical information systems for clinical process improvement

    PubMed Central

    2013-01-01

    Background Current policies encourage healthcare institutions to acquire clinical information systems (CIS) so that captured data can be used for secondary purposes, including clinical process improvement. Such policies do not account for the extra work required to repurpose data for uses other than direct clinical care, making their implementation problematic. This paper aims to analyze the strategies employed by clinical units to use data effectively for both direct clinical care and clinical process improvement. Methods Ethnographic methods were employed. A total of 54 contextual interviews with health professionals spanning various disciplines and 18 hours of observation were carried out in 5 intensive care units in England using an advanced CIS. Case studies of how the extra work was achieved in each unit were derived from the data and then compared. Results We found that extra work is required to repurpose CIS data for clinical process improvement. Health professionals must enter data not required for clinical care and manipulation of this data into a machine-readable form is often necessary. Ambiguity over who should be responsible for this extra work hindered CIS data usage for clinical process improvement. We describe 11 strategies employed by units to accommodate this extra work, distributing it across roles. Seven of these motivated data entry by health professionals and four addressed the machine readability of data. Many of the strategies relied heavily on the skill and leadership of local clinical customizers. Conclusions To realize the expected clinical process improvements by the use of CIS data, clinical leaders and policy makers need to recognize and support the redistribution of the extra work that is involved in data repurposing. Adequate time, funding, and appropriate motivation are needed to enable units to acquire and deliver the necessary skills in CIS customization. PMID:23574920

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

    PubMed

    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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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. PMID:14508143

  11. 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

  12. 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

  13. 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

  14. 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

  15. Traumatic brain injury: advanced multimodal neuromonitoring from theory to clinical practice.

    PubMed

    Cecil, Sandy; Chen, Patrick M; Callaway, Sarah E; Rowland, Susan M; Adler, David E; Chen, Jefferson W

    2011-04-01

    Traumatic brain injury accounts for nearly 1.4 million injuries and 52 000 deaths annually in the United States. Intensive bedside neuromonitoring is critical in preventing secondary ischemic and hypoxic injury common to patients with traumatic brain injury in the days following trauma. Advancements in multimodal neuromonitoring have allowed the evaluation of changes in markers of brain metabolism (eg, glucose, lactate, pyruvate, and glycerol) and other physiological parameters such as intracranial pressure, cerebral perfusion pressure, cerebral blood flow, partial pressure of oxygen in brain tissue, blood pressure, and brain temperature. This article highlights the use of multimodal monitoring in the intensive care unit at a level I trauma center in the Pacific Northwest. The trends in and significance of metabolic, physiological, and hemodynamic factors in traumatic brain injury are reviewed, the technical aspects of the specific equipment used to monitor these parameters are described, and how multimodal monitoring may guide therapy is demonstrated. As a clinical practice, multimodal neuromonitoring shows great promise in improving bedside therapy in patients with traumatic brain injury, ultimately leading to improved neurological outcomes. PMID:20592189

  16. Analysis of clinical efficacy of CyberKnife® treatment for locally advanced pancreatic cancer

    PubMed Central

    Song, Yongchun; Yuan, Zhiyong; Li, Fengtong; Dong, Yang; Zhuang, Hongqing; Wang, Jingsheng; Chen, Huaming; Wang, Ping

    2015-01-01

    Objective To evaluate the efficacy and safety of CyberKnife® treatment for locally-advanced pancreatic cancer (LAPC). Methods The efficacy of CyberKnife® treatment was analyzed in 59 LAPC patients treated between October 2006 and September 2014. The median tumor volume was 27.1 mL (13.0–125.145 mL). The median prescribed dose was 45 Gy (35–50 Gy), delivered in 5 fractions (3–8 fractions). The overall survival (OS) rates and freedom from local progression (FFLP) rates were estimated using the Kaplan–Meier survival curve. Results The median follow-up for all patients was 10.9 months (3.2–48.7 months) and 15.6 months (3.9–37.6 months) among surviving patients. The median OS was 12.5 months, and the 1-year and 2-year survival rates were 53.9% and 35.1%, respectively. The 1-year FFLP rate was 90.8% based on the computed tomography (CT) evaluation. Grade 1–2 acute and late-stage gastrointestinal (GI) reactions were observed in 61% of the patients. One patient experienced grade 3 toxicity. Conclusion Excellent clinical efficacy was obtained after treatment of LAPC using CyberKnife®, with minimal toxicity. PMID:26109866

  17. X-ray phase-contrast imaging of the breast—advances towards clinical implementation

    PubMed Central

    Herzen, J; Willner, M; Grandl, S; Scherer, K; Bamberg, F; Reiser, M F; Pfeiffer, F; Hellerhoff, K

    2014-01-01

    Breast cancer constitutes about one-quarter of all cancers and is the leading cause of cancer death in women. To reduce breast cancer mortality, mammographic screening programmes have been implemented in many Western countries. However, these programmes remain controversial because of the associated radiation exposure and the need for improvement in terms of diagnostic accuracy. Phase-contrast imaging is a new X-ray-based technology that has been shown to provide enhanced soft-tissue contrast and improved visualization of cancerous structures. Furthermore, there is some indication that these improvements of image quality can be maintained at reduced radiation doses. Thus, X-ray phase-contrast mammography may significantly contribute to advancements in early breast cancer diagnosis. Feasibility studies of X-ray phase-contrast breast CT have provided images that allow resolution of the fine structure of tissue that can otherwise only be obtained by histology. This implies that X-ray phase-contrast imaging may also lead to the development of entirely new (micro-) radiological applications. This review provides a brief overview of the physical characteristics of this new technology and describes recent developments towards clinical implementation of X-ray phase-contrast imaging of the breast. PMID:24452106

  18. 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.

  19. 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…

  20. 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).

  1. 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.

  2. 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

  3. 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. PMID:26636472

  4. Decolorization and mineralization of Allura Red AC aqueous solutions by electrochemical advanced oxidation processes.

    PubMed

    Thiam, Abdoulaye; Sirés, Ignasi; Garrido, José A; Rodríguez, Rosa M; Brillas, Enric

    2015-06-15

    The decolorization and mineralization of solutions containing 230 mg L(-1) of the food azo dye Allura Red AC at pH 3.0 have been studied upon treatment by electrochemical oxidation with electrogenerated H2O2 (EO-H2O2), electro-Fenton (EF) and photoelectro-Fenton (PEF). Experiments were performed with a stirred tank reactor containing a boron-doped diamond (BDD) or Pt anode and an air-diffusion cathode to generate H2O2. The main oxidants were hydroxyl radicals formed at the anode surface from water oxidation and in the bulk from Fenton's reaction between H2O2 and added Fe(2+). The oxidation ability increased in the sequence EO-H2O2 < EF < PEF and faster degradation was always obtained using BDD. PEF process with BDD yielded almost total mineralization following similar trends in SO4(2-), ClO4(-) and NO3(-) media, whereas in Cl(-) medium, mineralization was inhibited by the formation of recalcitrant chloroderivatives. GC-MS analysis confirmed the cleavage of the −N=N− bond with formation of two main aromatics in SO4(2-) medium and three chloroaromatics in Cl(-) solutions. The effective oxidation of final oxalic and oxamic acids by BDD along with the photolysis of Fe(III)-oxalate species by UVA light accounted for the superiority of PEF with BDD. NH4(+), NO3(-) and SO4(2-) ions were released during the mineralization. PMID:25734532

  5. "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

  6. 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. PMID:24507951

  7. 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…

  8. 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

  9. The ITER divertor Thomson scattering system: engineering and advanced hardware solutions

    NASA Astrophysics Data System (ADS)

    Mukhin, E. E.; Semenov, V. V.; Razdobarin, A. G.; Tolstyakov, S. Yu; Kochergin, M. M.; Kurskiev, G. S.; Berezutsky, A. A.; Podushnikova, K. A.; Masyukevich, S. V.; Chernakov, P. V.; Borovkov, A. I.; Modestov, V. S.; Nemov, A. S.; Voinov, A. S.; Kornev, A. F.; Stupnikov, V. K.; Borisov, A. A.; Baranov, G. N.; Koval, A. N.; Makushina, A. F.; Yelizarov, B. A.; Kukushkin, A. S.; Encheva, A.; Andrew, P.

    2012-02-01

    A divertor Thomson scattering (TS) system being developed for ITER has incorporated proven solutions from currently available TS systems. On the other hand any ITER diagnostic has to operate in a hostile environment and very restricted access geometry. Therefore the operation in an environment of intensive stray light, plasma background radiation, the necessity meet the requirement using only a 20 mm gap between divertor cassettes for plasma diagnosis as well as to measure plasma temperatures as low as 1 eV severely constrain the divertor TS diagnostic design. The challenging solutions of this novel diagnostic system which has to ensure its steady performance and also the operability and maintenance are the focus of this report. One of the most demanding parts of the in-vessel diagnostic equipment development is the design assessment using different engineering analyses. The task definition and first results of thermal, e/m and seismic analyses are provided. The process of further improving of the design involves identification of susceptible areas and multiple iterations of the design, as needed. One of the key points for all Thomson scattering diagnostics are the laser capabilities. A high-performance and high-power laser system using a steady-state and high-repetitive mode Nd:YAG laser (2J, 50-100Hz, 3ns) has been developed. The reduced laser pulse duration matched with high-speed low-noise APD detector can be very important under high background light level. For diagnostics such as Thomson scattering and Raman spectroscopy, a high-degree of discrimination against stray light at the laser wavelength is required for successful detection of wavelength-shifted light from the laser-plasma interaction region. For this case of high stray light level, a triple grating polychromator characterized by high rejection and high transmission has been designed and developed. The novel polychromator design minimizes stray light while still maintaining a relatively high

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

    PubMed

    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-response, tailoring

  11. A clinical exploration of neoadjuvant chemotherapy with tegafur, gimeracil, and oteracil potassium capsules combined with oxaliplatin for advanced gastric cancer

    PubMed Central

    Lv, Xinting; Zhang, Li; Huang, Renjun; Song, Weiyong

    2015-01-01

    Background: Advanced gastric cancer refers to tumor invasion into the gastric muscularis propria or even the layer beyond, and has low early gastric cancer diagnosis rate. Purpose: To determine the clinical efficacy and side effects of neoadjuvant chemotherapy with tegafur, gimeracil, and oteracil potassium capsules (TGOP) combined with oxaliplatin (SOX regimen) in patients with advanced gastric cancer. Methods: We evaluated 25 patients with advanced gastric cancer who were admitted and treated with neoadjuvant chemotherapy with the SOX regimen (intravenous injection of 130 mg/m2 oxaliplatin on day 1 followed by oral administration of 60 mg TGOP twice daily on days 1-14), every 3 weeks. The clinical efficacy and side effects of the SOX regimen were evaluated after two courses of treatment, before surgery. Results: Of the 25 patients enrolled in this study, 23 completed two courses of neoadjuvant chemotherapy, and of these, 12 achieved downstaging as determined by the clinical TNM stage, resulting in a total response rate of 52.2%. The 23 patients underwent surgery, with 22 receiving radical resection (95.7%). Among these 23 patients, R0 resection was achieved in 16 (69.6%) and pathological complete remission was observed in one. Conclusion: Neoadjuvant chemotherapy with TGOP combined with oxaliplatin was effective for advanced gastric cancer and had tolerable side effects. PMID:26770529

  12. 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

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

    PubMed

    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

  14. 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.

  15. 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

  16. Unequal burden of disease, unequal participation in clinical trials: solutions from African American and Latino community members.

    PubMed

    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

    2013-02-01

    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

  17. Advances in adsorption of surfactants and their mixtures at solid/solution interfaces.

    PubMed

    Zhang, Rui; Somasundaran, P

    2006-11-16

    Surfactants and their mixtures can drastically change the interfacial properties and hence are used in many industrial processes such as dispersion/flocculation, flotation, emulsification, corrosion inhibition, cosmetics, drug delivery, chemical mechanical polishing, enhanced oil recovery, and nanolithography. A review of studies on adsorption of single surfactant as well as mixtures of various types (anionic-cationic, anionic-nonionic, cationic-nonionic, cationic-zwitterionic and nonionic-nonionic) is presented here along with mechanisms involved. Results obtained using techniques such as zeta potential, flotation, AFM, specular neutron reflectivity, small angle neutron scattering, fluorescence, ESR, Raman spectroscopy, ellipsometry, HPLC and ATR-IR are reviewed along with those from traditional techniques to elucidate the mechanisms of adsorption and particularly to understand synergistic/antagonistic interactions at solution/liquid interfaces and nanostructures of surface aggregates. In addition, adsorption of several mixed surfactant systems is considered due to their industrial relevance. Finally an attempt is made to derive structure-property relationships to provide a solid foundation for the design and use of surfactant formulations for industrial applications. PMID:17052678

  18. Significant diethyl phthalate (DEP) degradation by combined advanced oxidation process in aqueous solution.

    PubMed

    Na, Seungmin; Ahn, Yun-Gyong; Cui, Mingcan; Khim, Jeehyeong

    2012-06-30

    Ultrasound (US) combined with ultraviolet (UV) irradiation and a titanium dioxide (TiO(2)) catalyst was used to effectively remove diethyl phthalate (DEP) from aqueous solutions. Single (sonolysis, photolysis, photocatalysis) and combined (sonophotolysis, sonophotocatalysis) processes were performed to confirm the synergistic effects and DEP degradation mechanism. Using only US, the optimum frequency for DEP degradation was 283 kHz. At this frequency a high rate of hydrogen peroxide (H(2)O(2)) formation was observed of approximately 0.32 mM min(-1). The pseudo-first order degradation rate constants were 10(-2)-10(-4) min(-1) depending on the process. Significant degradation and mineralization (TOC) of DEP were observed with the sonophotolytic and sonophotocatalytic processes. Moreover, synergistic effects of 1.29 and 1.95 were exhibited at the sonophotocatalytic and sonophotolytic DEP degradation, respectively. Furthermore, additional advantageous reactions may occur in the heterogeneous sonophotocatalytic process due to interactions between US, UV, and the photocatalyst. PMID:22406850

  19. 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. PMID:21054243

  20. 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.

  1. 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

  2. [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. PMID:25666087

  3. [Clinical trial of a seven-peptide vaccine and tegafur-uracil/leucovorin as combination therapy for advanced colorectal cancer].

    PubMed

    Inoue, Keisuke; Sugiura, Fumiaki; Kogita, Akihiro; Yoshioka, Yasumasa; Sukegawa, Yasushi; Hida, Jinichi; Okuno, Kiyotaka

    2014-10-01

    We conducted a clinical trial of a seven-peptide vaccine in combination with tegafur-uracil/Leucovorin for advanced colorectal cancer. These antigenic peptides were derived from 5 proteins identified as cancer-testis antigens(ring finger protein 43 [RNF43], translocase of outer mitochondrial membrane 34[TOMM34], maternal embryonic leucine zipper kinase[MELK], forkhead box M1[FOXM1], and holliday junction recognition protein[HJURP])and 2 vascular endothelial growth factor receptors(VEGFR1 and VEGFR2). Thirty patients with advanced colorectal cancer were enrolled. We found that 25 patients had Grade 1 injection-site redness/induration and 1 patient had Grade 3 anaphylaxis. Tumor imaging revealed that 3 patients had a partial response (PR), 15 had stable disease(SD)and 12 had progressive disease(PD). This trial showed that treatment with the seven-peptide vaccine and UFT/LV was well tolerated and feasible for advanced colorectal cancer. PMID:25335716

  4. 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

  5. 25-Hydroxyvitamin D isomerizes to pre-25-hydroxyvitamin D in solution: considerations for calibration in clinical measurements.

    PubMed

    Bedner, Mary; Lippa, Katrice A

    2015-10-01

    Reference standards for the vitamin D metabolites 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, and 3-epi-25-hydroxyvitamin D3 were evaluated using liquid chromatography (LC) with ultraviolet (UV) absorbance and mass spectrometric (MS) detection to assess purity. The chromatograms for solutions of all three 25(OH)D compounds, obtained using a pentafluorophenyl (PFP) stationary phase, revealed peaks that increased in area over time and had MS spectra that were nearly identical to the parent compound, indicating isomers had formed in solution that were unrelated to the reference standard purity. However, when the purity evaluations were completed with a cyanopropyl stationary phase, the isomeric products coeluted with the parent compounds and were not observable. The rates of formation of the isomeric products were found to increase when heated and were confirmed to be pre-25-hydroxyvitamin D compounds using spectral information from both MS detection and nuclear magnetic resonance (NMR) spectroscopy. The rates of conversion of 25(OH)D3 to pre-25(OH)D3 was studied in solutions of ethanol and bovine serum albumin (BSA) in phosphate-buffered saline (PBS). The solutions prepared with BSA/PBS were found to form twice as much pre-25(OH)D3 as the solutions in ethanol. The isomerization of 25(OH)D in solution has implications for calibration of 25(OH)D in clinical measurements, which are discussed. PMID:26359234

  6. The intention of advanced practice registered nurses to remain in positions at family planning clinics serving low-income women.

