Sample records for advanced clinical usefulness

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

    Directory of Open Access Journals (Sweden)

    Wu Helen W


    Full Text Available Abstract 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

  2. Advances in clinical toxicology. (United States)

    Boehnert, M T; Lewander, W J; Gaudreault, P; Lovejoy, F H


    New data are reviewed in two areas in the management of the acute overdose: gastrointestinal decontamination and systemic antidotes. The mechanism and effectiveness of Ipecac syrup, gastric aspiration and lavage, activated charcoal, gastrointestinal dialysis, and saline cathartics are discussed. Special problems posed by disc batteries and packet ingestion of cocaine (in transporting contraband) are highlighted. The pharmacology and uses of pyridoxine and naloxone as antidotes are detailed.

  3. Clinical advances on Cardiac Insuffiency

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    Angel Julio Romero Cabrera


    Full Text Available Cardiac insuffiency is a complex clinical syndrome which constitutes a common final path to get in by the majority of the cardiac diseases. Studies based on the communitarian surveys shows that from 30 to 40 % of the patients decease within the first year of the diagnosis. The rest of the patients (from 60 to 70 % die within the 5 years after being diagnosed. For this reason it has been called as the ¨cancer of cardiology¨. The objective of this article is to update the advances reached in the clinical and therapeutic aspects of this important syndrome.

  4. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice (United States)


    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

  5. Advances in the Use of Stem Cells in Veterinary Medicine: From Basic Research to Clinical Practice. (United States)

    Markoski, Melissa Medeiros


    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.

  6. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness (United States)

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


    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

  7. Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique - Skin Autofluorescence. (United States)

    Oleniuc, Mihaela; Secara, Irina; Onofriescu, Mihai; Hogas, Simona; Voroneanu, Luminita; Siriopol, Dimitrie; Covic, Adrian


    . The Autofluorescence Reader may be useful as a clinical tool for rapid assessment of risk for advanced glycation end-products related long-term complications, not only in diabetes, but in other conditions associated with advanced glycation end-products accumulation as well.

  8. Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection

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    Yu SS


    Full Text Available Steven S Yu, David I Quinn, Tanya B Dorff Division of Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA Abstract: Clear cell (cc renal cell carcinoma (RCC is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib’s designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC. Keywords: cabozantinib, renal cell carcinoma, kidney cancer, clear cell carcinoma, tyrosine kinase inhibitor

  9. Clinical use of dopamine antagonist sulpiride to advance first ovulation in transitional mares. (United States)

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


    Artificial photoperiod treatment is currently the best method to hasten the first ovulation of the breeding season in winter anoestrus mares. However, this is not easy to apply in large herds of mares and, to be effective, has to be planned in the northern hemisphere in December at the latest. Pharmacological treatments have been proposed as alternatives: GnRH agonists, progesterone or its synthetic agonist Altrenogest, and dopamino-antagonists, as pherphenazine, domperidone or sulpiride. Dopamino-antagonists protocols, beginning at a given day of the year, gave controversial results in terms of hastening ovulation. The aim of this study was to evaluate the efficacy of an up-to-21-d long dopamine antagonist (sulpiride) treatment on mares at the beginning of the spring transition for its ability to hasten estrous cyclicity. In Study 1, 49 seasonally-acyclic standardbred mares, maintained in paddocks under natural photoperiod, were treated with 1 mg/kg/d sulpiride at the evidence of the first follicle with of 25 mm in diameter until ovulation for a maximum of 21 d (Group S(1); n = 34) or left untreated (Group C(1); n = 15). Group S(1) and C(1) mares showed a follicle of 35 mm in diameter after 8 and 22 d (median; P 0.05) and 50.0% and 61.1% of the remaining became pregnant in the following cycles (P > 0.05), respectively. Beginning with 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.

  10. [Clinical trials with advanced therapy medicinal products]. (United States)

    Schüssler-Lenz, M; Schneider, C K


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

  11. The ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications

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    Tsang JJ


    Full Text Available Jovian J Tsang,1,2 Harold L Atkins2,3 1Department of Biochemistry, University of Ottawa, 2Cancer Therapeutics, Ottawa Hospital Research Institute, 3Blood and Marrow Transplant Program, The Ottawa Hospital, Ottawa, ON, Canada Abstract: Hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. This is followed by hematopoietic stem cell (HSC transplantation (HSCT to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. Autologous HSC grafts may contain cancer cells and purging could further improve treatment outcomes. Similarly, allogeneic HSCT may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell depletion. Viral agents that selectively replicate in specific cell populations are being studied in experimental models of cancer and immunological diseases and have potential applications in the context of HSC graft engineering. This review describes preclinical studies involving oncolytic virus strains of adenovirus, herpes simplex virus type 1, myxoma virus, and reovirus as ex vivo purging agents for HSC grafts, as well as in vitro and in vivo experimental studies using oncolytic coxsackievirus, measles virus, parvovirus, vaccinia virus, and vesicular stomatitis virus to eradicate hematopoietic malignancies. Alternative ex vivo oncolytic virus strategies are also outlined that aim to reduce the risk of relapse following autologous HSCT and mitigate morbidity and mortality due to graft-versus-host disease in allogeneic HSCT. Keywords: hematopoietic stem cells, oncolytic virus, hematopoietic stem cell transplantation, stem cell graft purging, hematopoietic malignancy, graft vs host disease

  12. The ex vivo purge of cancer cells using oncolytic viruses: recent advances and clinical implications. (United States)

    Tsang, Jovian J; Atkins, Harold L


    Hematological malignancies are treated with intensive high-dose chemotherapy, with or without radiation. This is followed by hematopoietic stem cell (HSC) transplantation (HSCT) to rescue or reconstitute hematopoiesis damaged by the anticancer therapy. Autologous HSC grafts may contain cancer cells and purging could further improve treatment outcomes. Similarly, allogeneic HSCT may be improved by selectively purging alloreactive effector cells from the graft rather than wholesale immune cell depletion. Viral agents that selectively replicate in specific cell populations are being studied in experimental models of cancer and immunological diseases and have potential applications in the context of HSC graft engineering. This review describes preclinical studies involving oncolytic virus strains of adenovirus, herpes simplex virus type 1, myxoma virus, and reovirus as ex vivo purging agents for HSC grafts, as well as in vitro and in vivo experimental studies using oncolytic coxsackievirus, measles virus, parvovirus, vaccinia virus, and vesicular stomatitis virus to eradicate hematopoietic malignancies. Alternative ex vivo oncolytic virus strategies are also outlined that aim to reduce the risk of relapse following autologous HSCT and mitigate morbidity and mortality due to graft-versus-host disease in allogeneic HSCT.

  13. 咪唑安定临床应用进展%Advances in the clinical use of midazolam

    Institute of Scientific and Technical Information of China (English)

    刘红菊; 黄宇光


    Midazolam,a benzodiazepine with short half-life,perfect potency,and slight influence on hemodynamics,has a pharmacologic profile including sedation,anticonvulsant and anterograde amnesia.Lots of attention was paid to the use of midazolam in premedication of general anesthesia,conscious sedation for outpatients in short procedures or examinations,sedation in intensive care units(ICU),treatment of childhood status epilepticus,and intrathecal analgesia.This review focuses on the advance in clinical use of midazolam.%咪唑安定具有镇静、抗惊厥和顺行性遗忘等作用,其半衰期短,效能强,对血流动力学影响轻微.咪唑安定在麻醉术前用药、门诊短小手术或检查操作、ICU镇静、小儿癫痫持续状态的控制及椎管内辅助镇痛等领域的应用,都受到了较多关注.现就咪唑安定在以上领域的研究进展作一综述.

  14. Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience. (United States)

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


    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.

  15. Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy. (United States)

    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


    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

  16. Clinical significance of geographic miss when using conventional four field radiotherapy technique in treatment of locally advanced carcinoma cervix

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    A Gulia


    Full Text Available Background: Although conventional four- field radiotherapy based on bony landmarks has been traditionally used, areas of geographical miss due to individual variation in pelvic anatomy have been identified with advanced imaging techniques. AIMS: The primary aim of this study is to evaluate the geographical miss in patientswhen using the conventional four-field planningplanning and to find out the impact of 3-D conformal CT based in patients with locally advanced carcinoma cervix.Materials and Methods: In 50 patients, target volume delineation was done on planning computed tomography (CT scans, according to guidelines by Taylor et al. Patients were treated with modified four field plan, except for the superior, where field border was kept at L4-L5 interspace A dosimetric comparison was done between the conventional four-field based on bony landmarks and the target volume delineated on computed tomography. The disease free survival, pelvic and para aortic nodal free survival, distant failures free survival were calculated using Kaplan Meir Product Limit Method. Results: Patients were followed-up for a median period of 11 months. The median V95 for conventional and modified extended four field plans were 89.4% and 91.3% respectively. Patients with V95 for modified extended pelvic fields less than 91.3% had a trend toward inferior disease free survival (mean DFS 9.8 vs. 13.9 months though the difference was not statistically significant log rank test.Conclusions: Our preliminary data shows trend toward lower DFS in patients with inadequate target volume coverage. We recommend routine use of CT based planning for four field technique.

  17. Treatment of liver cancer of middle and advanced stages using ultrasound-guided percutaneous ethanol injection combined with radiofrequency ablation: A clinical analysis (United States)



    Liver cancer is a malignancy of the digestive system and has a high morbidity and mortality rate. Local intervention has become a viable option in identifying liver treatment. The aim of the present study was to analyze the clinical effects of treating liver cancer in middle and advanced stages using ultrasound-guided percutaneous ethanol injection (PEI) in tumors combined with radiofrequency ablation (RFA). A total of 100 patients with stage III–IV liver cancers were selected to participate in the study. Patients were divided into groups. In group A, treatment was initiated with PEI and after 1–2 weeks RFA was applied while in group B treatment was initiated with RFA and after 1–2 weeks PEI was applied. Patients in group C received PEI and RFA simultaneously. The clinical effects in the 3 groups were compared after 6-month follow ups. The volume of tumor ablation necrosis in group A was significantly greater than that in the groups B and C, while the size was significantly smaller compared to groups B and C after ablation. For group A, the complete ablation rate was significantly higher than that in groups B and C, and the differences were statistically significant (P<0.05). Liver damage indices, including raising levels of glutamic-pyruvic transaminase and total bilirubin, were significantly decreased in group A (P<0.05). The survival rate in group A was also significantly higher than in groups B and C (P<0.05). In conclusion, for patients with liver cancer in middle and advanced stages, the treatment method using PEI followed by RFA was more beneficial in terms of improving the tumor ablation rate, alleviating liver damages and increasing survival rates. PMID:26998128

  18. Advanced and controlled drug delivery systems in clinical disease management

    NARCIS (Netherlands)

    Brouwers, JRBJ


    Advanced and controlled drug delivery systems are important for clinical disease management. In this review the most important new systems which have reached clinical application are highlighted. Microbiologically controlled drug delivery is important for gastrointestinal diseases like ulcerative co

  19. Technological advances in perioperative monitoring: Current concepts and clinical perspectives. (United States)

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


    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.

  20. Clinical Usefulness of {sup 18}F-Fluorodeoxyglucose-Positron Emission Tomography in Patients With Locally Advanced Pancreatic Cancer Planned to Undergo Concurrent Chemoradiation Therapy

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    Chang, Jee Suk; Choi, Seo Hee; Lee, Youngin; Kim, Kyung Hwan [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Park, Jeong Youp; Song, Si Young [Department of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Cho, Arthur; Yun, Mijin; Lee, Jong Doo [Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); Seong, Jinsil, E-mail: [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)


    Purpose: To assess the role of coregistered {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting radiographically occult distant metastasis (DM) at staging in patients with locally advanced pancreatic cancer (LAPC) and to study whether FDG-PET parameters can predict relatively long-term survival in patients who are more likely to benefit from chemoradiation therapy (CRT). Methods and Materials: From our institutional database, we identified 388 LAPC patients with M0 on conventional computed tomography (CT) who were planned to undergo CRT. Coregistered FDG-PET staging was offered to all patients, and follow-up FDG-PET was used at the clinical discretion of the physician. Results: FDG-PET detected unsuspected CT-occult DM in 33% of all 388 patients and allowed them to receive systemic therapy immediately. The remaining 260 patients (PET-M0) underwent CRT selectively as an initial treatment. Early DM arose in 13.1% of 260 patients, and the 1-year estimated locoregional recurrence rate was 5.4%. Median overall survival (OS) and progression-free survival (PFS) were 14.6 and 9.3 months, respectively, at a median follow-up time of 32.3 months (range, 10-99.1 months). Patients with a baseline standardized uptake value (SUV) <3.5 and/or SUV decline ≥60% had significantly better OS and PFS than those having none, even after adjustment for all potential confounding variables (all P<.001). Conclusions: FDG-PET can detect radiographically occult DM at staging in one-third of patients and spare them from the potentially toxic therapy. Additionally, FDG-PET parameters including baseline SUV and SUV changes may serve as useful clinical markers for predicting the prognosis in LAPC patients.

  1. Uses of clinical algorithms. (United States)

    Margolis, C Z


    The clinical algorithm (flow chart) is a text format that is specially suited for representing a sequence of clinical decisions, for teaching clinical decision making, and for guiding patient care. A representative clinical algorithm is described in detail; five steps for writing an algorithm and seven steps for writing a set of algorithms are outlined. Five clinical education and patient care uses of algorithms are then discussed, including a map for teaching clinical decision making and protocol charts for guiding step-by-step care of specific problems. Clinical algorithms are compared as to their clinical usefulness with decision analysis. Three objections to clinical algorithms are answered, including the one that they restrict thinking. It is concluded that methods should be sought for writing clinical algorithms that represent expert consensus. A clinical algorithm could then be written for any area of medical decision making that can be standardized. Medical practice could then be taught more effectively, monitored accurately, and understood better.

  2. Mentoring for retention and advancement in the multigenerational clinical laboratory. (United States)

    Laudicina, R J


    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".

  3. Advances in Clinical PET/MRI Instrumentation. (United States)

    Herzog, Hans; Lerche, Christoph


    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.

  4. Clinical evaluation of accelerated hyperfractionated irradiation for locally advanced head and neck cancer with concomitant use of daily low-dose Carboplatin (CBDCA)

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    Hatano, Kazuo; Sekiya, Yuichi; Araki, Hitoshi [Chiba Cancer Center (Japan)


    From May 1994 to May 1996, 39 patients with locally advanced head and neck cancer were treated with accelerated hyperfractionated irradiation (1.6 Gy, twice daily, 10 times a week, with minimum interval of 6 hours between fractions and the total tumor dose to 70.4 Gy) and concomitant use of daily low-dose Carboplatin (30 mg/body). The average age was 64.2 years (38-85). The median follow-up period was 16.4 months with a range of 2-36 months. Complete response rate was 66.7%. The organ preservation rates were almost acceptable in advanced cases. The major acute toxicity was stomatitis, but no therapeutic interruption was observed. Grade 4 laryngeal late sequelae was observed in 2 cases. We think this method is effective for locally advanced head and neck cancer but total dose should be reduced to 67.2 Gy for laryngeal and hypopharyngeal cancer. (author)

  5. [Advanced data analysis and visualization for clinical laboratory]. (United States)

    Inada, Masanori; Yoneyama, Akiko


    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.

  6. Lung Cancer Clinical Trials: Advances in Immunotherapy (United States)

    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  7. Recent advances in dengue pathogenesis and clinical management. (United States)

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


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

  8. Recent advances in basic and clinical nanomedicine. (United States)

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


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

  9. Advances and applications of molecular cloning in clinical microbiology. (United States)

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


    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.

  10. Advances in functional magnetic resonance imaging: technology and clinical applications. (United States)

    Dickerson, Bradford C


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

  11. Student Pharmacists’ Clinical Interventions in Advanced Pharmacy Practice Experiences at a Community Nonteaching Hospital


    Shogbon, Angela O.; Lundquist, Lisa M.


    Objective. To assess student pharmacists’ clinical interventions in advanced pharmacy practice experiences (APPEs) at a community nonteaching hospital and evaluate completed interventions based on the type of documentation method used.

  12. How should we manage information needs, family anxiety, depression, and breathlessness for those affected by advanced disease: development of a Clinical Decision Support Tool using a Delphi design.

    NARCIS (Netherlands)

    Vliet, L.M. van; Harding, R.; Bausewein, C.; Payne, S.; Higginson, I.J.


    Background: Clinicians request guidance to aid the routine use and interpretation of Patient Reported Outcome Measures (PROMs), but tools are lacking. We aimed to develop a Clinical Decision Support Tool (CDST) focused on information needs, family anxiety, depression, and breathlessness (measured us

  13. Recent advances in medical imaging: anatomical and clinical applications. (United States)

    Grignon, Bruno; Mainard, Laurence; Delion, Matthieu; Hodez, Claude; Oldrini, Guillaume


    The aim of this paper was to present an overview of the most important recent advances in medical imaging and their potential clinical and anatomical applications. Dramatic changes have been particularly observed in the field of computed tomography (CT) and magnetic resonance imaging (MRI). Computed tomography (CT) has been completely overturned by the successive development of helical acquisition, multidetector and large area-detector acquisition. Visualising brain function has become a new challenge for MRI, which is called functional MRI, currently based principally on blood oxygenation level-dependent sequences, which could be completed or replaced by other techniques such as diffusion MRI (DWI). Based on molecular diffusion due to the thermal energy of free water, DWI offers a spectrum of anatomical and clinical applications, ranging from brain ischemia to visualisation of large fibrous structures of the human body such as the anatomical bundles of white matter with diffusion tensor imaging and tractography. In the field of X-ray projection imaging, a new low-dose device called EOS has been developed through new highly sensitive detectors of X-rays, allowing for acquiring frontal and lateral images simultaneously. Other improvements have been briefly mentioned. Technical principles have been considered in order to understand what is most useful in clinical practice as well as in the field of anatomical applications. Nuclear medicine has not been included.

  14. Treatment of localized gingival recession using the free rotated papilla autograft combined with coronally advanced flap by conventional (macrosurgery and surgery under magnification (microsurgical technique: A comparative clinical study

    Directory of Open Access Journals (Sweden)

    Suraj Pandey


    Full Text Available Background: The aim of the present study was to evaluate and compare the conventional (macro-surgical and microsurgical approach in performing the free rotated papilla autograft combined with coronally advanced flap surgery in treatment of localized gingival recession. Materials and Methods: A total of 20 sites from 10 systemically healthy patients were selected for the study. The selected sites were randomly divided into experimental site A and experimental site B by using the spilt mouth design. Conventional (macro-surgical approach for site A and micro-surgery for site B was applied in performing the free rotated papilla autograft combined with coronally advanced flap. Recession depth (RD, recession width (RW clinical attachment level (CAL. and width of keratinized tissue (WKT. were recorded at baseline, 3 months and 6 months post-operatively. Results: Both (macro- and microsurgery groups showed significant clinical improvement in all the parameters (RD, RW, CAL and WKT. However, on comparing both the groups, these parameters did not reach statistical significance. Conclusion: Both the surgical procedures were equally effective in treatment of localized gingival recession by the free rotated papilla autograft technique combined with coronally advanced flap. However, surgery under magnification (microsurgery may be clinically better than conventional surgery in terms of less post-operative pain and discomfort experienced by patients at the microsurgical site.

  15. Clinical Research on Use of Oxaliplcrtin in Combination with HCPT, LV and 5FU in a Regimen for Advanced Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    GuoqingHu; QiangFu; MaolinJin; JieLi; LiangxiPan; YuxianBai; HuaijinWang; JianweiZhang; DingYu


    OBJECTIVE To observe the effects and adverse reactions of a OXA-HCPT LV/5FU 3 regimen for patients with advanced gastric cancer.METHODS OHLF3 regimen: OXA 130 mg/m2iv d 1, HCPT6 mg/m2, iv d 1-5, LV 200 mg/m2iv 2 h followed by a 5FU 400 mg/m2 iv bolus and 5FU 600mg/m2 iv d 1-3, were given, every 21 days as 1 cycle. Assessment of the tumor was conducted after 3 cycles and the effective cases were confirmed after 4 weeks.RESULTS Among 39 patients, 36 were actually evaluable. Overall response rates (CR + PR} were 50%' the major adverse reactions were mild hematological toxicity, nausea and vomiting and peripheral nerve abnormalities.CONCLUSION The OHLF 3 regimen using OXA and HCPT is effective and results in mild toxicity when used in combined chemotherapy for advanced gastric cancer.

  16. Nurse cannulation: introducing an advanced clinical skill.

    LENUS (Irish Health Repository)

    Hoctor, Bridget


    Many patients admitted to emergency departments (EDs) require therapy delivered by cannula. Mid-Western Regional Hospital, Tipperary, used to run a system in which many patients had to endure two invasive procedures: on arrival their blood was taken by nurses and later they were cannulated by doctors. To reduce the number of procedures, ED nurses initiated a project to extend their skills to include cannulation. The new system of nurse cannulation at triage has also helped reduce waiting times.

  17. Clinical comparison of Colgate Total Advanced Fresh vs a commercially available fluoride breath-freshening toothpaste in reducing breath odor overnight: a multiple-use study. (United States)

    Niles, Hollandra P; Hunter, Catherine M; Vazquez, Joe; Williams, Malcolm I; Cummins, Diane


    The objective of this randomized, crossover study was to compare the effectiveness of Colgate Total Advanced Fresh toothpaste to a commercially available breath-freshening dentifrice containing fluoride for its ability to reduce volatile sulfur compounds (VSC) responsible for breath odor overnight. The study followed a two-treatment, two-period crossover design. Subjects were given a test product, along with a soft-bristled toothbrush, and instructed to brush their teeth for 1 minute, twice daily (once in the morning and the evening) using the assigned dentifrice for 7 consecutive days. After their evening brushing on the seventh day, subjects reported to the testing facility without oral hygiene, eating, or drinking for the overnight evaluation. After a washout period, subjects repeated the same regimen, now using the other test product. The levels of breath VSC were evaluated instrumentally using a gas chromatograph equipped with a flame photometric detector.

  18. Introducing Advanced Clinical Reasoning to an Adult Learning Disability Service (United States)

    Stansfield, Jois; Matthews, Alison


    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…

  19. Building the Clinical Bridge to Advance Education, Research, and Practice Excellence

    Directory of Open Access Journals (Sweden)

    Marilyn Svejda


    Full Text Available The University of Michigan School of Nursing and the Health System partnered to develop an undergraduate clinical education model as part of a larger project to advance clinical education, practice, and scholarship with education serving as the clinical bridge that anchors all three areas. The clinical model includes clusters of clinical units as the clinical home for four years of a student's education, clinical instruction through team mentorship, clinical immersion, special skills preparation, and student portfolio. The model was examined during a one-year pilot with junior students. Stakeholders were largely positive. Findings showed that Clinical Faculty engaged in more role modeling of teaching strategies as Mentors assumed more direct teaching used more clinical reasoning strategies. Students reported increased confidence and competence in clinical care by being integrated into the team and the Mentor's assignment. Two new full time faculty roles in the Health System support education, practice, and research.

  20. Breast cancer stem cells: current advances and clinical implications. (United States)

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


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

  1. Basic principles and clinical advancements of muscle electrotransfer

    DEFF Research Database (Denmark)

    Hojman, Pernille


    Muscle electrotransfer covers the delivery of molecules to muscle tissue by means of electric pulses. This method has proven highly efficient in transferring, in particular, plasmid DNA to muscles, resulting in long-term expression of the transferred genes. DNA electrotransfer to muscle tissue has...... clinical potential within DNA vaccination, systemic delivery of therapeutic proteins and correction of gene defects in muscles. In the recent years, DNA electrotransfer to muscle tissue has reached clinical advancement with 8 on-going clinical trials. In the present review, I will draw on the experiences...... obtained from the clinical studies, in understanding the mechanistic and practical advantages and limits of muscle electrotransfer. The effect of applying electric pulses to muscle tissue will be described in details, while present and future clinical applications are reviewed....

  2. Advances in the research of promotion effect of Aloe vera on wound healing and its clinical use%芦荟促进创面愈合的机制及临床应用研究进展

    Institute of Scientific and Technical Information of China (English)

    宋信福; 陈晓东


    Aloe vera has been widely investigated and used as folk medicine since ancient time.Biologically active substances in its gel include polysaccharides,glycoprotein,enzymes,anthraquinones or phenolic compounds,vitamins,minerals,and so on,which play important roles in anti-inflammatory response,antimicrobial,antiviral,antioxidant activity,immunoregulation effects,and especially in wound healing.In this paper,we review the advances in the mechanism and clinical application of Aloe vera and its extract on wound healing,so as to provide new ideas for the treatment of various kinds of wounds.

  3. Advance directives: prerequisites and usefulness. (United States)

    van Asselt, D


    Advance directives allow competent persons to extend their right of self-determination into the future, by recording choices that are intended to influence their future care should they become unable to make choices. They are considered tools to facilitate end-of-life decision making. Advance directives are a form of anticipatory decision-making. This article will focus on instruction directives against a certain treatment, so-called advance refusals. The most important legal requirement is the acknowledgement of patient autonomy. This condition is met in all European countries. The legal uncertainties surrounding advance refusals are focused on practical modalities rather than on the validity of the general principle. According to leading ethics the underlying moral rule of advanced directives is that all truly autonomous refusals of treatment must be respected, no matter what the consequences. Physicians find it hard to adhere to the wishes and choices of patients as expressed in directives. They find the text ambiguous. Another weakness is that directives give little information about what in the patient's view constitutes a good quality of life. Some health professionals lack the willingness to step outside their own value systems and fully embrace that of the patient. Empathic skills are required. Very few persons create an advance directive. Furthermore, of the created directives only some are accessible when patients are admitted to hospital. However, when directives are available they usually influence medical treatment decisions.

  4. Coronary Stents: The Impact of Technological Advances on Clinical Outcomes. (United States)

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


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

  5. Developing an advanced practice nurse-led liver clinic. (United States)

    McAfee, Jean L


    End-stage liver disease (ESLD) is a leading cause of digestive disease deaths in the United States and continues to increase exponentially every year. Best practice does not currently recognize or utilize a clinic practice model for ESLD management. Advanced practice registered nurses (APRNs) can impact ESLD disease management by implementing an outpatient clinic care model to focus on treatment compliance, patient education, improvement of patient outcomes, and reduction in hospital admission rates for ESLD patients. A review of 15 research articles was completed to determine the impact APRNs can make on chronic care of ESLD patients. Results from the review support APRN analysis, assessment, diagnosis, treatment, intervention, and evaluation of ESLD patients. The literature reviewed also demonstrates that ESLD patients have improved symptom management when maintained in an outpatient setting, allowing for decreased hospital and insurance expenditures. Following evaluation of the evidence, it was concluded that an APRN-led ESLD clinic merits further study.

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

    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


    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.

  7. Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies (United States)

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


    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.

  8. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results (United States)

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


    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.

  9. The biology of infertility: research advances and clinical challenges (United States)

    Matzuk, Martin M; Lamb, Dolores J


    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

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


    Conway, Jeannine M.; Ahmed, Ghada F


    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).

  11. What clinical activities do advanced-practice registered dietitian nutritionists perform? Results of a Delphi study. (United States)

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


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

  12. Identifying components of advanced-level clinical nutrition practice: a Delphi study. (United States)

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


    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. Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    John F. Flynn


    Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

  14. Clinical relevance of advanced glycation endproducts for vascular surgery. (United States)

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


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

  15. Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. (United States)

    Burstein, Harold J; Krilov, Lada; Aragon-Ching, Jeanny B; Baxter, Nancy N; Chiorean, E Gabriela; Chow, Warren Allen; De Groot, John Frederick; Devine, Steven Michael; DuBois, Steven G; El-Deiry, Wafik S; Epstein, Andrew S; Heymach, John; Jones, Joshua Adam; Mayer, Deborah K; Miksad, Rebecca A; Pennell, Nathan A; Sabel, Michael S; Schilsky, Richard L; Schuchter, Lynn Mara; Tung, Nadine; Winkfield, Karen Marie; Wirth, Lori J; Dizon, Don S


    . Importantly, the advances described in this report would not have been possible without the individuals who volunteered to participate in clinical trials as part of their treatment. To turn the promising vision of a cancer moonshot into meaningful advances, we need sustained, robust federal funding for continued research and innovation. Approximately 30% of the research highlighted in this report was funded, at least in part, through federal dollars appropriated to the National Institutes of Health or the National Cancer Institute. Without this federal investment-unique internationally in scale, duration, and impact for decades-I fear we may lose the forward momentum needed to further the progress we see highlighted in this report. Federal lawmakers can further fuel progress by advancing initiatives that facilitate the use of big data to achieve the common good of high-quality care for all patients. Such programs, like ASCO's CancerLinQ, will rapidly increase the pace of progress and dramatically expand the reach of treatment advances to the millions of patients who are living with cancer today or who will do so in the future. This investment will yield medical, scientific, economic, and societal benefits for years to come. Much work still lies ahead. Many questions remain about how cancer develops and spreads and how best to treat it. As you read through Clinical Cancer Advances 2017, I hope you are as inspired as I am by the gains the clinical cancer research community has made over the past year and by the promise of a new era of advances just over the horizon. Daniel F Hayes, MD, FASCO, FACP ASCO President, 2016 to 2017.

  16. Right person, right skills, right job: the contribution of objective structured clinical examinations in advancing staff nurse experts. (United States)

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


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

  17. Advanced Carbon Fiber Nears Broad Automotive Use

    Institute of Scientific and Technical Information of China (English)


    General Motors and Teijin Limited, a leader in the carbon fiber and composites industry, will co-develop advanced carbon fiber composite technologies for potential high-volume use globally in GM cars, trucks and crossovers.

  18. Recent technological advances in computed tomography and the clinical impact therein. (United States)

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


    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.

  19. Test Review: Advanced Clinical Solutions for WAIS-IV and WMS-IV (United States)

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


    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…

  20. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care (United States)

    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.

  1. Sample Preparation and Extraction in Small Sample Volumes Suitable for Pediatric Clinical Studies: Challenges, Advances, and Experiences of a Bioanalytical HPLC-MS/MS Method Validation Using Enalapril and Enalaprilat

    Directory of Open Access Journals (Sweden)

    Bjoern B. Burckhardt


    Full Text Available In USA and Europe, medicines agencies force the development of child-appropriate medications and intend to increase the availability of information on the pediatric use. This asks for bioanalytical methods which are able to deal with small sample volumes as the trial-related blood lost is very restricted in children. Broadly used HPLC-MS/MS, being able to cope with small volumes, is susceptible to matrix effects. The latter restrains the precise drug quantification through, for example, causing signal suppression. Sophisticated sample preparation and purification utilizing solid-phase extraction was applied to reduce and control matrix effects. A scale-up from vacuum manifold to positive pressure manifold was conducted to meet the demands of high-throughput within a clinical setting. Faced challenges, advances, and experiences in solid-phase extraction are exemplarily presented on the basis of the bioanalytical method development and validation of low-volume samples (50 μL serum. Enalapril, enalaprilat, and benazepril served as sample drugs. The applied sample preparation and extraction successfully reduced the absolute and relative matrix effect to comply with international guidelines. Recoveries ranged from 77 to 104% for enalapril and from 93 to 118% for enalaprilat. The bioanalytical method comprising sample extraction by solid-phase extraction was fully validated according to FDA and EMA bioanalytical guidelines and was used in a Phase I study in 24 volunteers.

  2. Predicting Clinical Outcomes Using Molecular Biomarkers. (United States)

    Burke, Harry B


    Over the past 20 years, there has been an exponential increase in the number of biomarkers. At the last count, there were 768,259 papers indexed in directly related to biomarkers. Although many of these papers claim to report clinically useful molecular biomarkers, embarrassingly few are currently in clinical use. It is suggested that a failure to properly understand, clinically assess, and utilize molecular biomarkers has prevented their widespread adoption in treatment, in comparative benefit analyses, and their integration into individualized patient outcome predictions for clinical decision-making and therapy. A straightforward, general approach to understanding how to predict clinical outcomes using risk, diagnostic, and prognostic molecular biomarkers is presented. In the future, molecular biomarkers will drive advances in risk, diagnosis, and prognosis, they will be the targets of powerful molecular therapies, and they will individualize and optimize therapy. Furthermore, clinical predictions based on molecular biomarkers will be displayed on the clinician's screen during the physician-patient interaction, they will be an integral part of physician-patient-shared decision-making, and they will improve clinical care and patient outcomes.

  3. Recent advances in targeted proteomics for clinical applications. (United States)

    Domon, Bruno; Gallien, Sebastien


    MS-based approaches using targeted methods have been widely adopted by the proteomics community to study clinical questions such as the evaluation of biomarkers. At present, the most widely used targeted MS method is the SRM technique typically performed on a triple quadrupole instrument. However, the high analytical demands for performing clinical studies in combination with the extreme complexity of the samples involved are a serious challenge. The segmentation of the biomarker evaluation workflow has only partially alleviated these issues by differently balancing the analytical requirements and throughput at different stages of the process. The recent introduction of targeted high-resolution and accurate-mass analyses on fast sequencing mass spectrometers operated in parallel reaction monitoring (PRM) mode offers new avenues to conduct clinical studies and thus overcome some of the limitations of the triple quadrupole instrument. This article discusses the attributes and specificities of the PRM technique, in terms of experimental design, execution, and data analysis, and the implications for biomarker evaluation. The benefits of PRM on data quality and the impact on the consistency of results are highlighted and the definitive progress on the overall output of clinical studies, including high throughput, is discussed.