    PubMed

    Cheng, An-Lin; Kelly, Patricia J; Carlson, Kimberly; Witt, Jacki

    2014-01-01

    Federally funded Title X Family Planning Clinics are critical safety nets for reproductive health services in which advanced practice nurses (APRNs) provide the majority of care. The goal of this study was to identify factors affecting APRN's intention to remain in positions at these clinics. An Internet-administered survey was completed by 406 APRNs working in Title X clinics. The survey, based on a causal model of retention adapted for APRN practice, included 10 factors. Factor significance and model selection criteria were used to determine model fit. Intention to remain in current positions was associated with greater family responsibilities and lower levels of involvement in professional associations. Less routinization, more integration, and a greater sense of distributive justice were significant causal paths to job satisfaction (a significant mediator for intention to remain). Results provide Title X administrators information that can guide them in policy development to maximize APRN retention. PMID:24503318

  7. 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

  8. Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer

    PubMed Central

    2014-01-01

    Background Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD8+ T cells with diverse TCR specificities, possessing non-MHC-restricted cytolytic activities against tumor cells. Clinical studies have confirmed benefit and safety of CIK cell-based therapy for patients with malignancies. This clinical trial was conducted to evaluate efficacy and safety of genetically modified dendritic cells in combination with Cytokine-Induced Killer Cell (gmDCs-CIK) treatment of patients with RCC. Methods 28 patients with advanced renal cancer were admitted to Affiliated Hospital of Academy of Military Medical Sciences from December 2010 to March 2012 and treated by gmDCs-CIK. Clinical efficacy and safety between pre- and post-treatment were compared. Results This analysis showed an objective response rate (ORR) of 39% and a disease control rate (DCR) of as 75%. There is no significant relationship between clinical efficacy and whether metastasis occurred or not (P > 0.05). There is no significant relationship between ORR and cycles of treatment (P > 0.05), but DCR was significantly related with cycles of treatment (P < 0.05). No clinically significant side effects were observed. There were no significant changes of T cell subsets including CD3+, CD4+, CD8+, CD4+ CD25+ Treg cells except Th1 in peripheral blood between day 30 after immunotherapy and 1 day before immunotherapy in 11 patients. Conclusion DC-CIK is feasible and effective in treating advanced renal cancer and thus provides a new approach. Trial registration ClinicalTrials.gov Identifier: NCT01924156. Registration date: August 14, 2013. PMID:24720900

  9. 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

  10. Implementing clinical guidelines for chronic obstructive pulmonary disease: barriers and solutions

    PubMed Central

    Overington, Jeff D.; Huang, Yao C.; Abramson, Michael J.; Brown, Juliet L.; Goddard, John R.; Bowman, Rayleen V.; Fong, Kwun M.

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a complex chronic lung disease characterised by progressive fixed airflow limitation and acute exacerbations that frequently require hospitalisation. Evidence-based clinical guidelines for the diagnosis and management of COPD are now widely available. However, the uptake of these COPD guidelines in clinical practice is highly variable, as is the case for many other chronic disease guidelines. Studies have identified many barriers to implementation of COPD and other guidelines, including factors such as lack of familiarity with guidelines amongst clinicians and inadequate implementation programs. Several methods for enhancing adherence to clinical practice guidelines have been evaluated, including distribution methods, professional education sessions, electronic health records (EHR), point of care reminders and computer decision support systems (CDSS). Results of these studies are mixed to date, and the most effective ways to implement clinical practice guidelines remain unclear. Given the significant resources dedicated to evidence-based medicine, effective dissemination and implementation of best practice at the patient level is an important final step in the process of guideline development. Future efforts should focus on identifying optimal methods for translating the evidence into everyday clinical practice to ensure that patients receive the best care. PMID:25478199

  11. 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. PMID:26910896

  12. 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

  13. Practical Guidance on How to Handle Levodopa/Carbidopa Intestinal Gel Therapy of Advanced PD in a Movement Disorder Clinic

    PubMed Central

    Pedersen, Stephen Wørlich; Clausen, Jesper; Gregerslund, Mie Manon

    2012-01-01

    Continuous dopaminergic delivery is recognized for the capacity to ameliorate symptoms in Parkinson’s disease (PD). In advanced PD the short comings of orally administered Levodopa/Carbidopa include fluctuations resulting in unstable effect and dyskinesia. Levodopa/Carbidopa intestinal gel, LCIG, (Duodopa®, Abbott Laboratories) is delivered continuously through a percutaneous endoscopic gastrostomy with the inner tube placed in the duodenum by means of a device (CADD legacy Duodopa pump (CE 0473)). The therapy implies continuous dopaminergic delivery directly to the duodenum and is therefore unaffected by gastric emptying and represents a major adjuvant in the treatment of advanced PD with significant improvement in motor and non-motor symptoms. The aim of this paper is to suggest the prerequisites for a LCIG clinic and propose a feasible set-up and lean organization of a movement disorder clinic. Secondly, the paper proposes practical handling of patients in LCIG treatment for advanced PD based on experience and initiation of LCIG treatment and follow-up in forty patients. PMID:22848335

  14. [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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy.

    PubMed

    Weidemann, Frank; Maier, Sebastian K G; Störk, Stefan; Brunner, Thomas; Liu, Dan; Hu, Kai; Seydelmann, Nora; Schneider, Andreas; Becher, Jan; Canan-Kühl, Sima; Blaschke, Daniela; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Nordbeck, Peter

    2016-07-15

    Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holter electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holter ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 ± 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses ≥3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter-defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holter ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with

  20. Advanced Practice Registered Nurses and Physician Assistants in Sleep Centers and Clinics: A Survey of Current Roles and Educational Background

    PubMed Central

    Colvin, Loretta; Cartwright, Ann; Collop, Nancy; Freedman, Neil; McLeod, Don; Weaver, Terri E.; Rogers, Ann E.

    2014-01-01

    Study Objectives: To survey Advanced Practice Registered Nurse (APRN) and Physician Assistant (PA) utilization, roles and educational background within the field of sleep medicine. Methods: Electronic surveys distributed to American Academy of Sleep Medicine (AASM) member centers and APRNs and PAs working within sleep centers and clinics. Results: Approximately 40% of responding AASM sleep centers reported utilizing APRNs or PAs in predominantly clinical roles. Of the APRNs and PAs surveyed, 95% reported responsibilities in sleep disordered breathing and more than 50% in insomnia and movement disorders. Most APRNs and PAs were prepared at the graduate level (89%), with sleep-specific education primarily through “on the job” training (86%). All APRNs surveyed were Nurse Practitioners (NPs), with approximately double the number of NPs compared to PAs. Conclusions: APRNs and PAs were reported in sleep centers at proportions similar to national estimates of NPs and PAs in physicians' offices. They report predominantly clinical roles, involving common sleep disorders. Given current predictions that the outpatient healthcare structure will change and the number of APRNs and PAs will increase, understanding the role and utilization of these professionals is necessary to plan for the future care of patients with sleep disorders. Surveyed APRNs and PAs reported a significant deficiency in formal and standardized sleep-specific education. Efforts to provide formal and standardized educational opportunities for APRNs and PAs that focus on their clinical roles within sleep centers could help fill a current educational gap. Citation: Colvin L, Cartwright Ann, Collop N, Freedman N, McLeod D, Weaver TE, Rogers AE. Advanced practice registered nurses and physician assistants in sleep centers and clinics: a survey of current roles and educational background. J Clin Sleep Med 2014;10(5):581-587. PMID:24812545

  1. [Advance of femtosecond small incision lenticule extraction (SMILE) in clinic application].

    PubMed

    Liang, Gang; Zhang, Fengju

    2016-01-01

    Femtosecond small incision lenticule extraction (SMILE) had been performed in clinic more than 5 years in China. With the gradual development of the technology, SMILE has caused more and more attention because of the remarkable clinical effect, micro incision, minimally invasive and refractive stability. The reuse of the refractive lenticule (RL) from SMILE has recently become extensive focus, which brings potential method to corneal refractive surgery from subtraction to addition. This review has clarified the technology of SMILE on the aspects of corneal refractive correct, the clinical effect of reuse the materials (RL), the basis of related research and the possible improvement in the future. PMID:26899224

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

    PubMed

    Bested, Alison C; Logan, Alan C; Selhub, Eva M

    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

  3. 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

  4. 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. PMID:10108501

  5. 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

  6. 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

  7. 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. PMID:26422540

  8. 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…

  9. 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

  10. 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

  11. Clinical Hurdles and Possible Solutions in the Implementation of Closed-Loop Control in Type 1 Diabetes Mellitus

    PubMed Central

    Zisser, Howard

    2011-01-01

    From an engineering perspective, controlling blood glucose appears to be a fairly straightforward single input (glucose), single output (insulin) control problem. Unfortunately, mimicking Mother Nature turns out to be a complex endeavor. The primary hurdle in developing a useful, safe closed-loop control algorithm for an artificial pancreas is the time delays associated with current continuous glucose monitors and subcutaneously delivered insulins. This article will provide a brief history of the artificial pancreas, outline the main clinical hurdles restricting its current implementation, and list possible solutions for success. PMID:22027329

  12. Randomized, controlled, clinical trial of rice versus glucose oral rehydration solutions in infants and young children with acute watery diarrhoea.

    PubMed

    Faruque, A S; Hoque, S S; Fuchs, G J; Mahalanabis, D

    1997-12-01

    A randomized clinical trial was carried out to compare a packaged ready-to-mix rice oral rehydration solution (ORS) to the standard glucose ORS for the treatment of childhood diarrhoea. Children were of either gender, aged 3-35 months, presenting with a history of watery diarrhoea for 72 h or less. The main outcomes examined were stool output, ORS intake, duration of diarrhoea and nutritional recovery during follow-up at 16 d of illness. Stool output in the first 24 h (106 vs 107 g kg(-1)), ORS intake in clinic (93 vs 102 ml per motion) and duration of diarrhoea (88 h vs 81 h) were similar in the two treatment groups. The few episodes that became persistent were similar (2%) in the two groups. The weight gain during follow-up was similar in the two ORS groups. PMID:9475306

  13. Patient-controlled encrypted genomic data: an approach to advance clinical genomics

    PubMed Central

    2012-01-01

    Background The revolution in DNA sequencing technologies over the past decade has made it feasible to sequence an individual’s whole genome at a relatively low cost. The potential value of the information generated by genomic technologies for medicine and society is enormous. However, in order for exome sequencing, and eventually whole genome sequencing, to be implemented clinically, a number of major challenges need to be overcome. For instance, obtaining meaningful informed-consent, managing incidental findings and the great volume of data generated (including multiple findings with uncertain clinical significance), re-interpreting the genomic data and providing additional counselling to patients as genetic knowledge evolves are issues that need to be addressed. It appears that medical genetics is shifting from the present “phenotype-first” medical model to a “data-first” model which leads to multiple complexities. Discussion This manuscript discusses the different challenges associated with integrating genomic technologies into clinical practice and describes a “phenotype-first” approach, namely, “Individualized Mutation-weighed Phenotype Search”, and its benefits. The proposed approach allows for a more efficient prioritization of the genes to be tested in a clinical lab based on both the patient’s phenotype and his/her entire genomic data. It simplifies “informed-consent” for clinical use of genomic technologies and helps to protect the patient’s autonomy and privacy. Overall, this approach could potentially render widespread use of genomic technologies, in the immediate future, practical, ethical and clinically useful. Summary The “Individualized Mutation-weighed Phenotype Search” approach allows for an incremental integration of genomic technologies into clinical practice. It ensures that we do not over-medicalize genomic data but, rather, continue our current medical model which is based on serving the patient’s concerns

  14. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation

    PubMed Central

    Rincon, Melvin Y.; VandenDriessche, Thierry; Chuah, Marinee K.

    2015-01-01

    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 Ca2+-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. PMID:26239654

  15. 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. PMID:26239654

  16. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease.

    PubMed

    Lewiecki, E Michael; Baron, Roland; Bilezikian, John P; Gagel, Robert E; Leonard, Mary B; Leslie, William D; McClung, Michael R; Miller, Paul D

    2016-01-01

    The 2015 Santa Fe Bone Symposium was a venue for healthcare professionals and clinical researchers to present and discuss the clinical relevance of recent advances in the science of skeletal disorders, with a focus on osteoporosis and metabolic bone disease. Symposium topics included new developments in the translation of basic bone science to improved patient care, osteoporosis treatment duration, pediatric bone disease, update of fracture risk assessment, cancer treatment-related bone loss, fracture liaison services, a review of the most significant studies of the past year, and the use of telementoring with Bone Health Extension for Community Healthcare Outcomes, a force multiplier to improve the care of osteoporosis in underserved communities. PMID:26750746

  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. Barrett's esophagus and cancer risk: how research advances can impact clinical practice.

    PubMed

    di Pietro, Massimiliano; Alzoubaidi, Durayd; Fitzgerald, Rebecca C

    2014-07-01

    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

  19. The efficacy and safety of nivolumab in the treatment of advanced melanoma: a meta-analysis of clinical trials

    PubMed Central

    Jin, Conghui; Zhang, Xunlei; Zhao, Kuiling; Xu, Jun; Zhao, Min; Xu, Xiaohong

    2016-01-01

    Background Nivolumab has become a therapeutic regimen for the treatment of patients with advanced melanoma. The goal of this study was to assess the efficacy and safety of nivolumab in patients with advanced melanoma. Methods A systematic search from January 2008 to August 2015 with “nivolumab” and “advanced melanoma” as search terms was performed for possible clinical trials. According to the hazard ratio and the 95% confidence interval (CI) for progression-free survival (PFS), rates of objective response, complete response, partial response, rates of toxic effects, and the efficacy and safety of nivolumab were assessed. Using the software Review Manager (version 5.3) a meta-analysis was performed. Results There were four trials with 1,910 patients included. Based on the four trials, the pooled hazard ratio of PFS was 0.53 (95% CI, 0.43–0.66; P<0.001). The pooled risk ratio for the objective response rate, complete response, and partial response was 2.98% (95% CI, 2.38%–3.73%; P<0.001), 3.71% (95% CI, 2.67%–5.14%; P<0.001), and 2.51% (95% CI, 2.12%–2.99%; P<0.001), respectively. Nivolumab plus ipilimumab therapy significantly increased the risk of grade 3/4 rash and fatigue. Conclusion Nivolumab-based therapy prolonged PFS in treatment of advanced melanoma, with less adverse effects. Nivolumab appears to be a favorable treatment option as a novel, targeted anticancer agent, for patients with advanced melanoma. PMID:27051297

  20. 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

  1. 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

  2. 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

  3. Academia, advocacy, and industry: a collaborative method for clinical research advancement.

    PubMed

    Vanzo, Rena J; Lortz, Amanda; Calhoun, Amy R U L; Carey, John C

    2014-07-01

    Professionals who work in academia, advocacy, and industry often carry out mutually exclusive activities related to research and clinical care. However, there are several examples of collaboration among such professionals that ultimately allows for improved scientific and clinical understanding. This commentary recounts our particular experience (a collaboration between geneticists at the Universities of Minnesota and Utah, the 4p- Support Group, and Lineagen, Inc) and reviews other similar projects. We formally propose this collaborative method as a conduit for future clinical research programs. Specifically, we encourage academicians, directors of family/advocacy/support groups, and members of industry to establish partnerships and document their experiences. The medical community as a whole will benefit from such partnerships and, specifically, families will teach us lessons that could never be learned in a laboratory or textbook. PMID:24700599

  4. From PET/CT to PET/MRI: advances in instrumentation and clinical applications.

    PubMed

    Hu, Zhenhua; Yang, Weidong; Liu, Haixiao; Wang, Kun; Bao, Chengpeng; Song, Tianming; Wang, Jing; Tian, Jie

    2014-11-01

    Multimodality imaging of positron emission tomography/computed tomography (PET/CT) provides both metabolic information and the anatomic structure, which is significantly superior to either PET or CT alone and has greatly improved its clinical applications. Because of the higher soft-tissue contrast of magnetic resonance imaging (MRI) and no extra ionizing radiation, PET/MRI imaging is the hottest topic currently. PET/MRI is swiftly making its way into clinical practice. However, it has many technical difficulties to overcome, such as photomultiplier tubes, which cannot work properly in a magnetic field, and the inability to provide density information on the object for attenuation correction. This paper introduces the technique process of PET/MRI and summarizes its clinical applications, including imaging in oncology, neurology, and cardiology. PMID:25058336

  5. 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

  6. 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

  7. Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome

    PubMed Central

    Hagerman, Randi; Hagerman, Paul

    2014-01-01

    Summary Fragile X syndrome, the leading heritable form of cognitive impairment, is caused by epigenetic silencing of the fragile X (FMR1) gene consequent to large expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, “premutation” expansions (55–200 repeats) can give rise to a family of neurodevelopmental (ADHD, autism spectrum disorder, seizure disorder) and neurodegenerative (FXTAS) clinical phenotypes through an entirely distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Basic cellular, animal, and human studies have helped to elucidate the underlying RNA toxicity mechanism, while clinical research is providing a more nuanced picture of the spectrum of clinical involvement. Whereas advances on both mechanistic and clinical fronts are driving new approaches to targeted treatment, two important issues/needs are emerging: to define the extent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and medical disorders, and to redefine FXTAS in light of its differing presentations and associated features. PMID:23867198

  8. Translational research platforms integrating clinical and omics data: a review of publicly available solutions.

    PubMed

    Canuel, Vincent; Rance, Bastien; Avillach, Paul; Degoulet, Patrice; Burgun, Anita

    2015-03-01

    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

  9. 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

  10. 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

  11. 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. PMID:25243597

  12. Advancing and Sustaining a Clinical Teacher Preparation Partnership: An Exploratory Qualitative Case Study

    ERIC Educational Resources Information Center

    Garrido, Melissa Downey

    2012-01-01

    The national call to "turn [teacher education] upside down" (National Council for Accreditation of Teacher Education, Report of the Blue Ribbon Panel on Clinical Preparation and Partnerships for Improved Student Learning [NCATE], 2010, p. ii) and states' subsequent commitments to pilot recommendations necessitates study of…

  13. 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

  14. In the End What Matters Most? A Review of Clinical Endpoints in Advanced Breast Cancer

    PubMed Central

    McLeod, Deanna; Batist, Gerald; Robidoux, André; Martins, Ilídio R. S.; Mackey, John R.

    2011-01-01

    Many agents are being studied for the treatment of metastatic breast cancer (MBC), yet few studies have demonstrated longer overall survival (OS), the primary measure of clinical benefit in MBC. This paper examines the key endpoints in clinical trials and U.S. Food and Drug Administration (FDA) approvals of drugs for MBC. PubMed was searched (1980 to October 2009) for reports of phase III trials investigating chemotherapy and/or targeted therapy agents in MBC. FDA approval histories (1996–2009) for cytotoxic and biological agents indicated for MBC were reviewed. Of the 73 phase III MBC trials reviewed, a strikingly small proportion of trials demonstrated a gain in OS duration (12%, n = 9). OS gains were less frequently noted in first-line trials (8%) than in trials of second-line plus other lines of therapy (22%). Few trials were designed with the capacity to detect OS effects. Among 37 phase III trials conducted in the last 15 years, only three systemic therapies were approved for first-line use and nine were approved for use as second-line or other lines of therapy. Of these, only four were supported by results showing longer survival times. There is substantial discordance among the design and conduct of clinical trials, FDA drug approval, and the current view of OS as the ultimate measure of clinical benefit. There is an urgent need to reassess standards for clinical benefit in MBC and to establish guidelines for study design and conduct and drug approval. In the end, what matters most is ensuring rapid access to safe and effective oncology treatments. PMID:21212428

  15. 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

  16. 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.

  17. Description of the clinical practice of advanced practice nurses in family-centered early intervention in two rural settings.

    PubMed

    Kang, R; Barnard, K; Oshio, S

    1994-12-01

    The purpose of this study was to describe the scope of clinical practice of advanced practice nurses who were involved in a project designed to increase access of families with at-risk and disabled young children, newborn to 3 years of age, to early intervention services in rural Washington State. The findings from this study are based on the retrospective review of records of clients seen by the advanced practice nurses. Nursing diagnoses and nursing interventions were assigned to chart recordings. The most frequently occurring nursing diagnoses assigned to parents were Altered Parenting, Altered Family Processes, Fear, Noncompliance, and Knowledge Deficit. The most frequently occurring nursing diagnoses assigned to children were Impaired Physical Mobility, Impaired Verban Communication, Altered Nutrition: Less than Body Requirements, Sensory-Perceptual Alteration, and Altered Thought Processes. Categories of nursing intervention recorded most frequently were Monitoring, Planning and Information. Discussion of findings addresses the roles and reimbursement of advanced practice nurses who provide family-centered early intervention services in rural communities. PMID:7870654

  18. 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

  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 study of recombinant interferon alpha-2 (Sch 30500) in advanced gynecological cancers].

    PubMed

    Kasamatsu, T; Ohmi, K; Takeuchi, S; Takamizawa, H; Matsuzawa, M; Kawana, T; Ueda, K; Kubo, H; Tsumuji, Y; Kawashima, Y

    1985-08-01

    Recombinant interferon alpha-2 (Sch 30500) was administered to 29 patients with advanced gynecological cancers (14 patients with cancer of the cervix, 8 with ovarian cancer, 4 with uterine sarcoma, 2 with endometrial cancer and 1 with unclassified cancer). No antitumor effects (CR and PR) were noted in 23 evaluable patients. Side effects observed were fever, tachycardia, diarrhea, chills, general fatigue, anorexia, nausea and vomiting. In some patients, leukopenia, decrease of hemoglobin and elevation of SGOT and SGPT were observed. No production of antibody for Sch 30500 was noted. PMID:3896157

  1. Advanced Renal Failure in Patients with Sickle Cell Anemia: Clinical Course and Prognosis

    PubMed Central

    Cruz, Iluminado A.; Hosten, Adrian O.; Dillard, Martin G.; Castro, Oswaldo L.

    1982-01-01

    Advanced renal failure occurred in nine adult sickle cell disease patients. There were six men and three women with a mean age of 38.6 years. Eight patients had homozygous SS disease, one had sickle cell thalassemia. Three patients had acute renal failure from which they partially recovered. Six developed endstage kidney disease requiring dialysis. Two of these received a kidney transplant, and there was one death in the immediate postoperative period. Angina pectoris, hyperkalemia, and severe anemia complicated chronic dialysis, suggesting that early transplantation should be considered for sickle cell anemia patients with renal failure. PMID:6757451

  2. PTEN polymorphisms contribute to clinical outcomes of advanced lung adenocarcinoma patients treated with platinum-based chemotherapy.

    PubMed

    Yang, Yang; Xu, Wen; Liu, Di; Ding, Xi; Su, Bo; Sun, Yifeng; Gao, Wen

    2016-06-01

    This study aimed to elucidate the impact of PTEN single nucleotide polymorphism (SNP) on clinical outcomes for advanced lung adenocarcinoma (LAC) patients treated with platinum-based chemotherapy. Three functional SNPs (rs11202607 G>A, rs701848 A>G, and rs11202592 G>C) of PTEN gene were genotyped by using DNA from blood samples of 618 advanced LAC patients, and their relationships with clinical outcomes were analyzed. The carriers of homozygous mutant of rs701848 and rs11202592 polymorphisms revealed significantly worse overall survival (OS) than those with heterozygote or wild-type homozygote (18.83 vs. 21.47 vs. 24.37 months, P = 0.034 and 13.40 vs. 19.03 vs. 21.90 months, P = 0.025, respectively). Subgroup analysis revealed that this association was particularly significant in tumor-lymph-node metastasis (TNM) stage III patients. The objective response rates (ORR) and disease control rates (DCR) of patients with genotype AA, AG, and GG in PTEN rs701848 polymorphism were statistically different (24.1 vs 16.6 vs 12.2 %, P = 0.017 and 82.7 vs 76.0 vs 70.2 %, P = 0.029, respectively). Haplotype analysis revealed a protective effect of the haplotype G-A-A (in the order of rs11202592, rs701848, and rs11202607) on chemotherapy efficacy and survival. Taken together, PTEN polymorphisms may contribute to survival and chemotherapy efficacy of advanced LAC patients treated with platinum-based agents. PMID:26695147

  3. 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

  4. The use of metronidazole and amoxicillin in the treatment of advanced periodontal disease. A prospective, controlled clinical trial.

    PubMed

    Berglundh, T; Krok, L; Liljenberg, B; Westfelt, E; Serino, G; Lindhe, J

    1998-05-01

    The present clinical trial was performed to study the effect of systemic administration of metronidazole and amoxicillin as an adjunct to mechanical therapy in patients with advanced periodontal disease. 16 individuals, 10 female and 6 male, aged 35-58 years, with advanced periodontal disease were recruited. A baseline examination included assessment of clinical, radiographical, microbiological and histopathological characteristics of periodontal disease. The 16 patients were randomly distributed into 2 different samples of 8 subjects each. One sample of subjects received during the first 2 weeks of active periodontal therapy, antibiotics administered via the systemic route (metronidazole and amoxicillin). During the corresponding period, the 2nd sample of subjects received a placebo drug (placebo sample). In each of the 16 patients, 2 quadrants (1 in the maxilla and 1 in the mandible) were exposed to non-surgical subgingival scaling and root planing. The contralateral quadrants were left without subgingival instrumentation. Thus, 4 different treatment groups were formed; group 1: antibiotic therapy but no scaling, group 2: antibiotic therapy plus scaling, group 3: placebo therapy but no scaling, group 4: placebo therapy plus scaling. Re-examinations regarding the clinical parameters were performed, samples of the subgingival microbiota harvested and 1 soft tissue biopsy from 1 scaled and 1 non-scaled quadrant obtained 2 months and 12 months after the completion of active therapy. The teeth included in groups 1 and 3 were following the 12-month examination exposed to non-surgical periodontal therapy, and subsequently exited from the study. Groups 2 and 4 were also re-examined 24 months after baseline. The findings demonstrated that in patients with advanced periodontal disease, systemic administration of metronidazole plus amoxicillin resulted in (i) an improvement of the periodontal conditions, (ii) elimination/suppression of putative periodontal pathogens such as

  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. Effectiveness of sub gingival irrigation of an indigenous 1% curcumin solution on clinical and microbiological parameters in chronic periodontitis patients: A pilot randomized clinical trial

    PubMed Central

    Gottumukkala, Sruthima N. V. S.; Koneru, Suneetha; Mannem, Satheesh; Mandalapu, Narendra

    2013-01-01

    Aim: The aim of this study is to evaluate the efficacy of 1% curcumin (CU) solution and compare it with conventional irrigant i.e., 0.2% chlorhexidine (CHX) gluconate and a positive control (saline) as an adjunct to thorough scaling and root planing. Materials and Methods: A total of 23 patients with non-adjacent probing pocket depths (PPDs) ≥5mm were randomly assigned to CHX, CU and positive control irrigation groups and subjected to randomized single blinded clinical control trial. The clinical parameters bleeding on probing, redness, plaque index, PPD and microbiological parameter N-benzoyl-DL-arginine-2-naphthylamide (BANA) test were evaluated at baseline, 1, 3 and 6 months interval. Results: At 1 month evaluation, CU group showed better results compared with the other groups. However, by the end of the study period CHX group showed the best results with as light recurrence in the CU group. The results of BANA test showed similar results for both CU and CHX group throughout the study period. Conclusion: The results of this study show a mild to moderate beneficiary effect of CU irrigation when used as an adjunct to Scaling and root planing. Further studies may be required using varied concentrations of the drug to improve the substantivity of the drug and also to prevent early re-colonization of periodontal pathogens. PMID:24015007

  7. Anxiety, Substance Use, and Their Co-Occurrence: Advances in Clinical Science

    PubMed Central

    Zvolensky, Michael J.; Buckner, Julia D.; Norton, Peter J.; Smits, Jasper A. J.

    2011-01-01

    Research and clinical literatures are replete with examples that psychological disorders are related to drug use, abuse, and dependence. The preponderance of scientific work addressing relations among psychopathological processes and drug use, abuse, and dependence has been focused primarily on psychotic disorders, major depression, antisocial personality disorder, and attention deficit hyperactivity disorder. This corpus of empirical work has indicated that there are clinically meaningful relations among particular types of psychopathology and the onset and maintenance of substance use behaviors and disorders and, in turn, that substance use and use-related problems can impact vulnerability for psychopathology. Within this public health context, it is striking that despite the fact that anxiety disorders are one of the most common classes of psychological problems (Kessler et al., 2005), there has been limited programmatic study of the relations between anxiety vulnerability processes and substance use disorders. PMID:21857769

  8. Advances in the medical research and clinical applications on the plasma DNA

    PubMed Central

    Chen, Yuanyuan; Wu, Zhanhe

    2014-01-01

    Plasma DNA has had a strong impact and influence on basic medical research and clinical practice since the discovery of low levels of plasma DNA in healthy individuals under different physiological conditions. Although the source of circulating DNA still requires further investigation, a wide range of research has also proven the value of qualitative and quantitative measurements of plasma DNA in many disease conditions. The use of plasma DNA has a biomarker is advantageous due to accessibility, reliability, reproducibility, sensitivity, specific and relatively low cost. Recently, the detection of circulating (plasma) DNA quantitative changes have been using in the studies on the tumor gene mutations and to monitor disease progressing and to predict the disease prognosis. Such technique also has been using other many different fields, particularly in prenatal diagnosis, for which plasma DNA testing is preferable due to non-invasiveness. This article reviews the research progression and clinical applications of plasma DNA in the last several years. PMID:26835332

  9. Current advances in research and clinical applications of PLGA-based nanotechnology

    PubMed Central

    Lü, Jian-Ming; Wang, Xinwen; Marin-Muller, Christian; Wang, Hao; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2009-01-01

    Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases. PMID:19435455

  10. 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

  11. 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. PMID:26668752

  12. 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

  13. 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

  14. 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

  15. Latest research and clinical treatment of advanced-stage epithelial ovarian cancer

    PubMed Central

    Coleman, Robert L.; Monk, Bradley J.; Sood, Anil K.; Herzog, Thomas J.

    2013-01-01

    The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free and overall survival, although the cure rates have only modestly been affected. Maintenance therapy holds promise, but studies have yet to identify an agent and/or strategy that can affect survival. Recurrent disease is largely an incurable state; however, current intervention with selected surgery, combination and targeted therapy and investigational protocols are impacting progression-free survival. Ovarian cancer is a diverse and genomically complex disease, which commands global attention. Rational investigation must balance the high rate of discovery with lagging clinical investigation and limited patient resources. Nevertheless, armamentarium growth offers unprecedented opportunities for patients suffering with this disease. This Review presents and reviews the contemporary management of the disease spectrum termed epithelial ‘ovarian’ cancer and introduces the direction and early results of clinical investigation. PMID:23381004

  16. Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Ryu, In Sun; Lee, Jeong Hyun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Cho, Kyung-Ja

    2015-10-01

    Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP. PMID:25149290

  17. 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

  18. Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer.