  4. Clinical Uses of Probiotics. (United States)

    Islam, Saif Ul


    Probiotics are live nonpathogenic microorganisms. Many of these microorganisms are part of the normal human gut flora, where they live in a symbiotic relationship. Probiotics have been used to treat gastrointestinal (GI) and non-GI medical conditions. However, the data supporting their use are often conflicting, especially for non-GI-associated illnesses. The strongest evidence supporting the use of probiotics is related to the treatment of acute diarrhea and pouchitis. Atopic eczema in children and genitourinary infections are the only non-GI-related medical conditions where probiotics may have some beneficial effects. Product selection and dosing are not the same in all conditions, and the beneficial effects of each probiotic strain cannot be generalized.The purpose of this article is to provide most recent information about probiotics and its uses. In contrast with previously published reviews on probiotics, we also discuss the composition of various products (Table 1), indications for their use (Table 2), product selection, and dosing of probiotics.Probiotics are safe and appear to exert some beneficial effects in GI-related illnesses. The use of probiotics in non-GI illnesses is not sufficiently supported by current data.

  5. [Image guided and robotic treatment--the advance of cybernetics in clinical medicine]. (United States)

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


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

  6. Comparison of allogeneic stem cell transplantation and non-transplant approaches in elderly patients with advanced myelodysplastic syndrome: optimal statistical approaches and a critical appraisal of clinical results using non-randomized data.

    Directory of Open Access Journals (Sweden)

    Ronald Brand

    Full Text Available Allogeneic stem cell transplantation (ASCT from related or unrelated donors may cure patients with myelodysplastic syndromes (MDS, a heterogeneous group of clonal stem cell disorders. We analysed 384 elderly patients (55-69 years with advanced MDS who received either ASCT (n=247 and were reported to The European Group for Blood and Marrow Transplantation (EBMT or a non -transplant approach (n=137 reported to the Düsseldorf registry. Besides an attempt to answer the question of "comparison", the purpose of this work is to explain the difficulties in comparing a non-transplant with a transplant cohort, when death before transplant is likely but unknown and the selection of patients for transplant is based on assumptions. It shows which methods are almost always biased and that even the most sophisticated approaches crucially rely on clinical assumptions. Using the most appropriate model for our data, we derive an overall univariate non-significant survival disadvantage for the transplant cohort (HR: 1.29, p = 0.11. We show that such an "average" hazard ratio is however misleading due to non-proportionality of the hazards reflecting early treatment related mortality, the occurring of which is logically correlated with the interval between diagnosis and transplant creating a disproportional drop in the (reconstructed survival curve of the transplanted patients. Also in multivariate analysis (correcting for age > 60 (HR: 1.4, p = 0.02 and abnormal cytogenetics (HR: 1.46, p = 0.01, transplantation seems to be worse (HR: 1.39, p = 0.05 but only in the (incorrect but commonly applied model without time varying covariates. The long term (time depending hazard ratio is shown to be virtually 1 and overall survival is virtually identical in both groups. Nonetheless no conclusion can be reached from a clinical point of view without assumptions which are by their very nature untestable unless all patients would be followed from diagnosis.

  7. Opioid-induced constipation: advances and clinical guidance (United States)

    Nelson, Alfred D.; Camilleri, Michael


    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

  8. Advanced circuit simulation using Multisim workbench

    CERN Document Server

    Báez-López, David; Cervantes-Villagómez, Ofelia Delfina


    Multisim is now the de facto standard for circuit simulation. It is a SPICE-based circuit simulator which combines analog, discrete-time, and mixed-mode circuits. In addition, it is the only simulator which incorporates microcontroller simulation in the same environment. It also includes a tool for printed circuit board design.Advanced Circuit Simulation Using Multisim Workbench is a companion book to Circuit Analysis Using Multisim, published by Morgan & Claypool in 2011. This new book covers advanced analyses and the creation of models and subcircuits. It also includes coverage of transmissi

  9. Test Review: Advanced Clinical Solutions for WAIS-IV and WMS-IV (United States)

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


    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…

  10. Clinical significance of preoperative regional intra-arterial infusion chemotherapy for advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Cheng-Wu Zhang; Shou-Chun Zou; Dun Shi; Da-Jian Zhao


    AIM: Preoperative intra-arterial infusion chemotherapy could increase the radical resection rate of advanced gastric cancer, but its effect on the long-term survival has not been assessed. This study was designed to evaluate the clinical significance of preoperative intra-arterial infusion chemotherapy for advanced gastric cancer.METHODS: Clinicopathological data of 91 patients who underwent curative resection for advanced gastric cancer were collected. Among them, 37 patients undertaken preoperative intra-arterial infusion chemotherapy were used as the interventional chemotherapy group, and the remaining 54 patients as the control group. Eleven factors including clinicopathological variables, treatment procedures and molecular biological makers that might contribute to the long-term survival rate were analyzed using Cox multivariate regression analysis.RESULTS: The 5-year survival rate was 52.5% and 39.8%,respectively, for the interventional group and the control group (P<0.05). Cox multivariate regression analysis revealed that the TNM stage (P<0.001), preoperative intraarterial infusion chemotherapy (P = 0.029) and growth pattern (P = 0.042) were the independent factors for the long-term survival of patients with advanced gastric cancer.CONCLUSION: Preoperative intra-arterial infusion chemotherapy plays an important role in improving the prognosis of advanced gastric cancer.

  11. The value of clinical electrophysiology in the assessment of the eye and visual system in the era of advanced imaging. (United States)

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


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

  12. Clinical Holistic Health: Advanced Tools for Holistic Medicine

    Directory of Open Access Journals (Sweden)

    Søren Ventegodt


    Full Text Available 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

  13. Using Local Data To Advance Quantitative Literacy


    Stephen Sweet; Susanne Morgan; Danette Ifert Johnson


    In this article we consider the application of local data as a means of advancing quantitative literacy. We illustrate the use of three different sources of local data: institutional data, Census data, and the National College Health Assessment survey. Our learning modules are applied in courses in sociology and communication, but the strategy of using local data can be integrated beyond these disciplinary boundaries. We demonstrate how these data can be used to stimulate student interests in...

  14. Using Local Data To Advance Quantitative Literacy

    Directory of Open Access Journals (Sweden)

    Stephen Sweet


    Full Text Available In this article we consider the application of local data as a means of advancing quantitative literacy. We illustrate the use of three different sources of local data: institutional data, Census data, and the National College Health Assessment survey. Our learning modules are applied in courses in sociology and communication, but the strategy of using local data can be integrated beyond these disciplinary boundaries. We demonstrate how these data can be used to stimulate student interests in class discussion, advance analytic skills, as well as develop capacities in written and verbal communication. We conclude by considering concerns that may influence the types of local data used and the challenges of integrating these data in a course in which quantitative analysis is not typically part of the curriculum.

  15. Nausea and vomiting in advanced cancer: the Cleveland Clinic protocol. (United States)

    Gupta, Mona; Davis, Mellar; LeGrand, Susan; Walsh, Declan; Lagman, Ruth


    Nausea and vomiting are common and distressing symptoms in advanced cancer. Both are multifactorial and cause significant morbidity, nutritional failure, and reduced quality of life. Assessment includes a detailed history, physical examination and investigations for reversible causes. Assessment and management will be influenced by performance status, prognosis, and goals of care. Several drug classes are effective with some having the added benefit of multiple routes of administration. It is our institution's practice to recommend metoclopramide as the first drug with haloperidol as an alternative antiemetic. Dexamethasone should be used for patients with central nervous system metastases or bowel obstruction. If your patient is near death, empiric metoclopramide, haloperidol or chlorpromazine is used without further investigation. For patients with a better prognosis, we exclude reversible causes and use the same first-line antiemetics, metoclopramide and haloperidol. For those who do not respond to first-line single antiemetics, olanzapine is second line and ondansetron is third. Rarely do we use combination therapy or cannabinoids. Olanzapine as a single agent has a distinct advantage over antiemetic combinations. It improves compliance, reduces drug interactions and has several routes of administration. Antiemetics, anticholinergics, octreotide and dexamethasone are used in combination to treat bowel obstruction. In opiod-na'ive patients, we prefer haloperidol, glycopyrrolate and an opioid as the first-line treatment and add or substitute octreotide and dexamethasone in those who do not respond. Non-pharmacologic interventions (mechanical stents and percutaneous endoscopic gastrostomy tubes) are used when nausea is refractory to medical management or for home-going management to relieve symptoms, reduce drug costs and rehospitalization.

  16. [Implementation of bedside training and advanced objective structured clinical examination (OSCE) trial to learn and confirm about pharmacy clinical skills]. (United States)

    Tokunaga, Jin; Takamura, Norito; Ogata, Kenji; Setoguchi, Nao; Sato, Keizo


    Bedside training for fourth-year students, as well as seminars in hospital pharmacy (vital sign seminars) for fifth-year students at the Department of Pharmacy of Kyushu University of Health and Welfare have been implemented using patient training models and various patient simulators. The introduction of simulation-based pharmaceutical education, where no patients are present, promotes visually, aurally, and tactilely simulated learning regarding the evaluation of vital signs and implementation of physical assessment when disease symptoms are present or adverse effects occur. A patient simulator also promotes the creation of training programs for emergency and critical care, with which basic as well as advanced life support can be practiced. In addition, an advanced objective structured clinical examination (OSCE) trial has been implemented to evaluate skills regarding vital signs and physical assessments. Pharmacists are required to examine vital signs and conduct physical assessment from a pharmaceutical point of view. The introduction of these pharmacy clinical skills will improve the efficacy of drugs, work for the prevention or early detection of adverse effects, and promote the appropriate use of drugs. It is considered that simulation-based pharmaceutical education is essential to understand physical assessment, and such education will ideally be applied and developed according to on-site practices.

  17. Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology. (United States)

    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


    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

  18. Clinical trials update: Medical management of advanced breast cancer. (United States)

    Major, Maureen A


    Selection of treatment for metastatic breast cancer depends on several factors: the status of estrogen receptors or progesterone receptors on breast cancer cells and the expression levels of human epidermal growth factor receptor-2. The presence of estrogen or progesterone receptors typically indicates slower-growing tumors that may be amenable to hormonal manipulation, which provides significant disease control while offering a better toxicity profile than conventional chemotherapy. The understanding of hormonal therapies in patients with postmenopausal metastatic breast cancer has advanced greatly in the past several decades. Aromatase inhibitors, although used initially as second-line therapy, recently have proved to be as effective as tamoxifen, if not superior to it, as first-line therapy for metastatic breast cancer. New data also suggest that letrozole provides significantly better objective responses than anastrozole as second-line therapy. Exemestane, a steroidal aromatase inhibitor, is an effective third-line therapy. Fulvestrant, an estrogen receptor antagonist with no known agonist effect, provides a new option for hormonal therapy. For patients with metastatic breast cancer and overexpression of human epidermal growth factor receptor-2 on tumor cells, the monoclonal antibody trastuzumab is the preferred option, either in combination with paclitaxel as first-line treatment, or as a single agent for second-line therapy. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed, potentially extending patient survival rates and improving quality of life.


    Directory of Open Access Journals (Sweden)



    Full Text Available The water has an essential role in the functioning of ecosystems by integrating the complex physical, chemical, and biological processes that sustain life. Water is a key factor in determining the productivity of ecosystems, biodiversity and species composition. Water is also essential for humanity: water supply systems for population, agriculture, fisheries, industries, and hydroelectric power depend on water supplies. The modelling of hydrological processes is an important activity for water resources management, especially now, when the climate change is one of the major challenges of our century, with strong influence on hydrological processes dynamics. Climate change and needs for more knowledge in water resources require the use of advanced hydroinformatic tools in hydrological processes modelling. The rationale and purpose of advanced hydroinformatic tools is to develop a new relationship between the stakeholders and the users and suppliers of the systems: to offer the basis (systems which supply useable results, the validity of which cannot be put in reasonable doubt by any of the stakeholders involved. For a successful modelling of hydrological processes also need specialists well trained and able to use advanced hydro-informatics tools. Results of modelling can be a useful tool for decision makers to taking efficient measures in social, economical and ecological domain regarding water resources, for an integrated water resources management.

  20. Recent advances towards the clinical application of DNA vaccines. (United States)

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


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

  1. A review of Raman spectroscopy advances with an emphasis on clinical translation challenges in oncology (United States)

    Jermyn, Michael; Desroches, Joannie; Aubertin, Kelly; St-Arnaud, Karl; Madore, Wendy-Julie; De Montigny, Etienne; Guiot, Marie-Christine; Trudel, Dominique; Wilson, Brian C.; Petrecca, Kevin; Leblond, Frederic


    There is an urgent need for improved techniques for disease detection. Optical spectroscopy and imaging technologies have potential for non- or minimally-invasive use in a wide range of clinical applications. The focus here, in vivo Raman spectroscopy (RS), measures inelastic light scattering based on interaction with the vibrational and rotational modes of common molecular bonds in cells and tissue. The Raman ‘signature’ can be used to assess physiological status and can also be altered by disease. This information can supplement existing diagnostic (e.g. radiological imaging) techniques for disease screening and diagnosis, in interventional guidance for identifying disease margins, and in monitoring treatment responses. Using fiberoptic-based light delivery and collection, RS is most easily performed on accessible tissue surfaces, either on the skin, in hollow organs or intra-operatively. The strength of RS lies in the high biochemical information content of the spectra, that characteristically show an array of very narrow peaks associated with specific chemical bonds. This results in high sensitivity and specificity, for example to distinguish malignant or premalignant from normal tissues. A critical issue is that the Raman signal is often very weak, limiting clinical use to point-by-point measurements. However, non-linear techniques using pulsed-laser sources have been developed to enable in vivo Raman imaging. Changes in Raman spectra with disease are often subtle and spectrally distributed, requiring full spectral scanning, together with the use of tissue classification algorithms that must be trained on large numbers of independent measurements. Recent advances in instrumentation and spectral analysis have substantially improved the clinical feasibility of RS, so that it is now being investigated with increased success in a wide range of cancer types and locations, as well as for non-oncological conditions. This review covers recent advances and

  2. Clinical use of brain volumetry. (United States)

    Giorgio, Antonio; De Stefano, Nicola


    Magnetic resonance imaging (MRI)-based brain volumetry is increasingly being used in the clinical setting to assess brain volume changes from structural MR images in a range of neurologic conditions. Measures of brain volumes have been shown to be valid biomarkers of the clinical state and progression by offering high reliability and robust inferences on the underlying disease-related mechanisms. This review critically examines the different scenarios of the application of MRI-based brain volumetry in neurology: 1) supporting disease diagnosis, 2) understanding mechanisms and tracking clinical progression of disease, and 3) monitoring treatment effect. These aspects will be discussed in a wide range of neurologic conditions, with particular emphasis on Alzheimer's disease and multiple sclerosis.

  3. The BPS Diploma in Advanced Pharmacology: a training opportunity for clinical pharmacologists. (United States)

    Hall, Judith M


    Coinciding with its 75th anniversary, the British Pharmacological Society (BPS) has launched a Diploma in Advanced Pharmacology (BPS Dip Pharmacol). This award is open to clinical and non-clinical scientists and those in related occupations. The Diploma is designed to appeal to those who want to further their pharmacological knowledge or gain an appreciation of basic and clinical aspects of the subject through participation in an advanced programme of non-clinical and clinical pharmacological study. The Diploma is unique in the UK. It provides not only a mechanism for continuing and updating education in basic pharmacology, clinical pharmacology, and therapeutics, but also a range of networking opportunities for non-clinical and clinical scientists in industry and academia.

  4. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Jain S


    Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

  5. Mentoring clinical ladder advancement with a facilitated prep class. (United States)

    Winslow, Susan A; Blankenship, Jean


    The authors describe a strategy for encouraging participation and overcoming reluctance of staff to participate in an optional professional advancement career ladder program. A facilitated prep class in a computer skills laboratory provides nurses with the framework for completing application requirements in a casual, supportive atmosphere.

  6. Advancing description and explanation in clinical linguistics: a legacy of Martin J. Ball. (United States)

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


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

  7. Advanced Optics Experiments Using Nonuniform Aperture Functions

    CERN Document Server

    Wood, Lowell T


    A method to create instructive, nonuniform aperture functions using spatial frequency filtering is described. The diffraction from a single slit in the Fresnel limit and the interference from a double slit in the Fraunhofer limit are spatially filtered to create electric field distributions across an aperture to produce apodization, inverse apodization or super-resolution, and apertures with phase shifts across their widths. The diffraction effects from these aperture functions are measured and calculated. The excellent agreement between the experimental results and the calculated results makes the experiment ideal for use in an advanced undergraduate or graduate optics laboratory to illustrate experimentally several effects in Fourier optics.

  8. Clinical evaluation of chemoradiotherapy for advanced cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kaneyasu, Yuko; Okawa, Tomohiko [Tokyo Women`s Medical Coll. (Japan); Okawa-Kita, Midori


    Locally advanced cervical cancer has a poor prognosis, poor survival rate, and high local failure rate. A number of questions regarding the optimal agents and schedule of concurrent chemoradiation remain unanswered. To improve the cure rate for advanced or recurrent cervix cancer, we studied intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. We analyzed 52 cases of advanced or recurrent cervical cancer treated by IAIC with or without radiotherapy. IAIC regimen was separated into two groups: group I consisted of 5-FU+MMC{+-}ADM (30 cases) and group II of CDDP+MMC{+-}5-FU (22 cases). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 cases). The overall response rate (CR+PR) was 71%, 87% in patients receiving radiotherapy, 50% in those without radiotherapy, and 100% in primary cases. The five-year survival rate was 20% in primary cases, 14% in recurrent cases, 3% in group I and 38% in group II by chemotherapy regimen. Severe (more than grade III) hematological acute side effects were found in 48% of all cases, but recovered by interruption of drugs. In 7 cases in which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases and severe pain of leg or gluteal region which need narcotics in 2 cases. These data suggest that IAIC mainly with cisplatin with or without radiotherapy is one of the effective treatments for advanced or recurrent cervical cancer. But we should check blood flow distribution periodically, and control the concentration of drugs. To improve the survival rate for advanced or recurrent cervical cancer, we should discuss neoadjuvant chemotherapy followed by chemoradiotherapy and maintenance systemic chemotherapy. (author)

  9. Clinical impact of extensive molecular profiling in advanced cancer patients. (United States)

    Cousin, Sophie; Grellety, Thomas; Toulmonde, Maud; Auzanneau, Céline; Khalifa, Emmanuel; Laizet, Yec'han; Tran, Kevin; Le Moulec, Sylvestre; Floquet, Anne; Garbay, Delphine; Robert, Jacques; Hostein, Isabelle; Soubeyran, Isabelle; Italiano, Antoine


    Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0-9). The most common primary tumour types were lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%) and sarcoma (10.2%). The median patient age was 63 years (range 19-88). A total of 292 patients (51.4%) presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28%) were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%). The two main reasons for non-inclusion were non-progressive disease (31.5%) and general status deterioration (25%). Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment) >1.3.Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.

  10. IMITS: Information and Clinical Technologies for the Advancement of Healthcare (United States)


    the system as a whole and the success of the operations will be dependent on the communication and interpersonal skills of the various parties...identified either through clinical observation (erythema, edema, induration, purulent drainage, foul odor, warmth at the wound site, or fever >37.8...of the five clinical signs: erythema, edema or induration, warmth at the wound site or fever > 37.8 degrees C, tenderness, and increasing pain at the

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

    Directory of Open Access Journals (Sweden)

    Erik E. Langenau


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

  12. Major clinical research advances in gynecologic cancer in 2015 (United States)


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

  13. Advanced monolithic pixel sensors using SOI technology (United States)

    Miyoshi, Toshinobu; Arai, Yasuo; Asano, Mari; Fujita, Yowichi; Hamasaki, Ryutaro; Hara, Kazuhiko; Honda, Shunsuke; Ikegami, Yoichi; Kurachi, Ikuo; Mitsui, Shingo; Nishimura, Ryutaro; Tauchi, Kazuya; Tobita, Naoshi; Tsuboyama, Toru; Yamada, Miho


    We are developing advanced pixel sensors using silicon-on-insulator (SOI) technology. A SOI wafer is used; top silicon is used for electric circuit and bottom silicon is used as a sensor. Target applications are high-energy physics, X-ray astronomy, material science, non-destructive inspection, medical application and so on. We have developed two integration-type pixel sensors, FPIXb and INTPIX7. These sensors were processed on single SOI wafers with various substrates in n- or p-type and double SOI wafers. The development status of double SOI sensors and some up-to-date test results of n-type and p-type SOI sensors are shown.

  14. Pulmonary contusion: an update on recent advances in clinical management. (United States)

    Cohn, Stephen M; Dubose, Joseph J


    Pulmonary contusion is a common finding after blunt chest trauma. The physiologic consequences of alveolar hemorrhage and pulmonary parenchymal destruction typically manifest themselves within hours of injury and usually resolve within approximately 7 days. Clinical symptoms, including respiratory distress with hypoxemia and hypercarbia, peak at about 72 h after injury. The timely diagnosis of pulmonary contusion requires a high degree of clinical suspicion when a patient presents with trauma caused by an appropriate mechanism of injury. The clinical diagnosis of acute parenchymal lung injury is usually confirmed by thoracic computed tomography, which is both highly sensitive in identifying pulmonary contusion and highly predictive of the need for subsequent mechanical ventilation. Management of pulmonary contusion is primarily supportive. Associated complications such as pneumonia, acute respiratory distress syndrome, and long-term pulmonary disability, however, are frequent sequelae of these injuries.

  15. Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances

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    Humayun, Mark S; Chader, Gerald; Greenbaum, Elias


    Artificial sight is a frontier area of modern ophthalmology combining the multidisciplinary skills of surgical ophthalmology, biomedical engineering, biological physics, and psychophysical testing. Many scientific, engineering, and surgical challenges must be surmounted before widespread practical applications can be realized. The goal of Artificial Sight is to summarize the state-of-the-art research in this exciting area, and to describe some of the current approaches and initiatives that may help patients in a clinical setting. The Editors are active researchers in the fields of artificial sight, biomedical engineering and biological physics. They have received numerous professional awards and recognition for their work. The artificial sight team at the Doheny Eye Institute, led by Dr. Mark Humayun, is a world leader in this area of biomedical engineering and clinical research. Key Features Introduces and assesses the state of the art for a broad audience of biomedical engineers, biophysicists, and clinical...

  16. Preliminary Data from an Advanced Dementia Consult Service: Integrating Research, Education, and Clinical Expertise (United States)

    Catic, Angela G.; Mitchell, Susan L.


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

  17. Twelve-year results of a direct-bonded partial prosthesis in a patient with advanced periodontitis: a clinical report. (United States)

    Minami, Hiroyuki; Minesaki, Yoshito; Suzuki, Shiro; Tanaka, Takuo


    Prosthodontic treatment for patients with advanced periodontitis is a therapeutic challenge. A minimally invasive technique is preferred to preserve the remaining mobile abutment teeth. This report describes the initial clinical treatment and 12-year follow-up of a direct-bonded prosthesis reinforced with a cast metal framework, used as a conservative treatment option to replace periodontally involved maxillary lateral incisors.

  18. Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma. (United States)

    Lepesant, P; Crinquette, M; Alkeraye, S; Mirabel, X; Dziwniel, V; Cribier, B; Mortier, L


    Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

  19. Secondary use of clinical data. (United States)

    Elkin, Peter L; Trusko, Brett E; Koppel, Ross; Speroff, Ted; Mohrer, Daniel; Sakji, Saoussen; Gurewitz, Inna; Tuttle, Mark; Brown, Steven H


    Clinicians involved in clinical care generate daily volumes of important data. This data is important for continuity of care, referrals to specialists and back to the patient's medical home. The same data can be used to generate alerts to improve the practice and to generate care activities to ensure that all appropriate care services are provided for the patient given their known medical histories using electronic quality (eQuality) monitoring. For many years we have used patient records as a data source for human abstraction of clinical research data. With the advent of electronic health record (EHR) data we can now make use of computable EHR data that can perform retrospective research studies more rapidly and lower the activation energy necessary to ask the next important question using electronic studies (eStudies). Barriers to these eStudies include: the lack of interoperable data between and among practices, the lack of computable definitions of measures, the lack of training of health professionals to use Ontology based Informatics tools that allow the execution of this type of logic, common methods need to be developed to distribute computable best practice rules to ensure rapid dissemination of evidence, better translating research into practice.

  20. Autosomal dominant polycystic kidney disease: recent advances in clinical management [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Zhiguo Mao


    Full Text Available The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD go back at least 500 years to the late 16th 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 21st century. In this commentary, we consider how clinical management is likely to change in the coming decade.

  1. Thermochemoradiotherapy for advanced or recurrent head and neck cancer. Analysis of clinical results and background variables

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    Hoshina, Hideyuki; Takagi, Ritsuo; Nagashima, Katsuhiro; Fujita, Hajime; Miyamoto, Takeshi; Sohma, Yoh; Fukuda, Jun-ichi; Imai, Nobuyuki; Nagata, Masaki [Niigata Univ. (Japan). Faculty of Dentistry


    Eighteen patients with 25 unresectable advanced or recurrent head and neck cancers (squamous cell carcinomas) received thermochemotherapy in combination with radiotherapy. The total radiation dose ranged from 50 to 82 Gy (mean, 65.6 Gy). Patients received thermochemotherapy twice a week, for a total number of 8.8 sessions, on average. The temperature in the tumor, as a result of the hyperthermia, was over 42 deg C in 185 (84.5%) of the 219 treatments. Three kinds of heating systems were used: a 13.56-MHz radiofrequency system, a 2450-MHz microwave system, and a radiofrequency interstitial system. The total amount of administered CDDP ranged from 40 to 300 mg (mean, 110 mg), combined with PEP and/or 5FU. Background factors (tumor factors and treatment factors) were investigated in detail, and the clinical results (tumor response and the 5-year cumulative focal control rate) were evaluated. The relationship between these two results was then analyzed using univariate and multivariate statistics. The clinical results of patients with a WHO histological classification of grade 3 were poor compared with patients with a classification of grade 1 or 2. The difference between these two results was significant when analyzed using univariate statistics, but not significant when analyzed using multivariate statistics. The clinical results of patients with primary lesions surrounded by bony tissues were slightly poor compared with those of patients whose lesions were surrounded by soft tissues, but the difference between these two results was not significant. Successful treatment of refractory recurrent tumors, large tumor masses, and diffuse invasive carcinomas was not affected by the treatment factors (heating systems, heating sessions, radiation dose, and CDDP dose and drug combination). These results suggest that refractory recurrence, proximity to bony tissues, tumor size, and histological malignancy might not be prognostic variables for thermochemoradiotherapy strategy

  2. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jill P Smith


    Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

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

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    Asmar R


    Full Text Available Ramsey Asmar,1 Jessica Yang,1 Richard D Carvajal1,2 1Department of Medicine, College of Physicians and Surgeons, 2Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA Abstract: 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. Keywords: nivolumab, immune checkpoint inhibitors, PD-1, melanoma

  4. Advanced Pre-clinical Research Approaches and Models to Studying Pediatric Anesthetic Neurotoxicity

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    Cheng eWang


    Full Text Available Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of anesthetic procedures. A great deal of concern has recently arisen regarding the safety of anesthesia in infants and children. Because of obvious limitations, it is not possible to thoroughly explore the effects of anesthetic agents on neurons in vivo in human infants or children. However, the availability of some advanced pre-clinical research approaches and models, such as imaging technology both in vitro and in vivo, stem cell and nonhuman primate experimental models, have provided potentially invaluable tools for examining the developmental effects of anesthetic agents. This review discusses the potential application of some sophisticaled research approaches, e.g., calcium imaging, in stem cell-derived in vitro models, especially human embryonic neural stem cells, along with their capacity for proliferation and their potential for differentiation, to dissect relevant mechanisms underlying the etiology of the neurotoxicity associated with developmental exposures to anesthetic agents. Also, this review attempts to discuss several advantages for using the developing rhesus monkey models (in vivo, when combined with dynamic molecular imaging approaches, in addressing critical issues related to the topic of pediatric sedation/anesthesia. These include the relationships between anesthetic-induced neurotoxicity, dose response, time-course and developmental stage at time of exposure (in vivo studies, serving to provide the most expeditious platform toward decreasing the uncertainty in extrapolating pre-clinical data to the human condition.

  5. Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany. (United States)

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


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

  6. [Research advance on clinical blood transfusion and tumor therapy]. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Sina Kianoush


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

  8. Clinical Application of Total Knee Arthroplasty on Patients with Advanced Knee Osteoarthritis

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    WU Zhi-sen; ZHENG Chen-xiao; QI Liang; CHANG Shang-yi


    Objective:To investigate the clinical value of total knee arthroplasty (TKA) on patients with advanced knee osteoarthritis. Methods:The clinical data and efficacy of 26 patients with advanced knee osteoarthritis (26 knees) who were given TKA in our department from June 2012 to May 2013 were retrospectively observed and analyzed. The knee function scores before operation and after follow up were evaluated according to American HSS scoring standard. Results:At the end of follow up, of the 26 patients, 18 were excellent, 6 were good and 2 were not bad in knee function and mobility without sense of pain, which was regarded to be associated with the poor enthusiasm in knee function training, and the total rate of excellent and good was 92.3%. Conclusion:TKA has signiifcant clinical value and favorable efifcacy on patients with advanced knee osteoarthritis.

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

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    Moore, Kevin L., E-mail:; Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California 92093 (United States); Kagadis, George C. [Department of Medical Physics, School of Medicine, University of Patras, Rion, GR 26504 (Greece); McNutt, Todd R. [Department of Radiation Oncology and Molecular Radiation Science, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21231 (United States); Mutic, Sasa [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri 63110 (United States)


    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.

  10. Clinical Application of Total Knee Arthroplasty on Patients with Advanced Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    WU Zhi-sen


    Full Text Available Objective: To investigate the clinical value of total knee arthroplasty (TKA on patients with advanced knee osteoarthritis. Methods: The clinical data and efficacy of 26 patients with advanced knee osteoarthritis (26 knees who were given TKA in our department from June 2012 to May 2013 were retrospectively observed and analyzed. The knee function scores before operation and after follow up were evaluated according to American HSS scoring standard. Results: At the end of follow up, of the 26 patients, 18 were excellent, 6 were good and 2 were not bad in knee function and mobility without sense of pain, which was regarded to be associated with the poor enthusiasm in knee function training, and the total rate of excellent and good was 92.3%. Conclusion: TKA has significant clinical value and favorable efficacy on patients with advanced knee osteoarthritis.

  11. Evaluating the impact of a pre-rotation workshop on student preparation for clinical advanced pharmacy practice experiences

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    Medina MS


    Full Text Available Objectives: This pilot study was designed to evaluate the impact of a pre-rotation workshop (PRW on pharmacy students’ clinical skills and preparation for clinical Advanced Pharmacy Practice Experiences (APPE involving direct patient care. Methods: Randomized controlled trial of an educational intervention with Institutional Review Board approval. PRW activities designed to simulate rotation activities around five competencies, patient charts, medication histories, SOAP notes, patient presentations, and professionalism. Endpoints were evaluated using clinical rotation preceptors’ evaluation of performance and students’ performance on objective structured clinical exams (OSCE.Results: Eight fourth-year students and eight GPA matched controls (20% of the total class were selected to voluntarily participate. The PRW demonstrated a positive impact on students’ clinical skills and preparation for rotations by improving OSCE performance. However, no significant differences were found between groups when comparing preceptor evaluations of skills on rotations. These results are limited by the small sample size, potential OSCE “test-wiseness” effects, lack of OSCE evaluator blinding to study groups, potential case specificity effects due to the limited number of cases used on the OSCE and possible lack of sensitivity of the rotation evaluation tool to capture true differences among the experimental and control group participants.Conclusion: The PRW was successful at advancing students’ clinical skills and preparation for rotations and may be considered as a tool to help bridge didactic to clinical experiences in the Pharm.D. curriculum.

  12. Clinical use of glutamine supplementation. (United States)

    Wernerman, Jan


    Endogenous production of glutamine may become insufficient during critical illness. The shortage of glutamine is reflected as a decrease in plasma concentration, which is a prognostic factor for poor outcome in sepsis. Because glutamine is a precursor for nucleotide synthesis, rapidly dividing cells are most likely to suffer from a shortage. Therefore, exogenous glutamine supplementation is necessary. In particular, when i.v. nutrition is given, extra glutamine supplementation becomes critical, because most present formulations for i.v. use do not contain any glutamine for technical reasons. The major part of endogenously produced glutamine comes from skeletal muscle. For patients staying a long time in the intensive care unit (ICU), the muscle mass decreases rapidly, which leaves a tissue of diminishing size to maintain the export of glutamine. The metabolic and nutritional adaptation in long-staying ICU patients is poorly studied and is one of the fields that needs more scientific evidence for clinical recommendations. To date, there is evidence to support the clinical use of glutamine supplementation in critically ill patients, in hematology patients, and in oncology patients. Strong evidence is presently available for i.v. glutamine supplementation to critically ill patients on parenteral nutrition. This must be regarded as the standard of care. For patients on enteral nutrition, more evidence is needed. To guide administration of glutamine, there are good arguments to use measurement of plasma glutamine concentration for guidance. This will give an indication for treatment as well as proper dosing. Most patients will have a normalized plasma glutamine concentration by adding 20-25 g/24 h. Furthermore, there are no reported adverse or negative effects attributable to glutamine supplementation.