    PubMed

    Chung, Moon Jae; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Song, Si Young

    2014-09-01

    Second-line chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer has shown disappointing survival outcomes due to rapid disease progression and performance deterioration. The aim of this phase II trial was to evaluate the efficacy and safety of adoptive immunotherapy using ex vivo-expanded, cytokine-induced killer (CIK) cells in gemcitabine-refractory advanced pancreatic cancer. Patients with advanced pancreatic cancer who showed disease progression during gemcitabine-based chemotherapy were enrolled in this study. For generation of CIK cells, peripheral blood samples were collected from each patient and cultured with anti-CD3 monoclonal antibody and IL-2. Patients received CIK cells intravenously 10 times, every week for 5 weeks and then every other week for 10 weeks. Twenty patients were enrolled between November 2009 and September 2010. The disease control rate was 25 % (4/16 patients). The median progression-free survival (PFS) was 11.0 weeks (95 % CI 8.8-13.2), and the median overall survival (OS) was 26.6 weeks (95 % CI 8.6-44.6). Grade 3 toxicities included general weakness in two patients and thrombocytopenia in one patient. Grade 4 hematologic or non-hematologic toxicity was not observed. Patients showed improvement in pancreatic pain, gastrointestinal distress, jaundice, body image alterations, altered bowel habits, health satisfaction, and sexuality when assessing quality of life (QoL). Adoptive immunotherapy using CIK cells showed comparable PFS and OS to survival data of previous trials that assessed conventional chemotherapies while maintaining tolerability and showing encouraging results in terms of patient QoL in gemcitabine-refractory advanced pancreatic cancer (clinicalTrials.gov number NCT00965718). PMID:24916038

  19. The Clinical Significance of MiR-148a as a Predictive Biomarker in Patients with Advanced Colorectal Cancer

    PubMed Central

    Takahashi, Masanobu; Cuatrecasas, Miriam; Balaguer, Francesc; Hur, Keun; Toiyama, Yuji; Castells, Antoni; Boland, C. Richard; Goel, Ajay

    2012-01-01

    Aim Development of robust prognostic and/or predictive biomarkers in patients with colorectal cancer (CRC) is imperative for advancing treatment strategies for this disease. We aimed to determine whether expression status of certain miRNAs might have prognostic/predictive value in CRC patients treated with conventional cytotoxic chemotherapies. Methods We studied a cohort of 273 CRC specimens from stage II/III patients treated with 5-fluorouracil-based adjuvant chemotherapy and stage IV patients subjected to 5-fluorouracil and oxaliplatin-based chemotherapy. In a screening set (n = 44), 13 of 21 candidate miRNAs were successfully quantified by multiplex quantitative RT-PCR. In the validation set comprising of the entire patient cohort, miR-148a expression status was assessed by quantitative RT-PCR, and its promoter methylation was quantified by bisulfite pyrosequencing. Lastly, we analyzed the associations between miR-148a expression and patient survival. Results Among the candidate miRNAs studied, miR-148a expression was most significantly down-regulated in advanced CRC tissues. In stage III and IV CRC, low miR-148a expression was associated with significantly shorter disease free-survival (DFS), a worse therapeutic response, and poor overall survival (OS). Furthermore, miR-148a methylation status correlated inversely with its expression, and was associated with worse survival in stage IV CRC. In multivariate analysis, miR-148a expression was an independent prognostic/predictive biomarker for advanced CRC patients (DFS in stage III, low vs. high expression, HR 2.11; OS in stage IV, HR 1.93). Discussion MiR-148a status has a prognostic/predictive value in advanced CRC patients treated with conventional chemotherapy, which has important clinical implications in improving therapeutic strategies and personalized management of this malignancy. PMID:23056401

  20. 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

  1. Clinical Applications of Geometrical Field Matching in Radiotherapy Based on a New Analytical Solution

    SciTech Connect

    Hernandez, Victor; Arenas, Meritxell; Pons, Ferran; Sempau, Josep

    2011-07-01

    A new analytical formalism has been published recently that provides all the parameters necessary for geometrical field matching in radiotherapy. The present work applies the general expressions for craniospinal irradiation, breast irradiation with a supraclavicular half-field, and breast irradiation with a supraclavicular full-field. We also explore the formalism as a tool to analyze and compare different techniques. Field matching is achieved by imposing both parallelism and coincidence between the side planes of adjacent fields. The rotation angles and either the field aperture for a certain isocenter position or the isocenter coordinates for a given field aperture are supplied. All of the already known exact solutions are reproduced. New expressions for the field aperture and for the isocenter coordinates, which were not previously available, are also computed. If tangential fields at a fixed source-to-skin distance are used together with a supraclavicular full-field, different apertures for each tangential field are required to achieve a correct match. If an isocentric technique for the tangential fields or a supraclavicular half-field is used, this complication is avoided. The breast technique with the supraclavicular half-field is recommended, because it presents several advantages with respect to the supraclavicular full-field. This formalism provides a useful tool in cases where matching of adjacent fields is necessary.

  2. 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.

  3. Perimetric progression using the Visual Field Index and the Advanced Glaucoma Intervention Study score and its clinical correlations

    PubMed Central

    Gros-Otero, Juan; Castejón, Miguel; Paz-Moreno, Javier; Mikropoulos, Dimitrios; Teus, Miguel

    2014-01-01

    Purpose To evaluate the association between clinical parameters and the diagnosis of progression using VFI (Visual Field Index) and AGIS (Advanced Glaucoma Intervention Study) score in primary open angle glaucoma. Methods Retrospective study of 517 visual fields of 78 eyes with primary open angle glaucoma analyzed with VFI and AGIS score. Clinical data registered included: age, sphere, pachimetry, basal intraocular pressure (IOP), and IOP during the follow up. Results Only the AGIS score diagnosis of progression was associated with the clinical parameters registered. Among the analyzed data, the mean IOP during follow up (p = 0.0005) and IOP at the third month of follow up (p = 0.004) were statistically associated with progression using the AGIS criteria. Conclusion The diagnosis of perimetric progression using the AGIS score in the current study was closer to the real functional progression than the diagnosis using the VFI, as the former was associated with known risk factors for progression in glaucoma. PMID:25182851

  4. [Domains in the clinical practice of Clinical Nursing Experts in Germany and their correspondence with the internationally described "Advanced Nursing Practice"].

    PubMed

    Mendel, Simon; Feuchtinger, Johanna

    2009-06-01

    In spite of a growing trend toward academic education and increasing numbers of "nursing experts" functioning as change agents in Germany, actual nursing experts as in the internationally described Advanced Nursing Practice (ANP) are scarce. Drawing from a ten-year experience in implementing the international concept, the University Hospital Freiburg (UKF), Germany, constitutes a notable exception, as it presently employs ten clinically practicing nursing experts. Based on this background of educating nursing experts, this presentation aims at describing the implementation of the nursing expert's role and its fit and conformance with the international ANP. A 3-stage Delphi design was used for interviewing all the nursing experts at the hospital (n = 10) about their expert opinions; in addition, all nursing managers (n = 7) as well as unit and team leaders (n = 49) were asked about their opinion to relevant functions and domains of nursing experts. The following clinical practice domains of nursing experts were identified: Direct patient care, patient education, support and supervision of nurses, maintenance and expansion of professional skills and knowledge of the nursing staff, counselling of managers, quality assurance and organizational development, theory to practice transfer, nursing research, maintenance of own professional skills and knowledge and continuing education, and publicity work. Additionally, a three-year nursing education, a longer lasting professional experience, a degree in nursing science or nursing education, and specialist skills in the respective area of expertise were identified as credentials for nursing expert practice. The nursing expert concept at UKF shows elements of the international ANP with similarities to the role of a Clinical Nurse Specialist. PMID:19496033

  5. Clinical challenges in HIV/AIDS: Hints for advancing prevention and patient management strategies.

    PubMed

    Sued, Omar; Figueroa, María Inés; Cahn, Pedro

    2016-08-01

    Acquired immune deficiency syndrome has been one of the most devastating epidemics of the last century. The current estimate for people living with the HIV is 36.9 million. Today, despite availability of potent and safe drugs for effective treatment, lifelong therapy is required for preventing HIV re-emergence from a pool of latently infected cells. However, recent evidence show the importance to expand HIV testing, to offer antiretroviral treatment to all infected individuals, and to ensure retention through all the cascade of care. In addition, circumcision, pre-exposure prophylaxis, and other biomedical tools are now available for included in a comprehensive preventive package. Use of all the available tools might allow cutting the HIV transmission in 2030. In this article, we review the status of the epidemic, the latest advances in prevention and treatment, the concept of treatment as prevention and the challenges and opportunities for the HIV cure agenda. PMID:27117711

  6. 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

  7. 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. PMID:26395136

  8. PET/SPECT molecular imaging in clinical neuroscience: recent advances in the investigation of CNS diseases

    PubMed Central

    Lu, Feng-Mei

    2015-01-01

    Molecular imaging is an attractive technology widely used in clinical practice that greatly enhances our understanding of the pathophysiology and treatment in central nervous system (CNS) diseases. It is a novel multidisciplinary technique that can be defined as real-time visualization, in vivo characterization and qualification of biological processes at the molecular and cellular level. It involves the imaging modalities and the corresponding imaging agents. Nowadays, molecular imaging in neuroscience has provided tremendous insights into disturbed human brain function. Among all of the molecular imaging modalities, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have occupied a particular position that visualize and measure the physiological processes using high-affinity and high-specificity molecular radioactive tracers as imaging probes in intact living brain. In this review, we will put emphasis on the PET/SPECT applications in Alzheimer’s disease (AD) and Parkinson’s disease (PD) as major CNS disorders. We will first give an overview of the main classical molecular neuroimaging modalities. Then, the major clinical applications of PET and SPECT along with molecular probes in the fields of psychiatry and neurology will be discussed. PMID:26029646

  9. A Psychometric Evaluation of an Advanced Pharmacy Practice Experience Clinical Competency Framework

    PubMed Central

    Doty, Randell E.; Nemire, Ruth E.

    2015-01-01

    Objective. To assess the psychometric properties of the clinical competency framework known as the System of Universal Clinical Competency Evaluation in the Sunshine State (SUCCESS), including its internal consistency and content, construct, and criterion validity. Methods. Sub-competency items within each hypothesized competency pair were subjected to principal components factor analysis to demonstrate convergent and discriminant validity. Varimax rotation was conducted for each competency pair (eg, competency 1 vs competency 2, competency 1 vs competency 3, competency 2 vs competency 3). Internal consistency was evaluated using Cronbach alpha. Results. Of the initial 78 pairings, 44 (56%) demonstrated convergent and discriminant validity. Five pairs of competencies were unidimensional. Of the 34 pairs where at least 1 competency was multidimensional, most (91%) were from competencies 7, 11, and 12, indicating modifications were warranted in those competencies. After reconfiguring the competencies, 76 (94%) of the 81 pairs resulted in 2 factors as required. A unidimensional factor emerged when all 13 of the competencies were entered into a factor analysis. The internal consistency of all of the competencies was satisfactory. Conclusion. Psychometric evaluation shows the SUCCESS framework demonstrates adequate reliability and validity for most competencies. However, it also provides guidance where improvements are needed as part of a continuous quality improvement program. PMID:25861100

  10. Advancing Clinical Practice and Policy through Guidelines. The Role of the American Thoracic Society

    PubMed Central

    Gould, Michael K.

    2013-01-01

    In the face of an overwhelmingly large and growing medical literature, providers often turn to clinical practice guidelines to inform the decisions they make with patients. By systematically appraising the evidence and providing transparent recommendations for practice, guidelines have the potential to improve both bedside decision-making and health policy. This potential has not been fully realized because most guidelines lack transparency, are tainted by conflicts of interest, or fail to employ rigorous methods to appraise the evidence. To address the shortcomings of past guidelines, the Institute of Medicine (IOM) published recommendations for trustworthy guidelines, effectively setting the “gold standard” for what constitutes a high-quality guideline. Along with many other groups that develop guidelines, the American Thoracic Society (ATS) is rapidly evolving processes for development and implementation to meet many of the IOM standards. This Pulmonary Perspective describes the rapidly changing landscape of clinical practice guidelines, the role of the ATS in this landscape, and the activities the ATS is engaged in to ensure that the guidelines it produces are of the highest quality with the broadest impact. PMID:23392437

  11. Leveraging effective clinical registries to advance medical care quality and transparency.

    PubMed

    Klaiman, Tamar; Pracilio, Valerie; Kimberly, Laura; Cecil, Kate; Legnini, Mark

    2014-04-01

    Policy makers, payers, and the general public are increasingly focused on health care quality improvement. Measuring quality requires robust data systems that collect data over time, can be integrated with other systems, and can be analyzed easily for trends. The goal of this project was to study effective tools and strategies in the design and use of clinical registries with the potential to facilitate quality improvement, value-based purchasing, and public reporting on the quality of care. The research team worked with an expert panel to define characteristics of effectiveness, and studied examples of effective registries in cancer, cardiovascular care, maternity, and joint replacement. The research team found that effective registries were successful in 1 or more of 6 key areas: data standardization, transparency, accuracy/completeness of data, participation by providers, financial sustainability, and/or providing feedback to providers. The findings from this work can assist registry designers, sponsors, and researchers in implementing strategies to increase the use of clinical registries to improve patient care and outcomes. PMID:24152057

  12. 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

  13. Nuclear magnetic resonance based metabolomics and liver diseases: Recent advances and future clinical applications

    PubMed Central

    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”. PMID:26755887

  14. 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

  15. The 3R principle: advancing clinical application of human pluripotent stem cells

    PubMed Central

    2013-01-01

    The first derivation of human embryonic stem cells brought with it a clear understanding that animal models of human disease might be replaced by an unlimited supply of human cells for research, drug discovery, and drug development. With the advent of clinical trials using human pluripotent stem cell-based therapies, it is both timely and relevant to reflect on factors that will facilitate future translation of this technology. Human pluripotent cells are increasingly being used to investigate the molecular mechanisms that underpin normal and pathological human development. Their differentiated progeny are also being used to identify novel pharmaceuticals, to screen for toxic effects of known chemicals, and to investigate cell or tissue transplantation strategies. The intrinsic assumption of these research efforts is that the information gained from these studies will be more accurate, and therefore of greater relevance, than traditional investigations based on animal models of human disease and injury. This review will therefore evaluate how animals and animal-derived products are used for human pluripotent stem cell research, and will indicate how efforts to further reduce or remove animals and animal products from this research will increase the clinical translation of human pluripotent stem cell technologies through drug discovery, toxicology screening, and cell replacement therapies. PMID:23510719

  16. 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

  17. Advances in WNK signaling of salt and potassium metabolism: clinical implications.

    PubMed

    Arroyo, Juan Pablo; Gamba, Gerardo

    2012-01-01

    Recent evidence due to the discovery of a family of kinases implicated in arterial hypertension now points to the underlying molecular mechanisms that dictate Na(+), K(+) and water handling in the nephron. These new key players need to be understood in order to fully comprehend the pathophysiology, manifestations, and treatment of common clinical entities such as hypovolemic shock, congestive heart failure, primary hyperaldosteronism, nephrotic syndrome and hypertension. It is through the analysis of the volume status and electrolyte abnormalities that commonly present with these diseases that we can begin to create a link between the abstract concept of a kinase regulation and how a patient will respond to a particular treatment. This review is an attempt to bridge that gap. PMID:22508439

  18. [Advances in Pathogenesis and Related Clinical Research of Thromboembolism in Patients with Thalassemia after Splenectomy].

    PubMed

    Sun, Na; Cheng, Peng; Deng, Dong-Hong

    2016-06-01

    Thalassemia is the most common human hereditary hemolytic anemia. Due to splenomegaly and hypersp-lenism, splenectomy can be used as a means of treatment for thalassemia. Various complications following splenectomy, however, especially thromboembolic complications are remarkable. This review summarizes the incidence, clinical manifestations and development time of thromboembolism. The pathogenesis of thromboembolism after splenectomy in thalassemia, such as abnormal platelet number and function, changes in red cell membrane, endothelial cell damage, dysfunction of other procoagulant and anticoagulant factors, and local factors associated with splenectomy are elaborated and the trategies to prevent and treat the thromboembolic events in thalassemia after splenectomy, including the attention to risk factors associated with splenectomy, a reassessment of splenectomy, regular blood transfusion to reduce the ratio of abnormal red blood cells, treatment with anticoagulant and antiplatelet drugs, application of hydroxyurea and stem cell transplantation are discussed. PMID:27342540

  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. 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. PMID:16999004

  1. Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations

    PubMed Central

    Sweet, Kendra; Pinilla-Ibarz, Javier; Zhang, Ling

    2014-01-01

    The treatment for chronic myeloid leukemia has changed significantly over the past 15 years, and as of now, there are five BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1) tyrosine kinase inhibitors that have gained approval for treatment of this disease. All five are very effective drugs, and the decision surrounding which to use in specific patients is based on numerous factors. Bosutinib is one of the newer tyrosine kinase inhibitors to gain approval, and has been studied in the first-line setting as well as after failure of other tyrosine kinase inhibitors. It is an SRC-ABL1 (steroid receptor co-activator-ABL1) inhibitor that works in the presence of most kinase domain mutations. The primary side effects of bosutinib are gastrointestinal upsets. In the appropriate clinical setting, bosutinib can be considered a valuable addition to the armamentarium of treatments available for chronic myeloid leukemia. PMID:25045255

  2. 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

  3. 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

  4. [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

  5. 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.

  6. 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

    2015-01-01

    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

  7. Extravascular lung water in critical care: recent advances and clinical applications.

    PubMed

    Jozwiak, Mathieu; Teboul, Jean-Louis; Monnet, Xavier

    2015-12-01

    Extravascular lung water (EVLW) is the amount of fluid that is accumulated in the interstitial and alveolar spaces. In lung oedema, EVLW increases either because of increased lung permeability or because of increased hydrostatic pressure in the pulmonary capillaries, or both. Increased EVLW is always potentially life-threatening, mainly because it impairs gas exchange and reduces lung compliance. The only technique that provides an easy measurement of EVLW at the bedside is transpulmonary thermodilution. The validation of EVLW measurements by thermodilution was based on studies showing reasonable correlations with gravimetry or thermo-dye dilution in experimental and clinical studies. EVLW should be indexed to predicted body weight. This indexation reduces the proportion of ARDS patients for whom EVLW is in the normal range. Compared to non-indexed EVLW, indexed EVLW (EVLWI) is better correlated with the lung injury score and the oxygenation and it is a better predictor of mortality of patients with acute lung injury or acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution also provides the pulmonary vascular permeability index (PVPI), which is an indirect reflection of the integrity of the alveolocapillary barrier. As clinical applications, EVLWI and PVPI may be useful to guide fluid management of patients at risk of fluid overload, as during septic shock and ARDS. High EVLWI and PVPI values predict mortality in several categories of critically ill patients, especially during ARDS. Thus, fluid administration should be limited when EVLWI is already high. Whatever the value of EVLWI, PVPI may indicate that fluid administration is particularly at risk of aggravating lung oedema. In the acute phase of haemodynamic resuscitation during septic shock and ARDS, high EVLWI and PVPI values may warn of the risk of fluid overload and prevent excessive volume expansion. At the post-resuscitation phase, they may prompt initiation of fluid removal thereby

  8. 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

  9. 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

  10. Advanced 3-D analysis, client-server systems, and cloud computing-Integration of cardiovascular imaging data into clinical workflows of transcatheter aortic valve replacement.