  13. [Clinical competence certification for advanced heart failure: an emerging need also in Italy?]. (United States)

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


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

  14. Clinical report of the treatment of locally advanced lung cancer. (United States)

    Petrovich, Z; Mietlowski, W; Ohanian, M; Cox, J


    This paper discusses the results of the treatment of 345 patients entered in the Veterans Administration Lung Group Protocol 13L. The study was activated March 1972, and closed for the patient accesion March 1975. All patients had a histological diagnosis of primary lung cancer considered clinically non-resectable or inoperable. Patients were equally randomized into two groups, radiotherapy alone or radiotherapy with chemotherapy. The analysis of the data included: treatment regimen, radiation dose, initial performance status, performance status change, cell type, duration of survival, quality of survival and age. The strongest influence on median survival was the level of radiation dose. The small cell carcinoma patients treated with radiotherapy and chemotherapy showed significant improvement in the median survival (38.2 weeks) over the patients treated with radiotherapy alone (20.6 weeks). The patients treated with radiotherapy and chemotherapy also showed improvement in performance status more frequently than the patients treated with radiotherapy alone. Other parameters of the analysis will be presented.

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

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    Guilherme dos Santos Trento


    Full Text Available 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.

  16. Advanced optic fabrication using ultrafast laser radiation (United States)

    Taylor, Lauren L.; Qiao, Jun; Qiao, Jie


    Advanced fabrication and finishing techniques are desired for freeform optics and integrated photonics. Methods including grinding, polishing and magnetorheological finishing used for final figuring and polishing of such optics are time consuming, expensive, and may be unsuitable for complex surface features while common photonics fabrication techniques often limit devices to planar geometries. Laser processing has been investigated as an alternative method for optic forming, surface polishing, structure writing, and welding, as direct tuning of laser parameters and flexible beam delivery are advantageous for complex freeform or photonics elements and material-specific processing. Continuous wave and pulsed laser radiation down to the nanosecond regime have been implemented to achieve nanoscale surface finishes through localized material melting, but the temporal extent of the laser-material interaction often results in the formation of a sub-surface heat affected zone. The temporal brevity of ultrafast laser radiation can allow for the direct vaporization of rough surface asperities with minimal melting, offering the potential for smooth, final surface quality with negligible heat affected material. High intensities achieved in focused ultrafast laser radiation can easily induce phase changes in the bulk of materials for processing applications. We have experimentally tested the effectiveness of ultrafast laser radiation as an alternative laser source for surface processing of monocrystalline silicon. Simulation of material heating associated with ultrafast laser-material interaction has been performed and used to investigate optimized processing parameters including repetition rate. The parameter optimization process and results of experimental processing will be presented.


    Directory of Open Access Journals (Sweden)

    Oleksandr Luppo


    Full Text Available Purpose: Concept of Flexible Use of Airspace (FUA allows to eliminate many problems on the basis of civil-military coordination, but there are still a lot of areas for improvement. These improvements will be implemented in the Advanced Flexible Use of Airspace (AFUA concept. Methods: We examine the airspace structure in the frames of AFUA concept, which includes variable profile areas, temporary reserved and temporary segregated areas, danger or restricted areas. Mission Trajectory in AFUA which allows designing ad-hoc structures delineation at short notice is also examined. Regarding the performance enhancements of AFUA we compare these with FUA concept. Examination of AFUA structure gives us better view of the functions and opportunities of this concept. Result: AFUA concept provides many advantages for the civil aviation stakeholders and includes many other positive sides. Variable Profile Areas provide more flexibility, particularly in a high density traffic area and any combination of basic volume possible. Collaborative decision-making will increase the situational awareness of both parties and help to decrease the transit between airbases and training areas, allows military to use larger airspaces for missions on an absolute time-limited basis. As a result of mission trajectory implementation in AFUA concept general air traffic crossing are possible in all type of airspace structures, after coordination or under specific permanent agreements. The use of Centralized AFUA Services will allow the central collection, integration and provision of ASM data in support of continuous collaborative network processes, in such a way improving operational performance during the planning and execution phases (predictability, flexibility, better use of capacity, enhanced flight efficiency, real time sharing of information, better management of available airspace. Discussion: Given the important contribution that AFUA brings into air traffic management

  18. Advances in basic and clinical immunology in 2014. (United States)

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


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

  19. Recent clinical and translational advances in pediatric hypertension. (United States)

    Falkner, Bonita


    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

  20. Advances and perspectives in lung cancer imaging using multidetector row computed tomography. (United States)

    Coche, Emmanuel


    The introduction of multidetector row computed tomography (CT) into clinical practice has revolutionized many aspects of the clinical work-up. Lung cancer imaging has benefited from various breakthroughs in computing technology, with advances in the field of lung cancer detection, tissue characterization, lung cancer staging and response to therapy. Our paper discusses the problems of radiation, image visualization and CT examination comparison. It also reviews the most significant advances in lung cancer imaging and highlights the emerging clinical applications that use state of the art CT technology in the field of lung cancer diagnosis and follow-up.

  1. Skin autofluorescence, a non-invasive marker of advanced glycation end products: clinical relevance and limitations. (United States)

    Da Moura Semedo, Cidila; Webb, M'Balu; Waller, Helen; Khunti, Kamlesh; Davies, Melanie


    Advanced glycation end products (AGEs) are protein-bound compounds derived from glycaemic and oxidative stress that contain fluorescent properties, which can be non-invasively measured as skin autofluorescence (SAF) by the AGE Reader. SAF has been demonstrated to be a biomarker of cumulative skin AGEs and potentially may be a better predictor for the development of chronic complications and mortality in diabetes than glycated haemoglobin A1c. However, there are several confounding factors that should be assessed prior to its broader application: these include presence of other fluorescent compounds in the skin that might be measured (eg, fluorophores), skin pigmentation and use of skin creams. The aim of this article is to provide a theoretical background of this newly developed method, evaluate its clinical relevance and discuss the potential confounding factors that need further analysis.

  2. Recent advances in computational methods and clinical applications for spine imaging

    CERN Document Server

    Glocker, Ben; Klinder, Tobias; Li, Shuo


    This book contains the full papers presented at the MICCAI 2014 workshop on Computational Methods and Clinical Applications for Spine Imaging. The workshop brought together scientists and clinicians in the field of computational spine imaging. The chapters included in this book present and discuss the new advances and challenges in these fields, using several methods and techniques in order to address more efficiently different and timely applications involving signal and image acquisition, image processing and analysis, image segmentation, image registration and fusion, computer simulation, image based modeling, simulation and surgical planning, image guided robot assisted surgical and image based diagnosis. The book also includes papers and reports from the first challenge on vertebra segmentation held at the workshop.

  3. Myositis registries and biorepositories: powerful tools to advance clinical, epidemiologic and pathogenic research (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Kaichun Li


    Full Text Available 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.

  5. Differential pharmacology and clinical utility of sonidegib in advanced basal cell carcinoma (United States)

    Wahid, Mohd; Jawed, Arshad; Dar, Sajad Ahmad; Mandal, Raju K; Haque, Shafiul


    Patients suffering from advanced basal cell carcinoma (BCC) have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region. The primary efficacy analyses showed that 18 patients in the 200 mg group and 35 patients in the 800 mg group show an objective response (Central Review Committee) that corresponds to 43% (95% confidence interval [CI]: 28–59) and 38% (95% CI: 28–48) in their respective categories. Disease control was found in 93% (39 patients) and 80% (74 patients) of the patients administered 200 and 800 mg sonidegib, respectively. The adverse events were assessed by the Central Review Committee as well as the investigator review team as per the guidelines of National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. The most frequently found adverse events reported in BOLT trials were muscle spasms, alopecia, dysgeusia (taste disturbance), nausea, elevated blood creatine kinase and fatigue. Comparatively, the patients administered 200 mg sonidegib showed fewer adverse events than those in the 800 mg sonidegib category. Thus, the benefit of using the 200 mg dose of sonidegib outweighs the associated risks and it can be inferred that it would be judicious to choose doses of lesser strength. PMID:28182134

  6. Clinical Study of Endostar Combined with DP Protocol in Treatment of Advanced Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Wen-ying DENG


    Full Text Available Objective: To observe the clinical outcomes of Endostar combined with DP regimen for treating advanced esophageal cancer.Methods: A total of 62 patients with advanced esophageal cancer admitted from May, 2011 to May, 2013 were enrolled for a prospective, randomized controlled trial and 2 cases were excluded from the study because of Ⅳ degree of digestive tract reaction and myelosuppression. Therefore, 60 cases could be evaluated, and then divided into combined group (given Endostar+DP plan and single chemotherapy group, 30 cases in each group. The level of VEGF, tumor size and CT perfusion (CTP parameters, including blood flow (BF, blood volume (BV, mean transit time (MTT, and permeability surface (PS before and after treatment were determined for comparison. Kaplan-Merier method was used to analyze the overall survival (OS of 2 groups.Results: The efficacy of combined group was superior to single chemotherapy group. The level of vascular endothelial growth factor (VEGF in combined group was obviously lower than that in single chemotherapy group after treatment (P<0.01. Compared with treatment before in combined group, BF, BV and PS decreased while MTT increased after treatment (P<0.05. However, there were no significant differences in single chemotherapygroup before and after treatment (P>0.05. The median OS was 30 months (95%CI: 20.935-39.065 for combined group and 21 months (95%CI: 15.109-26.591 for single chemotherapy group, respectively (P=0.048. The 1-, 2- and 3-year survival rates were 86.2%, 59.3% and 36.6% in combined group, and 70.8%, 32.1% and 17.8% in single chemotherapy group, respectively.Conclusion: Endostar can down-regulate the expression of VEGF, improve the state of hypertransfusion and high permeability of tumor vessels, has better curative effect without slighter adverse reactions, and prolong the survival time of patients with advanced esophageal cancer when combined with chemotherapy.

  7. Clinical Study of Endostar Combined with DP Protocol in Treatment of Advanced Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    DENG Wen-ying; LI Ning; LUO Su-xia


    Objective: To observe the clinical outcomes of Endostar combined with DP regimen for treating advanced esophageal cancer. Methods: A total of 62 patients with advanced esophageal cancer admitted from May, 2011 to May, 2013 were enrolled for a prospective, randomized controlled trial and 2 cases were excluded from the study because ofⅣ degree of digestive tract reaction and myelosuppression. Therefore, 60 cases could be evaluated, and then divided into combined group (given Endostar+DP plan) and single chemotherapy group, 30 cases in each group. The level of VEGF, tumor size and CT perfusion (CTP) parameters, including blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS) before and after treatment were determined for comparison. Kaplan-Merier method was used to analyze the overall survival (OS) of 2 groups. Results:The efifcacy of combined group was superior to single chemotherapy group. The level of vascular endothelial growth factor (VEGF) in combined group was obviously lower than that in single chemotherapy group after treatment (P0.05). The median OS was 30 months (95%CI: 20.935-39.065) for combined group and 21 months (95%CI: 15.109-26.591) for single chemotherapy group, respectively (P=0.048). The 1-, 2- and 3-year survival rates were 86.2%, 59.3% and 36.6% in combined group, and 70.8%, 32.1% and 17.8% in single chemotherapy group, respectively. Conclusion: Endostar can down-regulate the expression of VEGF, improve the state of hypertransfusion and high permeability of tumor vessels, has better curative effect without slighter adverse reactions, and prolong the survival time of patients with advanced esophageal cancer when combined with chemotherapy.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  9. Application of next-generation sequencing in clinical oncology to advance personalized treatment of cancer

    Institute of Scientific and Technical Information of China (English)

    Yan-Fang Guan; Gai-Rui Li; Rong-Jiao Wang; Yu-Ting Yi; Ling Yang; Dan Jiang; Xiao-Ping Zhang; Yin Peng


    With the development and improvement of new sequencing technology,next-generation sequencing (NGS) has been applied increasingly in cancer genomics research over the past decade.More recently,NGS has been adopted in clinical oncology to advance personalized treatment of cancer.NGS is used to identify novel and rare cancer mutations,detect familial cancer mutation carriers,and provide molecular rationale for appropriate targeted therapy.Compared to traditional sequencing,NGS holds many advantages,such as the ability to fully sequence all types of mutations for a large number of genes (hundreds to thousands) in a single test at a relatively low cost.However,significant challenges,particularly with respect to the requirement for simpler assays,more flexible throughput,shorter turnaround time,and most importantly,easier data analysis and interpretation,will have to be overcome to translate NGS to the bedside of cancer patients.Overall,continuous dedication to apply NGS in clinical oncology practice will enable us to be one step closer to personalized medicine.

  10. [Advanced curriculum for clinical assessment and skill in new age pharmacist education]. (United States)

    Kiuchi, Yuji; Masuda, Yutaka; Kamei, Daisuke; Kogo, Mari; Nakamura, Akihiro


    In Showa University School of pharmacy, 7 competencies for outcome-based education were set up in 2011. We are now creating sequential curriculum in order to achieve these competencies. As a member of team medical treatment, pharmacist must share a patient's information with other members, assess each patient's condition, propose the best medication with evidence, and also check the effect of medication. Therefore, many active practices in a hospital and community and problem-based learning (PBL) tutorials are carried out in curriculum in School of Pharmacy. As a training for the future pharmacists who positively perform primary care with responsibility in community pharmacy, students study the method of clinical assessment (assessment of condition of disease from the patient's complain, and choice of appropriate proposal). Furthermore, the exercise and training of parenteral medication, physical assessment, and first aid, etc. are also taken in the curriculums as new clinical skill. The systematic and gradual interprofessional education curriculum for the team medical education has been carried out aiming at training of active members in medical team in a hospital and community. At this symposium, I will introduce these systematic advanced curriculums for the pharmacist of a new age, and to show the usefulness and learning effect.

  11. Proceedings of the 2015 Santa Fe Bone Symposium: Clinical Applications of Scientific Advances in Osteoporosis and Metabolic Bone Disease. (United States)

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


    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.

  12. Using Disguised Clinical Case Material (United States)

    Kantrowitz, Judy L.


    When, why, and how clinicians decide to write about clients are ethical concerns. There are risks and potential clinical ramifications as well as responsibilities for how these decisions are made. On the basis of 141 interviews with psychoanalysts who have published in 3 major national and international psychoanalytic journals, the author explores…

  13. [Clinical application value of prognostic nutritional index for predicting survival in patients with advanced non-small cell lung cancer]. (United States)

    Xu, W J; Kang, Y M; Zhou, L; Chen, F F; Song, Y H; Zhang, C Q


    Objective: To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: 123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC. Results: PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001). Conclusion: PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.

  14. Multiple Pathogen Detection Using Biosensors: Advancements and Challenges (United States)

    Advancements in biosensor research have considerably impacted clinical diagnostics for human health. Efforts in capitalizing on the sensitivity of biosensors for food pathogen detection are evident in the food safety/security research community. For practical application with foods that normally h...

  15. A Method for Increasing Elders' Use of Advance Directives. (United States)

    Luptak, Marilyn K.; Boult, Chad


    Studied effectiveness of intervention to help frail elders to record advance directives (ADs). In collaboration with physicians and lay volunteer, social worker provided information/counseling to elderly subjects, families, and proxies in series of visits to geriatric evaluation and management clinic. Seventy-one percent of subjects recorded ADs.…

  16. Basic and Clinical Research Against Advanced Glycation End Products (AGEs): New Compounds to Tackle Cardiovascular Disease and Diabetic Complications. (United States)

    Nenna, Antonio; Spadaccio, Cristiano; Lusini, Mario; Ulianich, Luca; Chello, Massimo; Nappi, Francesco


    Diabetes is a major risk factor for cardiovascular disease, and recent advances in research indicate that a detailed understanding of the pathophysiology of its effects is mandatory to reduce diabetes-related mortality and morbidity. Advanced Glycation End Products (AGEs) play a central role in the genesis and progression of complications of both type 1 and type 2 diabetes mellitus, and have been found to be important even in non-diabetic patients as a marker of cardiovascular disease. AGEs have a profound impact on patient's prognosis regardless of the glycemic control, and therefore pharmacologic approaches against AGEs accumulation have been proposed over the years to treat cardiovascular diseases, parallel to a more detailed understanding of AGEs pathophysiology. Compounds with anti-AGEs effects are currently under investigation in both pre-clinical and clinical scenarios, and many of the drugs previously used to treat specific diseases have been found to have AGE-inhibitory effects. Some products are still in "bench evaluation", whereas others have been already investigated in clinical trials with conflicting evidences. This review aims at summarizing the mechanisms of AGEs formation and accumulation, and the most relevant issues in pre-clinical and clinical experiences in anti-AGEs treatment in cardiovascular research.

  17. Current technological advances in magnetic resonance with critical impact for clinical diagnosis and therapy. (United States)

    Runge, Val M


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

  18. Advanced regenerator testing in the Raytheon dual-use cryocoolerr

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, B. R.; Bellis, L.; Ellis, M. J.; Conrad, T. J. [Raytheon Space and Airborne Systems 2000 E. El Segundo Blvd., El Segundo, CA 90245 (United States)


    Significant progress has been made on the Raytheon low cost space cryocooler called the Dual-Use Cryocooler (DUC). Most notably, the DUC has been integrated and tested with an advanced regenerator. The advanced regenerator is a drop-in replacement for stainless steel screens and has shown significant thermodynamic performance improvements. This paper will compare the performance of two different regenerators and explain the benefits of the advanced regenerator.

  19. Advancing Medication Reconciliation in an Outpatient Internal Medicine Clinic through a Pharmacist-Led Educational Initiative

    Directory of Open Access Journals (Sweden)

    Sarah M. Westberg, Pharm.D.


    Full Text Available Objectives: To develop and deliver an effective pharmacist-led educational initiative to clinic staff to advance medication reconciliation in the electronic medical record of an outpatient internal medicine clinic.Methods: An educational initiative designed to improve the ability of nursing staff in medication reconciliation was launched in the outpatient internal medicine clinic of a regional healthcare system. The education was provided by the pharmacist to clinic nursing staff, including registered nurses, licensed practical nurses, and certified medical assistants. The impact of this training was measured through pre-initiation and post-implementation surveys, competency assessments and an audit. Results: The educational initiative was successfully designed and delivered to clinic nursing staff. Assessment of the initiative found that all nursing staff completing competency assessments successfully passed. Pre-initiation- and post-implementation- survey responses on the self-assessed ability to gather and document accurate medication lists did not show significant changes. Informal observations in the clinic indicated that this initiative changed the culture of the clinic, creating increased awareness of the importance of accurate medications and increased emphasis on medication reconciliation.Conclusions: The expertise of pharmacists can be utilized to educate nursing staff on the skills and abilities necessary to gather and document accurate medication lists. This study did not find measurable changes in the accuracy of medication lists in this clinic. Future research is needed to determine the best methods to train health professionals in medication reconciliation to ensure accurate medication lists in the outpatient setting.

  20. Clinical Research of Crizotinib in Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Haibo ZHU


    Full Text Available At present, in the treatment of non-small cell lung cancer (NSCLC, targeted therapy has an important status. After epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs, crizotinib targeted at EML4-ALK fusion gene becomes a significant drug of molecular targeted therapy in NSCLC. Phase I and II clinical trials prove that crizotinib is effective for treatment of activating EML4-ALK mutation in advanced NSCLC patients, little side-effect, and well tolerated. Recently, crizotinib can inhibit ROS1 receptor tyrosine kinase and show extraordinary significant antitumor activity in ROS1-rearranged NSCLC. Drug resistance also exists in crizotinib. The mechanism of drug resistance needs further research. In this study, a review is performed in the mechanism and pharmacokinetics of crizotinib, and the clinical progress of treatment in advanced NSCLC.

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

    Directory of Open Access Journals (Sweden)

    G. Astrid Limb


    Full Text Available 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.

  2. Mechanical Design Optimization Using Advanced Optimization Techniques

    CERN Document Server

    Rao, R Venkata


    Mechanical design includes an optimization process in which designers always consider objectives such as strength, deflection, weight, wear, corrosion, etc. depending on the requirements. However, design optimization for a complete mechanical assembly leads to a complicated objective function with a large number of design variables. It is a good practice to apply optimization techniques for individual components or intermediate assemblies than a complete assembly. Analytical or numerical methods for calculating the extreme values of a function may perform well in many practical cases, but may fail in more complex design situations. In real design problems, the number of design parameters can be very large and their influence on the value to be optimized (the goal function) can be very complicated, having nonlinear character. In these complex cases, advanced optimization algorithms offer solutions to the problems, because they find a solution near to the global optimum within reasonable time and computational ...

  3. Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols

    Directory of Open Access Journals (Sweden)

    H Madry


    Full Text Available Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

  4. Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer.


    Bajetta, E; Zilembo, N.; Buzzoni, R.; Noberasco, C.; Di Leo, A; Bartoli, C.; Merson, M; Sacchini, V.; Moglia, D; Celio, L.


    Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermo...

  5. Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice. (United States)

    Netter, Jeanne; Douard, Richard; Durdux, Catherine; Landi, Bruno; Berger, Anne; Taieb, Julien


    More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the 'gold standard' for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer remain justified in future to achieve a high level of proof in keeping with evidence-based medical standards.

  6. Residency training in advance care planning: can it be done in the outpatient clinic? (United States)

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


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

  7. [Clinical psychodiagnosis using psychophysiologic procedures]. (United States)

    Grünberger, J; Linzmayer, L; Saletu, B


    The present paper presents several new psychophysiological test methods and measures, which have been developed by the authors for utilization in the field of psychopathology and psychopharmacology. The main advantage of these new techniques seems to lie in the fact, that control and evaluation procedures are microprocessor-assisted which ensures objectivity, reliability and validity. The multidimensionality, e.g. the possibility to concomitantly evaluate several variables at the same time, and the economics, e.g. the short time effort involved in completing the tests, are further advantages. By means of the newly developed techniques several sensitive measures may be obtained which are of great value in the diagnostic process as well as in the assessment of drug effects in clinical psychopharmacology.

  8. The clinical observation of neoadjuvant chemotherapy in locally advanced breast cancer with DX regimen

    Institute of Scientific and Technical Information of China (English)

    Miao Zhang; Jianing Qiu; Shuxian Qu; Yaling Han; Zhaozhe Liu; Xiaodong Xie


    Objective:The recent clinical curative ef ect and adverse events of docetaxel and capecitabine (DX) of neo-adjuvant chemotherapy in patients with local y advanced breast cancer was discussed. Methods:The data of 72 cases of neoadjuvant chemotherapy (DX) in local y advanced breast cancer after 4 cycles were retrospectively analyzed. Docetaxel 75 mg/m2 by infusion 1 h on d1, capecitabine 2000 mg/m2 by oral for twice daily on d1–14, 21 days was a cycle. Results:Al 72 patients were assessed for ef icacy and adverse events. The total ef ective rate was 80.5%(58/72), including pathological complete response (pCR) was 7 (9.7%), clinical complete remission (cCR) was 15(20.8%), clinical partial response (PR) was 43 (59.7%), stable disease (SD) was 8 (11.1%) and progressive disease (PD) was 6 (8.3%). The main adverse events were gastrointestinal reactions and bone marrow suppression. The 3 to 4 degrees of adverse reactions including granulocytopenia in 7 patients (20.6%), hand-foot syndrome in 6 patients (15.2%). Conclusion:The DX regimen provide a favorable ef icacy and safety profile in patients with local y advanced breast cancer for neoadjuvant chemotherapy.

  9. Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma

    Directory of Open Access Journals (Sweden)

    Anna Minchom


    Full Text Available Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7% achieved disease control. Median duration of response was 11 months (95% CI: 9–13. On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1% patients who failed to respond to first-line therapy achieved disease control. Eight (2.1% patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months. On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

  10. The Clinical Significance of Cathepsin D and p53 Expression in Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun-Sang; Lee, Sheng-Jin; Kim, Jin-Man; Cho, Moon-June [Chungnam National University, Daejeon (Korea, Republic of)


    Cathepsin D (CD) is a lysosomal acid proteinase that is related to malignant progression, invasion, and a poor prognosis in several tumors. The aim of this study was to evaluate the prognostic clinical significance of CD and p53 expression in pretreatment biopsy specimens from patients with locally advanced rectal cancer who were treated with preoperative chemoradiation. Eighty-nine patients with locally advanced rectal cancer (cT3/T4 or N+) were included in this study. Preoperative chemoradiation consisted of a dose of 50.4 Gy of pelvic radiation and two concurrent cycles of administration of 5-fluorouracil and leucovorin. Surgery was performed six weeks after chemoradiation. CD and p53 expression in pretreatment formalin-fixed paraffin-embedded tumor biopsy specimens were assessed by immunohistochemical staining using a CD and p53 monoclonal antibodies. The threshold value for a positive stain in tumor tissue and stromal cells was 1+ intensity in 10% of the tumors or stromal cells, respectively. Positive CD expression was found in 57 (64%) of the tumors and 32 (35%) of the stromal cell specimens. There was no association with CD expression of the tumor or stromal cells and patient characteristics. There was a correlation between tumor CD expression with stromal cell CD expression (p=0.01). Overexpression of p53 was not a significant prognostic factor. The 5-year overall survival (OS) and disease-free survival (DFS) rates were not different between tumor CD-negative and positive patient biopsy samples (69% vs. 65%, 60% vs. 61%, respectively). The 5-year OS rates in the tumor-negative/stromal cell-negative, tumor-negative/stromal cell-positive, tumor-positive/stromal cell-negative and tumor-positive/ stromal cell-positive biopsy samples were 75%, 28%, 62%, and 73%, respectively. Stromal cell staining only without positive tumor staining demonstrated the worst overall survival prognosis for patients (p=0.013). Overexpression of p53 in rectal biopsy tissue was not

  11. Gold Nanoparticles and Nanocomposites in Clinical Diagnostics Using Electrochemical Methods

    Directory of Open Access Journals (Sweden)

    Pranjal Chandra


    Full Text Available Progress and development in clinical diagnostics certainly focus upon the advances in the nanomaterials, particularly gold nanoparticles (AuNPs that offer promise to solve the biocompatible and sensitive detection systems. This paper focuses on the recent application of AuNPs in clinical diagnosis. Various important methods of AuNPs synthesis and their application in clinical detection of various biomolecules using electrochemical detection methods have been described. AuNPs alone and in various composites are also described based on the various biosensors design recently published for the detection of cancer biomarkers, proteins, bacteria, and cancer cells. The effect of AuNPs type and size in clinical detection has also been briefly illustrated.

  12. Professional excellence and career advancement in nursing: a conceptual framework for clinical leadership development. (United States)

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


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

  13. The Systemic Evaluation and Clinical Significance of Immunological Function for Advanced Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jialing WANG


    Full Text Available Background and objective The actual evaluation of immunological function is significant for studing the tumor development and devising a treatment in time. The aim of this study is to evaluate the immunological function of advanced lung cancer patients systematically, and to discuss the clinical significance. Methods The nucleated cell amounts of advanced lung cancer patients and the healthy individuals were counted. The immune cell subsets and the levels of IL-4, INF-γ, perforin and granzyme in CD8+T cells by the flow cytometry were measured. The proliferation activity and the inhibition ratio of immune cells to several tumor cell lines were evaluated by MTT assay. Results The absolute amounts and subsets of T, B, NK cells of advanced lung cancer patients were lower than the healthy individuals (P < 0.05; However, the proportion of regulatory T cells of advanced lung cancer patients (4.00±1.84% was lower than the healthy individuals (1.27±0.78% (P < 0.05. The positive rates of IFN-γ perforin, granzyme in CD8+T cells decreased while them in IL-4 did not in the advanced lung cancer patients compared to the healthy control group (P < 0.05. The proliferation activity of immune cells, the positive rate of PPD masculine and the inhibition ratio to tumor cells in the advanced lung cancer patients was lower than the healthy subsets obviously (P < 0.05. Conclusion There was a significant immune depression in the advanced lung cancer patients compared to the healthy individuals.

  14. Clinical Decision Support Systems: A Useful Tool in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Kolostoumpis G.


    Full Text Available The possibility of supporting in decision – making shows an increase in recent years. Based on mathematic simulation tools, knowledge databases, processing methods, medical data and methods, artificial intelligence for coding of the available knowledge and for resolving complex problems arising into clinical practice. Aim: the aim of this review is to present the development of new methods and modern services, in clinical practice and the emergence in their implementation. Data and methods: the methodology that was followed included research of articles that referred to health sector and modern technologies, at the electronic data bases “pubmed” and “medline”. Results: Is a useful tool for medical experts using characteristics and medical data used by the doctors. Constitute innovation for the medical community, and ensure the support of clinical decisions with an overall way by providing a comprehensive solution in the light of the integration of computational decision support systems into clinical practice. Conclusions: Decision Support Systems contribute to improving the quality of health services with simultaneous impoundment of costs (i.e. avoid medical errors

  15. Advances in renal (patho)physiology using multiphoton microscopy. (United States)

    Sipos, A; Toma, I; Kang, J J; Rosivall, L; Peti-Peterdi, J


    Multiphoton excitation fluorescence microscopy is a state-of-the-art confocal imaging technique ideal for deep optical sectioning of living tissues. It is capable of performing ultrasensitive, quantitative imaging of organ functions in health and disease with high spatial and temporal resolution which other imaging modalities cannot achieve. For more than a decade, multiphoton microscopy has been successfully used with various in vitro and in vivo experimental approaches to study many functions of different organs, including the kidney. This study focuses on recent advances in our knowledge of renal (patho)physiological processes made possible by the use of this imaging technology. Visualization of cellular variables like cytosolic calcium, pH, cell-to-cell communication and signal propagation, interstitial fluid flow in the juxtaglomerular apparatus (JGA), real-time imaging of tubuloglomerular feedback (TGF), and renin release mechanisms are reviewed. A brief summary is provided of kidney functions that can be measured by in vivo quantitative multiphoton imaging including glomerular filtration and permeability, concentration, dilution, and activity of the intrarenal renin-angiotensin system using this minimally invasive approach. New visual data challenge a number of existing paradigms in renal (patho)physiology. Also, quantitative imaging of kidney function with multiphoton microscopy has tremendous potential to eventually provide novel non-invasive diagnostic and therapeutic tools for future applications in clinical nephrology.

  16. Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques

    Directory of Open Access Journals (Sweden)

    D'Arcy Ryan CN


    Full Text Available Abstract In clinical neurology, a comprehensive understanding of consciousness has been regarded as an abstract concept - best left to philosophers. However, times are changing and the need to clinically assess consciousness is increasingly becoming a real-world, practical challenge. Current methods for evaluating altered levels of consciousness are highly reliant on either behavioural measures or anatomical imaging. While these methods have some utility, estimates of misdiagnosis are worrisome (as high as 43% - clearly this is a major clinical problem. The solution must involve objective, physiologically based measures that do not rely on behaviour. This paper reviews recent advances in physiologically based measures that enable better evaluation of consciousness states (coma, vegetative state, minimally conscious state, and locked in syndrome. Based on the evidence to-date, electroencephalographic and neuroimaging based assessments of consciousness provide valuable information for evaluation of residual function, formation of differential diagnoses, and estimation of prognosis.

  17. Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques. (United States)

    Gawryluk, Jodie R; D'Arcy, Ryan C N; Connolly, John F; Weaver, Donald F


    In clinical neurology, a comprehensive understanding of consciousness has been regarded as an abstract concept--best left to philosophers. However, times are changing and the need to clinically assess consciousness is increasingly becoming a real-world, practical challenge. Current methods for evaluating altered levels of consciousness are highly reliant on either behavioural measures or anatomical imaging. While these methods have some utility, estimates of misdiagnosis are worrisome (as high as 43%)--clearly this is a major clinical problem. The solution must involve objective, physiologically based measures that do not rely on behaviour. This paper reviews recent advances in physiologically based measures that enable better evaluation of consciousness states (coma, vegetative state, minimally conscious state, and locked in syndrome). Based on the evidence to-date, electroencephalographic and neuroimaging based assessments of consciousness provide valuable information for evaluation of residual function, formation of differential diagnoses, and estimation of prognosis.

  18. Advances in imaging-genetic relationships for Alzheimer's disease: clinical implications. (United States)

    Bagnoli, Silvia; Piaceri, Irene; Sorbi, Sandro; Nacmias, Benedetta


    Alzheimer's disease (AD) is the most common cause of dementia and represents a major public health problem. From a clinical perspective, AD is devastating to patients and their families. The genetic approach to the study of dementia undoubtedly continues to provide a significant contribution to understanding the pathogenesis, diagnosis and therapeutic perspectives, but also raises important ethical implications. With advances in new technology, including genetics and PET/MRI scanning, the role of genetic studies and neuroimaging is being redefined as an aid in the clinical diagnosis of AD, and also in presymptomatic evaluation. Here, we review some of the issues related to the neuroimaging-genetic relationship in AD with a possible clinical implication as a preclinical biomarker for dementia and also for tracking disease progression.

  19. Le fort I maxillary advancement using distraction osteogenesis. (United States)

    Combs, Patrick D; Harshbarger, Raymond J


    Treatment of maxillary hypoplasia has traditionally involved conventional Le Fort I osteotomies and advancement. Advancements of greater than 10 mm risk significant relapse. This risk is greater in the cleft lip and palate population, whose anatomy and soft tissue scarring from prior procedures contributes to instability of conventional maxillary advancement. Le Fort I advancement with distraction osteogenesis has emerged as viable, stable treatment modality correction of severe maxillary hypoplasia in cleft, syndromic, and noncleft patients. In this article, the authors provide a review of current data and recommendations concerning Le Fort I advancement with distraction osteogenesis. In addition, they outline their technique for treating severe maxillary hypoplasia with distraction osteogenesis using internal devices.

  20. Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation End-products in Head and Neck Cancer: A Systematic Review. (United States)

    Nguyen, Austin; Bhavsar, Sheila; Riley, Erinn; Caponetti, Gabriel; Agrawal, Devendra


    Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. Data synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.

  1. Clinical Value of High Mobility Group Box 1 and the Receptor for Advanced Glycation End-products in Head and Neck Cancer: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Nguyen, Austin


    Full Text Available Introduction High mobility group box 1 is a versatile protein involved in gene transcription, extracellular signaling, and response to inflammation. Extracellularly, high mobility group box 1 binds to several receptors, notably the receptor for advanced glycation end-products. Expression of high mobility group box 1 and the receptor for advanced glycation end-products has been described in many cancers. Objectives To systematically review the available literature using PubMed and Web of Science to evaluate the clinical value of high mobility group box 1 and the receptor for advanced glycation end-products in head and neck squamous cell carcinomas. Data synthesis A total of eleven studies were included in this review. High mobility group box 1 overexpression is associated with poor prognosis and many clinical and pathological characteristics of head and neck squamous cell carcinomas patients. Additionally, the receptor for advanced glycation end-products demonstrates potential value as a clinical indicator of tumor angiogenesis and advanced staging. In diagnosis, high mobility group box 1 demonstrates low sensitivity. Conclusion High mobility group box 1 and the receptor for advanced glycation end-products are associated with clinical and pathological characteristics of head and neck squamous cell carcinomas. Further investigation of the prognostic and diagnostic value of these molecules is warranted.

  2. Recent advances in bone regeneration using adult stem cells. (United States)

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet


    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration.

  3. Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward clinical utility. (United States)

    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


    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.

  4. Clinical observation of capecitabine monotherapy in elderly patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    Miao Zhang; Zhaozhe Liu Co-first author; Zhendong Zheng; Tao Han; Yaling Han; Min Song; Xiaodong Xie


    Objective The aim of the study was to evaluate the safety and ef icacy of capecitabine mono-chemo-therapy in elderly patients with advanced breast cancer. Methods The data from 36 cases of capecitabine monotherapy in elderly patients with advanced breast cancer were retrospectively analyzed. Oral administration of capecitabine 2000 mg/m2 twice daily (D1–14) for 21 days constituted a cycle. The ef ect of the disease and main adverse reactions were evaluated every 2 cycles. Results The data from 36 elderly patients were studied. The median number of chemotherapy cycles was 4. The total ef ective rate was 30.6% (11/36) and the disease control rate was 72.2% (26/36). The number of patients with clinical complete remission was 2, clinical partial response was 9, stable disease was 15, and progressive disease was 10. Where treatment was ef ective, the median time to progression was 6 months and the median overal survival was 9.5 months. The main adverse events were gastroin-testinal reactions, bone marrow suppression, and oral mucositis; most of the reactions were grade 1 to 2. Grade 3 to 4 adverse reactions included granulocytopenia in 2 patients (12.5%) and hand-foot syndrome in 1 patient (6.7%). Conclusion Capecitabine monotherapy was ef ective in control ing disease progression, and adverse reactions were tolerated by elderly patients with advanced breast cancer.

  5. Advanced Aqueous Phase Catalyst Development using Combinatorial Methods Project (United States)

    National Aeronautics and Space Administration — The use of combinatorial methods is proposed to rapidly screen catalyst formulations for the advanced development of aqueous phase oxidation catalysts with greater...

  6. Research and development of advanced materials using ion beam

    Energy Technology Data Exchange (ETDEWEB)

    Namba, Susumu [Nagasaki Inst. of Applied Science, Nagasaki (Japan)


    A wide range of research and development activities of advanced material synthesis using ion beams will be discussed, including ion beam applications to the state-of-the-art electronics from giant to nano electronics. (author)

  7. Using Clinical Cases to Teach General Chemistry (United States)

    Dewprashad, Brahmadeo; Kosky, Charles; Vaz, Geraldine S.; Martin, Charlotte L.


    A clinical study was designed and used to show the relationship of health and medicine, in a typical clinical scenario, where many chemical principles are involved and that an integrated knowledge of chemistry and biology is essential to the understanding, diagnosing and treating of illnesses. A case study would be a positive learning experience…

  8. Cognitive development in advanced mathematics using technology (United States)

    Tall, David


    This paper considers cognitive development in mathematics and its relationship with computer technology, with special emphasis on the use of visual imagery and symbols and the later shift to formal axiomatic theories. At each stage, empirical evidence is presented to show how these forms of thinking are enhanced, changed, or impeded by the use of technology.

  9. Evaluation of two preoparative chemotherapy regimens for complete operability of advanced gastric adenocarcinoma: a clinical trial

    Directory of Open Access Journals (Sweden)

    S. Sedighi


    Full Text Available Background: This prospective phase III study was designed to compare the activity of two combinations chemotherapy drugs in advanced gastric adenocarcinoma Methods: In a double blinded clinical trial, From Jan. 2002 to Jan. 2005, ninety patients with advanced gastric adenocarcinoma were randomly assigned to 1 Cisplatin and continuous infusion of 5FU and Epirubicin (ECF, and 2 Cisplatin and continuous infusion of 5FU with Docetaxel (TCF. Reduction in tumor mass, overall survival (OS, time to progression (TTP, and safety were measured outcome. Results: About 90% of patients had stage III or IV disease and the most common sites of tumor spread were peritoneal surfaces, liver and Paraaortic lymph nodes in either group. The objective clinical response rate (more than 50% decreases in tumor mass was 38% and 43% in ECF and TCF group respectively. Global quality of life increased (p=0 002 and symptoms of pain and insomnia decreased after chemotherapy. Patients in TCF had more grade one or two skin reactions, neuropathy and diarrhea. Fourteen patients underwent surgery. Complete microscopic (R0 resection had done in two of ECF and six of TCF tumors (p=0.015. Two cases in TCF group showed complete pathologic response. Median TTP was nine months and 10 months in ECF and TCF group respectively. Median OS was 12 months in both groups. Conclusion: Although there wasn’t statistically significant difference regarded to clinical response or survival between two groups, TCF showed more complete pathologic response.

  10. Recent advances in bone regeneration using adult stemcells

    Institute of Scientific and Technical Information of China (English)

    Hadar Zigdon-Giladi; Utai Rudich; Gal Michaeli Geller; Ayelet Evron


    Bone is a highly vascularized tissue reliant on theclose spatial and temporal association between bloodvessels and bone cells. Therefore, cells that participatein vasculogenesis and osteogenesis play a pivotalrole in bone formation during prenatal and postnatalperiods. Nevertheless, spontaneous healing of bonefracture is occasionally impaired due to insufficientblood and cellular supply to the site of injury. In thesecases, bone regeneration process is interrupted, whichmight result in delayed union or even nonunion ofthe fracture. Nonunion fracture is difficult to treatand have a high financial impact. In the last decade,numerous technological advancements in bone tissueengineering and cell-therapy opened new horizon inthe field of bone regeneration. This review starts withpresentation of the biological processes involved inbone development, bone remodeling, fracture healingprocess and the microenvironment at bone healingsites. Then, we discuss the rationale for using adultstem cells and listed the characteristics of the availablecells for bone regeneration. The mechanism of actionand epigenetic regulations for osteogenic differentiationare also described. Finally, we review the literature fortranslational and clinical trials that investigated the useof adult stem cells (mesenchymal stem cells, endothelialprogenitor cells and CD34+ blood progenitors) for boneregeneration.

  11. Advanced Plasma Diagnostic Analysis using Neural Networks (United States)

    Tritz, Kevin; Reinke, Matt


    Machine learning techniques, specifically neural networks (NN), are used with sufficient internal complexity to develop an empirically weighted relationship between a set of filtered X-ray emission measurements and the electron temperature (Te) profile for a specific class of discharges on NSTX. The NN response matrix is used to calculate the Te profile directly from the filtered X-ray diode measurements which extends the electron temperature time response from the 60Hz Thomson Scattering profile measurements to fast timescales (>10kHz) and greatly expands the applicability of Te profile information to fast plasma phenomena, such as ELM dynamics. This process can be improved by providing additional information which helps the neural network refine the relationship between Te and the corresponding X-ray emission. NN supplement limited measurements of a particular quantity using related measurements with higher time or spatial resolution. For example, the radiated power (Prad) determined using resistive foil bolometers is related to similar measurements using AXUV diode arrays through a complex and slowly time-evolving quantum efficiency curve in the VUV spectral region. Results from a NN trained using Alcator C-Mod resistive foil bolometry and AXUV diodes are presented, working towards hybrid Prad measurements with the quantitative accuracy of resistive foil bolometers and with the enhanced temporal and spatial resolution of the unfiltered AXUV diode arrays. Work supported by Department of Energy Grant #: DE-FG02-09ER55012.

  12. Managing Dyspnea in Patients with Advanced Chronic Obstructive Pulmonary Disease: A Canadian Thoracic Society Clinical Practice Guideline

    Directory of Open Access Journals (Sweden)

    Darcy D Marciniuk


    Full Text Available Dyspnea is a cardinal symptom of chronic obstructive pulmonary disease (COPD, and its severity and magnitude increases as the disease progresses, leading to significant disability and a negative effect on quality of life. Refractory dyspnea is a common and difficult symptom to treat in patients with advanced COPD. There are many questions concerning optimal management and, specifically, whether various therapies are effective in this setting. The present document was compiled to address these important clinical issues using an evidence-based systematic review process led by a representative interprofessional panel of experts.

  13. The clinical relevance of assessing advanced glycation endproducts accumulation in diabetes. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Hillebrands Jan-Luuk


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

  15. Intrusion Detection System Using Advanced Honeypots

    CERN Document Server

    Singh, Ram Kumar


    The exponential growth of Internet traffic has made public servers increasingly vulnerable to unauthorized accesses and intrusions. In addition to maintaining low latency for the client, filtering unauthorized accesses has become one of the major concerns of a server maintainer. This implementation of an Intrusion Detection System distinguishes between the traffic coming from clients and the traffic originated from the attackers, in an attempt to simultaneously mitigate the problems of both latency and security. We then present the results of a series of stress and scalability tests, and suggest a number of potential uses for such a system. As computer attacks are becoming more and more difficult to identify the need for better and more efficient intrusion detection systems increases. The main problem with current intrusion detection systems is high rate of false alarms. Using honeypots provides effective solution to increase the security.

  16. Palliative care in advanced kidney disease: a nurse-led joint renal and specialist palliative care clinic. (United States)

    Harrison, Kerry; Watson, Sarah


    The National Service Framework for Renal Services Part 2 identifies quality requirements for end-of-life care for individuals with kidney failure, recognizing the potential to forge closer relationships between renal and specialist palliative care providers. This article describes a pilot project set up by two Clinical Nurse Specialists, one working in hospice specialist palliative care and the other in renal palliative care within an acute trust. The purpose of the pilot was to work in collaboration to run a streamlined nurse-led clinic that would meet the palliative care needs of chronic kidney disease (CKD) Stage 5 patients and their carers. To achieve this the clinic would have to provide optimal symptom management, empower patients to make their own choices, and support them with advance care planning underpinned by the End of Life Care Strategy. The partnership also aimed to promote service improvement and practice development using transference of knowledge, skills, and expertise. Initial informal feedback, including a very small patient survey, suggests that the clinic was well received by patients, carers, and other health professionals. The clinic is ongoing and deserves more formal evaluation to encourage future service development.

  17. Soil aquifer treatment using advanced primary effluent

    KAUST Repository

    Sharma, Saroj K.


    Soil aquifer treatment (SAT) using primary effluent (PE) is an attractive option for wastewater treatment and reuse in many developing countries with no or minimal wastewater treatment. One of the main limitations of SAT of PE is rapid clogging of the infiltration basin due to high suspended solid concentrations. Some pre-treatment of PE before infiltration is likely to reduce this limitation, improve performance of SAT and help to implement this technology effectively. The effects of three pre-treatment options namely sedimentation (SED), coagulation (COAG) and horizontal roughing filtration (HRF) on SAT were analyzed by conducting laboratory-scale batch and soil column experiments. The sedimentation and coagulation pre-treatments led to less head loss development and reduction of clogging effect. The head loss development in soil column using PE + COAG and PE + SED was reduced by 85 and 72%, respectively, compared to PE alone without any pretreatment. The overall dissolved organic carbon (DOC) removal of pre-treatments and soil column collectively were 34, 44, 51 and 43.5% for PE without any pre-treatment, PE + SED, PE+ COAG and PE + HRF, respectively. Coagulation pre-treatment of PE was found to be the most effective option in terms of suspended solids, DOC and nitrogen removal. Sedimentation pre-treatment of PE could be attractive where land is relatively less expensive for the construction of sedimentation basins. © IWA Publishing 2011.

  18. Control of Smart Building Using Advanced SCADA (United States)

    Samuel, Vivin Thomas

    For complete control of the building, a proper SCADA implementation and the optimization strategy has to be build. For better communication and efficiency a proper channel between the Communication protocol and SCADA has to be designed. This paper concentrate mainly between the communication protocol, and the SCADA implementation, for a better optimization and energy savings is derived to large scale industrial buildings. The communication channel used in order to completely control the building remotely from a distant place. For an efficient result we consider the temperature values and the power ratings of the equipment so that while controlling the equipment, we are setting a threshold values for FDD technique implementation. Building management system became a vital source for any building to maintain it and for safety purpose. Smart buildings, refers to various distinct features, where the complete automation system, office building controls, data center controls. ELC's are used to communicate the load values of the building to the remote server from a far location with the help of an Ethernet communication channel. Based on the demand fluctuation and the peak voltage, the loads operate differently increasing the consumption rate thus results in the increase in the annual consumption bill. In modern days, saving energy and reducing the consumption bill is most essential for any building for a better and long operation. The equipment - monitored regularly and optimization strategy is implemented for cost reduction automation system. Thus results in the reduction of annual cost reduction and load lifetime increase.

  19. Serumferritin - diagnostic relevance and clinical usefulness

    Energy Technology Data Exchange (ETDEWEB)

    Linkesch, W. (Vienna Univ. (Austria). 2. Medizinische Klinik)


    The introduction of a WHO Standard for serumferritin effected a standardisation of different methods, improving quality and security for clinical routine diagnostic purposes. Therefore the clinical evaluation of serumferritin gained even more importance. For evaluation of iron stores of children, pregnant women, population studies, patients on hemodialysis or patients with rheumatoid arthritis low serumferritin values give safe results. In addition serumferritin is of clinical usefulness in monitoring therapy of both iron deficiency and iron overload. Evaluating a single serumferritin value one should consider the total clinical situation of the patient. As some tumors can produce and secrete serumferritin, e.g. acute myeloblastic leukemia, germ cell tumors, malignant melanoma, serumferritin might be helpful in monitoring the malignant disease. The ongoing characterization of tissue isoferritin, especially acidic isoferritin, may eventually lead to a clinically significant diagnostic marker of neoplasia.

  20. Advancing gut microbiome research using cultivation

    DEFF Research Database (Denmark)

    Sommer, Morten OA


    Culture-independent approaches have driven the field of microbiome research and illuminated intricate relationships between the gut microbiota and human health. However, definitively associating phenotypes to specific strains or elucidating physiological interactions is challenging for metagenomic...... approaches. Recently a number of new approaches to gut microbiota cultivation have emerged through the integration of high-throughput phylogenetic mapping and new simplified cultivation methods. These methodologies are described along with their potential use within microbiome research. Deployment of novel...... cultivation approaches should enable improved studies of xenobiotic tolerance and modification phenotypes and allow a drastic expansion of the gut microbiota reference genome catalogues. Furthermore, the new cultivation methods should facilitate systematic studies of the causal relationship between...

  1. Advanced Steganography Algorithm using Encrypted secret message

    Directory of Open Access Journals (Sweden)

    Joyshree Nath


    Full Text Available In the present work the authors have introduced a new method for hiding any encrypted secret message inside a cover file. For encrypting secret message the authors have used new algorithm proposed by Nath et al(1. For hiding secret message we have used a method proposed by Nath et al(2. In MSA(1 method we have modified the idea of Play fair method into a new platform where we can encrypt or decrypt any file. We have introduced a new randomization method for generating the randomized key matrix to encrypt plain text file and to decrypt cipher text file. We have also introduced a new algorithm for encrypting the plain text multiple times. Our method is totally dependent on the random text_key which is to be supplied by the user. The maximum length of the text_key can be of 16 characters long and it may contain any character(ASCII code 0 to 255. We have developed an algorithm to calculate the randomization number and the encryption number from the given text_key. The size of the encryption key matrix is 16x16 and the total number of matrices can be formed from 16 x 16 is 256! which is quite large and hence if someone applies the brute force method then he/she has to give trail for 256! times which is quite absurd. Moreover the multiple encryption method makes the system further secured. For hiding secret message in the cover file we have inserted the 8 bits of each character of encrypted message file in 8 consecutive bytes of the cover file. We have introduced password for hiding data in the cover file. We propose that our new method could be most appropriate for hiding any file in any standard cover file such as image, audio, video files. Because the hidden message is encrypted hence it will be almost impossible for the intruder to unhide the actual secret message from the embedded cover file. This method may be the most secured method in digital water marking.

  2. The expanding role of the clinical haematologist in the new world of advanced therapy medicinal products. (United States)

    Lowdell, Mark W; Thomas, Amy


    Advanced therapy medicinal products (ATMPs) represent the current pinnacle of 'patient-specific medicines' and will change the nature of medicine in the near future. They fall into three categories; somatic cell-therapy products, gene therapy products and cells or tissues for regenerative medicine, which are termed 'tissue engineered' products. The term also incorporates 'combination products' where a human cell or tissue is combined with a medical device. Plainly, many of these new medicines share similarities with conventional haematological stem cell transplant products and donor lymphocyte infusions as well as solid organ grafts and yet ATMPs are regulated as medicines and their development has remained predominantly in academic settings and within specialist centres. However, with the advent of commercialisation of dendritic cell vaccines, chimeric antigen receptor (CAR)-T cells and genetically modified autologous haematopoietic stem cells to cure single gene-defects in β-thalassaemia and haemophilia, the widespread availability of these therapies needs to be accommodated. Uniquely to ATMPs, the patient or an allogeneic donor is regularly part of the manufacturing process. All of the examples given above require procurement of blood, bone marrow or an apheresate from a patient as a starting material for manufacture. This can only occur in a clinical facility licensed for the procurement of human cells for therapeutic use and this is likely to fall to haematology departments, either as stem cell transplant programmes or as blood transfusion departments, to provide under a contract with the company that will manufacture and supply the final medicine. The resource implications associated with this can impact on all haematology departments, not just stem cell transplant units, and should not be under-estimated.

  3. Advanced Ice Velocity Mapping Using Landsat 8 (United States)

    Klinger, M. J.; Scambos, T. A.; Fahnestock, M. A.; Haran, T. M.


    Improved image-to-image cross correlation software is applied to pairs of sequential Landsat 8 satellite imagery to accurately measure ice surface velocity over ice sheets and glaciers (±0.1 pixel displacement, 15 meter pixels). The high radiometric fidelity of Landsat 8's panchromatic band (12-bit), and exceptional geolocation accuracy (typically ±5 m) supports the generation of ice velocity fields over very short time intervals (e.g., 16-, 32-, or 48-day repeat images of the same scene location). The high radiometry supports velocity mapping in areas with very subtle topographic detail, including un-crevassed sastrugi regions on ice dome flanks or the ice sheet interior. New Python-based software presently under development (named PyCorr), takes two sequential Landsat 8 OLI scenes (or suitably processed ETM+ or TM scenes) and matches small sub-scenes ('chips') between the images based on similarity in their gray-scale value patterns, using an image correlation algorithm. Peak fitting in the region of maximum correlation for a chip pair yields sub-pixel fits to the feature offset vector. Vector editing after the image correlation runs seeks to eliminate spurious and cloud-impacted vectors, and correct residual geo-location error. This processing is based on plausible values of ice strain rates and known areas of near-zero ice flow (rock outcrops, ice dome areas, etc.). In preliminary processing, we have examined ~800 Landsat 8 image pairs having <20% cloud cover spanning the near-coastal Antarctic ice sheet during the 2013-14 summer season.

  4. Magnetic resonance enterography in Crohn's disease: optimal use in clinical practice and clinical trials. (United States)

    Rimola, Jordi; Panés, Julián; Ordás, Ingrid


    The purpose of this review is to provide a practical appraisal of the usefulness of magnetic resonance enterography in the management of Crohn's disease and the potential utilities that this imaging modality may have in clinical research. Also, we review some basic technical considerations that clinicians should know to understand the value and limitations of the technique. Lastly, we outline the future trends and potential contributions of new technological advances in the field of magnetic resonance imaging that can improve the classic magnetic resonance enterography technique.


    Institute of Scientific and Technical Information of China (English)

    DING Jing; SHI Xue-min


    In the present paper, the authors review recent advances in clinical and experimental studies on acupuncture treatment of cerebral hemorrhage(CH). Regarding clinical studies, the resuscitation-inducing needling maneuver, and main points of Shuigou(水沟GV 26),Baihui(百会 GV 20) and scalp-points Motor Area(MS 6), Sensory Area(MS 7), etc. are often involved. Concerning experimental studies, the underlying mechanisms of acupuncture of GV-26+"Neiguan"(内关 PC 6), GV-20,GV-26+GV-20, etc. in improving acute CH are introduced. In a word, acupuncture therapy works well in improving clinical symptoms and signs of CH patients, and acupuncture stimulation induced ameilioration of cerebral blood flow, favorable modulation of some bioactive substances as excitatory and inhibitory amino acids, endothelin, CGRP, heat shock protein 70, etc. and neuro-endocrine-immune network may contribute to the effect of acupuncture on CH. In addition, acupuncture combined with medicine and earlier application of acupuncture therapy in the acute stage of CH are recommended in clinical practice.

  6. Advances in classification, basic mechanisms and clinical science in ankylosing spondylitis and axial spondyloarthritis. (United States)

    Robinson, P C; Benham, H


    The field of spondyloarthritis (SpA) has seen huge advances over the past 5 years. The classification of axial disease has been redefined by the axial SpA criteria that incorporate disease captured before radiographic damage is evident as well as established erosive sacroiliac joint disease. Our knowledge of genetics and basic immunological pathways has progressed significantly. In addition, revolutionary progress has been achieved with the availability of tumour necrosis factor inhibitors for treating patients with moderate to severe disease. In parallel, several of novel biomarkers have been identified that show significant promise for the future. Advances in magnetic resonance imaging have helped define positive disease. We have identified that T1 and short tau inversion recovery sequences are best for the diagnosis of axial SpA, and gadolinium contrast is not additive for diagnosis. Progress has been made in identifying potential agents and strategies that reduce radiographic progression. Several referral strategies aimed at appropriate identification of patients have been trialled and found to be effective. There is still substantial work ahead, but the advances of the last 5 years have made a huge and tangible difference at the clinical coalface, and we suggest that this trend will continue.

  7. Special issue of clinical pharmacology: advances and applications in new protein therapeutics modulating tumor immunity

    Directory of Open Access Journals (Sweden)

    Frankel AE


    Full Text Available Arthur E Frankel Department of Internal Medicine, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA Until recent decades, the role of the immune system in harnessing tumor growth was based on anecdotal observations of increased cancers in immune-compromised patients, the benefits of graft-versus-leukemia in allogeneic stem cell transplants, and the limited but reproducible anticancer activity of several lymphokines, including interferon and interleukin (IL-2. Vaccine studies and infusions of "activated" lymphocytes yielded variable clinical responses and disease control. An improved understanding of the molecular and cell mechanisms of the innate and adaptive immune system in cancer-bearing animals and the discovery of an immune-suppressive tumor microenvironment then led to development and testing of a battery of new drug and cell-based approaches to trigger antitumor immunity. This issue of Clinical Pharmacology: Advances and Applications highlights some of the new protein-based compounds that are radically changing the cancer therapeutic landscape. The purpose of this collection of reviews is to inform the readership regarding the importance of the seismic change in cancer therapeutics and stimulate efforts to find novel niches and combinations of agents similar to recent advances in the application of cancer pathway inhibitors.

  8. Clinical and Immune Effects of Lenalidomide in Combination with Gemcitabine in Patients with Advanced Pancreatic Cancer (United States)

    Ullenhag, Gustav J.; Mozaffari, Fariba; Broberg, Mats; Mellstedt, Håkan; Liljefors, Maria


    Purpose To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer. Patients and Methods Patients with advanced pancreatic cancer were treated in first line with lenalidomide orally for 21 days of a 28 days cycle and the standard regimen for gemcitabine. In Part I, which we previously have reported, the dose of lenalidomide was defined (n = 12). In Part II, every other consecutive patient was treated with either lenalidomide (Group A, n = 11) or gemcitabine (Group B, n = 10) during cycle 1. From cycle 2 on, all Part II patients received the combination. Results A significant decrease in the proliferative response of peripheral blood mononuclear cells and the frequency of DCs were noted in patients at baseline compared to healthy control donors while the frequencies of CD4+ and CD8+ T cells, NK-cells and MDSCs were significantly higher in patients compared to controls. In Group A, a significant increase in the absolute numbers of activated (HLA-DR+) CD4 and CD8 T cells and CD8 effector memory T cells (pLenalidomide augmented T cell reactivities, which were abrogated by gemcitabine. However, addition of lenalidomide to gemcitabine seemed to have no therapeutic impact compared to gemcitabine alone in this non-randomized study. Trial Registration NCT01547260 PMID:28099502

  9. The consequences of using advanced physical assessment skills in medical and surgical nursing: A hermeneutic pragmatic study (United States)

    Zambas, Shelaine I.; Smythe, Elizabeth A.; Koziol-Mclain, Jane


    Aims and objectives The aim of this study was to explore the consequences of the nurse's use of advanced assessment skills on medical and surgical wards. Background Appropriate, accurate, and timely assessment by nurses is the cornerstone of maintaining patient safety in hospitals. The inclusion of “advanced” physical assessment skills such as auscultation, palpation, and percussion is thought to better prepare nurses for complex patient presentations within a wide range of clinical situations. Design This qualitative study used a hermeneutic pragmatic approach. Method Unstructured interviews were conducted with five experienced medical and surgical nurses to obtain 13 detailed narratives of assessment practice. Narratives were analyzed using Van Manen's six-step approach to identify the consequences of the nurse's use of advanced assessment skills. Results The consequences of using advanced assessment skills include looking for more, challenging interpretations, and perseverance. The use of advanced assessment skills directs what the nurse looks for, what she sees, interpretation of the findings, and her response. It is the interpretation of what is seen, heard, or felt within the full context of the patient situation, which is the advanced skill. Conclusion Advanced assessment skill is the means to an accurate interpretation of the clinical situation and contributes to appropriate diagnosis and medical management in complex patient situations. Relevance to clinical practice The nurse's use of advanced assessment skills enables her to contribute to diagnostic reasoning within the acute medical and surgical setting. PMID:27607193

  10. Interprofessional education in the clinical setting: A qualitative look at the preceptor's perspective in training advanced practice nursing students. (United States)

    Chen, Angel K; Rivera, Josette; Rotter, Nicole; Green, Emily; Kools, Susan


    With the shift towards interprofessional education to promote collaborative practice, clinical preceptors are increasingly working with trainees from various professions to provide patient care. It is unclear whether and how preceptors modify their existing precepting approach when working with trainees from other professions. There is little information on strategies for this type of precepting, and how preceptors may foster or impede interprofessional collaboration. The purpose of this qualitative description pilot study was to identify current methods preceptors use to teach trainees from other professions in the clinical setting, particularly advanced practice nursing and medical trainees, and to identify factors that support or impede this type of precepting. Data collected through observations and interviews were analyzed by the research team using thematic analysis procedures. Three major themes were identified: 1) a variety of teaching approaches and levels of engagement with trainees of different professions, 2) preceptor knowledge gaps related to curricula, goals, and scope of practice of trainees from other professions, and 3) administrative, structural and logistical elements that impact the success of precepting trainees from different professions in the clinical setting. This study has implications for faculty development and evaluation of current precepting practices in clinical settings.

  11. Recent advances in gastrointestinal oncology - updates and insights from the 2009 annual meeting of the American Society of Clinical Oncology

    Directory of Open Access Journals (Sweden)

    Hsueh Chung-Tsen


    Full Text Available Abstract We have reviewed the pivotal presentations related to gastrointestinal malignancies from 2009 annual meeting of the American Society of Clinical Oncology with the theme of "personalizing cancer care". We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. Adding trastuzumab to chemotherapy improved the survival of patients with advanced gastric cancer overexpressing human epidermal growth factor receptor 2. Gemcitabine plus cisplatin has become a new standard for first-line treatment of advanced biliary cancer. Octreotide LAR significantly lengthened median time to tumor progression compared with placebo in patients with metastatic neuroendocrine tumors of the midgut. Addition of oxaliplatin to fluoropyrimidines for preoperative chemoradiotherapy in patients with stage II or III rectal cancer did not improve local tumor response but increased toxicities. Bevacizumab did not provide additional benefit to chemotherapy in adjuvant chemotherapy for stage II or III colon cancer. In patients with resected stage II colon cancer, recurrence score estimated by multigene RT-PCR assay has been shown to provide additional risk stratification. In stage IV colorectal cancer, data have supported the routine use of prophylactic skin treatment in patients receiving antibody against epidermal growth factor receptor, and the use of upfront chemotherapy as initial management in patients with synchronous metastasis without obstruction or bleeding from the primary site.

  12. Clinical observation of raltitrexed/bevacizumab combined with irinotecan or oxaliplation for advanced colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jianwei Yang; Wei Gao; Jinyuan Lin; Yan Meng; Shuzhen Zhang; Tong Wang


    Objective: The aim of the study was to investigate the ef icacy and safety of raltitrexed/bevacizumab in combina-tion with irinotecan or oxaliplation for advanced colorectal cancer as the second-line and second-line above treatments. Meth-ods: Fifteen cases of advanced colorectal cancer were enrol ed to receive regimens including raltitrexed/bevacizumab com-bined with irinotecan or oxaliplation. Two cases were treated with raltitrexed + bavacizumab regimen, 9 cases with raltitrexed+ bavacizumab + irinotecan regimen, and 4 cases with raltitrexed + bevacizumab + oxaliplation regimen. The doses of the drugs were as fol ows: bevacizumab 5 mg/kg ivgtt, d1; raltitrexed 2.0 mg/m2 ivgtt 15 min, d2; irinotecan 180 mg/m2 ivgtt 1 h, d2; and oxaliplatin 85 mg/m2 ivgtt 2 h, d2. Two weeks was a cycle for each regimen. Results: The ef icacy of the 15 patients could be evaluated. Two cases were in PR ,10 cases in SD, 3 cases in PD, the response rate was 13.3%, and the disease control rate was 80.0%. The median progress-free survival was 5.1 months (95% CI: 3.404-6.813 months), and the median overal survival was 11.5 months (95% CI: 8.985-13.930 months). The adverse ef ects included anorexia, nausea/vomit-ing, fatigue, leucopenia, thrombocytopenia, etc, and the main 3-4 grades adverse ef ects were anorexia, nausea/vomiting, fatigue, and thrombocytopenia. Conclusion: Raltitrexed/bevacizumab combined with irinotecan or oxaliplatin as the second-line and second-line above treatments for advanced colorectal cancer has high disease control rates, and the adverse ef ect is wel tolerated. The combined regimen can be recommended as a phase III clinical research and second-line and second-lines above treatments for advanced colorectal cancer.

  13. 21 CFR 862.2500 - Enzyme analyzer for clinical use. (United States)


    ... (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Laboratory... use is a device intended to measure enzymes in plasma or serum by nonkinetic or kinetic measurement...

  14. The use of combinations of monoclonal antibodies in clinical oncology. (United States)

    Henricks, Linda M; Schellens, Jan H M; Huitema, Alwin D R; Beijnen, Jos H


    Treatment with monoclonal antibodies is becoming increasingly important in clinical oncology. These antibodies specifically inhibit signaling pathways in tumor growth and/or induce immunological responses against tumor cells. By combining monoclonal antibodies several pathways may be targeted simultaneously, potentially leading to additive or synergistic effects. Theoretically, antibodies are very suitable for use in combination therapy, because of limited overlapping toxicity and lack of pharmacokinetic interactions. In this article an overview is given of preclinical and clinical data on twenty-five different combinations of antibodies in oncology. Some of these combinations have proven clinical benefit, for example the combination of trastuzumab and pertuzumab in HER2-positive breast cancer, which exemplifies an additive or synergistic effect on antitumor activity in clinical studies and the combination of nivolumab and ipilimumab, which results in significant increases in progression-free and overall survival in patients with advanced melanoma. However, other combinations may lead to unfavorable results, such as bevacizumab with cetuximab or panitumumab in advanced colorectal cancer. These combinations result in shorter progression-free survival and increased toxicity compared to therapy with a single antibody. In summary, the different published studies showed widely varying results, depending on the combination of antibodies, indication and patient population. More preclinical and clinical studies are necessary to unravel the mechanisms behind synergistic or antagonistic effects of combining monoclonal antibodies. Most research on combination therapies is still in an early stage, but it is expected that for several tumor types the use of combination therapy of antibodies will become standard of care in the near future.