    PubMed

    Schoenhagen, Paul; Zimmermann, Mathis; Falkner, Juergen

    2013-06-01

    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

  11. 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.

  12. Clinical effect of a mixed solution of sodium hyaluronate and sodium carboxymethylcellulose during the transconjunctival approach for orbital wall reconstruction.

    PubMed

    Kang, Byung Wan; Lee, Hyo Seok; Oh, Han Jin; Yoon, Kyung Chul

    2012-08-01

    This study aimed to evaluate the anti-adhesive effect of a mixed solution of sodium hyaluronate and sodium carboxymethylcellulose (HACMC, Guardix-sol®) during the transconjunctival approach to orbital wall reconstruction. Eighty-seven patients who underwent orbital wall reconstruction by the transconjunctival approach were enrolled in this prospective study. We applied HACMC between the orbicularis oculi muscle and the orbital septum after surgery in 47 patients and did not use it in 40 patients. Lower lid retraction and marginal reflex distance 2 (MRD(2)) were measured to analyze the degree of postoperative adhesion at 1 week and 1, 3, and 6 months. The degree of MRD(2) showed clinically significant differences at postoperative 1 week and 1 month between the HACMC and control groups (p<0.05). Lower lid ectropion developed in two patients (5.0%) in the control group but did not occur in the HACMC group. In orbital wall reconstruction by the transconjunctival approach, the HACMC mixture solution is effective for preventing adhesion and lower lid ectropion during the early postoperative period. PMID:22977754

  13. Clinical Effect of a Mixed Solution of Sodium Hyaluronate and Sodium Carboxymethylcellulose During the Transconjunctival Approach for Orbital Wall Reconstruction

    PubMed Central

    Kang, Byung Wan; Lee, Hyo Seok; Oh, Han Jin

    2012-01-01

    This study aimed to evaluate the anti-adhesive effect of a mixed solution of sodium hyaluronate and sodium carboxymethylcellulose (HACMC, Guardix-sol®) during the transconjunctival approach to orbital wall reconstruction. Eighty-seven patients who underwent orbital wall reconstruction by the transconjunctival approach were enrolled in this prospective study. We applied HACMC between the orbicularis oculi muscle and the orbital septum after surgery in 47 patients and did not use it in 40 patients. Lower lid retraction and marginal reflex distance 2 (MRD2) were measured to analyze the degree of postoperative adhesion at 1 week and 1, 3, and 6 months. The degree of MRD2 showed clinically significant differences at postoperative 1 week and 1 month between the HACMC and control groups (p<0.05). Lower lid ectropion developed in two patients (5.0%) in the control group but did not occur in the HACMC group. In orbital wall reconstruction by the transconjunctival approach, the HACMC mixture solution is effective for preventing adhesion and lower lid ectropion during the early postoperative period. PMID:22977754

  14. 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

  15. 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.

  16. Real-time photoacoustic and ultrasound imaging: a simple solution for clinical ultrasound systems with linear arrays

    NASA Astrophysics Data System (ADS)

    Montilla, Leonardo G.; Olafsson, Ragnar; Bauer, Daniel R.; Witte, Russell S.

    2013-01-01

    Recent clinical studies have demonstrated that photoacoustic imaging (PAI) provides important diagnostic information during a routine breast exam for cancer. PAI enhances contrast between blood vessels and background tissue, which can help characterize suspicious lesions. However, most PAI systems are either not compatible with commercial ultrasound systems or inefficiently deliver light to the region of interest, effectively reducing the sensitivity of the technique. To address and potentially overcome these limitations, we developed an accessory for a standard linear ultrasound array that optimizes light delivery for PAI. The photoacoustic enabling device (PED) exploits an optically transparent acoustic reflector to help direct laser illumination to the region of interest. This study compares the PED with standard fiber bundle illumination in scattering and non-scattering media. In scattering media with the same incident fluence, the PED enhanced the photoacoustic signal by 18 dB at a depth of 5 mm and 6 dB at a depth of 20 mm. To demonstrate in vivo feasibility, we also used the device to image a mouse with a pancreatic tumor. The PED identified blood vessels at the periphery of the tumor, suggesting that PAI provides complementary contrast to standard pulse echo ultrasound. The PED is a simple and inexpensive solution that facilitates the translation of PAI technology to the clinic for routine screening of breast cancer.

  17. 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

  18. Real-time photoacoustic and ultrasound imaging: a simple solution for clinical ultrasound systems with linear arrays.

    PubMed

    Montilla, Leonardo G; Olafsson, Ragnar; Bauer, Daniel R; Witte, Russell S

    2013-01-01

    Recent clinical studies have demonstrated that photoacoustic imaging (PAI) provides important diagnostic information during a routine breast exam for cancer. PAI enhances contrast between blood vessels and background tissue, which can help characterize suspicious lesions. However, most PAI systems are either not compatible with commercial ultrasound systems or inefficiently deliver light to the region of interest, effectively reducing the sensitivity of the technique. To address and potentially overcome these limitations, we developed an accessory for a standard linear ultrasound array that optimizes light delivery for PAI. The photoacoustic enabling device (PED) exploits an optically transparent acoustic reflector to help direct laser illumination to the region of interest. This study compares the PED with standard fiber bundle illumination in scattering and non-scattering media. In scattering media with the same incident fluence, the PED enhanced the photoacoustic signal by 18 dB at a depth of 5 mm and 6 dB at a depth of 20 mm. To demonstrate in vivo feasibility, we also used the device to image a mouse with a pancreatic tumor. The PED identified blood vessels at the periphery of the tumor, suggesting that PAI provides complementary contrast to standard pulse echo ultrasound. The PED is a simple and inexpensive solution that facilitates the translation of PAI technology to the clinic for routine screening of breast cancer. PMID:23221479

  19. 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

  20. 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

  1. 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

  2. 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. PMID:27214312

  3. 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

  4. 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

  5. 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

  6. 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

  7. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    PubMed Central

    Everts, Bart; Pearce, Edward J.

    2014-01-01

    Dendritic cells (DCs) are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes. PMID:24847328

  8. 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

  9. 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

  10. The prognostic significance of left ventricular ejection fraction in patients with advanced cancer treated in phase I clinical trials

    PubMed Central

    Said, R.; Banchs, J.; Wheler, J.; Hess, K. R.; Falchook, G.; Fu, S.; Naing, A.; Hong, D.; Piha-Paul, S.; Ye, Y.; Yeh, E.; Wolff, R. A.; Tsimberidou, A. M.

    2014-01-01

    Background New targeted agents may cause acute cardiac events. The purpose of our study was to investigate the incidence and the prognostic significance of left ventricular ejection fraction (LVEF) in phase I trials. Patients and methods Between October 2008 and September 2011, the records of 1166 consecutive patients with advanced cancer treated in the Phase I Clinic who underwent echocardiography were retrospectively reviewed. Results Most of the patients were White (78%), and the most common tumor types were colorectal cancer and melanoma. Of 1166 patients, 177 (15.2%) patients had an LVEF of <50%. No difference in overall survival (OS) between patients with LVEF ≥ 50% and patients with LVEF < 50% was seen (median OS 7.4 versus 7.0 months, P = 0.84). Patients with LVEF ≤ 35% had shorter survival compared with those with LVEF between 35% and 50% (median 4.2 versus 8.0 months; P = 0.005). In multivariate analysis of patients with LVEF < 50%, independent factors predicting longer survival were LVEF > 35%, ≤2 prior systemic therapies, ≤2 metastatic sites, and normal lactate dehydrogenase and albumin levels. Conclusion Echocardiography would improve patient selection for enrollment in phase I clinical trials. These data suggest that it is safe to treat patients with LVEF between 35% and 50%. PMID:24356639

  11. Clinical use of dopamine antagonist sulpiride to advance first ovulation in transitional mares.

    PubMed

    Panzani, D; Zicchino, I; Taras, A; Marmorini, P; Crisci, A; Rota, A; Camillo, F

    2011-01-01

    sulpiride treatment when follicles were 25 mm in diameter resulted in a significant advancement of cyclicity in non-photo-stimulated mares. Pregnancy rates after artificial insemination of treated mares were similar to those of untreated animals. PMID:20875676

  12. P13.09ADVANCES IN CLINICAL APPLICATION OF BORON NEUTRON CAPTURE THERAPY (BNCT) IN GLIOBLASTOMA

    PubMed Central

    Detta, A.; Cruickshank, G.C.; Green, S.; Lockyer, N.P.; Ngoga, D.; Ghani, Z.; Phoenix, B.

    2014-01-01

    BNCT is a biologically targeted form of enhanced cellular radiotherapy where preferential accumulation of boron in the cancerous as opposed to adjacent normal cells is able to interact with incident neutrons to cause irreversible alpha particle DNA damage. The key to the implementation of this potentially powerful and selective therapy is the delivery of at least 30ppm 10B within the tumour tissue while minimising superfluous 10B in healthy tissue. It is thus an elegant technique for treating infiltrating tumours such as diffuse gliomas. In order to assess its clinical potential we carried out a pharmacokinetic study in glioblastoma patients where we sought to determine the optimal route of delivering a new formulation of the boronated drug (p-boronophenylalanine, BPA), its pharmacokinetic behaviour, toxicity profile, and cellular uptake. Using a number of analytical techniques, including inductively-coupled plasma mass spectrometry, secondary ion mass spectrometry (SIMS) and immunohistochemistry (IHC), boron was measured at various times in blood, urine, cerebrospinal fluid, extracellular fluid (ECF), and tumour-related solid tissue spanning 0.5 h pre- and up to 48 h post-BPA infusion in newly-diagnosed patients (n = 10). Blood was sampled through a central catheter whilst the ECF was sampled by parenchymal microdialysis catheters, placed remotely from the tumour site. Urine was collected over the same time period. Tumour and brain-around tumour (BAT) tissue was sampled stereotactically at 2.5 h and 3.5 h post-infusion. IHC expression levels of the BPA transporter molecule, L-amino acid transporter 1 (LAT-1), were recorded as % LAT-1 positive cells, and cellular boron levels were estimated as spatially resolved pixels in normalised-to-C+ isotopic SIMS images of the biopsies. There were no toxicity-related issues with this new formulation of BPA given at 375 mg/kg as a 2 h intravenous or intracarotid infusion with or without pre-infusion mannitol-induced BBB

  13. Percutaneous Endoscopic Lumbar Foraminotomy: An Advanced Surgical Technique and Clinical Outcomes

    PubMed Central

    Oh, Hyun-Kyong; Kim, Ho; Lee, Sang-Ho; Lee, Haeng-Nam

    2014-01-01

    BACKGROUND: Although several authors have reported the use of endoscopic techniques to treat lumbar foraminal stenosis, the practical application of these techniques has been limited to soft disc herniation. OBJECTIVE: To describe the details of the percutaneous endoscopic lumbar foraminotomy (ELF) technique for bony foraminal stenosis and to demonstrate the clinical outcomes. METHODS: Two years of prospective data were collected from 33 consecutive patients with lumbar foraminal stenosis who underwent ELF. The surgical outcomes were assessed using the visual analog scale, Oswestry Disability Index, and modified MacNab criteria. The procedure begins at the safer extraforaminal zone rather than the riskier intraforaminal zone. Then, a full-scale foraminal decompression can be performed using a burr and punches under endoscopic control. RESULTS: The mean age of the 18 female and 15 male patients was 64.2 years. The mean visual analog scale score for leg pain improved from 8.36 at baseline to 3.36 at 6 weeks, 2.03 at 1 year, and 1.97 at 2 years post-surgery (P < .001). The mean Oswestry Disability Index improved from 65.8 at baseline to 31.6 at 6 weeks, 19.7 at 1 year, and 19.3 at 2 years post-surgery (P < .001). Based on the modified MacNab criteria, excellent or good results were obtained in 81.8% of the patients, and symptomatic improvements were obtained in 93.9%. CONCLUSION: Percutaneous ELF under local anesthesia could be an efficacious surgical procedure for the treatment of foraminal stenosis. This procedure may offer safe and reproducible results, especially for elderly or medically compromised patients. ABBREVIATIONS: ELF,endoscopic lumbar foraminotomy ODI, Oswestry Disability Index VAS, visual analog scale PMID:24691470

  14. 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

  15. [Recent advances in clinical practice and in basic research on diabetic neuropathy].

    PubMed

    Yagihashi, Soroku

    2011-06-01

    With the drastic increase in the number of patients with diabetes, management of neuropathy has become a critical concern because of its intractability and the socio-economic burden it poses. Epidemiological studies have shown that the levels of blood glucose and glycated hemoglobin, the duration of diabetes, and hypertension are important risk factors for the development of neuropathy. Although guidelines for the diagnosis and clinical staging of diabetic neuropathy have been proposed, only nerve conduction studies can provide a reliable diagnosis of the condition. Currently, evaluation of small fiber abnormalities has been given great emphasis, because they often appear early in the course of diabetic neuropathy. Quantitative analysis of epidermal innervation is globally performed for determining the indices of small fiber neuropathy, and recently, laser microscopic evaluation of corneal innervation was proposed as a surrogate technique for skin or nerve biopsy, to serve as a quantitative marker for neuropathy. The advantages of the latter technique are that it is non-invasive and allows for repeated observations. However, the validity of this new method requires further confirmation. Investigations on the pathogenesis of diabetic neuropathy are also increasing and diversifying, and new theories are emerging. The polyol pathway, glycation, and proinflammatory reactions are implicated in peripheral nerve injuries. Further, downstream signaling represented by alterations in protein kinase C, poly (ADP-ribose) polymerase, mitogen-activated protein kinases, and mobilization of transcription factors are likely to result in the neuropathic phenotype. Studies are underway to investigate a novel mechanism of diabetic neuropathy, with a view to developing a highly effective treatment that will restore nerve function and structure. PMID:21613660

  16. Clinical outcomes and toxicity using Stereotactic Body Radiotherapy (SBRT) for advanced cholangiocarcinoma

    PubMed Central

    2012-01-01

    Background To report single-institutional clinical outcomes and toxicity with SBRT for cholangiocarcinoma. Methods From March 2009 to July 2011, 10 patients with 12 unresectable primary (n = 6) or recurrent (n = 6) cholangiocarcinoma lesions underwent abdominal SBRT. Sites treated included liver (n = 10), abdominal lymph nodes (n = 1), and adrenal gland (n = 1). SBRT was delivered in three (n = 2) or five (n = 10) consecutive daily fractions over one week. The median prescription dose was 55 Gy (range, 45–60). Treatment response was graded by RECIST v.1.1, and toxicities were scored by CTCAE v.4.0. Data was analyzed using the Kaplan-Meier method to determine rates of local control (LC), freedom from distant progression (FFDM) and overall survival (OS). Results The median follow-up was 14 months (range, 2–26 months). LC, defined as freedom from progression within the SBRT field, was 100%, but four patients treated to intrahepatic sites experienced progression elsewhere in the liver. Estimates for FFDM at 6 and 12 months were 73% and 31%, respectively. Sites of disease relapse included liver (n = 3), liver and lymph nodes (n = 1), liver and lungs (n = 1), lymph nodes (n = 1), and mesentery (n = 1). OS estimates for the cohort at 6 and 12 months were 83% and 73%, respectively. The most common Grade ≥2 early toxicities were Grade 2 nausea and vomiting (n = 5) and gastrointestinal pain (n = 2). Late ≥2 toxicities included Grade 2 gastrointestinal pain (n = 3), Grade 3 biliary stenosis (n = 1), and Grade 5 liver failure (n = 1). Conclusions SBRT shows promise as an effective local therapy for properly-selected patients with cholangiocarcinoma. Further follow-up is needed to better quantify the risk of late complications associated with SBRT. PMID:22553982

  17. Prognostic role of clinical, pathological and biological characteristics in patients with locally advanced breast cancer.

    PubMed Central

    Honkoop, A. H.; van Diest, P. J.; de Jong, J. S.; Linn, S. C.; Giaccone, G.; Hoekman, K.; Wagstaff, J.; Pinedo, H. M.