  15. Using Advance Organizers to Enhance Students' Motivation in Learning Biology (United States)

    Shihusa, Hudson; Keraro, Fred N.


    This study investigated the effect of using advance organizers on students' motivation to learn biology. The research design used was quasi-experimental design where the non-randomised Solomon Four group was adopted. The focus was on the topic pollution. The sample comprised of 166 form three (third grade in the secondary school cycle) students in…

  16. Nondestructive testing of advanced materials using sensors with metamaterials (United States)

    Rozina, Steigmann; Narcis Andrei, Danila; Nicoleta, Iftimie; Catalin-Andrei, Tugui; Frantisek, Novy; Stanislava, Fintova; Petrica, Vizureanu; Adriana, Savin


    This work presents a method for nondestructive evaluation (NDE) of advanced materials that makes use of the images in near field and the concentration of flux using the phenomenon of spatial resolution. The method allows the detection of flaws as crack, nonadhesion of coating, degradation or presence delamination stresses correlated with the response of electromagnetic sensor.

  17. Using Advanced Computer Vision Algorithms on Small Mobile Robots (United States)


    this approach is the implementation of advanced computer vision algorithms on small mobile robots . We demonstrate the implementation and testing of the...following two algorithms useful on mobile robots : (1) object classification using a boosted Cascade of classifiers trained with the Adaboost training

  18. Cancer proteomics: developments in technology, clinical use and commercialization. (United States)

    Yeat, Nai Chien; Lin, Charlotte; Sager, Monica; Lin, Jimmy


    In the last two decades, advances in genomic, transcriptomic and proteomic methods have enabled us to identify and classify cancers by their molecular profiles. Many anticipate that a molecular taxonomy of cancer will not only lead to more effective subtyping of cancers but also earlier diagnoses, more informative prognoses and more targeted treatments. This article reviews recent technological developments in the field of proteomics, recent discoveries in proteomic cancer biomarker research and trends in clinical use. Readers are also informed of examples of successful commercialization, and the future of proteomics in cancer diagnostics.

  19. Using e-technologies in clinical trials. (United States)

    Rosa, Carmen; Campbell, Aimee N C; Miele, Gloria M; Brunner, Meg; Winstanley, Erin L


    Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored.

  20. Center to Advance Palliative Care palliative care clinical care and customer satisfaction metrics consensus recommendations. (United States)

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


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

  1. Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-sheng; MIAO Li-yun; LIU Lu; CAI Hou-rong; DING Jing-jing; REN Sheng-xiang; ZHOU Cai-cun


    Background Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients.This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.Methods A total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study.Blood samples were collected before the initiation of erlotinib treatment,and the levels of IL-1,IL-2R,IL-6,and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA).Cutoff points were defined as the median levels of IL-1 (low (≤26.5 pg/ml) and high (>26.5 pg/ml)),IL-2R (low (≤115 pmol/L) and high (>15 pmol/L)),IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)),and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ ml)).Kaplan-Meier analysis was used to estimate the survival time,and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes,including time to progression (TTP) and overall survival (OS).Results Between January 2007 and May 2011,162 patients were enrolled.Their median age was 58 years.In this group,109 were males and 53 were females,74 were former or current smokers and 88 were non-smokers.A total of 122 patients had adenocarcinoma,27 had squamous cell carcinoma,and 13 had tumors with other types of histology.And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1,while 23 scored at 2-3.Expression of IL-1,IL-2R,and IL-6 was not significantly associated with age,gender,ECOG performance status,smoking status,or histology and stage of tumor.Only TNF-α was associated with smoking status (P=0.045).Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTp and OS than patients with high

  2. Advanced vehicles: Costs, energy use, and macroeconomic impacts (United States)

    Wang, Guihua

    Advanced vehicles and alternative fuels could play an important role in reducing oil use and changing the economy structure. We developed the Costs for Advanced Vehicles and Energy (CAVE) model to investigate a vehicle portfolio scenario in California during 2010-2030. Then we employed a computable general equilibrium model to estimate macroeconomic impacts of the advanced vehicle scenario on the economy of California. Results indicate that, due to slow fleet turnover, conventional vehicles are expected to continue to dominate the on-road fleet and gasoline is the major transportation fuel over the next two decades. However, alternative fuels could play an increasingly important role in gasoline displacement. Advanced vehicle costs are expected to decrease dramatically with production volume and technological progress; e.g., incremental costs for fuel cell vehicles and hydrogen could break even with gasoline savings in 2028. Overall, the vehicle portfolio scenario is estimated to have a slightly negative influence on California's economy, because advanced vehicles are very costly and, therefore, the resulting gasoline savings generally cannot offset the high incremental expenditure on vehicles and alternative fuels. Sensitivity analysis shows that an increase in gasoline price or a drop in alternative fuel prices could offset a portion of the negative impact.

  3. Assessment of advanced glycated end product accumulation in skin using auto fluorescence multispectral imaging


    Larsson, Marcus; Favilla, Riccardo; Strömberg, Tomas


    Several studies have shown that advanced glycation end products (AGE) play a role in both the microvascular and macrovascular complications of diabetes and are closely linked to inflammation and atherosclerosis. AGEs accumulate in skin and can be detected using their auto fluorescence (AF).A significant correlation exists between AGE AF and the levels of AGEs as obtained from skin biopsies. A commercial device, the AGE Reader, has become available to assess skin AF for clinical purposes but, ...

  4. Advances In Infection Surveillance and Clinical Decision Support With Fuzzy Sets and Fuzzy Logic. (United States)

    Koller, Walter; de Bruin, Jeroen S; Rappelsberger, Andrea; Adlassnig, Klaus-Peter


    By the use of extended intelligent information technology tools for fully automated healthcare-associated infection (HAI) surveillance, clinicians can be informed and alerted about the emergence of infection-related conditions in their patients. Moni--a system for monitoring nosocomial infections in intensive care units for adult and neonatal patients--employs knowledge bases that were written with extensive use of fuzzy sets and fuzzy logic, allowing the inherent un-sharpness of clinical terms and the inherent uncertainty of clinical conclusions to be a part of Moni's output. Thus, linguistic as well as propositional uncertainty became a part of Moni, which can now report retrospectively on HAIs according to traditional crisp HAI surveillance definitions, as well as support clinical bedside work by more complex crisp and fuzzy alerts and reminders. This improved approach can bridge the gap between classical retrospective surveillance of HAIs and ongoing prospective clinical-decision-oriented HAI support.

  5. The use of advanced computer simulation in structural design

    Energy Technology Data Exchange (ETDEWEB)

    Field, C.J.; Mole, A. [Arup, San Fransisco, CA (United States); Arkinstall, M. [Arup, Sydney (Australia)


    The benefits that can be gained from the application of advanced numerical simulation in building design were discussed. A review of current practices in structural engineering was presented along with an illustration of a range of international project case studies. Structural engineers use analytical methods to evaluate both static and dynamic loads. Structural design is prescribed by a range of building codes, depending on location, building type and loading, but often, buildings do not fit well within the codes, particularly if one wants to take advantage of new technologies and developments in design that are not covered by the code. Advanced simulation refers to the use of mathematical modeling to complex problems to allow a wider consideration of building types and conditions that can be designed reliably using standard practices. Advanced simulation is used to address virtual testing and prototyping, verifying innovative design ideas, forensic engineering, and design optimization. The benefits of advanced simulation include enhanced creativity, improved performance, cost savings, risk management, sustainable design solutions, and better communication. The following 5 case studies illustrated the value gained by using advanced simulation as an integral part of the design process: the earthquake resistant Maison Hermes in Tokyo; the seismic resistant braces known as the Unbonded Brace for use in the United States; a simulation of the existing Disney Museum to evaluate its capacity to resist earthquakes; simulation of the MIT Brain and Cognitive Science Project to evaluate the effect of different foundation types on the vibration entering the building; and, the Beijing Aquatic Center whose design was streamlined by optimized structural analysis. It was suggested that industry should encourage the transfer of technology from other professions and should try to collaborate towards a global building model to construct buildings in a more efficient manner. 7 refs

  6. In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application. (United States)

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


    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.

  7. Using Video Ethnography in Clinical Nurse Education

    DEFF Research Database (Denmark)

    Kjær, Malene; Sørensen, Erik Elgaard; Raudaskoski, Pirkko Liisa


    Training to become a nurse involves education in the clinical practice in hospital wards. It is a multifaceted and complex arena in which the student nurses not only have to learn about medical encounters but also how to interact with colleagues as well as patients and their families. By using...

  8. Personality Assessment Use by Clinical Neuropsychologists (United States)

    Smith, Steven R.; Gorske, Tad T.; Wiggins, Chauntel; Little, Jessica A.


    The present study is an exploration of the personality assessment practices of clinical neuropsychologists. Professional members of the National Academy of Neuropsychology and the International Neuropsychological Society (N = 404) were surveyed to examine use of several forms of personality, behavior, and emotional function measures. Results…

  9. Optimal restoration of dental esthetics and function with advanced implant-supported prostheses: a clinical report. (United States)

    Meulen, Peter van der; Linden, Wynand van der; Eeden, Ronnie van


    For more than 25 years, computer-aided design and computer-aided manufacturing (CAD/CAM) technology has been used in implant restorative dentistry. Today this technology offers a means of milling titanium frameworks that fit dental implants accurately. This report presents a restoratively driven protocol employing advanced implant restorative and surgical techniques. Treatment of a patient with advanced periodontitis with extensive loss of hard and soft tissues is presented. After extraction of the patient's remaining hopeless teeth, dental implants were placed, along with interim, fixed-margin abutments and abutment protection caps. Two days later, acrylic resin fixed-interim prostheses restored the patient's esthetics and partial masticatory function. After implant osseointegration, maxillary, and mandibular frameworks for definitive prostheses were milled from Ti alloy, using one specific CAD/CAM technology. The benefits of this technology are also discussed.

  10. Clinical advances on Cardiac Insuffiency Avances clínicos en insuficiencia cardiaca

    Directory of Open Access Journals (Sweden)

    Gerardo Rivero González


    Full Text Available Cardiac insuffiency is a complex clinical syndrome which constitutes a common final path to get in by the majority of the cardiac diseases. Studies based on the communitarian surveys shows that from 30 to 40 % of the patients decease within the first year of the diagnosis. The rest of the patients (from 60 to 70 % die within the 5 years after being diagnosed. For this reason it has been called as the ¨cancer of cardiology¨. The objective of this article is to update the advances reached in the clinical and therapeutic aspects of this important syndrome.

    La insuficiencia cardiaca es un síndrome clínico complejo que constituye una vía final común a la que van a llegar la mayoría de las enfermedades cardiacas. Los estudios basados en encuestas comunitarias muestran que entre el 30 – 40 % de los pacientes mueren dentro del primer año del diagnóstico y el 60 – 70 % dentro de los 5 años, por lo que ha sido denominada, como el ¨cáncer de la cardiología¨. El objetivo de este artículo consiste en actualizar los avances alcanzados en los aspectos clínicos y terapéuticos de este importante síndrome.

  11. Clinical Relevance of the Advanced Microbiologic and Biochemical Investigations in Periodontal Diagnosis: A Critical Analysis

    Directory of Open Access Journals (Sweden)

    Vishakha Grover


    Full Text Available New approaches to periodontal diagnosis, including advanced microbiologic, biochemical, and genetic tests, have been shown to provide the clinician with the information not available by traditional means. The purpose of a diagnostic test is to confirm, exclude, classify, or monitor disease to guide treatment. Their clinical value depends on whether the information they provide leads to improved patient outcomes. This can be assessed by randomized trials, which compare patient outcomes from the new diagnostic test versus the old test strategy. Being nonmandatory for marketing approval, such trials are not always feasible because of large sample sizes requirements. So, many diagnostic tests enter the practice without being critically analysed for any additional benefits. Effective diagnosis is just as essential as the selection of effective treatments for the success of periodontal therapy. So, the current paper aims to focus on the practical utility of this rapidly emerging plethora of periodontal diagnostic tools, emphasizing the critical issues surrounding the clinical application of microbiologic and biochemical investigations, employed for periodontal diagnosis.

  12. Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer. (United States)

    Bajetta, E.; Zilembo, N.; Buzzoni, R.; Noberasco, C.; Di Leo, A.; Bartoli, C.; Merson, M.; Sacchini, V.; Moglia, D.; Celio, L.


    Formestane is a selective inhibitor of oestrogen synthesis by aromatase enzymes and induces disease regression in breast cancer patients. This phase II randomised study was carried out to determine whether there were any differences in the effects of two different doses of formestane on oestradiol (E2) serum levels and to evaluate the corresponding clinical activity in post-menopausal patients with positive or unknown oestrogen receptor status pretreated or not for advanced disease. Furthermore, possible drug interference with adrenal steroidogenesis was assessed by measuring 17-hydroxycorticosteroid (17-OHCS) urinary levels. A total of 143 patients entered the study and were randomly assigned to receive formestane 250 mg (72 patients) or formestane 500 mg (71 patients), both given i.m. every 2 weeks. In comparison with baseline, E2 serum levels decreased by an average of 40% after only 15 days and remained unchanged thereafter, with no difference being observed between the two doses. The values of 17-OHCS remained unchanged during treatment in both groups. Objective responses were 28% (19/69) in the 250 mg and 46% (31/68) in the 500 mg group. In conclusion, the two formestane doses were equally effective in reducing E2 levels without affecting adrenal function, and in inducing a considerable percentage of clinical responses. PMID:8018527

  13. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis. (United States)

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


    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.

  14. Clinical evaluation of the effect of platelet rich plasma on the coronally advanced flap root coverage procedure

    Directory of Open Access Journals (Sweden)

    Sharashchandra Madhavarao Biradar


    Full Text Available 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.


    Energy Technology Data Exchange (ETDEWEB)

    David Liscinsky


    A multidisciplined team led by the United Technologies Research Center (UTRC) and consisting of Pratt & Whitney Power Systems (PWPS), the University of North Dakota Energy & Environmental Research Center (EERC), KraftWork Systems, Inc. (kWS), and the Connecticut Resource Recovery Authority (CRRA) has evaluated a variety of gasified biomass fuels, integrated into advanced gas turbine-based power systems. The team has concluded that a biomass integrated gasification combined-cycle (BIGCC) plant with an overall integrated system efficiency of 45% (HHV) at emission levels of less than half of New Source Performance Standards (NSPS) is technically and economically feasible. The higher process efficiency in itself reduces consumption of premium fuels currently used for power generation including those from foreign sources. In addition, the advanced gasification process can be used to generate fuels and chemicals, such as low-cost hydrogen and syngas for chemical synthesis, as well as baseload power. The conceptual design of the plant consists of an air-blown circulating fluidized-bed Advanced Transport Gasifier and a PWPS FT8 TwinPac{trademark} aeroderivative gas turbine operated in combined cycle to produce {approx}80 MWe. This system uses advanced technology commercial products in combination with components in advanced development or demonstration stages, thereby maximizing the opportunity for early implementation. The biofueled power system was found to have a levelized cost of electricity competitive with other new power system alternatives including larger scale natural gas combined cycles. The key elements are: (1) An Advanced Transport Gasifier (ATG) circulating fluid-bed gasifier having wide fuel flexibility and high gasification efficiency; (2) An FT8 TwinPac{trademark}-based combined cycle of approximately 80 MWe; (3) Sustainable biomass primary fuel source at low cost and potentially widespread availability-refuse-derived fuel (RDF); (4) An overall integrated

  16. Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.; Diamond, Deborah L.; Brown, Roslyn N.; Ibrahim, Yehia M.; Orton, Daniel J.; Piehowski, Paul D.; Purdy, David E.; Moore, Ronald J.; Danielson, William F.; Monroe, Matthew E.; Crowell, Kevin L.; Slysz, Gordon W.; Gritsenko, Marina A.; Sandoval, John D.; Lamarche, Brian L.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Simons, Brenna C.; McMahon, Brian J.; Bhattacharya, Renuka; Perkins, James D.; Carithers, Robert L.; Strom, Susan; Self, Steven; Katze, Michael G.; Anderson, Gordon A.; Smith, Richard D.


    Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is an imperative goal for the field of medicine. While mass spectrometry (MS)-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry (IMS) separations [1, 2] with liquid chromatography (LC) and MS to dramatically increase measurement sensitivity and throughput, further enabling future MS-based clinical applications. An initial application of the LC-IMS-MS platform for the analysis of blood serum samples from stratified post-liver transplant patients with recurrent fibrosis progression illustrates its potential utility for disease characterization and use in personalized medicine [3, 4].

  17. Clinical usefulness of wave intensity analysis. (United States)

    Sugawara, Motoaki; Niki, Kiyomi; Ohte, Nobuyuki; Okada, Takashi; Harada, Akimitsu


    Wave intensity (WI) is a hemodynamic index, which can evaluate the working condition of the heart interacting with the arterial system. It can be defined at any site in the circulatory system and provides a great deal of information. However, we need simultaneous measurements of blood pressure and velocity to obtain wave intensity, which has limited the clinical application of wave intensity, in spite of its potential. To expand the application of wave intensity in the clinical setting, we developed a real-time non-invasive measurement system for wave intensity based on a combined color Doppler and echo-tracking system. We measured carotid arterial WI in normal subjects and patients with various cardiovascular diseases. In the coronary artery disease group, the magnitude of the first peak of carotid arterial WI (W (1)) increased with LV max. dP/dt (r = 0.74, P WI can be obtained non-invasively using an echo-Doppler system in the clinical setting. This method will increase the clinical usefulness of wave intensity.

  18. Continuous glucose monitoring: current clinical use. (United States)

    Kim, Hun-Sung; Shin, Jeong-Ah; Chang, Jin-Sun; Cho, Jae-Hyoung; Son, Ho-Young; Yoon, Kun-Ho


    Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real-time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed-loop system have proven to be optimistic. CGM-integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

  19. The use of biomarkers in clinical osteoporosis. (United States)

    Cabral, Hebert Wilson Santos; Andolphi, Bruna Ferreira Galone; Ferreira, Brunna Vila Coutinho; Alves, Danielle Cristina Filgueira; Morelato, Renato Lírio; Chambo, Antônio; Borges, Lizânia Spinassé


    Osteoporosis is a disease of ascending character in the world population; in this context, bone biomarkers are being increasingly studied in order to aid in the diagnosis and monitoring of these patients. The main objective of this study was a literature review of articles whose main theme was the use of biomarkers for bone formation and degradation, and to evaluate their possible applicability in clinical practice. Literature review was performed through articles indexed and published in the last five years in the PubMed database. The findings of this study showed that most of the previously selected articles were published in the last two years, and the most cited markers were bone resorption, C-terminal collagen telopeptide (CTX), showing the highest correlation with the dynamics of bone, and the biomarker of bone formation, bone-specific alkaline phosphatase (BAP), which is increased in the event of fracture or may suggest another bone disease. There was an increase in published articles, associating different bone biomarkers and their clinical applicability, especially for treatment control. Our findings suggest that in recent years there has been significant increase in publications evaluating the use of bone turnover biomarkers for bone formation and resorption and their possible clinical applicability, especially in the monitoring of treatment. Still, we believe that further studies need to be conducted to confirm these findings, given the advantages that bone biomarkers can deliver in the clinical management of the disease.

  20. Advanced Powertrain Design Using Model-Based Design



    The use of alternative fuels and advanced powertrain technologies has been increasing over the past few years as vehicle emissions and fuel economy have become prominent in both manufacturer needs and consumer demands. With more hybrids emerging from all automotive manufacturers, the use of computer modeling has quickly taken a lead in the testing of these innovative powertrain designs. Although on-vehicle testing remains an important part of the design process, modeling and simulation is pro...

  1. Advanced Statistical Signal Processing Techniques for Landmine Detection Using GPR (United States)


    Processing Techniques for Landmine Detection Using GPR The views, opinions and/or findings contained in this report are those of the author(s) and should not...AGENCY NAME(S) AND ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 landmine Detection, Signal...310 Jesse Hall Columbia, MO 65211 -1230 654808 633606 ABSTRACT Advanced Statistical Signal Processing Techniques for Landmine Detection Using GPR Report

  2. Advance care planning - a multi-centre cluster randomised clinical trial

    DEFF Research Database (Denmark)

    Rietjens, Judith A C; Korfage, Ida J; Dunleavy, Lesley


    BACKGROUND: Awareness of preferences regarding medical care should be a central component of the care of patients with advanced cancer. Open communication can facilitate this but can occur in an ad hoc or variable manner. Advance care planning (ACP) is a formalized process of communication between...... patients, relatives and professional caregivers about patients' values and care preferences. It raises awareness of the need to anticipate possible future deterioration of health. ACP has the potential to improve current and future healthcare decision-making, provide patients with a sense of control....... If a patient dies within a year after inclusion, a relative will be asked to complete a questionnaire on end-of-life care. Use of medical care will be assessed by checking medical files. The primary endpoint is patients' quality of life at 2.5 months post-inclusion. Secondary endpoints are the extent to which...

  3. Comprehensive clinical study of concurrent chemotherapy breathing IMRT middle part of locally advanced esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jae Hong; Moon, Seong Kwon [Dept. of Radiation Oncology, College of Medicine, Soonchunhyang University , Asan (Korea, Republic of); Kim, Seung Chul [Dept. of Radiology, Songho College, Hoengseong (Korea, Republic of)


    The standard treatment of locally advanced type of mid-esophageal cancer is concurrent chemoradiation therapy (CRT). We evaluated the feasibility of chemotherapy with adding docetaxel to the classical basic regimens of cisplatin plus 5-fluorouracil (5-FU) and radiotherapy up to 70.2 Gy using dose escalations for esophageal cancer. It was possible to escalate radiation treatment dose up to 70.2 Gy by the respiratory-gated intensity- modulated radiotherapy (gated-IMRT) based on the 4DCT-simulation, with improving target coverage and normal tissue (ex., lung, heart, and spinal cord) sparing. This study suggested that the definitive chemo-radiotherapy with docetaxel, cisplatin, and 5-fluorouracil (i.e., DCF-R) and gating IMRT is tolerable and active in patients with locally advanced mid-esophageal cancer (AEC)

  4. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation. (United States)

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


    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.

  5. Advancing the High Throughput Identification of Liver Fibrosis Protein Signatures Using Multiplexed Ion Mobility Spectrometry* (United States)

    Baker, Erin Shammel; Burnum-Johnson, Kristin E.; Jacobs, Jon M.; Diamond, Deborah L.; Brown, Roslyn N.; Ibrahim, Yehia M.; Orton, Daniel J.; Piehowski, Paul D.; Purdy, David E.; Moore, Ronald J.; Danielson, William F.; Monroe, Matthew E.; Crowell, Kevin L.; Slysz, Gordon W.; Gritsenko, Marina A.; Sandoval, John D.; LaMarche, Brian L.; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo M.; Simons, Brenna C.; McMahon, Brian J.; Bhattacharya, Renuka; Perkins, James D.; Carithers, Robert L.; Strom, Susan; Self, Steven G.; Katze, Michael G.; Anderson, Gordon A.; Smith, Richard D.


    Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography - ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization. PMID:24403597

  6. Advancing the high throughput identification of liver fibrosis protein signatures using multiplexed ion mobility spectrometry. (United States)

    Baker, Erin Shammel; Burnum-Johnson, Kristin E; Jacobs, Jon M; Diamond, Deborah L; Brown, Roslyn N; Ibrahim, Yehia M; Orton, Daniel J; Piehowski, Paul D; Purdy, David E; Moore, Ronald J; Danielson, William F; Monroe, Matthew E; Crowell, Kevin L; Slysz, Gordon W; Gritsenko, Marina A; Sandoval, John D; Lamarche, Brian L; Matzke, Melissa M; Webb-Robertson, Bobbie-Jo M; Simons, Brenna C; McMahon, Brian J; Bhattacharya, Renuka; Perkins, James D; Carithers, Robert L; Strom, Susan; Self, Steven G; Katze, Michael G; Anderson, Gordon A; Smith, Richard D


    Rapid diagnosis of disease states using less invasive, safer, and more clinically acceptable approaches than presently employed is a crucial direction for the field of medicine. While MS-based proteomics approaches have attempted to meet these objectives, challenges such as the enormous dynamic range of protein concentrations in clinically relevant biofluid samples coupled with the need to address human biodiversity have slowed their employment. Herein, we report on the use of a new instrumental platform that addresses these challenges by coupling technical advances in rapid gas phase multiplexed ion mobility spectrometry separations with liquid chromatography and MS to dramatically increase measurement sensitivity and throughput, further enabling future high throughput MS-based clinical applications. An initial application of the liquid chromatography--ion mobility spectrometry-MS platform analyzing blood serum samples from 60 postliver transplant patients with recurrent fibrosis progression and 60 nontransplant patients illustrates its potential utility for disease characterization.

  7. Clinical interpretation and use of stroke scales. (United States)

    Kasner, Scott E


    No single outcome measure can describe or predict all dimensions of recovery and disability after acute stroke. Several scales have proven reliability and validity in stroke trials, including the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS), the Barthel index (BI), the Glasgow outcome scale (GOS), and the stroke impact scale (SIS). Several scales have been combined in stroke trials to derive a global statistic to better define the effect of acute interventions, although this composite statistic is not clinically tenable. In practice, the NIHSS is useful for early prognostication and serial assessment, whereas the BI is useful for planning rehabilitative strategies. The mRS and GOS provide summary measures of outcome and might be most relevant to clinicians and patients considering early intervention. The SIS was designed to measure the patient's perspective on the effect of stroke. Familiarity with these scales could improve clinicians' interpretation of stroke research and their clinical decision-making.

  8. [Fifty years of clinical use of warfarin]. (United States)

    Quintero-González, Jesús Alberto


    Warfarin is the most utilized oral anticoagulant for the long term prophylaxes of thrombosis. Its use has been increased as new clinical conditions, capable of leading to thrombosis, have been detected. Due to the special characteristics of warfarin, such as the variability of doses for each individual, the narrow margin between adequate and inadequate doses, interaction with multiple pharmaceutical products, interference of its action by vitamin K present in the diet and the possibility of hemorrhagic complications or thrombotic recurrence, this drug requires a very careful dosage and strict laboratory and clinical monitoring. Despite being in the market for more than de fifty years and its many disadvantages, warfarin has not been substituted for the new oral anticoagulants. In 1999, warfarin was positioned eleventh on the list of the most used medicines in the world.

  9. A Clinical Tissue Oximeter Using NIR Time-Resolved Spectroscopy. (United States)

    Fujisaka, Shin-ichi; Ozaki, Takeo; Suzuki, Tsuyoshi; Kamada, Tsuyoshi; Kitazawa, Ken; Nishizawa, Mitsunori; Takahashi, Akira; Suzuki, Susumu


    The tNIRS-1, a new clinical tissue oximeter using NIR time-resolved spectroscopy (TRS), has been developed. The tNIRS-1 measures oxygenated, deoxygenated and total hemoglobin and oxygen saturation in living tissues. Two-channel TRS measurements are obtained using pulsed laser diodes (LD) at three wavelengths, multi-pixel photon counters (MPPC) for light detection, and time-to-digital converters (TDC) for time-of-flight photon measurements. Incorporating advanced semiconductor devices helped to make the design of this small-size, low-cost and low-power TRS instrument possible. In order to evaluate the correctness and reproducibility of measurement data obtained with the tNIRS-1, a study using blood phantoms and healthy volunteers was conducted to compare data obtained from a conventional SRS device and data from an earlier TRS system designed for research purposes. The results of the study confirmed the correctness and reproducibility of measurement data obtained with the tNIRS-1. Clinical evaluations conducted in several hospitals demonstrated a high level of usability in clinical situations and confirmed the efficacy of measurement data obtained with the tNIRS-1.

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

    Institute of Scientific and Technical Information of China (English)


    Advanced stage hepatocellular carcinoma (HCC) is acategory of disease defined by radiological, clinical andhepatic function parameters, comprehending a widerange of patients with different general conditions. Themain therapeutic option is represented by sorafenibtreatment, a multi-kinase inhibitor with anti-proliferativeand anti-angiogenic effect. Trans-arterial Radio Embolizationalso represents a promising new approach tointermediate/advanced HCC. Post-marketing clinicalstudies showed that only a portion of patients actuallybenefits from sorafenib treatment, and an even smallerpercentage of patients treated shows partial/completeresponse on follow-up examinations, up against relevantcosts and an incidence of drug related adverse effects.Although the treatment with sorafenib has shown asignificant increase in mean overall survival in differentstudies, only a part of patients actually shows realbenefits, while the incidence of drug related significantadverse effects and the economic costs are relativelyhigh. Moreover, only a small percentage of patientsalso shows a response in terms of lesion dimensionsreduction. Being able to properly differentiate patientswho are responding to the therapy from non-respondersas early as possible is then still difficult and couldbe a pivotal challenge for the future; in fact it couldspare several patients a therapy often difficult to bear,directing them to other second line treatments (many ofwhich are at the moment still under investigation). Forthis reason, some supplemental criteria to be added tothe standard modified Response Evaluation Criteriain Solid Tumors evaluation are being searched for. Inparticular, finding some parameters (cellular density,perfusion grade and enhancement rate) able to predictthe sensitivity of the lesions to anti-angiogenic agentscould help in stratifying patients in terms of treatmentresponsiveness before the beginning of the therapyitself, or in the first weeks of sorafenib treatment

  11. Apparatus for advancing a wellbore using high power laser energy (United States)

    Zediker, Mark S.; Land, Mark S.; Rinzler, Charles C.; Faircloth, Brian O.; Koblick, Yeshaya; Moxley, Joel F.


    Delivering high power laser energy to form a borehole deep into the earth using laser energy. Down hole laser tools, laser systems and laser delivery techniques for advancement, workover and completion activities. A laser bottom hole assembly (LBHA) for the delivery of high power laser energy to the surfaces of a borehole, which assembly may have laser optics, a fluid path for debris removal and a mechanical means to remove earth.

  12. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Wu Xiwei


    Full Text Available Abstract Background MicroRNAs (miRNAs have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC, and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Methods The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. Results More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. Conclusions Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.

  13. Advanced fusion MHD power conversion using the CFAR (compact fusion advanced Rankine) cycle concept

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, M.A.; Campbell, R.; Logan, B.G. (California Univ., Davis, CA (USA); Lawrence Livermore National Lab., CA (USA))


    The CFAR (compact fusion advanced Rankine) cycle concept for a tokamak reactor involves the use of a high-temperature Rankine cycle in combination with microwave superheaters and nonequilibrium MHD disk generators to obtain a compact, low-capital-cost power conversion system which fits almost entirely within the reactor vault. The significant savings in the balance-of-plant costs are expected to result in much lower costs of electricity than previous concepts. This paper describes the unique features of the CFAR cycle and a high- temperature blanket designed to take advantage of it as well as the predicted performance of the MHD disk generators using mercury seeded with cesium. 40 refs., 8 figs., 3 tabs.

  14. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells. (United States)

    Kawser Hossain, Mohammed; Abdal Dayem, Ahmed; Han, Jihae; Kumar Saha, Subbroto; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo


    Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  15. Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Mohammed Kawser Hossain


    Full Text Available Diabetes mellitus (DM is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.

  16. Supercomputing - Use Cases, Advances, The Future (2/2)

    CERN Document Server

    CERN. Geneva


    Supercomputing has become a staple of science and the poster child for aggressive developments in silicon technology, energy efficiency and programming. In this series we examine the key components of supercomputing setups and the various advances – recent and past – that made headlines and delivered bigger and bigger machines. We also take a closer look at the future prospects of supercomputing, and the extent of its overlap with high throughput computing, in the context of main use cases ranging from oil exploration to market simulation. On the second day, we will focus on software and software paradigms driving supercomputers, workloads that need supercomputing treatment, advances in technology and possible future developments. Lecturer's short bio: Andrzej Nowak has 10 years of experience in computing technologies, primarily from CERN openlab and Intel. At CERN, he managed a research lab collaborating with Intel and was part of the openlab Chief Technology Office. Andrzej also worked closely and i...

  17. Limb salvage using advanced technologies: a case report. (United States)

    Frykberg, Robert G; O'Connor, Rachel M; Tallis, Arthur; Tierney, Edward


    Patients with severe acute and chronic lower extremity wounds often present a significant challenge in terms of limb salvage. In addition to control of infection, assuring adequate perfusion and providing standard wound care, advanced modalities are often required to facilitate final wound closure. We herein present a case study on a diabetic patient with gangrene and necrotising soft-tissue infection who underwent a forefoot pedal amputation to control the sepsis. Despite his non invasive vascular studies demonstrating poor healing potential at this level, he was not deemed suitable for revascularisation by our vascular surgeons and ankle-level amputation was recommended. Nonetheless, over a 5-month period using multiple advanced wound care therapies, wound closure was ultimately achieved.