    1998-01-01

    Forty-two patients with clinical stage IIIA or IIIB breast cancer were treated with neoadjuvant chemotherapy followed by mastectomy and radiotherapy. The median follow-up was 32 months (range 10-72 months) and the median time to progression was 17 months (range 10-30 months). A multivariate analysis showed that a longer disease-free survival (DFS) was related to more chemotherapy cycles given (P = 0.003), a better pathological response to chemotherapy (P = 0.04) and fewer positive axillary lymph nodes (P = 0.05). A better overall survival (OS) was related to more chemotherapy cycles given (P = 0.03) and better pathological response to chemotherapy (P = 0.04). In patients with residual tumour after neoadjuvant chemotherapy, high levels of staining for Ki-67 was correlated with a worse DFS (P = 0.008). Other biological characteristics, including oestrogen receptor status, microvessel density (CD31 staining), P-glycoprotein (P-gp) staining and nuclear accumulation of p53, were not independent prognostic factors for either DFS or OS. If both P-gp and p53 were expressed, DFS and OS were worse in the uni- and multivariate analysis. The preliminary results of this phase II study suggest that coexpression of P-gp/p53 and a high level of staining for Ki-67 after chemotherapy are associated with a worse prognosis, and that prolonged neoadjuvant chemotherapy and the attainment of a pathological complete remission are important factors in determining outcome for patients with this disease. PMID:9484820

  18. Comparison of a basic and an advanced pharmacotherapy-related clinical decision support system in a hospital care setting in the Netherlands

    PubMed Central

    Derijks, Hieronymus J; Conemans, Jean M H; Hermens, Walter A J J; Wensing, Michel; De Smet, Peter A G M

    2011-01-01

    Objective To compare the clinical relevance of medication alerts in a basic and in an advanced clinical decision support system (CDSS). Design A prospective observational study. Materials and methods We collected 4023 medication orders in a hospital for independent evaluation in two pharmacotherapy-related decision support systems. Only the more advanced system considered patient characteristics and laboratory test results in its algorithms. Two pharmacists assessed the clinical relevance of the medication alerts produced. The alert was considered relevant if the pharmacist would undertake action (eg, contact the physician or the nurse). The primary analysis concerned the positive predictive value (PPV) for clinically relevant medication alerts in both systems. Results The PPV was significantly higher in the advanced system (5.8% vs 17.0%; p<0.05). Significant differences were found in the alert categories: drug–(drug) interaction (9.9% vs 14.8%; p<0.05), drug–age interaction (2.9% vs 73.3%; p<0.05), and dosing guidance (5.6% vs 16.9%; p<0.05). Including laboratory values and other patient characteristics resulted in a significantly higher PPV for the advanced CDSS compared to the basic medication alerts (12.2% vs 23.3%; p<0.05). Conclusion The advanced CDSS produced a higher proportion of clinically relevant medication alerts, but the number of irrelevant alerts remained high. To improve the PPV of the advanced CDSS, the algorithms should be optimized by identifying additional risk modifiers and more data should be made electronically available to improve the performance of the algorithms. Our study illustrates and corroborates the need for cyclic testing of technical improvements in information technology in circumstances representative of daily clinical practice. PMID:21890873

  19. Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study.

    PubMed

    Yamaue, Hiroki; Tsunoda, Takuya; Tani, Masaji; Miyazawa, Motoki; Yamao, Kenji; Mizuno, Nobumasa; Okusaka, Takuji; Ueno, Hideki; Boku, Narikazu; Fukutomi, Akira; Ishii, Hiroshi; Ohkawa, Shinichi; Furukawa, Masayuki; Maguchi, Hiroyuki; Ikeda, Masafumi; Togashi, Yosuke; Nishio, Kazuto; Ohashi, Yasuo

    2015-07-01

    Gemcitabine is a key drug for the treatment of pancreatic cancer; however, with its limitation in clinical benefits, the development of another potent therapeutic is necessary. Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis, and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide (elpamotide). Based on the promising results of this phase I trial, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been carried out for pancreatic cancer. The eligibility criteria included locally advanced or metastatic pancreatic cancer. Patients were assigned to either the Active group (elpamotide + gemcitabine) or Placebo group (placebo + gemcitabine) in a 2:1 ratio by the dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test was applied to the statistical analysis in this study to evaluate the time-lagged effect of immunotherapy appropriately. A total of 153 patients (Active group, n = 100; Placebo group, n = 53) were included in the analysis. No statistically significant differences were found between the two groups in the prolongation of overall survival (Harrington-Fleming P-value, 0.918; log-rank P-value, 0.897; hazard ratio, 0.87, 95% confidence interval [CI], 0.486-1.557). Median survival time was 8.36 months (95% CI, 7.46-10.18) for the Active group and 8.54 months (95% CI, 7.33-10.84) for the Placebo group. The toxicity observed in both groups was manageable. Combination therapy of elpamotide with gemcitabine was well tolerated. Despite the lack of benefit in overall survival, subgroup analysis suggested that the patients who experienced severe injection site reaction, such as ulceration and erosion, might have better survival. PMID:25867139

  20. Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy.

    PubMed

    Paré, L; Marcuello, E; Altés, A; del Río, E; Sedano, L; Salazar, J; Cortés, A; Barnadas, A; Baiget, M

    2008-10-01

    To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1-118 and XPD 751 polymorphisms were significant (P=0.02 and P=0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance (P=0.008). In the univariate analysis for PFS, ERCC1-118 and XPD 751 were significant (P=0.003 and P=0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P=0.02). Finally, ERCC1-118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P=0.006 and P=0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P=0.022 and P=0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments. PMID:18797464

  1. Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy

    PubMed Central

    Paré, L; Marcuello, E; Altés, A; Río, E del; Sedano, L; Salazar, J; Cortés, A; Barnadas, A; Baiget, M

    2008-01-01

    To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1-118 and XPD 751 polymorphisms were significant (P=0.02 and P=0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance (P=0.008). In the univariate analysis for PFS, ERCC1-118 and XPD 751 were significant (P=0.003 and P=0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P=0.02). Finally, ERCC1-118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P=0.006 and P=0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P=0.022 and P=0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments. PMID:18797464

  2. A Phase I Clinical Trial of Safingol in Combination with Cisplatin in Advanced Solid Tumors

    PubMed Central

    Dickson, Mark A.; Carvajal, Richard D.; Merrill, Alfred H.; Gonen, Mithat; Cane, Lauren M.; Schwartz, Gary K.

    2011-01-01

    Purpose Sphingosine 1-phosphate (S1P) is an important mediator of cancer cell growth and proliferation. Production of S1P is catalyzed by sphingosine kinase 1 (SphK). Safingol, (L-threo-dihydrosphingosine) is a putative inhibitor of SphK. We conducted a phase I trial of safingol (S) alone and in combination with cisplatin (C). Experimental Design A 3+3 dose escalation was used. For safety, S was given alone 1 week before the combination. S + C were then administered every 3 weeks. S was given over 60–120 minutes (min), depending on dose. 60 min later, C was given over 60 min. The C dose of 75 mg/m2 was reduced in cohort 4 to 60 mg/m2 due to excessive fatigue. Results 43 patients were treated. 41 were evaluable for toxicity and 37 for response. The maximum tolerated dose (MTD) was S 840 mg/m2 over 120 min C 60 mg/m2, every 3 weeks. DLTs attributed to cisplatin included fatigue and hyponatremia. DLT from S was hepatic enzyme elevation. S pharmacokinetic parameters were linear throughout the dose range with no significant interaction with C. Patients treated at or near the MTD achieved S levels of > 20 µM and maintained levels ≥ 5 µM for 4 hours. The best response was stable disease in 6 patients for on average 3.3 months (range 1.8 – 7.2 m). One patient with adrenal cortical cancer had significant regression of liver and lung metastases and another had prolonged stable disease. S was associated with a dose-dependent reduction in S1P in plasma. Conclusions Safingol, the first putative SphK inhibitor to enter clinical trials, can be safely administered in combination with cisplatin. Reversible dose-dependent hepatic toxicity was seen, as expected from preclinical data. Target inhibition was achieved with downregulation of S1P. The recommended phase 2 dose is S 840 mg/m2 and C 60 mg/m2, every 3 weeks. PMID:21257722

  3. Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

    PubMed Central

    Duan, Jinghua; Vogt, Frederick G; Li, Xiaojian; Hayes, Don; Mansour, Heidi M

    2013-01-01

    The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders. PMID:24092972

  4. Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma.

    PubMed

    Shi, Wei-hong; Wu, Qing-quan; Li, Su-qing; Yang, Tong-xin; Liu, Zi-hao; Tong, Yu-suo; Tuo, Lei; Wang, Shan; Cao, Xiu-Feng

    2015-04-01

    Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC. PMID:25731728

  5. Challenges and Solutions in Optimizing Execution Performance of a Clinical Decision Support-Based Quality Measurement (CDS-QM) Framework

    PubMed Central

    Tippetts, Tyler J; Warner, Phillip B; Kukhareva, Polina V; Shields, David E; Staes, Catherine J; Kawamoto, Kensaku

    2015-01-01

    Given the close relationship between clinical decision support (CDS) and quality measurement (QM), it has been proposed that a standards-based CDS Web service could be leveraged to enable QM. Benefits of such a CDS-QM framework include semantic consistency and implementation efficiency. However, earlier research has identified execution performance as a critical barrier when CDS-QM is applied to large populations. Here, we describe challenges encountered and solutions devised to optimize CDS-QM execution performance. Through these optimizations, the CDS-QM execution time was optimized approximately three orders of magnitude, such that approximately 370,000 patient records can now be evaluated for 22 quality measure groups in less than 5 hours (approximately 2 milliseconds per measure group per patient). Several key optimization methods were identified, with the most impact achieved through population-based retrieval of relevant data, multi-step data staging, and parallel processing. These optimizations have enabled CDS-QM to be operationally deployed at an enterprise level. PMID:26958259

  6. 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

  7. 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

  8. 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

  9. 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

  10. First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: Patients' outcome and analysis of prognostic factors.

    PubMed

    Vivaldi, Caterina; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Catanese, Silvia; Fornaro, Lorenzo; Lencioni, Monica; Falcone, Alfredo; Vasile, Enrico

    2016-08-15

    FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC). The Gruppo Oncologico Nord Ovest (GONO) FOLFOXIRI regimen demonstrated efficacy in metastatic colorectal cancer. We aimed to evaluate activity and tolerability of FOLFOXIRI regimen in patients with aPC and to explore putative prognostic factors. One hundred thirty-seven consecutive aPC patients were treated with FOLFOXIRI in our institution between 2008 and 2014. Clinical, laboratory and pathological data were collected and their association with activity, progression free survival (PFS) and overall survival (OS) was investigated. After a median follow up of 30 months, median PFS and OS were 8.0 months (95% CI 6.19-9.81) and 12 months (95% CI 9.75-14.25), respectively. Response rate was 38.6%, while disease-control rate 72.2%. At multivariate analysis liver metastases (p = 0.019; Hazard Ratio, HR, 0.59, 95% Confidence Interval, CI, 0.380.96), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 (p = 0.001; HR 2.26, 95%CI 1.42-3.59) and neutrophil-lymphocyte ratio (NLR)> 4 (p= 0.002; HR: 2.42; 95% CI 1.38-4.25) were associated with poorer OS. We categorized 119 pts with complete available data as good-risk (0 factors, 38 pts), intermediate-risk (1 factor, 49 pts) and poor-risk (≥2 factors, 32 pts). Median OS for these three groups were 17.6, 11.1 and 7.4 months, respectively (p < 0.001). FOLFOXIRI is active and feasible in aPC. Prognosis of aPC pts treated with FOLFOXIRI is influenced by easily available factors: our analysis revealed ECOG PS, liver metastases and NLR as the most important predictors of survival. These factors could be helpful for treatment decision and clinical trial design. PMID:27038273

  11. Advanced medical imaging protocol workflow-a flexible electronic solution to optimize process efficiency, care quality and patient safety in the National VA Enterprise.

    PubMed

    Medverd, Jonathan R; Cross, Nathan M; Font, Frank; Casertano, Andrew

    2013-08-01

    Radiologists routinely make decisions with only limited information when assigning protocol instructions for the performance of advanced medical imaging examinations. Opportunity exists to simultaneously improve the safety, quality and efficiency of this workflow through the application of an electronic solution leveraging health system resources to provide concise, tailored information and decision support in real-time. Such a system has been developed using an open source, open standards design for use within the Veterans Health Administration. The Radiology Protocol Tool Recorder (RAPTOR) project identified key process attributes as well as inherent weaknesses of paper processes and electronic emulators of paper processes to guide the development of its optimized electronic solution. The design provides a kernel that can be expanded to create an integrated radiology environment. RAPTOR has implications relevant to the greater health care community, and serves as a case model for modernization of legacy government health information systems. PMID:23288437

  12. 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

  13. 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

  14. EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10)

    PubMed Central

    Vázquez, Sergio; Casal, Joaquín; Afonso Afonso, Francisco Javier; Fírvida, José Luis; Santomé, Lucía; Barón, Francisco; Lázaro, Martín; Pena, Carolina; Amenedo, Margarita; Abdulkader, Ihab; González-Arenas, Carmen; Fachal, Laura; Vega, Ana

    2016-01-01

    Purpose This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. Patients and methods All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. Results Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8–15.3) months and 17.8 (95% confidence interval: 13.9–21.6) months, respectively, in patients carrying sensitizing mutations. Conclusion The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC. PMID:26893581

  15. Mycobacterium tuberculosis induces apoptosis in gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis.

    PubMed Central

    Duarte, R; Kindlelán, J M; Carracedo, J; Sánchez-Guijo, P; Ramírez, R

    1997-01-01

    Antigens from inactivated Mycobacterium tuberculosis H37Ra induce activation in a subpopulation of gamma/delta (gamma/delta) T lymphocytes in a manner that resembles that of superantigens from alpha/beta T cells. After culture in vitro with H37Ra proteins, gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis (ACF-TBC) display cytotoxic activity against homotypic target cells exposed to H37Ra. Cytotoxicity by gamma/delta T lymphocytes from ACF-TBC patients occurs in a range similar to that observed in healthy subjects. Following activation, H37Ra-stimulated gamma/delta T lymphocytes from healthy subjects did proliferate in the presence of exogenous recombinant human interleukin 2. However, under the same conditions, gamma/delta T lymphocytes from ACF-TBC patients not only did not proliferate but died by apoptosis. These results suggest that in gamma/delta T lymphocytes from patients with ACF-TBC, antigens from M. tuberculosis may induce cell activation that leads to apoptotic cell death. PMID:9008275

  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. 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

  18. 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

  19. 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

  20. Physicochemical characterization and aerosol dispersion performance of organic solution advanced spray-dried cyclosporine A multifunctional particles for dry powder inhalation aerosol delivery

    PubMed Central

    Wu, Xiao; Zhang, Weifen; Hayes, Don; Mansour, Heidi M

    2013-01-01

    In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug – cyclosporine A – for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, respirable fraction, and fine particle fraction. In addition, novel multifunctional inhalation aerosol powder formulations of cyclosporine A with lung surfactant-mimic phospholipids were also successfully designed and developed by advanced organic solution cospray drying in closed mode. The lung surfactantmimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-snglycero- 3-(phosphor-rac-1-glycerol). These cyclosporine A lung surfactant-mimic aerosol powder formulations were comprehensively characterized. Powder X-ray diffraction and differential scanning calorimetry confirmed that the phospholipid bilayer structure in the solid state was preserved following advanced organic solution spray drying in closed mode. These novel multifunctional inhalation powders were optimized for DPI delivery with excellent aerosol dispersion performance and high aerosol performance parameters. PMID:23569375

  1. Colloids versus crystalloids as priming solutions for cardiopulmonary bypass: a meta-analysis of prospective, randomised clinical trials.