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

    DEFF Research Database (Denmark)

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


    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...

  19. Argus T® versus Advance® Sling for postprostatectomy urinary incontinence: A randomized clinical trial (United States)

    Lima, João Paulo Cunha; Pompeo, Antonio Carlos Lima; Bezerra, Carlos Alberto


    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. Advanced age and the clinical outcomes of transcatheter aortic valve implan-tation

    Institute of Scientific and Technical Information of China (English)

    Osama Alsara; Ahmad Alsarah; Heather Laird-Fick


    Aortic valve stenosis (AS) is common in the elderly. Although surgical replacement of the valve has been the gold standard of management, many patients have been excluded from surgery because they were very old, frail, or had co-morbidities that increased operative risks. In the last decade, transcatheter aortic valve implantation (TAVI) has emerged as a new treatment option suitable for these patients. This article reviews the available literature on the role of TAVI in elderly patients with severe aortic stenosis. Published studies showed that elderly individuals who underwent TAVI experienced better in-hospital recovery, and similar short and mid-term mortality compared to those underwent surgical treatment of AS. However, long-term outcomes of TAVI in elderly patients are still unknown. The available data in the literature on the ef-fect of advanced age on clinical outcomes of TAVI are limited, but the data that are available suggest that TAVI is a beneficial and tolerable procedure in very old patients. Some of the expected complications after TAVI are reported more in the oldest patients such as vascular in-jures. Other complications were comparable in TAVI patients regardless of their age group. However, very old patients may need closer monitoring to avoid further morbidities and mortality.

  1. [Domains in the clinical practice of Clinical Nursing Experts in Germany and their correspondence with the internationally described "Advanced Nursing Practice"]. (United States)

    Mendel, Simon; Feuchtinger, Johanna


    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.

  2. Comprehensive genomic sequencing and the molecular profiles of clinically advanced breast cancer. (United States)

    Ross, Jeffrey S; Gay, Laurie M


    Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events. By rapidly analysing many genes in parallel, NGS technologies can make efficient use of precious biopsy material. Comprehensive genomic profiling (CGP) by NGS can reveal targetable, clinically relevant genomic alterations that can stratify tumours by predicted sensitivity to a variety of therapies, including HER2- or MTOR-targeted therapies, immunotherapies, and other kinase inhibitors. Many clinically relevant genomic alterations would not be identified by IHC or hotspot testing, but can be detected by NGS. In addition to the most common breast carcinoma subtypes, rare subtypes analysed with CGP also harbour clinically relevant genomic alterations that can potentially direct therapy selection, illustrating that CGP is a powerful tool for guiding treatment across all breast cancer subtypes.

  3. A myofeedback instrument for clinical use. (United States)

    McCarthy, C F; De Luca, C J


    As a result of a collaborative effort by engineers, physical therapists, and patients, a myofeedback device called Myochirp was designed and constructed. This device was field-tested in six busy medical centers to determine its acceptance and usefulness to clinicians in the daily activities of their environments. As a result of this field evaluation, a second-generation device was constructed incorporating the suggested improvements. The second-generation Myochirp was accepted by physical therapists as a compact, portable, and lightweight device that was convenient and easy to use. The salient feature of the device which rendered it so useful in clinical environments was the dry electrode used to detect the electromyographic signals. Its usefulness as a myofeedback instrument was determined by the variety of its applications to treatment needs and by its ability to obtain immediate and quantifiable data that could be documented.

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

    Directory of Open Access Journals (Sweden)

    Trakadis Yannis J


    Full Text Available Abstract 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

  5. Modified coronally advanced flap with and without orthodontic button application in management of multiple proximate gingival recession defects: A randomized clinical trial


    Sumedh Khobragade; Abhay Kolte; Rajashri Kolte; Tushar Shrirao; Anushree Potey


    Background: Gingival recession indicates oral display of the root surface due to apical movement of gingival margin. Coronally advanced flap (CAF) is often used periodontal plastic surgical technique to accomplish root coverage. The purpose of this clinical trial is to assess and compare the effectiveness of modified CAF with orthodontic button application (CAF*B) and without orthodontic button application (CAF) for the correction of multiple recession defects. Materials and Methods: Twenty p...

  6. Modified coronally advanced flap with and without orthodontic button application in management of multiple proximate gingival recession defects: A randomized clinical trial


    Khobragade, Sumedh; Kolte, Abhay; Kolte, Rajashri; Shrirao, Tushar; Potey, Anushree


    Background: Gingival recession indicates oral display of the root surface due to apical movement of gingival margin. Coronally advanced flap (CAF) is often used periodontal plastic surgical technique to accomplish root coverage. The purpose of this clinical trial is to assess and compare the effectiveness of modified CAF with orthodontic button application (CAF+B) and without orthodontic button application (CAF) for the correction of multiple recession defects. Materials and Methods: Twenty p...

  7. Almanac 2012: Cell therapy in cardiovascular disease. The national society journals present selected research that has driven recent advances in clinical cardiology


    Jones A. Daniel; Choudry Fizzah; Mathur Anthony


    The rapid translation from bench to bedside that has been seen in the application of regenerative medicine to cardiology has led to exciting new advances in our understanding of some of the fundamental mechanisms related to human biology. The first generation of cells used in phase I-II trials (mainly bone marrow mononuclear cells) are now entering phase III clinical trials with the goal of producing a cell based therapeutic that can change the outcome of cardiac disease. First generation cel...

  8. Advances in X-ray detectors for clinical and preclinical Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Panetta, Daniele


    Computed tomography (CT) is a non-invasive X-ray diagnostic technique that allows reconstructing cross sections of a patient's body, providing detailed information about structure and anatomy of organs and, in some extent, also about their functionality. Since the development of the first CT scanner for clinical use in the ‘70s, several improvements especially in solid-state X-ray detector technology with growing detection efficiency and fast response have led to the current configuration of modern ultra-fast, low dose whole body CT scanners. Such developments brought great advantages in the clinical settings in terms of image quality, dose effectiveness, imaging throughput, but also extending considerably the field of clinical application that were initially foreseen. Parallel to the roadmap of clinical CT technology, dedicated systems for high-resolution preclinical CT (or micro-CT) have seen a considerable growth in the last two decades, taking advantage of the modern technology of high granularity flat-panel X-ray detectors (FPD). This article aims at reviewing the milestones of the evolution of X-ray detector technology that have traced the roadmap of development of CT and micro-CT. An outlook of the current and future trends on energy resolved clinical and preclinical CT with photon counting detectors will be also given. - Highlights: • Evolution of X-ray detectors has marked the roadmap of CT technology development. • Digital flat-panel detectors have lead to the introduction of the CBCT concept. • CBCT systems with resolution below 0.1 mm are widely used in the preclinical field. • Photon-counting spectral imaging is foreseen to dominate the future of CT roadmap.

  9. Beyond BRAF(V600): clinical mutation panel testing by next-generation sequencing in advanced melanoma. (United States)

    Siroy, Alan E; Boland, Genevieve M; Milton, Denái R; Roszik, Jason; Frankian, Silva; Malke, Jared; Haydu, Lauren; Prieto, Victor G; Tetzlaff, Michael; Ivan, Doina; Wang, Wei-Lien; Torres-Cabala, Carlos; Curry, Jonathan; Roy-Chowdhuri, Sinchita; Broaddus, Russell; Rashid, Asif; Stewart, John; Gershenwald, Jeffrey E; Amaria, Rodabe N; Patel, Sapna P; Papadopoulos, Nicholas E; Bedikian, Agop; Hwu, Wen-Jen; Hwu, Patrick; Diab, Adi; Woodman, Scott E; Aldape, Kenneth D; Luthra, Rajyalakshmi; Patel, Keyur P; Shaw, Kenna R; Mills, Gordon B; Mendelsohn, John; Meric-Bernstam, Funda; Kim, Kevin B; Routbort, Mark J; Lazar, Alexander J; Davies, Michael A


    The management of melanoma has evolved owing to improved understanding of its molecular drivers. To augment the current understanding of the prevalence, patterns, and associations of mutations in this disease, the results of clinical testing of 699 advanced melanoma patients using a pan-cancer next-generation sequencing (NGS) panel of hotspot regions in 46 genes were reviewed. Mutations were identified in 43 of the 46 genes on the panel. The most common mutations were BRAFV600 (36%), NRAS (21%), TP53 (16%), BRAFNon-V600 (6%), and KIT (4%). Approximately one-third of melanomas had >1 mutation detected, and the number of mutations per tumor was associated with melanoma subtype. Concurrent TP53 mutations were the most frequent events in tumors with BRAFV600 and NRAS mutations. Melanomas with BRAFNon-V600mutations frequently harbored concurrent NRAS mutations (18%), which were rare in tumors with BRAFV600 mutations (1.6%). The prevalence of BRAFV600 and KIT mutations were significantly associated with melanoma subtypes, and BRAFV600 and TP53 mutations were significantly associated with cutaneous primary tumor location. Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600 and NRAS mutations. These results enrich our understanding of the patterns and clinical associations of oncogenic mutations in melanoma.

  10. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ


    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

  11. [Clinical use of recombinant human thrombopoietin. Status and perspectives]. (United States)

    Hansen, P B; Hasselbalch, H C


    Thrombopoietin (TPO) is primarily produced by hepatocytes and regulates the production and differentiation of megakaryocytes and platelets in the bone marrow. The endogenous TPO level is increased when the megakaryocyte count is low, and high in aplastic anaemia and after myeloablative chemotherapy. TPO is cloned and manufactured by a recombinant technique for clinical use. Treatment with recombinant human TPO (rhTPO) after intensive chemotherapy may reduce the need for platelet transfusions. Administration of granulocyte colony-stimulating factor in combination with rhTPO has enhanced the mobilisation and harvest product of haematopoietic stem cells. Whether rhTPO is effective in the treatment of the myelodysplastic syndrome, aplastic anaemia, and other conditions with bone marrow insufficiency (including AIDS) is not yet known. In liver cirrhosis, the endogenous TPO level rapidly increases after liver transplantation. Accordingly, substitution of rhTPO may be indicated in advanced liver failure complicated by thrombocytopenia and bleeding.

  12. Cogeneration power plant concepts using advanced gas turbines

    Energy Technology Data Exchange (ETDEWEB)

    Huettenhofer, K.; Lezuo, A. [Siemens Power Generation, Erlangen (Germany)


    Cogeneration of heat and power (CHP) is undeniably the environmentally most favourable way of making efficient use of energy in the power generation industry. Cogeneration is also particularly appreciated by political decision makers because of its high yield from primary energy sources, and thus its contribution to the protection of the environment and the conservation of resources. Advanced gas turbines, along with an intelligent power plant design consisting of pre-engineered, modular power plant items, will help cogeneration to play an important role in future energy markets also from an economic point of view. (orig.)

  13. Clinical Use and Mechanisms of Infliximab Treatment on Inflammatory Bowel Disease: A Recent Update


    Yuan Guo; Nonghua Lu; Aiping Bai


    The pathogenesis and treatment of inflammatory bowel disease (IBD) have been recently advanced, while it is still challenged with high morbidity and poor prognosis. Infliximab, a monoclonal antibody of tumor necrosis factor (TNF), has emerged as an efficient treatment with many clinical benefits such as quick disease activity reduction and IBD patient life quality improvement. However, the biological effects of infliximab on IBD need to be elucidated. This paper reviewed the clinical use and ...

  14. Adjuvant radiotherapy for pathologically advanced prostate cancer a randomized clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Ian, M.; Thompson, J.R.; Catherine, M.; Tangen, P.H.; Paradelo, J.; Scott Lucia, M.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E.; Crawford, E.D


    Context - Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective - To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 NO MO prostate cancer. Design, Setting, and Patients - Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention - Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures - Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results - Among the 425 men, median follow-up was 10.6 years (inter-quartile range, 9.2-12.7 years). For metastasis-free survival,76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% Cl, 0.58-1.09; P =.16). PSA relapse (median PSA relapse-free survival

  15. Uses of coercion in addiction treatment: clinical aspects. (United States)

    Sullivan, Maria A; Birkmayer, Florian; Boyarsky, Beth K; Frances, Richard J; Fromson, John A; Galanter, Marc; Levin, Frances R; Lewis, Collins; Nace, Edgar P; Suchinsky, Richard T; Tamerin, John S; Tolliver, Bryan; Westermeyer, Joseph


    Coerced or involuntary treatment comprises an integral, often positive component of treatment for addictive disorders. By the same token, coercion in health care raises numerous ethical, clinical, legal, political, cultural, and philosophical issues. In order to apply coerced care effectively, health care professionals should appreciate the indications, methods, advantages, and liabilities associated with this important clinical modality. An expert panel, consisting of the Addiction Committee of the Group for the Advancement of Psychiatry, listed the issues to be considered by clinicians in considering coerced treatment. In undertaking this task, they searched the literature using Pubmed from 1985 to 2005 using the following search terms: addiction, alcohol, coercion, compulsory, involuntary, substance, and treatment. In addition, they utilized relevant literature from published reports. In the treatment of addictions, coercive techniques can be effective and may be warranted in some circumstances. Various dimensions of coercive treatment are reviewed, including interventions to initiate treatment; contingency contracting and urine testing in the context of psychotherapy; and pharmacological methods of coercion such as disulfiram, naltrexone, and the use of a cocaine vaccine. The philosophical, historical, and societal aspects of coerced treatment are considered.

  16. Educating advanced practice nurses in using social media in rural health care. (United States)

    Rutledge, Carolyn M; Renaud, Michelle; Shepherd, Laurel; Bordelon, Michele; Haney, Tina; Gregory, Donna; Ayers, Paula


    Health care in the United States is facing a crisis in providing access to quality care for those in underserved and rural regions. Advanced practice nurses are at the forefront of addressing such issues, through modalities such as health care technology. Many nursing education programs are seeking strategies for better educating students on technology utilization. Health care technology includes electronic health records, telemedicine, and clinical decision support systems. However, little focus has been placed on the role of social media in health care. This paper describes an educational workshop using standardized patients and hands-on experiences to introduce advanced practice nurses in a Doctor of Nursing Practice program to the role of social media in addressing issues inherent in the delivery of rural health care. The students explore innovative approaches for utilizing social media for patient and caregiver support as well as identify online resources that assist providers in a rural setting.

  17. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Jiang Chen


    Full Text Available Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS, immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients.

  18. Ambulance officers' use of online clinical evidence

    Directory of Open Access Journals (Sweden)

    Westbrook Mary T


    Full Text Available Abstract Background Hospital-based clinicians have been shown to use and attain benefits from online evidence systems. To our knowledge there have been no studies investigating whether and how ambulance officers use online evidence systems if provided. We surveyed ambulance officers to examine their knowledge and use of the Clinical Information Access Program (CIAP, an online evidence system providing 24-hour access to information to support evidence-based practice. Methods A questionnaire was completed by 278 ambulance officers in New South Wales, Australia. Comparisons were made between those who used CIAP and officers who had heard of, but not used CIAP. Results Half the sample (48.6% knew of, and 28.8% had used CIAP. Users were more likely to have heard of CIAP from a CIAP representative/presentation, non-users from written information. Compared to ambulance officers who had heard of but had not used CIAP, users were more likely to report better computer skills and that their supervisors regarded use of CIAP as a legitimate part of ambulance officers' clinical role. The main reasons for non-use were lack of access(49.0% and training(31.4%. Of users, 51.3% rated their skills at finding information as good/very good, 67.5% found the information sought all/most of the time, 87.3% believed CIAP had the potential to improve patient care and 28.2% had directly experienced this. Most access to CIAP occurred at home. The databases frequently accessed were MIMS (A medicines information database (73.8% and MEDLINE(67.5%. The major journals accessed were Journal of Emergency Nursing(37.5%, American Journal of Medicine(30.0% and JAMA(27.5%. Conclusion Over half of ambulance officers had not heard of CIAP. The proportion who knew about and used CIAP was also low. Reasons for this appear to be a work culture not convinced of CIAP's relevance to pre-hospital patient care and lack of access to CIAP at work. Ambulance officers who used CIAP accessed it

  19. Directions for advanced use of nuclear power in century XXI

    Energy Technology Data Exchange (ETDEWEB)

    Walter, C E


    Nuclear power can provide a significant contribution to electricity generation and meet other needs of the world and the US during the next century provided that certain directions are taken to achieve its public acceptance. These directions include formulation of projections of population, energy consumption, and energy resources over a responsible period of time. These projections will allow assessment of cumulative effects on the environment and on fixed resources. Use of fossil energy resources in a century of growing demand for energy must be considered in the context of long-term environmental damage and resource depletion. Although some question the validity of these consequences, they can be mitigated by use of advanced fast reactor technology. It must be demonstrated that nuclear power technology is safe, resistant to material diversion for weapon use, and economical. An unbiased examination of all the issues related to energy use, especially of electricity, is an essential direction to take.

  20. [Rationale for using nabumetone and clinical experience]. (United States)

    Roth, S H


    Nabumetone's position as one of the most commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) in the world today is based upon over a decade of clinical experience. The popularity of this drug lies in both its unique pharmacokinetic profile and special safety features in pharmacodynamic terms. This nonacidic prodrug with an active 6-methoxy-2-naphthylacetic acid (6-MNA) metabolite has COX-2 preferential features and is also devoid of enterohepatic recirculation. It is felt that these characteristics have provided the basis for its unique long term tolerability, documented in various at-risk osteoarthritis and rheumatoid arthritis populations. The excellent tolerability of nabumetone and its 24-hour half-life, which provides the advantages of a once-daily dosage regimen, make it uniquely suitable for long term anti-inflammatory therapy in arthritis. The tolerability profile of nabumetone has also demonstrated clear cost-effectiveness advantages, as confirmed by comparative and epidemiological studies. Selective COX-2 NSAIDs are likely to prove more expensive because of the increasing costs and demands of clinical research prior to FDA approval. These higher costs may limit and influence patient access, depending on the healthcare delivery system, and many years of experience will be required to document the putative tolerability advantages of these newer COX-2 inhibitor agents. In the meantime, it is comforting that nabumetone has established such an advantageous tolerability profile together with acknowledged efficacy.

  1. Recent advances in iterative reconstruction for clinical SPECT/PET and CT

    Energy Technology Data Exchange (ETDEWEB)

    Hutton, Brian F. (Inst. of Nuclear Medicine, Univ. College London, London (United Kingdom)), e-mail:


    Statistical iterative reconstruction is now widely used in clinical practice and has contributed to significant improvement in image quality in recent years. Although primarily used for reconstruction in emission tomography (both single photon emission computed tomography (SPECT) and positron emission tomography (PET)) there is increasing interest in also applying similar algorithms to x-ray computed tomography (CT). There is increasing complexity in the factors that are included in the reconstruction, a demonstration of the versatility of the approach. Research continues with exploration of methods for further improving reconstruction quality with effective correction for various sources of artefact

  2. Clinical challenges in HIV/AIDS: Hints for advancing prevention and patient management strategies. (United States)

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


    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.

  3. Beyond research: a primer for considerations on using viral metagenomics in the field and clinic

    NARCIS (Netherlands)

    Hall, Richard J; Draper, Jenny L; Nielsen, Fiona G G; Dutilh, Bas E


    Powered by recent advances in next-generation sequencing technologies, metagenomics has already unveiled vast microbial biodiversity in a range of environments, and is increasingly being applied in clinics for difficult-to-diagnose cases. It can be tempting to suggest that metagenomics could be used

  4. A Conceptual Venus Rover Mission Using Advanced Radioisotope Power Systems (United States)

    Evans, Michael; Shirley, James H.; Abelson, Robert Dean


    This concept study demonstrates that a long lived Venus rover mission could be enabled by a novel application of advanced RPS technology. General Purpose Heat Source (GPHS) modules would be employed to drive an advanced thermoacoustic Stirling engine, pulse tube cooler and linear alternator that provides electric power and cooling for the rover. The Thermoacoustic Stirling Heat Engine (TASHE) is a system for converting high-temperature heat into acoustic power which then drives linear alternators and a pulse tube cooler to provide both electric power and coolin6g for the rover. A small design team examined this mission concept focusing on the feasibility of using the TASHE system in this hostile environment. A rover design is described that would provide a mobile platform for science measurements on the Venus surface for 60 days, with the potential of operating well beyond that. A suite of science instruments is described that collects data on atmospheric and surface composition, surface stratigraphy, and subsurface structure. An Earth-Venus-Venus trajectory would be used to deliver the rover to a low entry angle allowing an inflated ballute to provide a low deceleration and low heat descent to the surface. All rover systems would be housed in a pressure vessel in vacuum with the internal temperature maintained by the TASHE at under 50 °C.

  5. Introduction to the special issue on advances in clinical and health-care knowledge management. (United States)

    Bali, Rajeev K; Feng, David Dagan; Burstein, Frada; Dwivedi, Ashish N


    Clinical and health-care knowledge management (KM) as a discipline has attracted increasing worldwide attention in recent years. The approach encompasses a plethora of interrelated themes including aspects of clinical informatics, clinical governance, artificial intelligence, privacy and security, data mining, genomic mining, information management, and organizational behavior. This paper introduces key manuscripts which detail health-care and clinical KM cases and applications.

  6. Clinical usefulness of hemoencephalography beyond the neurofeedback

    Directory of Open Access Journals (Sweden)

    Serra-Sala M


    Full Text Available Mireia Serra-Sala,1–3 Carme Timoneda-Gallart,1–3 Frederic Pérez-Álvarez1,2,4 1Fundació Carme Vidal NeuroPsicoPedagogia, 2Institut Recerca Qualitat de Vida Universitat de Girona, 3Facultat Educació Psychology University of Girona, 4Pediatric and Behavioral Neurology, University Hospital Doctor Josep Trueta, Girona, Spain Aim: Hemoencephalography (HEG is an emerging procedure for clinical application in attention-deficit hyperactivity disorder and other disorders, regardless of age. It is available to any research group for its relative simplicity and low cost and is a useful tool for assessing prefrontal-dependent functions. Older teenagers pose peculiarities in the prefrontal maturation, and we aim to establish HEG patterns that might have clinical applicability. Methods: The HEG patterns of 70 university students (56 women and 14 men, 21–48 years old, mean 31.84, SD 10.65, standard error of mean 0.31 were compared with those of 59 adolescents – 13–14-year-old secondary education students, 28 females and 31 males. The HEG patterns were obtained in response to the observation of shocking, unpleasant, and pleasant pictures. We use one-way and two-way analysis of variance to disentangle the differences between groups. All effects were analyzed with F-tests. Results: In all cases, university students and adolescents showed a decrease in prefrontal activity, indicative of differences in the emotional inner networks between groups, which are responsible for security–insecurity processing. Compared with university students, adolescents showed statistically significant differences in decreased activity in very unpleasant (shocking tests that demand increased security–insecurity processing. Adolescents showed lower decrease. In addition, adolescents, compared with university subjects, did not show statistically significantly decreased HEG activity compared with the baseline in very unpleasant tests. Conclusion: Teens showed

  7. A review on the clinical uses of SPECT/CT

    Energy Technology Data Exchange (ETDEWEB)

    Mariani, Giuliano; Bruselli, Laura [University of Pisa Medical School, Regional Center of Nuclear Medicine, Pisa (Italy); Kuwert, Torsten [Friedrich-Alexander-University, Clinic of Nuclear Medicine, Erlangen-Nuremberg (Germany); Kim, Edmund E. [MD Anderson Cancer Center, Nuclear Medicine Service, Houston, TX (United States); Flotats, Albert [Universitat Autonoma de Barcelona, Hospital de Sant Pau, Nuclear Medicine Department, Barcelona (Spain); Israel, Ora [Rambam Health Care Campus, Department of Nuclear Medicine, Haifa (Israel); Dondi, Maurizio [International Atomic Energy Agency, Nuclear Medicine Section, Division of Human Health, Vienna (Austria); Watanabe, Naoyuki [International Atomic Energy Agency, Nuclear Medicine Section, Division of Human Health, Vienna (Austria); Gunma Prefectural College of Health Sciences, Department of Radiological Technology, Gunma (Japan)


    In the era when positron emission tomography (PET) seems to constitute the most advanced application of nuclear medicine imaging, still the conventional procedure of single photon emission computed tomography (SPECT) is far from being obsolete, especially if combined with computed tomography (CT). In fact, this dual modality imaging technique (SPECT/CT) lends itself to a wide variety of useful diagnostic applications whose clinical impact is in most instances already well established, while the evidence is growing for newer applications. The increasing availability of new hybrid SPECT/CT devices with advanced technology offers the opportunity to shorten acquisition time and to provide accurate attenuation correction and fusion imaging. In this review we analyse and discuss the capabilities of SPECT/CT for improving sensitivity and specificity in the imaging of both oncological and non-oncological diseases. The main advantages of SPECT/CT are represented by better attenuation correction, increased specificity, and accurate depiction of the localization of disease and of possible involvement of adjacent tissues. Endocrine and neuroendocrine tumours are accurately localized and characterized by SPECT/CT, as also are solitary pulmonary nodules and lung cancers, brain tumours, lymphoma, prostate cancer, malignant and benign bone lesions, and infection. Furthermore, hybrid SPECT/CT imaging is especially suited to support the increasing applications of minimally invasive surgery, as well as to precisely define the diagnostic and prognostic profile of cardiovascular patients. Finally, the applications of SPECT/CT to other clinical disorders or malignant tumours is currently under extensive investigation, with encouraging results in terms of diagnostic accuracy. (orig.)

  8. Advance of Cellular Immunotherapy in Clinical and Translational Medicine of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Fei; YU Shao-rong; FENG Ji-feng


    Lung cancer is one of the most common cancers and ranks the ifrst in the mortality worldwide. The core of immunotherapy, especially cellular immunotherapy, is to activate the T cell-mediated tumor-killing effect in patients with tumors, so as to increase their anti-tumor effect. Surgery and radio- and chemotherapy cannot radically eliminate cancerous cells, but immunotherapy is an important supplementary method in killing tumor stem cells and non-proliferating cells. Cellular immunotherapy contains dendritic cells (DC), cytokine-induced killer (CIK), DC-CIK, natural killer T cells (NKT) and γδ T cells, which provides new techniques for the comprehensive treatment of lung cancer. Using CIK combined with DC, radiochemotherapy, radiofrequency ablation and monomers of Chinese medicine to induce CIK cells that directionally migrate to cancerous nest can increase tumor-killing ability and immunoregulatory ability of CIK cells, reduce adverse and toxic reactions and increase patients’ quality of life, and NKT cell and γδ T cell therapies have also been gradually perfected and promoted in clinical translation. This study mainly introduced the clinical translation of DC vaccines, CIK cells and DC-CIK treatment for lung cancer, hoping to provide new pathways and reference for the clinical treatment of lung cancer.

  9. Nuclear magnetic resonance based metabolomics and liver diseases: Recent advances and future clinical applications. (United States)

    Amathieu, Roland; Triba, Mohamed Nawfal; Goossens, Corentine; Bouchemal, Nadia; Nahon, Pierre; Savarin, Philippe; Le Moyec, Laurence


    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".

  10. Study on advancement of in vivo counting using mathematical simulation

    CERN Document Server

    Kinase, S


    To obtain an assessment of the committed effective dose, individual monitoring for the estimation of intakes of radionuclides is required. For individual monitoring of exposure to intakes of radionuclides, direct measurement of radionuclides in the body - in vivo counting- is very useful. To advance in a precision in vivo counting which fulfills the requirements of ICRP 1990 recommendations, some problems, such as the investigation of uncertainties in estimates of body burdens by in vivo counting, and the selection of the way to improve the precision, have been studied. In the present study, a calibration technique for in vivo counting application using Monte Carlo simulation was developed. The advantage of the technique is that counting efficiency can be obtained for various shapes and sizes that are very difficult to change for phantoms. To validate the calibration technique, the response functions and counting efficiencies of a whole-body counter installed in JAERI were evaluated using the simulation and m...

  11. Advanced methods of microscope control using μManager software

    Directory of Open Access Journals (Sweden)

    Arthur D Edelstein


    Full Text Available µManager is an open-source, cross-platform desktop application, to control a wide variety of motorized microscopes, scientific cameras, stages, illuminators, and other microscope accessories. Since its inception in 2005, µManager has grown to support a wide range of microscopy hardware and is now used by thousands of researchers around the world. The application provides a mature graphical user interface and offers open programming interfaces to facilitate plugins and scripts. Here, we present a guide to using some of the recently added advanced µManager features, including hardware synchronization, simultaneous use of multiple cameras, projection of patterned light onto a specimen, live slide mapping, imaging with multi-well plates, particle localization and tracking, and high-speed imaging.

  12. Clinical review: surgical management of locally advanced and recurrent colorectal cancer.

    LENUS (Irish Health Repository)

    Courtney, D


    Recurrent and locally advanced colorectal cancers frequently require en bloc resection of involved organs to achieve negative margins. The aim of this review is to evaluate the most current literature related to the surgical management of locally advanced and recurrent colorectal cancer.

  13. Topical corticosteroids: clinical pharmacology and therapeutic use. (United States)

    Miller, J A; Munro, D D


    The development of topical corticosteroids has enabled many dermatoses to be more effectively treated than previously, but there is also no doubt that misuse of these preparations can lead to troublesome local effects and potentially serious systemic problems. The most effective assay for comparing different compounds has been their vasoconstrictive activity, and this on the whole correlates well with clinical effect. To be effective, corticosteroid must be absorbed and the importance of concentration, occlusion, the type of vehicle, added penetrants such as urea and the anatomical site, on the amount of absorption and therefore on clinical activity has been demonstrated. Ointments have been shown to be more effective than creams but because of the considerable choice of potencies now available most dermatologists tend to prescribe the different formulations according to the wishes of the patient. For the same reason, dilution of the commercially marketed preparations is now not generally recommended. The main therapeutic activity of topical corticosteroids is their nonspecific anti-inflammatory effect, thought to be primarily a result of their action on the chemical mediators of inflammation. They have also been shown to be antimitotic which may well be relevant not only to the treatment of scaling dermatoses but also to their dermal thinning effect resulting from inhibition of fibroblasts. Combinations of corticosteroids with antibacterial and antifungal agents have been shown to be very effective in flexural eruptions and secondarily infected dermatoses. As a general rule, the use of topical corticosteroids in outpatients, unless badly misused, is not associated with any significant risk of adrenal axis suppression, but care must be exercised as to the amount prescribed, especially if large areas of the body are to be treated with highly potent preparations. Certain groups such as young children and patients with liver failure, and certain anatomical sites such

  14. Impact of individualized learning plans on United States senior medical students advanced clinical rotations

    Directory of Open Access Journals (Sweden)

    Amalia Guardiola


    Full Text Available The individualized learning plan (ILP is a tool that promotes self-directed learning. The aim of this pilot study was to look at the perception of the ILPs in United States senior medical school students as a way to improve their learning experience during their advanced practice clerkship. We conducted a survey of graduating medical students that contained both quantitative and open-ended questions regarding the students’ experiences with the ILP during their advanced practice clerkship from July 2014 to March 2016. We systematically identified and compiled themes among the qualitative responses. Responses from 294 out of 460 subjects were included for analysis (63.9%. Ninety students (30.6% reported that the ILP was definitely reviewed at the midpoint and 88 (29.9% at the final evaluation. One hundred sixty one students (54.8% felt the ILP provided a framework for learning. One hundred sixty one students (61.6% felt it was a useful tool in helping open a discussion between the student and faculty. The qualitative data was grouped by areas most mentioned and these areas of concern centered on lack of faculty knowledge about ILP, time to complete ILP, and uncertainty of appropriate goal setting. The majority of students perceive the ILP to be helpful. Our results suggest that active intervention is needed by dedicated and trained faculty to improve ILP utilization. It is recommended that faculty gives students examples of learning goals to create their own learning framework and encourages them to discuss and review the ILP.

  15. Clinical Education, the lessons learned from practical applications - Albanian issues, East Europe and the advanced international practices on Clinical Education

    Directory of Open Access Journals (Sweden)

    Alban Koci


    In legal clinics, students perform various tasks just as an attorney would do in the same job position, such as doing legal research, drafting briefs and other legal documents, and interviewing clients. Many jurisdictions even allow students to appear in court on behalf of clients, even in criminal defense. Legal clinics is part of the academic law program in the most of the law faculties all over the world and it has a great impact in the community’s life. Throughout legal clinics students not only get the opportunity to be part of an important experience, but also they can be effective and help the people in need with their work. This paper aims to bring attention to the importance of clinical education in the formation of young lawyers and how one can learn from experience. There will be discussed important issues about legal clinic, the objectives and its mission, how to apply it and the benefits legal clinic brings not only for the academic area but also for the society.

  16. The clinical implication of cancer-associated microvasculature and fibroblast in advanced colorectal cancer patients with synchronous or metachronous metastases.

    Directory of Open Access Journals (Sweden)

    Yoonjin Kwak

    Full Text Available BACKGROUND: We aimed to evaluate the clinical significance of microvessel density (MVD, lymphatic vessel density (LVD, and cancer-associated fibroblasts (CAFs in relation to tumor location in advanced colorectal cancer (CRC. METHODS: Using immunohistochemistry, we examined 181 advanced CRC patients for CD31 and D2-40 to measure MVD and LVD, respectively, α-smooth muscle actin (SMA and desmin to identify CAFs, and PTEN to examine genetic changes of CAFs. To evaluate the regional heterogeneity of these properties, we examined tissue from four sites (the center and periphery of the primary cancer, a distant metastasis, and a lymph node metastasis in each patient. RESULTS: MVD, LVD, and CAFs showed significant heterogeneity with respect to the tumor location. LVD was the greatest in the center of the primary cancers and the amount of CAFs was the lowest in distant metastases. In distant metastases, those from the lung had higher LVD and MVD, but fewer CAFs than those from the liver, peritoneum, or ovary. Patients with low MVD and LVD in the center of the primary cancer had worse outcomes and patients with few CAFs in distant metastases and in the primary tumor had a lower survival rate. PTEN expression in CAFs in distant metastases was lost in 11 of 181 CRC patients (6.1%, which was associated with a worse prognosis. CONCLUSIONS: The microenvironment, including cancer-associated microvasculature and fibroblasts, is heterogeneous with respect to the tumor location in CRC patients. Therefore, heterogeneity of microenvironments should be taken into account when managing CRC patients.

  17. GMP facilities for manufacturing of advanced therapy medicinal products for clinical trials: an overview for clinical researchers. (United States)

    Alici, Evren; Blomberg, Pontus


    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.


    Directory of Open Access Journals (Sweden)

    Zoltan KATO


    Full Text Available By purchasing a plane ticket or a cargo service, the passenger or the customer signs a contract with the airline company. From that moment on the airline company is responsible for all aspects of air travel, including the passenger' luggage (recording, handling to / from the aircraft etc.. Safe transport of passengers' luggage or cargo packages on airlines raises numerous problems for airlines and requires flexible, efficient solutions, appropriate to the specific requirements of each client. Annually millions of luggages get lost in airports around the world. This causes inconvenience to passengers and loss of resources and additional costs for the airlines. The aim of this paper is to examine how RFID(Radio Frequency Identification technology could be useful for advanced shipment tracking (Track and Trace in the airlines industry, by using rewritable passive RFID tags.

  19. Recent Advances on the Technologies to Increase Fertilizer Use Efficiency

    Institute of Scientific and Technical Information of China (English)

    YAN Xiang; JIN Ji-yun; HE Ping; LIANG Ming-zao


    To increase fertilizer use efficiency (FUE) and to minimize its negative impact on environment have been the focal points in the world for a long time. It is very important to increase FUE in China for its relatively low FUE and serious losses of nutrients. Recent advances of the technologies to increase FUE are reviewed in this article. These include site-specific and real-time nitrogen management, non-destructive quick test of the nitrogen status of plants, new types of slow release and controlled release fertilizers, site-specific nutrient management, and use of urease inhibitor and nitrification inhibitor to decrease nitrogen losses. Future outlook in technologies related to FUE improvement is also discussed.

  20. Developing novel 3D antennas using advanced additive manufacturing technology (United States)

    Mirzaee, Milad

    In today's world of wireless communication systems, antenna engineering is rapidly advancing as the wireless services continue to expand in support of emerging commercial applications. Antennas play a key role in the performance of advanced transceiver systems where they serve to convert electric power to electromagnetic waves and vice versa. Researchers have held significant interest in developing this crucial component for wireless communication systems by employing a variety of design techniques. In the past few years, demands for electrically small antennas continues to increase, particularly among portable and mobile wireless devices, medical electronics and aerospace systems. This trend toward smaller electronic devices makes the three dimensional (3D) antennas very appealing, since they can be designed in a way to use every available space inside the devise. Additive Manufacturing (AM) method could help to find great solutions for the antennas design for next generation of wireless communication systems. In this thesis, the design and fabrication of 3D printed antennas using AM technology is studied. To demonstrate this application of AM, different types of antennas structures have been designed and fabricated using various manufacturing processes. This thesis studies, for the first time, embedded conductive 3D printed antennas using PolyLactic Acid (PLA) and Acrylonitrile Butadiene Styrene (ABS) for substrate parts and high temperature carbon paste for conductive parts which can be a good candidate to overcome the limitations of direct printing on 3D surfaces that is the most popular method to fabricate conductive parts of the antennas. This thesis also studies, for the first time, the fabrication of antennas with 3D printed conductive parts which can contribute to the new generation of 3D printed antennas.

  1. Clinical usefulness of trypsin radioimmunoassay kit

    Energy Technology Data Exchange (ETDEWEB)

    Kanamori, Isao; Nakano, Satoshi; Hurukawa, Masakazu; Okumura, Yasuki; Higuchi, Chizuko; Yanase, Mikiko; Onogi, Michiteru


    From the clinical use of RIA-gnost trypsin kit, the following results were obtained. 1. Standard curve showed a steep and good curve was shown. 2. Incubation: The condition for the first incubation was set at the room temperature for 10-24 hours and that for the second incubation at the room temperature for 3-5 hours. With these settings, satisfactory results were obtained. 3. Reproducibility and recovery: The C.V. of the reproducibility and the recovery were considered superior, and the values were below 10 % and +-3 %, respectively. 4. Correlation between trypsin and serum elestase-1: An excellent positive correlation (coefficient of correlation r = 0.889) was shown. 5. Serum trypsin concentration of normal and pancreatic diseases: The normal range was from 100 to 500 ng/ml. Acute pancreatitis rose obviously. Diabetes mellitus and chronic pancreatitis was below 500 ng/ml and the pancreatic cancer showed a tendency to scatter in the range of 50-1 250 ng/ml. The above results indicated that serum trypsin can be easily measured with high precision by using this method. Thus the method is considered useful for the diagnosis of pancreatic diseases.

  2. Clinical Uses of Melatonin in Pediatrics

    Directory of Open Access Journals (Sweden)

    Emilio J. Sánchez-Barceló


    Full Text Available This study analyzes the results of clinical trials of treatments with melatonin conducted in children, mostly focused on sleep disorders of different origin. Melatonin is beneficial not only in the treatment of dyssomnias, especially delayed sleep phase syndrome, but also on sleep disorders present in children with attention-deficit hyperactivity, autism spectrum disorders, and, in general, in all sleep disturbances associated with mental, neurologic, or other medical disorders. Sedative properties of melatonin have been used in diagnostic situations requiring sedation or as a premedicant in children undergoing anesthetic procedures. Epilepsy and febrile seizures are also susceptible to treatment with melatonin, alone or associated with conventional antiepileptic drugs. Melatonin has been also used to prevent the progression in some cases of adolescent idiopathic scoliosis. In newborns, and particularly those delivered preterm, melatonin has been used to reduce oxidative stress associated with sepsis, asphyxia, respiratory distress, or surgical stress. Finally, the administration of melatonin, melatonin analogues, or melatonin precursors to the infants through the breast-feeding, or by milk formula adapted for day and night, improves their nocturnal sleep. Side effects of melatonin treatments in children have not been reported. Although the above-described results are promising, specific studies to resolve the problem of dosage, formulations, and length of treatment are necessary.

  3. Efficacy and toxicity in brain tumor treatment - quantitative Measurements using advanced MRI

    DEFF Research Database (Denmark)

    Ravn, Søren


    and are now being used for presurgical and radiation therapy (RT) planning. More advanced MRI sequences have gained attention. Sequences such as diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and functional magnetic resonance imaging (fMRI) have entered the clinical world concurrently......From the clinical introduction in the 1980s, MRI has grown to become an indispensable brain imaging modality, mainly due to its excellent ability to visualize soft tissues. Morphologically, T1- and T2-weighted brain tumor MRI have been part of routine diagnostic radiology for more than two decades...... with the introduction of magnets with higher field strength. Ongoing technical development has enabled a change from semiquantitative measurements to a true quantitative approach. This step is expected to have a great impact on the treatment of brain tumor patients in the future. The aim of this Ph.D. dissertation...

  4. Pulmonary hyperpolarized noble gas MRI: Recent advances and perspectives in clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zaiyi [Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Department of Radiology, Guangdong General Hospital Guangdong Academy of Medical Sciences (China); Araki, Tetsuro, E-mail: [Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Okajima, Yuka [Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States); Albert, Mitchell [Hyperpolarized Gas MRI Laboratory, Thunder Bay Regional Research Institute, Lakehead University (Canada); Hatabu, Hiroto [Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women' s Hospital, Harvard Medical School, Boston (United States)


    The invention of hyperpolarized (HP) noble gas MRI using helium-3 ({sup 3}He) or xenon-129 ({sup 129}Xe) has provided a new method to evaluate lung function. Using HP {sup 3}He or {sup 129}Xe for inhalation into the lung air spaces as an MRI contrast agent significantly increases MR signal and makes pulmonary ventilation imaging feasible. This review focuses on important aspects of pulmonary HP noble gas MRI, including the following: (1) functional imaging types, (2) applications for major pulmonary diseases, (3) safety considerations, and (4) future directions. Although it is still challenging to use pulmonary HP noble gas MRI clinically, the technology offers promise for the investigation of the microstructure and function of the lungs.

  5. Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

    Directory of Open Access Journals (Sweden)

    Dollinger Matthias M


    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12 were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS, time to progression (TTP, tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC formed part of the protocol. Results Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6] or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]. Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. Trial Registration Current Controlled Trials ISRCTN64487365.

  6. Leveraging effective clinical registries to advance medical care quality and transparency. (United States)

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


    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.

  7. Advanced Aqueous Phase Catalyst Development using Combinatorial Methods Project (United States)

    National Aeronautics and Space Administration — Combinatorial methods are proposed to develop advanced Aqueous Oxidation Catalysts (AOCs) with the capability to mineralize organic contaminants present in effluents...

  8. Recent advances using immunomodulators for inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Bjerrum, Jacob Tveiten; Herfarth, Hans


    Use of the immunomodulators thiopurines and methotrexate (MTX) in the treatment of inflammatory bowel disease (IBD), i.e., Crohn's disease and ulcerative colitis (UC), is considered to be good clinical practice. However, despite being administered to a considerable number of IBD patients over the...... on pharmacokinetics, pharmacogenetics, and therapeutic blood testing, as well as the occurrence of adverse events, when using AZA, 6-MP, and MTX in an attempt to determine a more up-to-date and rational treatment regimen in IBD....

  9. 21 CFR 888.4210 - Cement mixer for clinical use. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cement mixer for clinical use. 888.4210 Section... (CONTINUED) MEDICAL DEVICES ORTHOPEDIC DEVICES Surgical Devices § 888.4210 Cement mixer for clinical use. (a) Identification. A cement mixer for clinical use is a device consisting of a container intended for use in...

  10. Channel Estimation using Adaptive Filtering for LTE-Advanced

    Directory of Open Access Journals (Sweden)

    Saqib Saleem


    Full Text Available For demand of high data rates, enhanced system capacity and coverage, ITU made proposal for the standardization of next generation wireless communication systems, known as IMT-Advanced. To achieve these targets, a priori knowledge of the channel is required at the transmitter side. In this paper, three adaptive channel estimation techniques: Least Mean Square (LMS, Recursive Least Square (RLS and Kalman-Filtering Based, are compared in terms of performance and complexity. For performance, Mean Square Error (MSE and Symbol Error Rate (SER while for complexity, computational time is measured for variable channel impulse response (CIR lengths and channel taps. MATLAB Monte-Carlo Simulations are used to evaluate these techniques.

  11. Mars Atmospheric Characterization Using Advanced 2-Micron Orbiting Lidar (United States)

    Singh, U.; Engelund, W.; Refaat, T.; Kavaya, M.; Yu, J.; Petros, M.


    Mars atmospheric characterization is critical for exploring the planet. Future Mars missions require landing massive payloads to the surface with high accuracy. The accuracy of entry, descent and landing (EDL) of a payload is a major technical challenge for future Mars missions. Mars EDL depends on atmospheric conditions such as density, wind and dust as well as surface topography. A Mars orbiting 2-micron lidar system is presented in this paper. This advanced lidar is capable of measuring atmospheric pressure and temperature profiles using the most abundant atmospheric carbon dioxide (CO2) on Mars. In addition Martian winds and surface altimetry can be mapped, independent of background radiation or geographical location. This orbiting lidar is a valuable tool for developing EDL models for future Mars missions.

  12. Water quality management of aquifer recharge using advanced tools. (United States)

    Lazarova, Valentina; Emsellem, Yves; Paille, Julie; Glucina, Karl; Gislette, Philippe


    Managed aquifer recharge (MAR) with recycled water or other alternative resources is one of the most rapidly growing techniques that is viewed as a necessity in water-short areas. In order to better control health and environmental effects of MAR, this paper presents two case studies demonstrating how to improve water quality, enable reliable tracing of injected water and better control and manage MAR operation in the case of indirect and direct aquifer recharge. Two water quality management strategies are illustrated on two full-scale case studies, including the results of the combination of non conventional and advanced technologies for water quality improvement, comprehensive sampling and monitoring programs including emerging pollutants, tracer studies using boron isotopes and integrative aquifer 3D GIS hydraulic and hydrodispersive modelling.

  13. Recent advances in studies of meteorites using cosmogenic radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Reedy, Robert C. E-mail:


    The use of accelerator mass spectrometry (AMS) to measure cosmogenic radionuclides in meteorites has greatly enabled studies of cosmic-ray exposure histories. The high sensitivity of AMS has allowed measurements of samples that are very small or have very low activities. AMS measurements have much better accuracy and precision than usually possible with decay counting. AMS allows the routine measurements of many long-lived radionuclides, including some with half-lives not regularly measured previously or some made by neutron-capture reactions (such as {sup 36}Cl, {sup 41}Ca and {sup 59}Ni). These advancements have enabled many meteorite studies that previously were not often done, such as terrestrial ages. All aspects of a meteorite's cosmic-ray exposure history, its ages and geometries, now can be better studied.

  14. Mechanisms and clinical uses of capsaicin. (United States)

    Sharma, Surinder Kumar; Vij, Amarjit Singh; Sharma, Mohit


    Capsaicin is the active ingredient of chili peppers and gives them the characteristic pungent flavor. Understanding the actions of capsaicin led to the discovery of its receptor, transient receptor potential vanilloid subfamily member 1 (TRPV1). This receptor is found on key sensory afferents, and so the use of capsaicin to selectively activate pain afferents has been studied in animal and human models for various indications. Capsaicin is unique among naturally occurring irritant compounds because the initial neuronal excitation evoked by it is followed by a long-lasting refractory period, during which the previously excited neurons are no longer responsive to a broad range of stimuli. This process known as defunctionalisation has been exploited for therapeutic use of capsaicin in various painful conditions. We reviewed different studies on mechanisms of action of capsaicin and its utility in different clinical conditions. A beneficial role of capsaicin has been reported in obesity, cardiovascular and gastrointestinal conditions, various cancers, neurogenic bladder, and dermatologic conditions. Various theories have been put forth to explain these effects. Interestingly many of these pharmacological actions are TRPV1 independent. This review is aimed at providing an overview of these mechanisms and to also present literature which contradicts the proposed beneficial effects of capsaicin. Most of the literature comes from animal studies and since many of these mechanisms are poorly understood, more investigation is required in human subjects.

  15. Memantine: Pharmacological properties and clinical uses

    Directory of Open Access Journals (Sweden)

    Kumar Sudhir


    Full Text Available Memantine is a relatively new drug specially developed for use in moderate-to-severe dementia. It is an uncompetitive N-methyl-D-aspartate receptor antagonist and reduces glutamatergic excitotoxicity. Though Alzheimer's disease (AD is the commonest cause of dementia in the world, there is no 'cure' available for the same. Cholinesterase inhibitors such as donepezil and rivastigmine have been shown to provide symptomatic relief in patients with AD but have no effect on disease progression or survival. Moreover, they are not helpful in more severe stages of dementia. Memantine has been shown to cause modest improvement in clinical symptoms in severe stages of AD and may retard the disease progression. Moreover, it has been shown to be useful in various forms of dementia including AD, vascular dementia and Wernicke-Korsakoff psychosis. It is also the first drug to cause complete disappearance of pendular nystagmus due to multiple sclerosis. The current review focuses on the pharmacological properties of memantine and examines the recent evidence in favor of memantine.

  16. A novel dentifrice technology for advanced oral health protection: A review of technical and clinical data. (United States)

    Baig, Arif; He, Tao


    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.

  17. Recent advances of liquid chromatography-(tandem) mass spectrometry in clinical and forensic toxicology - An update. (United States)

    Remane, Daniela; Wissenbach, Dirk K; Peters, Frank T


    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.

  18. Clinical Comparison of Subepithelial Connective Tissue Grafts and Coronally Advanced Flaps with Emdogain in the Treatment of Gingival Recessions

    Directory of Open Access Journals (Sweden)

    F. Haghighati


    Full Text Available Objective: The aim of this study was to compare subepithelial connective tissue grafts (SCTG and coronally advanced flaps (CAF with the addition of Emdogain in the treatment of gingival recession.Materials and Methods: This interventional randomized controlled clinical trial involved eleven patients and 31 teeth demonstrating facial recessions of > 2 mm identified as Miller’s class I or II. Recession depth (RD, recession width (RW, probing depth (PD, clinical attachment level (CAL, and keratinized tissue (KT, weremeasured at baseline and at 4, 12 and 24 weeks postoperation. Before surgery the samples were randomized to receive either a CAF with Emdogain (test group or a connective tissue graft (control group. Data were analyzed using independent t-test and univariate analysis of variance.Results: Twenty-four weeks after therapy, the mean root coverage in the test and control cases was 50.24% and 65.82%, respectively. There was no significant difference between the two groups (P=0.759. Within the 24-week follow-up period both procedures resulted in statistically significant improvement in RD, RW and CAL, but not in PD. KT increased 0.7 mm in the SCTG group while it decreased 0.5 mm in the Emdogain group (P<0.05.Conclusion: The SCTG procedure provided better results in comparison to CAF with Emdogain. However the later method is easier and less technique-sensitive. Therefore it can be considered as a possible substitute for the treatment of gingival recessions,especially when increasing KT is not required.

  19. Clinical retrospective analysis of erlotinib in the treatment of elderly patients with advanced non-small cell lung cancer. (United States)

    Platania, Marco; Agustoni, Francesco; Formisano, Barbara; Vitali, Milena; Ducceschi, Monika; Pietrantonio, Filippo; Zilembo, Nicoletta; Gelsomino, Francesco; Pusceddu, Sara; Buzzoni, Roberto


    In order to evaluate the clinical efficacy and the safety profile of molecularly targeted therapies as a palliative approach in elderly populations affected by advanced thoracic neoplasms, we retrospectively studied, in terms of effectiveness and toxicities, a group of pretreated elderly metastatic non-small cell lung cancer (NSCLC) patients admitted to our institution and treated with erlotinib at standard daily/dose. Forty-three patients aged 70 years or older who had previously failed on chemotherapy or radiotherapy were treated with oral Eerlotinib (150 mg/d) until disease progression or unacceptable toxicity. Clinical data, pathological types, potential prognostic factors, efficacy and toxicity of erlotinib were included in this analysis. In our series we observed: objective responses in six patients (14%) and stable disease in 15 (35%). Skin rash was the most common side effect (67%). Grade 3-4 adverse events were observed in 16 cases (37%). The median overall survival and the median progression-free survival were 8.4 months (CI 95%: 0.7-43.6) and 3 months (CI 95%: 0.4-28.4), respectively. Patients with adenocarcinoma achieved the best disease control rate (p = 0.027), while not/former smokers showed a better response (p = 0.069). In our experience the use of erlotinib after chemotherapy failure in an unselected elderly population affected by NSCLC showed moderate efficacy and a moderate safety profile. However, erlotinib represents a valid option in this setting, but other factors such as biological information, comorbidities and concomitant medications need to be carefully take into consideration in this particular subset of cancer patients.

  20. Pharmacogenetics of Cytochrome P450 2B6 (CYP2B6: Advances on Polymorphisms, Mechanisms, and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ulrich M Zanger


    Full Text Available 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 nongenetic 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 to 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

  1. FBXW7 mutations in patients with advanced cancers: clinical and molecular characteristics and outcomes with mTOR inhibitors.

    Directory of Open Access Journals (Sweden)

    Denis L Jardim

    Full Text Available PURPOSE: FBXW7 is a tumor suppressor gene responsible for the degradation of several proto-oncogenes. Preclinical data suggest that FBXW7 mutations sensitize cells to mTOR inhibitors. Clinicopathologic characteristics of cancer patients with FBXW7 mutations and their responses to mTOR inhibitors remain unknown. METHODS: Using multiplex gene panels we evaluated how the FBXW7 mutation affected the cancer phenotype of patients referred to a phase I clinic starting January 2012. Whenever possible patients positive for FBXW7 mutation were treated with regimens containing an mTOR inhibitors and their outcomes were reviewed. RESULTS: FBXW7 mutations were detected in 17 of 418 patients (4.0%. Among tumor types with more than 10 patients tested, FBXW7 mutations occurred in colorectal cancer (7/49; 14.3%, squamous cell cancer of head and neck (2/18; 11.1%, liver (1/13; 7.7%, and ovarian cancers (1/40; 2.5%. No one clinical, pathological or demographic feature was characteristic of the FBXW7-mutated patient population. The mutation occurred in isolation in only 2/17 (12% patients, and KRAS was frequently found as a concomitant mutation, especially in patients with colorectal cancer (6/7; 86%. Ten patients were treated on a protocol containing an mTOR inhibitor, with a median time to treatment failure of 2.8 months (range, 1.3-6.8. One patient with liver cancer (fibrolamellar subtype continues to have a prolonged stable disease for 6.8+ months. CONCLUSION: In patients with advanced cancers, somatic mutations in FBXW7 usually occur with other simultaneous molecular aberrations, which can contribute to limited therapeutic efficacy of mTOR inhibitors.

  2. Advanced probabilistic risk analysis using RAVEN and RELAP-7

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    RAVEN, under the support of the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program [1], is advancing its capability to perform statistical analyses of stochastic dynamic systems. This is aligned with its mission to provide the tools needed by the Risk Informed Safety Margin Characterization (RISMC) path-lead [2] under the Department Of Energy (DOE) Light Water Reactor Sustainability program [3]. In particular this task is focused on the synergetic development with the RELAP-7 [4] code to advance the state of the art on the safety analysis of nuclear power plants (NPP). The investigation of the probabilistic evolution of accident scenarios for a complex system such as a nuclear power plant is not a trivial challenge. The complexity of the system to be modeled leads to demanding computational requirements even to simulate one of the many possible evolutions of an accident scenario (tens of CPU/hour). At the same time, the probabilistic analysis requires thousands of runs to investigate outcomes characterized by low probability and severe consequence (tail problem). The milestone reported in June of 2013 [5] described the capability of RAVEN to implement complex control logic and provide an adequate support for the exploration of the probabilistic space using a Monte Carlo sampling strategy. Unfortunately the Monte Carlo approach is ineffective with a problem of this complexity. In the following year of development, the RAVEN code has been extended with more sophisticated sampling strategies (grids, Latin Hypercube, and adaptive sampling). This milestone report illustrates the effectiveness of those methodologies in performing the assessment of the probability of core damage following the onset of a Station Black Out (SBO) situation in a boiling water reactor (BWR). The first part of the report provides an overview of the available probabilistic analysis capabilities, ranging from the different types of distributions available, possible sampling

  3. [Tick-borne rickettsioses in the Americas: clinical and epidemiological advances, and diagnostic challenges]. (United States)

    Hidalgo, Marylin; Faccini-Martínez, Álvaro A; Valbuena, Gustavo


    Rickettsioses are a group of zoonotic diseases caused by strict intracellular bacteria of the genus Rickettsia and Orientia which belong to the Rickettsiaceae family. Their ecology is influenced by environmental factors and the presence of specific vectors that determine the establishment and epidemiology in different world regions. In America, during the 20 th century, only three of these diseases were recognized: Rocky Mountain spotted fever, epidemic typhus and endemic typhus. However, since 2000, more than 10 different species that had previously been unknown in this continent have been described, both in arthropods and in clinical cases, fact that classifies them as emerging and re-emerging diseases. Given the clinical manifestations of the diseases caused by rickettsias, being the majority unspecific and, therefore, shared with other infectious diseases, especially viral and bacterial, they have been framed within the differential diagnoses of acute febrile syndrome in urban and tropical areas. Nowadays, there are direct and indirect diagnostic methods, which are useful in the definition of the infectious agent, in this case, the cause of rickettsioses.

  4. Using L1 in Teaching English to Advanced Students

    Directory of Open Access Journals (Sweden)

    Khalid Al Hariri


    Full Text Available Using L1 in the English classroom has long been considered as an unforgivable wrongdoing. Many English teachers who use L1 in the classroom feel guilty about it and in many cases do not admit it. Recent researchers started to question the validity of this claim suggesting contexts and situations in which using L1 can be very helpful in ELT and refuting, on the other hand, the claims upon which the idea of using L2 solely were built.  My paper will examine the attitudes of advanced English language learners toward using L1 in the class of English where the students and the teacher speak the same first language and will also examine the attitudes of a group of EFL and ESL teachers toward the same practice. The same questionnaire given to the students will be redesigned and given to a number of teachers so that the study will look at the viewpoints from both perspectives. Keywords:  L1, Code Switching, Interference of L1, ELT, TESOL

  5. Advanced Genetic Testing Comes to the Pain Clinic to Make a Diagnosis of Paroxysmal Extreme Pain Disorder

    Directory of Open Access Journals (Sweden)

    Ashley Cannon


    Full Text Available 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.

  6. Detecting exacerbations using the Clinical COPD Questionnaire

    Directory of Open Access Journals (Sweden)

    Trappenburg Jaap CA


    Full Text Available Abstract Background Early treatment of COPD exacerbations has shown to be important. Despite a non-negligible negative impact on health related quality of life, a large proportion of these episodes is not reported (no change in treatment. Little is known whether (low burden strategies are able to capture these unreported exacerbations. Methods The Clinical COPD Questionnaire (CCQ is a short questionnaire with great evaluative properties in measuring health status. The current explorative study evaluates the discriminative properties of weekly CCQ assessment in detecting exacerbations. Results In a multicentre prospective cohort study, 121 patients, age 67.4 ± 10.5 years, FEV1 47.7 ± 18.5% pred were followed for 6 weeks by daily diary card recording and weekly CCQ assessment. Weeks were retrospectively labeled as stable or exacerbation (onset weeks using the Anthonisen symptom diary-card algorithm. Change in CCQ total scores are significantly higher in exacerbation-onset weeks, 0.35 ± 0.69 compared to -0.04 ± 0.37 in stable weeks (p Conclusions Weekly CCQ assessment is a promising, low burden method to detect unreported exacerbations. Further research is needed to validate discriminative performance and practical implications of the CCQ in detecting exacerbations in daily care.

  7. Outcome Modeling Using Clinical DVH Data

    CERN Document Server

    Gordon, JJ


    Purpose: To quantify the ability of correlation and regression analysis to extract the normal lung dose-response function from dose volume histogram (DVH) data. Methods: A local injury model is adopted, in which radiation-induced damage (functional loss) G is the integral of the DVH with function R(D). RP risk is H(G) where H() is the sigmoid cumulative distribution of functional reserve. RP incidence is a Bernoulli function of risk. A homogeneous patient cohort is assumed, allowing non-dose-related factors to be ignored. Clinically realistic DVHs are combined with the injury model to simulate RP data. Results: Correlation analysis is often used to identify predictor variables that are correlated with outcome, for inclusion in a predictive model. In the local injury model, all DVH metrics VD contribute to damage. Correlation analysis therefore has limited value. The subset of VD significantly correlated with incidence varies randomly from trial to trial due to random variations in the DVH set, and does not ne...

  8. Electrochemical behavior of dental implant system before andafter clinical use

    Institute of Scientific and Technical Information of China (English)

    Chae-Heon CHUNG; Hee-Jung KIM; Yong-Tae JEONG; Mee-Kyoung SON; Yong-Hoon JEONG; Han-Cheol CHOE


    Electrochemical behavior of dental implant system before and after clinical use (in vivo and in vitro) was researched by using abutment and titanium fixture. To simulate an oral environment, the samples of clinically used and non-used implant systems as a working electrode were exposed to artificial saliva at (36.5±1) ℃. Electrochemical tests were carried out using a potentiostat. After electrochemical test, the corrosion morphology of each sample was investigated by FE-SEM and EDS. The corrosion potential and pitting potential of clinically used implant system are lower than those of non-used implant system, and clinically used implant system exhibits a lower range of passivation, indicating a less degree of inherent resistance against chloride ion. The polarization resistance decreases in the case of clinically used implant system, whereas, Rp for clinically non-used implant system increases compared with clinically used implant system.

  9. Using Simulated Sessions to Enhance Clinical Social Work Education (United States)

    Mooradian, John K.


    This article evaluates a learning method that used theatre students as family clients in an advanced social work practice course. Data from 47 advanced graduate students showed that observing peers conduct simulated sessions can be an effective and valued learning experience. Quantitative findings indicated that simulations are perceived to be…

  10. Anthropometric, biochemical and clinical assessment of malnutrition in Malaysian patients with advanced cirrhosis

    Directory of Open Access Journals (Sweden)

    Rampal Sanjay


    Full Text Available Abstract Background There is limited data on the nutritional status of Asian patients with various aetiologies of cirrhosis. This study aimed to determine the prevalence of malnutrition and to compare nutritional differences between various aetiologies. Methodology A cross-sectional study of adult patients with decompensated cirrhosis was conducted. Nutritional status was assessed using standard anthropometry, serum visceral proteins and subjective global assessment (SGA. Results Thirty six patients (mean age 59.8 ± 12.8 years; 66.7% males; 41.6% viral hepatitis; Child-Pugh C 55.6% with decompensated cirrhosis were recruited. Malnutrition was prevalent in 18 (50% patients and the mean caloric intake was low at 15.2 kcal/kg/day. SGA grade C, as compared to SGA grade B, demonstrated significantly lower anthropometric values in males (BMI 18.1 ± 1.6 vs 26.3 ± 3.5 kg/m2, p Conclusion Significant malnutrition in Malaysian patients with advanced cirrhosis is common. Alcoholic cirrhosis may have more malnutrition compared to other aetiologies of cirrhosis.

  11. 21 CFR 872.6660 - Porcelain powder for clinical use. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Porcelain powder for clinical use. 872.6660... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6660 Porcelain powder for clinical use. (a) Identification. Porcelain powder for clinical use is a device consisting of a mixture of...

  12. A pilot study using next-generation sequencing in advanced cancers: feasibility and challenges.

    Directory of Open Access Journals (Sweden)

    Glen J Weiss

    Full Text Available PURPOSE: New anticancer agents that target a single cell surface receptor, up-regulated or amplified gene product, or mutated gene, have met with some success in treating advanced cancers. However, patients' tumors still eventually progress on these therapies. If it were possible to identify a larger number of targetable vulnerabilities in an individual's tumor, multiple targets could be exploited with the use of specific therapeutic agents, thus possibly giving the patient viable therapeutic alternatives. EXPERIMENTAL DESIGN: In this exploratory study, we used next-generation sequencing technologies (NGS including whole genome sequencing (WGS, and where feasible, whole transcriptome sequencing (WTS to identify genomic events and associated expression changes in advanced cancer patients. RESULTS: WGS on paired tumor and normal samples from nine advanced cancer patients and WTS on six of these patients' tumors was completed. One patient's treatment was based on targets and pathways identified by NGS and the patient had a short-lived PET/CT response with a significant reduction in his tumor-related pain. To design treatment plans based on information garnered from NGS, several challenges were encountered: NGS reporting delays, communication of results to out-of-state participants and their treating oncologists, and chain of custody handling for fresh biopsy samples for Clinical Laboratory Improvement Amendments (CLIA target validation. CONCLUSION: While the initial effort was a slower process than anticipated due to a variety of issues, we demonstrate the feasibility of using NGS in advanced cancer patients so that treatments for patients with progressing tumors may be improved.

  13. Evaluation of Enhanced Risk Monitors for Use on Advanced Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Ramuhalli, Pradeep; Veeramany, Arun; Bonebrake, Christopher A.; Ivans, William J.; Coles, Garill A.; Hirt, Evelyn H.


    This study provides an overview of the methodology for integrating time-dependent failure probabilities into nuclear power reactor risk monitors. This prototypic enhanced risk monitor (ERM) methodology was evaluated using a hypothetical probabilistic risk assessment (PRA) model, generated using a simplified design of a liquid-metal-cooled advanced reactor (AR). Component failure data from industry compilation of failures of components similar to those in the simplified AR model were used to initialize the PRA model. Core damage frequency (CDF) over time were computed and analyzed. In addition, a study on alternative risk metrics for ARs was conducted. Risk metrics that quantify the normalized cost of repairs, replacements, or other operations and management (O&M) actions were defined and used, along with an economic model, to compute the likely economic risk of future actions such as deferred maintenance based on the anticipated change in CDF due to current component condition and future anticipated degradation. Such integration of conventional-risk metrics with alternate-risk metrics provides a convenient mechanism for assessing the impact of O&M decisions on safety and economics of the plant. It is expected that, when integrated with supervisory control algorithms, such integrated-risk monitors will provide a mechanism for real-time control decision-making that ensure safety margins are maintained while operating the plant in an economically viable manner.