    PubMed

    Himpe, D

    2003-01-01

    Using Cochrane methodology a review was performed of prospective randomized clinical trials comparing colloidal pump priming solutions for cardiopulmonary bypass. Dextrans were not considered. Database searches from 1966 through December 2002 delivered 265 articles. Seventeen studies finally met the eligibility criteria involving 997 patients. Summary odds ratio estimates from the 5 studies reporting mortality were 1.46 (n = 326; 95%-Confidence-Interval: .55 to 3.85; p = .49) for crystalloids against colloids and .74 (n = 150; 95%-Confidence-Interval: .17 to 3.36; p = .49) for albumin versus synthetic colloids. Most commonly used outcome measures further included postoperative blood loss, platelet-count, fluid-balance and, colloid osmotic pressures from which Standardized Mean Differences (SMD) and their 95%-Confidence-Interval (95%CI) were extracted. Colloids produced significantly higher oncotic pressures and less positive fluid-balances. Although across 9 studies postoperative bleeding between colloids and crystalloids did not differ (n = 663; SMD: -.03, 95%CI: -.18 to .12; p = .69), platelet counts significantly favoured crystalloids (n = 465; SMD: -.42; 95%CI: -.68 to -.16; p = .00). However, compared to albumin platelet counts were significantly disfavoured only by starches (n = 321; SMD: -.55; 95%CI: -.77 to -.32; p = .00). To conclude, using mere crystalloids produced more pronounced positive fluid balances and their avoidance as a single pump-prime component can be suggested. Since albumin is not necessarily associated with better outcomes and is more expensive, it is hard to continue its use. However, there is still insufficient evidence available to allow definitive conclusions. PMID:14598617

  2. Clinical Trial of Prophylactic Extended-Field Carbon-Ion Radiotherapy for Locally Advanced Uterine Cervical Cancer (Protocol 0508)

    PubMed Central

    Wakatsuki, Masaru; Kato, Shingo; Kiyohara, Hiroki; Ohno, Tatsuya; Karasawa, Kumiko; Tamaki, Tomoaki; Ando, Ken; Tsujii, Hirohiko; Nakano, Takashi; Kamada, Tadashi; Shozu, Makio

    2015-01-01

    To evaluate the efficacy and the toxicity of prophylactic extended-field carbon-ion radiotherapy (C-ion RT, Protocol 0508) for locally advanced squamous cell carcinoma of the uterine cervix in phase I / II clinical trial. Between May 2006 and January 2012, 26 patients of Protocol 0508 were treated with C-ion RT. The numbers of patients with stage IIB, IIIB, and IVA disease were 13, 11, and 2, respectively. Twenty patients had pelvic lymph node metastases. Median tumor size was 6.1 cm (range, 4.0–10.0 cm). The treatment consisted of extended-field irradiation of 39.0 gray equivalents (GyE) in 13 fractions, and additional 15.0 GyE in 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, 18.0 GyE in 2 fractions was given to GTV only. Total dose to the cervical tumor was 72.0 GyE over 20 fractions. The median follow-up period was 37 months. Twenty-one patients had grade 1 or 2 acute gastrointestinal toxicity, but all patients completed the treatment on schedule. There were no grade 3 or higher late complications, with 8 patients having grade 1 or 2 toxicities, 1 had grade 2 gastrointestinal toxicity and 2 had grade 2 genitourinary toxicity. Four patients (15.4%) developed local recurrence, and 8 patients (30.8%) had distant metastases. The 2-year local control rate, progression-free survival rate and overall survival rate were 83.6%, 61.5% and 73.1%, respectively. There were no severe acute or late complications in this trial. Prophylactic extended-field C-ion RT for locally advanced squamous cell carcinoma of the uterine cervix was a safe treatment. Although the number of patients in this study was small, the results support further investigations to confirm the therapeutic efficacy and to avoid or reduce toxicity. Trial Registration UMIN-CTR UMIN000016169 PMID:25993047

  3. 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.

  4. Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of KOS-862 (Epothilone D) in Patients with Advanced Solid Tumors and Lymphoma

    PubMed Central

    Konner, Jason; Grisham, Rachel N.; Park, Jae; O’Connor, Owen A.; Cropp, Gillian; Johnson, Robert; Hannah, Alison L.; Hensley, Martee L.; Sabbatini, Paul; Miranov, Svetlana; Danishefsky, Samuel; Hyman, David; Spriggs, David R.; Dupont, Jakob; Aghajanian, Carol

    2014-01-01

    Purpose To determine the maximum tolerated dose and safety of the epothilone, KOS-862, in patients with advanced solid tumors or lymphoma. Patients and Methods Patients were treated weekly for 3 out of 4 weeks (Schedule A) or 2 out of 3 weeks (Schedule B) with KOS-862 (16 – 120mg/m2). Pharmacokinetic (PK) sampling was performed during cycles 1 and 2; pharmacodynamic (PD) assessment for microtubule bundle formation (MTBF) was performed after the 1st dose, only at or above 100 mg/m2. Results Thirty-two patients were enrolled, and twenty-nine completed ≥1 cycle of therapy. Dose limiting toxicity [DLT] was observed at 120 mg/m2. PK data were linear from 16 to 100 mg/m2, with proportional increases in mean Cmax and AUCtot as a function of dose. Full PK analysis (mean±SD) at 100 mg/m2 revealed the following: half-life (t½) = 9.1 ± 2.2 hours; volume of distribution (Vz) = 119 ± 41 L/m2; clearance (CL) = 9.3 ± 3.2 L/h/m2. MTBF (n=9) was seen in 40% of PBMCs within 1 hour and in 15% of PBMC at 24-hours post infusion at 100 mg/m2. Tumor shrinkage (n=2, lymphoma), stable disease >3 months (n=5, renal, prostate, oropharynx, cholangiocarcinoma, and Hodgkin lymphoma), and tumor marker reductions (n=1, colorectal cancer/CEA) were observed. Conclusion KOS-862 was well tolerated with manageable toxicity, favorable PK profile, and the suggestion of clinical activity. The maximum tolerated dose was determined to be 100 mg/m2 weekly 3-on/1-off. MTBF can be demonstrated in PBMCs of patients exposed to KOS-862. PMID:22072399

  5. Clinical Specialists and Advanced Practitioners in Physical Therapy: A Survey of Physical Therapists and Employers of Physical Therapists in Ontario, Canada

    PubMed Central

    Gordon, Robert; Freeburn, Ryan; So, Colleen; Beauchamp, David; Landry, Michel D.; Switzer-McIntyre, Sharon; Evans, Cathy; Brooks, Dina

    2008-01-01

    Purpose: Opportunities to expand the role of physical therapists (PTs) have evolved to include clinical specialists and advanced practitioners, although the literature on these roles is limited. We examined perceptions of PTs and PT employers in Ontario regarding clinical specialization and advanced practice. Methods: Using a modified Dillman approach, a cross-sectional survey was conducted with 500 PTs and 500 PT employers in Ontario. Questionnaires were tailored to address specific issues related to each cohort. Results: Sixty percent of PTs and 53% of PT employers responded to the survey. Thirty-three percent of PT respondents already considered themselves “clinical specialists” (CS), and 8% considered themselves “advanced practitioners” (AP), although neither role is yet formally recognized in Canada. Both groups had substantial interest in pursuing formal recognition of CS and AP status. Respondents indicated that their primary motivation to pursue such roles was to enhance clinical reasoning skills with the goal of improving client outcomes (82% for the role of CS, 71% for the role of AP). Respondents supported the involvement of academic institutions in the process (60% for CS, 70% for AP). Conclusion: PTs and PT employers are supportive of the roles of the CS and AP within the profession, even though there is currently no formal recognition of either role in Canada. PMID:20145755

  6. [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

  7. 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

  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

    In the context of this review, civil unrest is defined as disharmony, expressive dissatisfaction and/or disagreement between members of a community, which leads to a situation of competitive aggression that may find expression as disruption of organisation, conflicts, damage to property and injuries. Such a breakdown of harmonious relationships, which may result in property damage and human injuries that may be threatening to life, varies in magnitude from participation of a very few individuals up to the involvement of large crowds of people, which may evolve into a full-scale riot. It is the latter situation often involving demonstrators, opposing groups and law enforcement personnel that can result in multiple casualties and present a very significant challenge to the resources of local healthcare institutions. The causation of civil unrest incidents is multifactorial and has generic, specific and potentiating elements. With the current national and international societal, political and discriminatory problems, it is likely that civil unrest incidents on both small and large scales will continue to occur at a high and possibly increasing rate on a worldwide basis, and for these not infrequent incidents, the medical community should be in a state of informed preparation. The circumstances of civil unrest incidents are very variable with respect to causation, overall magnitude, frequency, timing, geographical location, numbers of persons involved, demographics of participants, influence of extremists, confrontation with opposing groups and control measures used by law enforcement agencies. Methods used by police and security forces for the control of civil unrest incidents, if advanced negotiations with organisers and verbal warnings have failed, fall basically into two categories: physical and chemical measures. Physical methods include restraint holds, truncheons, batons, mounted horses, projectiles (such as bean bags, plastic and rubber bullets), water cannons

  9. A scatterometry based CD metrology solution for advanced nodes, including capability of handling birefringent layers with uniaxial anisotropy

    NASA Astrophysics Data System (ADS)

    Ke, Chih-Ming; Hu, Jimmy; Wang, Willie; Huang, Jacky; Chung, H. L.; Liang, C. R.; Shih, Victor; Liu, H. H.; Lee, H. J.; Lin, John; Fan, Y. D.; Yen, Tony; Wright, Noelle; Alvarez Sanchez, Ruben; Coene, Wim; Noot, Marc; Yuan, Kiwi; Wang, Vivien; Bhattacharyya, Kaustuve; van der Mast, Karel

    2009-03-01

    A brand new CD metrology technique that can address the need for accuracy, precision and speed in near future lithography is probably one of the most challenging items. CDSEMs have served this need for a long time, however, a change of or an addition to this traditional approach is inevitable as the increase in the need for better precision (tight CDU budget) and speed (driven by the demand for increase in sampling) continues to drive the need for advanced nodes. The success of CD measurement with scatterometry remains in the capability to model the resist grating, such as, CD and shape (side wall angle), as well as the under-lying layers (thickness and material property). Things are relatively easier for the cases with isotropic under-lying layers (that consists of single refractive or absorption indices). However, a real challenge to such a technique becomes evident when one or more of the under-lying layers are anisotropic. In this technical presentation the authors would like to evaluate such CD reconstruction technology, a new scatterometry based platform under development at ASML, which can handle bi-refringent non-patterned layers with uniaxial anisotropy in the underlying stack. In the RCWA code for the bi-refringent case, the elegant formalism of the enhanced transmittance matrix can still be used. In this paper, measurement methods and data will be discussed from several complex production stacks (layers). With inclusion of the bi-refringent modeling, the in-plane and perpendicular n and k values can be treated as floating parameters for the bi-refringent layer, so that very robust CD-reconstruction is achieved with low reconstruction residuals. As a function of position over the wafer, significant variations of the perpendicular n and k values are observed, with a typical radial fingerprint on the wafer, whereas the variations in the in-plane n and k values are seen to be considerably lower.

  10. 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

  11. 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

  12. Randomized clinical trial of adenosine 5'-triphosphate on tumor growth and survival in advanced lung cancer patients.

    PubMed

    Agteresch, Hendrik J; Burgers, Sjaak A; van der Gaast, Ate; Wilson, J H Paul; Dagnelie, Pieter C

    2003-09-01

    We recently reported that regular infusions of adenosine 5'-triphosphate (ATP) inhibited loss of body weight and quality of life in patients with non-small cell lung cancer (NSCLC). In the present paper we investigated whether ATP affects tumor growth and survival in the same group of patients. Fifty-eight NSCLC patients (stage IIIB or IV) were randomly assigned to receive either 10 i.v. 30-h ATP infusions every 2-4 weeks over a 24-week period (n = 28) or no ATP (control patients, n = 30). ATP was given for a median of 6.5 infusions. Differences in time to progression and survival between patients in both groups were tested by means of the log-rank test and Cox regression analysis. Forty-nine patients were evaluable for tumor response. None of the evaluable patients showed a complete or partial response. Median time to progression was 3.9 months [95% confidence interval (CI) = 2.3-5.5] in the ATP group compared to 3.0 months (95% CI = 2.4-3.7) in the control group (p = 0.71). Median survival was 5.6 months (95% CI = 1.1-10.1) for the ATP group and 4.7 months (95% CI = 2.6-6.8) for the control group (p = 0.68). ATP treatment was associated with a significant increase in survival in the subgroup of weight-losing patients with stage IIIB NSCLC: in this subgroup, median survival was 9.3 months (95% CI = 2.1-16.5) for ATP-treated patients versus 3.5 months (95% CI = 2.3-4.7) for control patients (between-group difference: p = 0.009). No significant effect of ATP was observed for weight-losing patients with stage IV NSCLC or for weight-stable NSCLC patients. Although ATP as a single therapy does not lead to tumor regression or increased survival in patients with advanced lung cancer, it may prolong survival in weight-losing patients with stage IIIB lung cancer. The latter finding is intriguing, but requires confirmation in larger clinical trials. PMID:14501386

  13. 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

  14. Electrical efficiency in modern waste to energy plants -- The advanced solutions adopted in a new Italian plant (Milan)

    SciTech Connect

    Lucchini, F.M.; Pezzella, B.

    1998-07-01

    The paper has the goal to give a general overview of the current approach for the design of modern Waste to Energy (WtE) plants. The thermal treatment of solid waste is an environmentally sound method to get rid of the garbage produced by everyone and to recover energy simultaneously. A typical waste to energy plant is divided in four segments: incineration/boiler, air pollution control, residues treatment and power generation. Still in the 80's a WtE plant was simply consisting of a these four segments without any particular effort in putting them together into a coordinated plant; therefore the results were very poor in term of overall plant performances even if the single segments were properly designed. This paper shows how this approach is changing and how the synergism between the segments allows to reach interesting performances in term of electric efficiency, always keeping in mind that power must be considered a by-product of the incinerator. Therefore all these efforts have to be done without affecting the burning capacity of the station. The new Milan WtE plant is taken as example throughout the paper. The first section of the paper tries to consider the Municipal Solid Waste as standard fuel; then focal point becomes the electrical efficiency of the plant. In the fourth section the flue gas cleaning system is approached, pointing out the gas quality at stack. Then in the fifth and sixth paragraphs all most important and innovative technical solutions of the Milan plant are shown with some details on water/steam cycle, giving also some availability results. Chapter seven shows some interesting key-figures, related to the combustion of 1,000 kg of MSW at 11 MJ/kg, with also some economical evaluations in term of investment cost per ton of waste per day.

  15. 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.

  16. 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

  17. 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.

  18. 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. PMID:26306242

  19. 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

  20. Clinical use of an epinephrine-reduced (1/400,000) articaine solution in short-time dental routine treatments--a multicenter study.

    PubMed

    Daubländer, Monika; Kämmerer, Peer W; Willershausen, Brita; Leckel, Michael; Lauer, Hans-Christoph; Buff, Siegmar; Rösl, Benita

    2012-08-01

    The addition of epinephrine in dental local anaesthesia results in a longer and deeper anaesthesia under almost ischemic conditions. For short-time dental treatments, epinephrine-reduced anaesthetics may offer shorter and more individual anaesthesia with reduced potential side effects. The aim of this study was a clinical evaluation of anaesthetic potency and adverse effects of an epinephrine-reduced articaine formulation in dental patients undergoing short-time routine treatment. In a prospective clinical, not interventional, study between January 2008 and February 2009, 908 patients undergoing short-time dental treatment in five medical centers were anaesthetized with 4% articaine 1:400,000 epinephrine (Ubistesin, 3M/ESPE, Seefeld, Germany). Efficacy and safety in clinical use were evaluated. A follow-up after 1 day was conducted by telephone survey. A mean amount of 1.3-ml anaesthetic solution was needed to achieve a complete or sufficient anaesthesia in 97% (n = 876) of cases. A second injection had to be done in 3.7% (n = 34) before and in 11.9% (n = 108) during treatment. Here, the second injection had to be applied after a mean of 48.6 min. The mean duration of soft tissue anaesthesia after infiltration was 146.6 min, after nerve block 187.7 min. The painful treatment took a mean of 50.2 min and the total treatment time summed up to 68.8 min. In 1.7% cases (n = 15), unwanted side effects were observed. The results indicate that a lower concentration of epinephrine in combination with the 4% articaine solution leads to a high success rate of efficacy. The clinical use of a 4% articaine 1:400,000 epinephrine solution can be stated as safe and effective in short dental routine treatments. Reconsiderations concerning limitations of indication or additional contraindications are not necessary. PMID:21861074

  1. New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions.

    PubMed

    Chuma, Makoto; Terashita, Katsumi; Sakamoto, Naoya

    2015-10-01

    Hepatocellular carcinoma (HCC) can be lethal due to its aggressive course and lack of effective systemic therapies for advanced disease. Sorafenib is the only systemic therapy that has demonstrated an overall survival benefit in patients with advanced HCC, and new agents for treatment of advanced HCC are needed. The multiple pathways involved in HCC oncogenesis, proliferation and survival provide many opportunities for the development of molecularly targeted therapies. Molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for treatment of advanced HCC. Agents targeting vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-mesenchymal-epithelial transition factor-1 and mammalian target of rapamycin signaling have been actively explored. This article focuses on the evaluation of molecular agents targeting pathogenic HCC and provides a review of recently completed phase III drug studies (e.g. involving sorafenib, sunitinib, brivanib, linifanib, erlotinib, everolimus, ramucirumab or orantinib) and ongoing drug studies (e.g. involving lenvatinib, regorafenib, tivantinib or cabozantinib) of molecularly targeted agents in advanced HCC, including a brief description of the biologic rationale behind these agents. PMID:25472913

  2. Health status measured by the Clinical COPD Questionnaire (CCQ) improves following post-acute pulmonary rehabilitation in patients with advanced COPD: a prospective observational study

    PubMed Central

    van Dam van Isselt, Eléonore F; Spruit, Monica; Groenewegen-Sipkema, Karin H; Chavannes, Niels H; Achterberg, Wilco P

    2014-01-01

    Aims: To evaluate outcomes of the Clinical Chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ) in patients with advanced COPD admitted for a post-acute pulmonary rehabilitation (PR) programme and to relate (change in) health status to lung function, degree of dyspnoea and (change in) functional capacity. Methods: This is a prospective observational study in patients with advanced COPD admitted for a post-acute PR programme in a skilled nursing facility. Health status (CCQ) and functional capacity were measured before and after rehabilitation. Results: Health status measured by the CCQ was severely impaired and showed significant and clinically relevant improvement during the post-acute PR programme. Moderate to strong correlations were found between CCQ scores and functional capacity on admission and at discharge. Moderate correlations were found between improvement in CCQ scores and improvement in functional capacity. No correlation was found between CCQ scores and lung function (forced expiratory volume in 1 s % predicted). Conclusions: Health status measured by the CCQ improves following a post-acute PR programme in patients with advanced COPD and correlates with improvement in functional capacity. These results suggest that the CCQ is sensitive to change in response to PR in this specific group of patients. PMID:24842278

  3. 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

  4. 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

  5. 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

  6. 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

  7. Preoperative bevacizumab combined with letrozole and chemotherapy in locally advanced ER- and/or PgR-positive breast cancer: clinical and biological activity

    PubMed Central

    Torrisi, R; Bagnardi, V; Cardillo, A; Bertolini, F; Scarano, E; Orlando, L; Mancuso, P; Luini, A; Calleri, A; Viale, G; Goldhirsch, A; Colleoni, M

    2008-01-01

    The antiangiogenic agent bevacizumab showed synergistic effects when combined with chemotherapy in advanced breast cancer. We presently investigated the activity of bevacizumab in combination with chemotherapy, including capecitabine and vinorelbine, and endocrine therapy, including letrozole (+triptorelin in premenopausal women), as primary therapy for patients with ER and/or PgR ⩾10% T2–T4a-c, N0–N2, M0 breast cancer. Biological end point included the proliferative activity (Ki67), whereas clinical end points were clinical response rate, pathological complete response (pCR) and tolerability. Circulating endothelial cells (CECs) and their progenitors, as surrogate markers of antiangiogenic activity, were measured at baseline and at surgery.Thirty-six women are evaluable. A clinical response rate of 86% (95% CI, 70–95) and no pCR were observed; Ki67 was significantly decreased by 71% (interquartile range, −82%, −62%). Toxicity was manageable: two grade 3 hypertension, four grade 3 deep venous thrombosis and no grade >2 proteinuria were observed. Treatment significantly decreased the percentage of viable CECs and prevented the chemotherapy-induced mobilisation of circulating progenitors. Basal circulating progenitors were positively associated with clinical response. In conclusion, bevacizumab is feasible and active in association with primary chemoendocrine therapy for ER-positive tumours in terms of proliferation inhibition, clinical response and antiangiogenic activity. PMID:18941458

  8. Update and clinical utility of alcaftadine ophthalmic solution 0.25% in the treatment of allergic conjunctivitis

    PubMed Central

    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. PMID:26185412

  9. 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. PMID:26185412

  10. 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

  11. [Clinical validation of the caries preventive effect of mouth rinses with a mineralizing solution on the recently erupted permanent dentition].

    PubMed

    Rodríguez Miró, M J; Rodríguez Lucas, A; Gispert Abreu, E; Fonte Martínez, M

    1989-01-01

    This research was performed with the purpose of learning about effect of oral rinsing, every two weeks, with mineralizing solution (Minersol) on recently erupted permanent dentition. Reduction obtained in the incidence of caries at one year term ranged between 49.2 and 82.1% for first molar teeth and 23.4 and 36.3% for second molar teeth; both differences were significant, but no reduction was obtained in the incidence of caries in the bicuspid teeth. Preventing effect obtained is attributed to ionic incorporation in enamel superficial levels, which decreases the diffusion of acids acting in demineralization. It is concluded that the use of mineralizing solution in those ages of eruption of permanent dentition reduces incidence of caries and, therefore, its use as preventing method is recommended. PMID:2701032

  12. Advance directives

    PubMed Central

    O’Sullivan, Rory; Mailo, Kevin; Angeles, Ricardo; Agarwal, Gina

    2015-01-01

    Abstract Objective To establish the prevalence of patients with advance directives in a family practice, and to describe patients’ perspectives on a family doctor’s role in initiating discussions about advance directives. Design A self-administered patient questionnaire. Setting A busy urban family medicine teaching clinic in Hamilton, Ont. Participants A convenience sample of adult patients attending the clinic over the course of a typical business week. Main outcome measures The prevalence of advance directives in the patient population was determined, and the patients’ expectations regarding the role of their family doctors were elucidated. Results The survey population consisted of 800 participants (a response rate of 72.5%) well distributed across age groups; 19.7% had written advance directives and 43.8% had previously discussed the topic of advance directives, but only 4.3% of these discussions had occurred with family doctors. In 5.7% of cases, a family physician had raised the issue; 72.3% of respondents believed patients should initiate the discussion. Patients who considered advance directives extremely important were significantly more likely to want their family doctors to start the conversation (odds ratio 3.98; P < .05). Conclusion Advance directives were not routinely addressed in the family practice. Most patients preferred to initiate the discussion of advance directives. However, patients who considered the subject extremely important wanted their family doctors to initiate the discussion. PMID:25873704

  13. 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

  14. Prevention of ventilator-associated pneumonia in the intensive care unit: A review of the clinically relevant recent advancements

    PubMed Central

    Keyt, Holly; Faverio, Paola; Restrepo, Marcos I.

    2014-01-01

    Ventilator-associated pneumonia (VAP) is one of the most commonly encountered hospital-acquired infections in intensive care units and is associated with significant morbidity and high costs of care. The pathophysiology, epidemiology, treatment and prevention of VAP have been extensively studied for decades, but a clear prevention strategy has not yet emerged. In this article we will review recent literature pertaining to evidence-based VAP-prevention strategies that have resulted in clinically relevant outcomes. A multidisciplinary strategy for prevention of VAP is recommended. Those interventions that have been shown to have a clinical impact include the following: (i) Non-invasive positive pressure ventilation for able patients, especially in immunocompromised patients, with acute exacerbation of chronic obstructive pulmonary disease or pulmonary oedema, (ii) Sedation and weaning protocols for those patients who do require mechanical ventilation, (iii) Mechanical ventilation protocols including head of bed elevation above 30 degrees and oral care, and (iv) Removal of subglottic secretions. Other interventions, such as selective digestive tract decontamination, selective oropharyngeal decontamination and antimicrobial-coated endotracheal tubes, have been tested in different studies. However, the evidence for the efficacy of these measures to reduce VAP rates is not strong enough to recommend their use in clinical practice. In numerous studies, the implementation of VAP prevention bundles to clinical practice was associated with a significant reduction in VAP rates. Future research that considers clinical outcomes as primary endpoints will hopefully result in more detailed prevention strategies. PMID:25109715

  15. 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. PMID:26149807

  16. Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural dissemination

    PubMed Central

    Yi, Eunjue; Kim, Daejoong; Cho, Sukki; Kim, Kwhanmien

    2016-01-01

    Background This study aimed to investigate the safety and feasibility of intrapleural perfusion hyperthermic chemotherapy (IPHC) followed by cytoreductive surgery as a part of multimodal strategy for the treatment of advanced lung adenocarcinoma. Methods Medical records of advanced lung cancer patients with pleural dissemination who underwent surgical treatment between 2003 and 2013 were reviewed retrospectively. Enrolled patients were divided into a surgery group comprising patients who underwent surgery only and an IPHC group, which consisted of patients who underwent surgery combined with IPHC. Results A total of 33 patients were enrolled in this study. Twenty-three patients underwent IPHC after surgical resection, and 10 patients underwent surgical resection only. The complication rate of the IPHC group was estimated to be 34.8% (8 cases), none of which included postoperative mortality. The complication rate of the surgery group was 40.0% (4 cases), which included one postoperative mortality. The 6-month, 1-year, and 3-year overall survival rates for the IPHC group were 95.7%, 91.3% and 38.6%, respectively, while those of the surgery group were 80.0%, 80.0% and 37.5%. The 6-month, 1-year and 3-year progression-free survival rates for the IPHC group were 87.0%, 47.8% and 24.3%, while those of surgery group were 44.4%, 33.3% and 0.0%, respectively. There were significant differences in overall survival rates between two groups (P=0.045); however, progression-free survival was not different between the two groups. Conclusions IPHC combined with cytoreductive surgery for advanced lung adenocarcinoma associated with pleural seeding could be performed safely and feasible. It would be part of multimodality therapy for certain category of advanced lung adenocarcinoma. However, the long-term benefits for survival is uncertain. More extensive and precisely designed studies are warranted to further evaluate the effectiveness of IPHC. PMID:27499943

  17. 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

  18. 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

  19. 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

  20. Evaluation of targeted therapies in advanced breast cancer: the need for large-scale molecular screening and transformative clinical trial designs.

    PubMed

    Fadoukhair, Z; Zardavas, D; Chad, M A; Goulioti, T; Aftimos, P; Piccart, M

    2016-04-01

    Breast cancer (BC) has been classified into four intrinsic subtypes through seminal studies employing gene expression profiling analysis of primary tumours, namely the luminal A and B subtypes, the human epidermal growth factor receptor 2-like subtype and the basal-like subtype. More recently, the emergence of high-throughput genomic sequencing techniques, such as next-generation or massive parallel sequencing has expanded our understanding of the complex genomic landscapes of BC, with marked intertumour heterogeneity seen among different patients. In addition, increasing evidence indicates intratumour heterogeneity, with molecular differences observed within one patient, both spatially and longitudinally. These phenomena have an impact on the clinical development of molecularly targeted agents, with the classical paradigm of population-based clinical trials being no longer efficient. In the era of genomically driven oncology, three complementary tools can accelerate the clinical development of targeted agents for advanced BC as follows: (i) the implementation of molecular profiling of metastatic tumour lesions, as exemplified by the AURORA (Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer) programme; (ii) serial assessments of circulating tumour DNA, allowing a more thorough molecular interrogation of metastatic tumour burden; and (iii) new innovative clinical trial designs able to address the challenges of the increasing molecular fragmentation of BC. PMID:26119941

  1. 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. PMID:25814257

  2. The Efficacy of Bevacizumab Compared with Other Targeted Drugs for Patients with Advanced NSCLC: A Meta-Analysis from 30 Randomized Controlled Clinical Trials

    PubMed Central

    Zhu, Min; Liu, Tianshu; Zhao, Naiqing

    2013-01-01

    Background The extent of the benefit of bevacizumab combined with chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) is still unclear. We performed this meta-analysis to compare the efficacy of bevacizumab with other commonly used targeted drugs for different patients with advanced NSCLC. Methods We searched PubMed, Cochrane Library, EMBASE and abstracts from the proceedings of the American Society of Clinical Oncology (ASCO), and identified 30 randomized controlled clinical trials published within 1999 to 2011 for meta-analysis. Results The outcomes of treatment efficacy included response rate, PFS and OS. Comparing bevacizumab (15 mg/kg) with chemotherapy to standard chemotherapy alone, for chemotherapy-naïve patients, the pooled OR of response rate was 2.741(95%CI: 2.046, 3.672), the pooled HR for disease progression was 0.645 (95%CI: 0.561, 0.743), and the pooled HR for death was 0.790 (95%CI: 0.674, 0.926), respectively. In addition, the adjusted HR for previously-treated patients was 0.680 (95%CI: 0.492, 0.942) comparing bevacizumab combined with chemotherapy to standard chemotherapy alone. Conclusions Bevacizumab accompanied by chemotherapy was found to significantly improve patients' response rate, progression free survival (PFS), and overall survival (OS) among chemotherapy-naïve patients compared to other targeted drugs in the treatment of non-small cell lung carcinoma (NSCLC). PMID:23614008

  3. Striatal FDOPA uptake and cognition in advanced non-demented Parkinson's disease: a clinical and FDOPA-PET study.

    PubMed

    van Beilen, Marije; Portman, Axel T; Kiers, Henk A L; Maguire, Ralph P; Kaasinen, Valtteri; Koning, Marthe; Pruim, Jan; Leenders, Klaus L

    2008-01-01

    This study sought to determine the nature of the relationship between cognition and striatal dopaminergic functioning in 28 patients with advanced Parkinson's disease (PD) using fluorodopa Positron emission tomography (FDOPA-PET) and neuropsychological test scores. Mental flexibility was related to putamen activity while mental organization (executive memory and fluency) was related to caudate FDOPA uptake. Interestingly, the caudate may be more important in the mental components of executive functioning, while the putamen may be more important in the motor components of executive functioning. PMID:18249027

  4. High RAB25 expression is associated with good clinical outcome in patients with locally advanced head and neck squamous cell carcinoma

    PubMed Central

    Téllez-Gabriel, Marta; Arroyo-Solera, Irene; León, Xavier; Gallardo, Alberto; López, Montserrat; Céspedes, Maria V; Casanova, Isolda; López-Pousa, Antonio; Quer, Miquel; Mangues, Maria A; Barnadas, Agustí; Mangues, Ramón; Pavón, Miguel A

    2013-01-01

    Currently there are no molecular markers able to predict clinical outcome in locally advanced head and neck squamous cell carcinoma (HNSCC). In a previous microarray study, RAB25 was identified as a potential prognostic marker. The aim of this study was to analyze the association between RAB25 expression and clinical outcome in patients with locally advanced HNSCC treated with standard therapy. In a retrospective immunohistochemical study (n = 97), we observed that RAB25-negative tumors had lower survival (log-rank, P = 0.01) than patients bearing positive tumors. In an independent prospective mRNA study (n = 117), low RAB25 mRNA expression was associated with poor prognosis. Using classification and regression tree analysis (CART) we established two groups of patients according to their RAB25 mRNA level and their risk of death. Low mRNA level was associated with poor local recurrence-free (log-rank, P = 0.005), progression-free (log-rank, P = 0.002) and cancer-specific (log-rank, P < 0.001) survival. Multivariate Cox model analysis showed that low expression of RAB25 was an independent poor prognostic factor for survival (hazard ratio: 3.84, 95% confidence interval: 1.93–7.62, P < 0.001). Patients whose tumors showed high RAB25 expression had a low probability of death after treatment. We also found lower RAB25 expression in tumors than in normal tissue (Mann–Whitney U, P < 0.001). Moreover, overexpression of RAB25 in the UM-SCC-74B HNSCC cell line increased cisplatin sensitivity, and reduced cell migration and invasion. Our findings support a tumor suppressor role for RAB25 in HNSCC and its potential use to identify locally advanced patients with a high probability of survival after genotoxic treatment. PMID:24403269

  5. How we used a patient visit tracker tool to advance experiential learning in systems-based practice and quality improvement in a medical student clinic.

    PubMed

    Chen, Chen Amy; Park, Ryan J; Hegde, John V; Jun, Tomi; Christman, Mitalee P; Yoo, Sun M; Yamasaki, Alisa; Berhanu, Aaron; Vohra-Khullar, Pamela; Remus, Kristin; Schwartzstein, Richard M; Weinstein, Amy R

    2016-01-01

    Poorly designed healthcare systems increase costs and preventable medical errors. To address these issues, systems-based practice (SBP) education provides future physicians with the tools to identify systemic errors and implement quality improvement (QI) initiatives to enhance the delivery of cost-effective, safe and multi-disciplinary care. Although SBP education is being implemented in residency programs and is mandated by the Accreditation Council for Graduate Medical Education (ACGME) as one of its core competencies, it has largely not been integrated into undergraduate medical education. We propose that Medical Student-Faculty Collaborative Clinics (MSFCCs) may be the ideal environment in which to train medical students in SBPs and QI initiatives, as they allow students to play pivotal roles in project development, administration, and management. Here we describe a process of experiential learning that was developed within a newly established MSFCC, which challenged students to identify inefficiencies, implement interventions, and track the results. After identifying bottlenecks in clinic operations, our students designed a patient visit tracker tool to monitor clinic flow and implemented solutions to decrease patient visit times. Our model allowed students to drive their own active learning in a practical clinical setting, providing early and unique training in crucial QI skills. PMID:25401409

  6. Genomic Profiling of Advanced-Stage Oral Cancers Reveals Chromosome 11q Alterations as Markers of Poor Clinical Outcome

    PubMed Central

    Ambatipudi, Srikant; Gerstung, Moritz; Gowda, Ravindra; Pai, Prathamesh; Borges, Anita M.; Schäffer, Alejandro A.; Beerenwinkel, Niko; Mahimkar, Manoj B.

    2011-01-01

    Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information