  14. Recent Advances in Fungal Hydrophobin Towards Using in Industry. (United States)

    Khalesi, Mohammadreza; Gebruers, Kurt; Derdelinckx, Guy


    Fungal hydrophobin is a family of low molecular weight proteins consisting of four disulfide bridges and an extraordinary hydrophobic patch. The hydrophobic patch of hydrophobins and the molecules of gaseous CO2 may interact together and form the stable CO2-nanobubbles covered by an elastic membrane in carbonated beverages. The nanobubbles provide the required energy to provoke primary gushing. Due to the hydrophobicity of hydrophobin, this protein is used as a biosurfactant, foaming agent or encapsulating agent in food products and medicine formulations. Increasing demands for using of hydrophobins led to a challenge regarding production and purification of this product. However, the main issue to use hydrophobin in the industry is the regulatory affairs: yet there is no approved legislation for using hydrophobin in food and beverages. To comply with the legislation, establishing a consistent method for obtaining pure hydrophobins is necessary. Currently, few research teams in Europe are focusing on different aspects of hydrophobins. In this paper, an up-to-date collection of highlights from those special groups about the bio-chemical and physicochemical characteristics of hydrophobins have been studied. The recent advances of those groups concerning the production and purification, positive applications and negative function of hydrophobin are also summarised.

  15. The development of conjunction use in advanced L2 speech

    Directory of Open Access Journals (Sweden)

    Marcin Jaroszek


    Full Text Available The article discusses the results of a longitudinal study of how the use of conjunctions, as an aspect of spoken discourse competence of 13 selected advanced students of English, developed throughout their 3-year English as a foreign language (EFL tertiary education. The analysis was carried out in relation to a number of variables, including 2 reference levels, one representing English native discourse and the other observed in teacher talk in actual EFL classes, language type exposure, as registered by the participants of the study on a weekly basis, and teaching procedures. The study investigated possible factors determining the development of 3 aspects of conjunction use: (a formal conjunctions, (b specific conjunctions, that is, those conjunctions that are both characteristic of natural English discourse and are underrepresented in L2 discourse, and (c conjunction diversity. The results point to a restricting effect of teacher talk on the development of specific conjunction use and conjunction diversity. These 2 aspects of conjunction use enjoyed only a slight rise, approaching the teacher reference level. On the other hand, formal conjunctions use did increase radically throughout the study, exceeding the native reference level. In this case teacher talk played a reinforcing role at most. As indicated in a correlational analysis, although there was a clear tendency of the participants’ development of conjunction use towards the native reference level, exposure to authentic English may not have been facilitative of the development of this discourse aspect. An interesting observation was made with reference to the effect of formal instruction on the development of conjunction use: Although the subjects did receive intensive training in conjunction use in the 1st semester of their EFL course, it was not until the 2nd year that their levels of formal conjunction use in spoken output increased. This suggests that formal instruction may have

  16. Use of the Berkeley Physics Laboratory to Teach an Advanced Physics Course (United States)

    Logan, James David


    Discusses a course, centered around 32 experiments taught for advanced students, designed to develop a laboratory strongly suggestive of contemporary research using relatively sophisticated apparatus. Its unique advantage lies in enriching advanced physics curriculum. (DF)

  17. Using clinical element models for pharmacogenomic study data standardization. (United States)

    Zhu, Qian; Freimuth, Robert R; Pathak, Jyotishman; Chute, Christopher G


    Standardized representations for pharmacogenomics data are seldom used, which leads to data heterogeneity and hinders data reuse and integration. In this study, we attempted to represent data elements from the Pharmacogenomics Research Network (PGRN) that are related to four categories, patient, drug, disease and laboratory, in a standard way using Clinical Element Models (CEMs), which have been adopted in the Strategic Health IT Advanced Research Project, secondary use of EHR (SHARPn) as a library of common logical models that facilitate consistent data representation, interpretation, and exchange within and across heterogeneous sources and applications. This was accomplished by grouping PGRN data elements into categories based on UMLS semantic type, then mapping each to one or more CEM attributes using a web-based tool that was developed to support curation activities. This study demonstrates the successful application of SHARPn CEMs to the pharmacogenomic domain. It also identified several categories of data elements that are not currently supported by SHARPn CEMs, which represent opportunities for further development and collaboration.

  18. Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems. (United States)

    Vaquero, Juan José; Kinahan, Paul


    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.

  19. Advances in umbilical cord blood stem cell expansion and clinical translation. (United States)

    Pineault, Nicolas; Abu-Khader, Ahmad


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

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

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


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

  1. Advanced Reservoir Imaging Using Frequency-Dependent Seismic Attributes

    Energy Technology Data Exchange (ETDEWEB)

    Fred Hilterman; Tad Patzek; Gennady Goloshubin; Dmitriy Silin; Charlotte Sullivan; Valeri Korneev


    Our report concerning advanced imaging and interpretation technology includes the development of theory, the implementation of laboratory experiments and the verification of results using field data. We investigated a reflectivity model for porous fluid-saturated reservoirs and demonstrated that the frequency-dependent component of the reflection coefficient is asymptotically proportional to the reservoir fluid mobility. We also analyzed seismic data using different azimuths and offsets over physical models of fractures filled with air and water. By comparing our physical model synthetics to numerical data we have identified several diagnostic indicators for quantifying the fractures. Finally, we developed reflectivity transforms for predicting pore fluid and lithology using rock-property statistics from 500 reservoirs in both the shelf and deep-water Gulf of Mexico. With these transforms and seismic AVO gathers across the prospect and its down-dip water-equivalent reservoir, fluid saturation can be estimated without a calibration well that ties the seismic. Our research provides the important additional mechanisms to recognize, delineate, and validate new hydrocarbon reserves and assist in the development of producing fields.

  2. Advanced trans-tibial socket fabrication using selective laser sintering. (United States)

    Rogers, Bill; Bosker, Gordon W; Crawford, Richard H; Faustini, Mario C; Neptune, Richard R; Walden, Gail; Gitter, Andrew J


    There have been a variety of efforts demonstrating the use of solid freeform fabrication (SFF) for prosthetic socket fabrication though there has been little effort in leveraging the strengths of the technology. SFF encompasses a class of technologies that can create three dimensional objects directly from a geometric database without specific tooling or human intervention. A real strength of SFF is that cost of fabrication is related to the volume of the part, not the part's complexity. For prosthetic socket fabrication this means that a sophisticated socket can be fabricated at essentially the same cost as a simple socket. Adding new features to a socket design becomes a function of software. The work at The University of Texas Health Science Center at San Antonio (UTHSCSA) and University of Texas at Austin (UTA) has concentrated on developing advanced sockets that incorporate structural features to increase comfort as well as built in fixtures to accommodate industry standard hardware. Selective laser sintering (SLS) was chosen as the SFF technology to use for socket fabrication as it was capable of fabricating sockets using materials appropriate for prosthetics. This paper details the development of SLS prosthetic socket fabrication techniques at UTHSCSA/UTA over a six-year period.

  3. Retrospective Analysis of Implant Overdenture Treatment in the Advanced Prosthodontic Clinic at the University of Illinois at Chicago. (United States)

    Marinis, Aristotelis; Afshari, Fatemeh S; Yuan, Judy Chia-Chun; Lee, Damian J; Syros, George; Knoernschild, Kent L; Campbell, Stephen D; Sukotjo, Cortino


    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

  4. Explaining clinical behaviors using multiple theoretical models

    Directory of Open Access Journals (Sweden)

    Eccles Martin P


    Full Text Available Abstract Background In the field of implementation research, there is an increased interest in use of theory when designing implementation research studies involving behavior change. In 2003, we initiated a series of five studies to establish a scientific rationale for interventions to translate research findings into clinical practice by exploring the performance of a number of different, commonly used, overlapping behavioral theories and models. We reflect on the strengths and weaknesses of the methods, the performance of the theories, and consider where these methods sit alongside the range of methods for studying healthcare professional behavior change. Methods These were five studies of the theory-based cognitions and clinical behaviors (taking dental radiographs, performing dental restorations, placing fissure sealants, managing upper respiratory tract infections without prescribing antibiotics, managing low back pain without ordering lumbar spine x-rays of random samples of primary care dentists and physicians. Measures were derived for the explanatory theoretical constructs in the Theory of Planned Behavior (TPB, Social Cognitive Theory (SCT, and Illness Representations specified by the Common Sense Self Regulation Model (CSSRM. We constructed self-report measures of two constructs from Learning Theory (LT, a measure of Implementation Intentions (II, and the Precaution Adoption Process. We collected data on theory-based cognitions (explanatory measures and two interim outcome measures (stated behavioral intention and simulated behavior by postal questionnaire survey during the 12-month period to which objective measures of behavior (collected from routine administrative sources were related. Planned analyses explored the predictive value of theories in explaining variance in intention, behavioral simulation and behavior. Results Response rates across the five surveys ranged from 21% to 48%; we achieved the target sample size for three of

  5. Almanac 2013: cardiac arrhythmias and pacing--an editorial overview of selected research that has driven recent advances in clinical cardiology. (United States)

    Liew, Reginald


    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.

  6. Extravascular lung water in critical care: recent advances and clinical applications. (United States)

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


    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

  7. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S


    Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based...... on dendritic cells pulsed with an allogenic tumor cell lysate. Twenty patients with advanced colorectal cancer were consecutively enrolled. Dendritic cells (DC) were generated from autologous peripheral blood mononuclear cells and pulsed with allogenic tumor cell lysate containing high levels of cancer...

  8. Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified

    Directory of Open Access Journals (Sweden)

    Xi LI


    Full Text Available Background and objective Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC patients with EGFR mutation and wild-type. Methods Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. Results The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type with advanced NSCLC were enrolled in this study. The patients’ overall objective response rate (ORR was 51.6 % and the disease control rate (DCR was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6% and diarrhea (16.1%. Conclusion Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.

  9. Recent Advances and Uses of Grape Flavonoids as Nutraceuticals

    Directory of Open Access Journals (Sweden)

    Vasil Georgiev


    Full Text Available Grape is one of the oldest fruit crops domesticated by humans. The numerous uses of grape in making wine, beverages, jelly, and other products, has made it one of the most economically important plants worldwide. The complex phytochemistry of the berry is characterized by a wide variety of compounds, most of which have been demonstrated to have therapeutic or health promoting properties. Among them, flavonoids are the most abundant and widely studied, and have enjoyed greater attention among grape researchers in the last century. Recent studies have shown that the beneficial health effects promoted by consumption of grape and grape products are attributed to the unique mix of polyphenolic compounds. As the largest group of grape polyphenols, flavonoids are the main candidates considered to have biological properties, including but not limited to antioxidant, anti-inflammatory, anti-cancer, antimicrobial, antiviral, cardioprotective, neuroprotective, and hepatoprotective activities. Here, we discuss the recent scientific advances supporting the beneficial health qualities of grape and grape-derived products, mechanisms of their biological activity, bioavailability, and their uses as nutraceuticals. The advantages of modern plant cell based biotechnology as an alternative method for production of grape nutraceuticals and improvement of their health qualities are also discussed.

  10. Technology advancement: a factor in increasing resource use (United States)

    Wilburn, David R.; Goonan, Thomas G.; Bleiwas, Donald I.


    The specter of mineral resource scarcity has been repeatedly raised as a concern because ever-growing populations with seemingly insatiable appetites for minerals place claims against a finite resource endowment. This report analyzes how technology has helped to ease resource constraints, and uses case studies of aluminum, copper, potash, and sulfur minerals to identify the effects of technology on resource supply. In spite of heightened demand for and increased loss of resources to environmental policy and urbanization, mineral producers historically have been able to continually expand production and lower costs. Specific production increases for the years 1900-98 were: aluminum (3,250 percent), copper (2,465 percent), potash (3,770 percent), and sulfur (6,000 percent). For the same period, constant-dollar (1998) prices decreased: aluminum (90 percent), copper (75 percent), potash (94 percent), and sulfur (89 percent). The application of technology has made available mineral deposits that were previously overlooked or considered non-viable. Using technology, producers can meet the demand for stronger, energy-efficient, more environmentally safe products with less physical material. Technologies have been developed to increase the amount of materials recycled and remanufactured. Technology development can occur in breakthroughs, but most often advances incrementally. Technological development is driven by the profit motive.

  11. Burnout prediction using advance image analysis coal characterization techniques

    Energy Technology Data Exchange (ETDEWEB)

    Edward Lester; Dave Watts; Michael Cloke [University of Nottingham, Nottingham (United Kingdom). School of Chemical Environmental and Mining Engineering


    The link between petrographic composition and burnout has been investigated previously by the authors. However, these predictions were based on 'bulk' properties of the coal, including the proportion of each maceral or the reflectance of the macerals in the whole sample. Combustion studies relating burnout with microlithotype analysis, or similar, remain less common partly because the technique is more complex than maceral analysis. Despite this, it is likely that any burnout prediction based on petrographic characteristics will become more accurate if it includes information about the maceral associations and the size of each particle. Chars from 13 coals, 106-125 micron size fractions, were prepared using a Drop Tube Furnace (DTF) at 1300{degree}C and 200 millisecond and 1% Oxygen. These chars were then refired in the DTF at 1300{degree}C 5% oxygen and residence times of 200, 400 and 600 milliseconds. The progressive burnout of each char was compared with the characteristics of the initial coals. This paper presents an extension of previous studies in that it relates combustion behaviour to coals that have been characterized on a particle by particle basis using advanced image analysis techniques. 13 refs., 7 figs.

  12. The use of advanced materials in space structure applications (United States)

    Eaton, D. C. G.; Slachmuylders, E. J.

    The last decade has seen the Space applications of composite materials become almost commonplace in the construction of configurations requiring high stiffness and/or dimensional stability, particularly in the field of antennas. As experience has been accumulated, applications for load carrying structures utilizing the inherent high specific strength/stiffness of carbon fibres have become more frequent. Some typical examples of these and their design development criteria are reviewed. As these structures and the use of new plastic matrices emerge, considerable attention has to be given to establishing essential integrity control requirements from both safety and cost aspects. The advent of manned European space flight places greater emphasis on such requirements. Attention is given to developments in the fields of metallic structures with discussion of the advantages and disadvantages of their application. The design and development of hot structures, thermal protection systems and air-breathing engines for future launch vehicles necessitates the use of the emerging metal/matrix and other advanced materials. Some of their important features are outlined. Means of achieving such objectives by greater harmonization within Europe are emphasized. Typical examples of on-going activities to promote such collaboration are described.

  13. Advanced Online Survival Analysis Tool for Predictive Modelling in Clinical Data Science. (United States)

    Montes-Torres, Julio; Subirats, José Luis; Ribelles, Nuria; Urda, Daniel; Franco, Leonardo; Alba, Emilio; Jerez, José Manuel


    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.

  14. Use of shield support on faces advanced in plastic strata

    Energy Technology Data Exchange (ETDEWEB)

    Pera, F.; Szentai, G.


    A new type of rock loading model is presented for shield support on faces advancing in plastic strata. Loading of strata is not independent of the speed of advance. The problem is approached on theoretical bases and is also illustrated by measurements carried out in practice. The interpretation of the active and passive loads is given and the loads are taken into account in different manner.

  15. Study on advancement of in vivo counting using mathematical simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kinase, Sakae [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment


    To obtain an assessment of the committed effective dose, individual monitoring for the estimation of intakes of radionuclides is required. For individual monitoring of exposure to intakes of radionuclides, direct measurement of radionuclides in the body - in vivo counting- is very useful. To advance in a precision in vivo counting which fulfills the requirements of ICRP 1990 recommendations, some problems, such as the investigation of uncertainties in estimates of body burdens by in vivo counting, and the selection of the way to improve the precision, have been studied. In the present study, a calibration technique for in vivo counting application using Monte Carlo simulation was developed. The advantage of the technique is that counting efficiency can be obtained for various shapes and sizes that are very difficult to change for phantoms. To validate the calibration technique, the response functions and counting efficiencies of a whole-body counter installed in JAERI were evaluated using the simulation and measurements. Consequently, the calculations are in good agreement with the measurements. The method for the determination of counting efficiency curves as a function of energy was developed using the present technique and a physiques correction equation was derived from the relationship between parameters of correction factor and counting efficiencies of the JAERI whole-body counter. The uncertainties in body burdens of {sup 137}Cs estimated with the JAERI whole-body counter were also investigated using the Monte Carlo simulation and measurements. It was found that the uncertainties of body burdens estimated with the whole-body counter are strongly dependent on various sources of uncertainty such as radioactivity distribution within the body and counting statistics. Furthermore, the evaluation method of the peak efficiencies of a Ge semi-conductor detector was developed by Monte Carlo simulation for optimum arrangement of Ge semi-conductor detectors for

  16. Advanced defect detection algorithm using clustering in ultrasonic NDE (United States)

    Gongzhang, Rui; Gachagan, Anthony


    A range of materials used in industry exhibit scattering properties which limits ultrasonic NDE. Many algorithms have been proposed to enhance defect detection ability, such as the well-known Split Spectrum Processing (SSP) technique. Scattering noise usually cannot be fully removed and the remaining noise can be easily confused with real feature signals, hence becoming artefacts during the image interpretation stage. This paper presents an advanced algorithm to further reduce the influence of artefacts remaining in A-scan data after processing using a conventional defect detection algorithm. The raw A-scan data can be acquired from either traditional single transducer or phased array configurations. The proposed algorithm uses the concept of unsupervised machine learning to cluster segmental defect signals from pre-processed A-scans into different classes. The distinction and similarity between each class and the ensemble of randomly selected noise segments can be observed by applying a classification algorithm. Each class will then be labelled as `legitimate reflector' or `artefacts' based on this observation and the expected probability of defection (PoD) and probability of false alarm (PFA) determined. To facilitate data collection and validate the proposed algorithm, a 5MHz linear array transducer is used to collect A-scans from both austenitic steel and Inconel samples. Each pulse-echo A-scan is pre-processed using SSP and the subsequent application of the proposed clustering algorithm has provided an additional reduction to PFA while maintaining PoD for both samples compared with SSP results alone.

  17. Corticosteroids: clinical pharmacology and therapeutic use. (United States)

    Swartz, S L; Dluhy, R G


    The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones. Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression. When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid

  18. Relationship of Clinical and Pathologic Nodal Staging in Locally Advanced Breast Cancer: Current Controversies in Daily Practice? (United States)

    De Felice, Francesca; Musio, Daniela; Bulzonetti, Nadia; Raffetto, Nicola; Tombolini, Vincenzo


    Systemic neo-adjuvant therapy plays a primary role in the management of locally advanced breast cancer. Without having any negative effect in overall survival, induction chemotherapy potentially assures a surgery approach in unresectable disease or a conservative treatment in technically resectable disease and acts on a well-vascularized tumor bed, without the modifications induced by surgery. A specific issue has a central function in the neo-adjuvant setting: lymph nodes status. It still represents one of the strongest predictors of long-term prognosis in breast cancer. The discussion of regional radiation therapy should be a matter of debate, especially in a pathological complete response. Currently, the indication for radiotherapy is based on the clinical stage before the surgery, even for the irradiation of the loco-regional lymph nodes. Regardless of pathological down-staging, radiation therapy is accepted as standard adjuvant treatment in locally advanced breast cancer. PMID:25247013

  19. Early clinical investigation of sulofenur with a daily schedule in advanced solid tumours

    DEFF Research Database (Denmark)

    Krarup-Hansen, A; Pedersen, H; Andersen, E


    modification for the individual patient at any given dose level; 38 patients with advanced solid malignant tumours were enrolled. Haemolytic anaemia was the main side effect. The toxicity was marked at dose levels of 600 and 700 mg/m2. Moderate methaemoglobinaemia also occurred. One case of reversible toxic...

  20. Recent advances in environmental monitoring using commercial microwave links (United States)

    Alpert, Pinhas; Guez, Oded; Messer, Hagit; David, Noam; Harel, Oz; Eshel, Adam; Cohen, Ori


    Recent advances in environmental monitoring using commercial microwave links Pinhas Alpert, H. Messer, N. David, O. Guez, O. Cohen, O. Harel, A. Eshel Tel Aviv University, Israel The propagation of electromagnetic radiation in the lower atmosphere, at centimeter wavelengths, is impaired by atmospheric conditions. Absorption and scattering of the radiation, at frequencies of tens of GHz, are directly related to the atmospheric phenomena, primarily precipitation, oxygen, mist, fog and water vapor. As was recently shown, wireless communication networks supply high resolution precipitation measurements at ground level while often being situated in flood prone areas, covering large parts of these hazardous regions. On the other hand, at present, there are no satisfactory real time flash flood warning facilities found to cope well with this phenomenon. I will exemplify the flash flood warning potential of the commercial wireless communication system for semi-arid region cases when floods occurred in the Judean desert in Israel with comparison to hydrological measurements in the Dead Sea area. In addition, I will review our recent improvements in monitoring rainfall as well as other-than-rain phenomena like, fog, dew, atmospheric moisture. References: N. David, P. Alpert, and H. Messer, "Technical Note: Novel method for water vapor monitoring using wireless communication networks measurements", Atmos. Chem. Phys., 9, 2413-2418, 2009. A. Rayitsfeld, R. Samuels, A. Zinevich, U. Hadar and P. Alpert,"Comparison of two methodologies for long term rainfall monitoring using a commercial microwave communication system", Atmospheric Research 104-105, 119-127, 2012. N. David, O. Sendik, H. Messer and P. Alpert, "Cellular network infrastructure-the future of fog monitoring?" BAMS (Oct. issue), 1687-1698, 2015. O. Harel, David, N., Alpert, P. and Messer, H., "The potential of microwave communication networks to detect dew using the GLRT- experimental study", IEEE Journal of Selected

  1. Strategies for casualty mitigation programs by using advanced tsunami computation (United States)

    IMAI, K.; Imamura, F.


    1. Purpose of the study In this study, based on the scenario of great earthquakes along the Nankai trough, we aim on the estimation of the run up and high accuracy inundation process of tsunami in coastal areas including rivers. Here, using a practical method of tsunami analytical model, and taking into account characteristics of detail topography, land use and climate change in a realistic present and expected future environment, we examined the run up and tsunami inundation process. Using these results we estimated the damage due to tsunami and obtained information for the mitigation of human casualties. Considering the time series from the occurrence of the earthquake and the risk of tsunami damage, in order to mitigate casualties we provide contents of disaster risk information displayed in a tsunami hazard and risk map. 2. Creating a tsunami hazard and risk map From the analytical and practical tsunami model (a long wave approximated model) and the high resolution topography (5 m) including detailed data of shoreline, rivers, building and houses, we present a advanced analysis of tsunami inundation considering the land use. Based on the results of tsunami inundation and its analysis; it is possible to draw a tsunami hazard and risk map with information of human casualty, building damage estimation, drift of vehicles, etc. 3. Contents of disaster prevention information To improve the hazard, risk and evacuation information distribution, it is necessary to follow three steps. (1) Provide basic information such as tsunami attack info, areas and routes for evacuation and location of tsunami evacuation facilities. (2) Provide as additional information the time when inundation starts, the actual results of inundation, location of facilities with hazard materials, presence or absence of public facilities and areas underground that required evacuation. (3) Provide information to support disaster response such as infrastructure and traffic network damage prediction

  2. Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation

    Directory of Open Access Journals (Sweden)

    Xiaowen JIANG


    Full Text Available Background and objective Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC treatment. Epithelial growth factor receptor (EGFR tyrosine kinase inhibitor (TKI can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS≥6 months] and analysis of the related risk factors for prognosis. Methods From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. Results The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010, Prior chemotherapy (P=0.001, Eastern Cooperative Oncology Group (ECOG score (P=0.001 were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1% and diarrhea (27 cases, 11.7%. Conclusion Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line.

  3. Supercomputing - Use Cases, Advances, The Future (1/2)

    CERN Document Server

    CERN. Geneva


    Supercomputing has become a staple of science and the poster child for aggressive developments in silicon technology, energy efficiency and programming. In this series we examine the key components of supercomputing setups and the various advances – recent and past – that made headlines and delivered bigger and bigger machines. We also take a closer look at the future prospects of supercomputing, and the extent of its overlap with high throughput computing, in the context of main use cases ranging from oil exploration to market simulation. On the first day, we will focus on the history and theory of supercomputing, the top500 list and the hardware that makes supercomputers tick. Lecturer's short bio: Andrzej Nowak has 10 years of experience in computing technologies, primarily from CERN openlab and Intel. At CERN, he managed a research lab collaborating with Intel and was part of the openlab Chief Technology Office. Andrzej also worked closely and initiated projects with the private sector (e.g. HP an...

  4. Immobilization biological activated carbon used in advanced drinking water treatment

    Institute of Scientific and Technical Information of China (English)


    Bacteria separated from a mature filter bed of groundwater treatment plants were incubated in a culture media containing iron and manganese. A consortium of 5 strains of bacteria removing iron and manganese were obtained by repeated enrichment culturing. It was shown from the experiments of effect factors that ironmanganese removal bacteria in the culture media containing both Fe and Mn grew better than in that containing only Fe, however, they were unable to grow in the culture media containing only Mn. When comparing the bacteria biomass in the case ofρ (DO) =2.8 mg/L andρ (DO) =9.0 mg/L, no significant difference was found.The engineering bacteria removing the organic and the bacteria removing iron and manganese were simultaneously inoculated into activated carbon reactor to treat the effluent of distribution network. The experimental results showed that by using IBAC ( Immobilization Biological Activated Carbon) treatment, the removal efficiency of iron, manganese and permanganate index was more than 98% , 96% and 55% , respectively. After the influent with turbidity of 1.5 NTU, color of 25 degree and offensive odor was treated, the turbidity and color of effluence were less than 0.5 NTU and 15 degree, respectively, and it was odorless. It is determined that the cooperation function of engineering bacteria and activated carbon achieved advanced drinking water treatment.

  5. Advances in the use of intravenous techniques in ambulatory anesthesia

    Directory of Open Access Journals (Sweden)

    Eng MR


    Full Text Available Matthew R Eng,1 Paul F White1,2 1Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2White Mountain Institute, The Sea Ranch, CA, USA Summary statement: Advances in the use of intravenous techniques in ambulatory anesthesia has become important for the anesthesiologist as the key perioperative physician in outpatient surgery. Key techniques and choices of anesthetics are important in accomplishing fast track goals of ambulatory surgery. Purpose of review: The anesthesiologist in the outpatient environment must focus on improving perioperative efficiency and reducing recovery times while accounting for patients' well-being and safety. This review article focuses on recent intravenous anesthetic techniques to accomplish these goals. Recent findings: This review is an overview of techniques in intravenous anesthesia for ambulatory anesthesia. Intravenous techniques may be tailored to accomplish outpatient surgery goals for the type of surgical procedure and individual patient needs. Careful anesthetic planning and the application of the plans are critical to an anesthesiologist's success with fast-track ambulatory surgery. Conclusion: Careful planning and application of intravenous techniques are critical to an anesthesiologist's success with fast-track ambulatory surgery. Keywords: intravenous anesthesia, outpatient anesthesia, fast-track surgery

  6. Selection of parameters for advanced machining processes using firefly algorithm

    Directory of Open Access Journals (Sweden)

    Rajkamal Shukla


    Full Text Available Advanced machining processes (AMPs are widely utilized in industries for machining complex geometries and intricate profiles. In this paper, two significant processes such as electric discharge machining (EDM and abrasive water jet machining (AWJM are considered to get the optimum values of responses for the given range of process parameters. The firefly algorithm (FA is attempted to the considered processes to obtain optimized parameters and the results obtained are compared with the results given by previous researchers. The variation of process parameters with respect to the responses are plotted to confirm the optimum results obtained using FA. In EDM process, the performance parameter “MRR” is increased from 159.70 gm/min to 181.6723 gm/min, while “Ra” and “REWR” are decreased from 6.21 μm to 3.6767 μm and 6.21% to 6.324 × 10−5% respectively. In AWJM process, the value of the “kerf” and “Ra” are decreased from 0.858 mm to 0.3704 mm and 5.41 mm to 4.443 mm respectively. In both the processes, the obtained results show a significant improvement in the responses.

  7. Pressure tube replication techniques using the advanced NDE system

    Energy Technology Data Exchange (ETDEWEB)

    Isherwood, A.; Jarron, D.; Travers, J.; Hanley, K. [Ontario Power Generation, Pickering, Ontario (Canada)]. E-mail:


    Periodic and in-service inspections of fuel channels are essential for the proper assessment of the structural integrity of these vital components. The arrival of new delivery devices for fuel channel inspections has driven new tooling for gathering and analyzing NDE data. The Advanced Non-Destructive Examination (ANDE) Replication System has been designed to compliment the ANDE Inspection System by providing a two plate replica system. These plates deliver a compound that makes a positive 3D mould of known ID flaws to gather information for flaw assessment. The two plate system, and the ability to retrieve and recharge the moulds in the reactor vault allows for gathering defect information with minimal critical path time. The ANDE Replication System was built on the foundation of CIGAR experience by a solid design team familiar with 3D CAD and manufacturing techniques. The tooling and controls went through a series of integration stages in the laboratory and then later with the Universal Delivery Machine (UDM) before being used on reactor starting in 2003. Once the inspection phase of an outage has been completed, the analysis team provides a list of flaw candidates that require 'root radius' information to complete the flaw assessment. This is a measure of how sharp the corners are in the defect. This data is used as part of the stress calculation that ultimately determines how many shutdown cycles that the reactor can have before that flaw must be re-inspected. The inspection tool is then swapped out of the delivery machine in the reactor vault using the versatile connectorized umbilical. The replication tool is loaded on the machine, charged with replica compound on each of the two plates, and then sent to the target channel(s). On channel, the operators use the same console as the ANDE Inspection System, but have a separate control system with a graphical display of the tool that shows its position in the channel with respect to the E-face. The axial

  8. Advanced reconstruction of attenuation maps using SPECT emission data only (United States)

    Salomon, André; Goedicke, Andreas; Aach, Til


    Today, attenuation corrected SPECT, typically performed using CT or Gadolinium line source based transmission scans, is more and more becoming standard in many medical applications. Moreover, the information about the material density distribution provided by these scans is key for other artifact compensation approaches in advanced SPECT reconstruction. Major drawbacks of these approaches are the additional patient radiation and hardware/maintenance costs as well as the additional workflow effort, e.g. if the CT scans are not performed on a hybrid scanner. It has been investigated in the past, whether it is possible to recover this structural information solely from the SPECT scan data. However, the investigated methods often result in noticeable image artifacts due to cross-dependences between attenuation and activity distribution estimation. With the simultaneous reconstruction method presented in this paper, we aim to effectively prevent these typical cross-talk artifacts using a-priori known atlas information of a human body. At first, an initial 3D shape model is coarsely registered to the SPECT data using anatomical landmarks and each organ structure within the model is identified with its typical attenuation coefficient. During the iterative reconstruction based on a modified ML-EM scheme, the algorithm simultaneously adapts both, the local activity estimation and the 3D shape model in order to improve the overall consistency between measured and estimated sinogram data. By explicitly avoiding topology modifications resulting in a non-anatomical state, we ensure that the estimated attenuation map remains realistic. Several tests with simulated as well as real patient SPECT data were performed to test the proposed algorithm, which demonstrated reliable convergence behaviour in both cases. Comparing the achieved results with available reference data, an overall good agreement for both cold as well as hot activity regions could be observed (mean deviation: -5.98%).

  9. Using Advanced Tensiometers to Monitor Temporal Variations in Pore Pressure (United States)

    Nichols, R. L.; Young, M. H.; Dixon, K. L.; Rossabi, J.; Hyde, W. K.; Holmes-Burns, H.


    The Savannah River Site has installed a comprehensive vadose zone monitoring system (VZMS) at it's low level radioactive waste disposal facility to collect the necessary information to calculate contaminant flux. The VZMS includes water content reflectometers, suction lysimeters, advanced tensiometers (ATs), water flux meters, access ports for neutron probes, and a tipping bucket rain gauge. Forty one ATs were installed from 1999 to 2001 at depths ranging from 2 to 60 feet and have been operated continuously. The installation depths were based on a hydrostatigraphic model developed from core logs, cone penetrometer logs, moisture content profiles, water retention curves model that were obtained during the phased installation of the VZMS. An AT consists of a porous cup installed at a prescribed depth with casing back to the surface and a pressure transducer that is lowered into the casing and connects with the porous cup. The pressure transducer transmits it's signal to a datalogger where the data is stored for future retrieval using a cellular phone communications package. Results from the 2 year operating period show that the AT calibrations are stable and t ATs are capable of extended monitoring of pore pressures in the 0 to 300 cm H2 O range. The ATs had sufficient resolution to detect the naturally occurring fluctuations in pore pressure (1 to 100 cm H2 O over 1 to 72 hours) that resulted from infiltration events at the site. The stable performance of the ATs combined with their ability to detect naturally occurring fluctuations in pore pressure make the ATs a useful tool in measuring temporal pore pressure variations for use in calibrating numerical models of fluid flow in variably saturated porous media.

  10. Recent Advances in Genome Editing Using CRISPR/Cas9. (United States)

    Ding, Yuduan; Li, Hong; Chen, Ling-Ling; Xie, Kabin


    The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is a versatile tool for genome engineering that uses a guide RNA (gRNA) to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM) puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding.

  11. Recent Advances in Genome Editing Using CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    Yuduan eDing


    Full Text Available AbstractThe CRISPR (clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-associated nuclease 9 system is a versatile tool for genome engineering that uses a guide RNA (gRNA to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding.

  12. Effect of integrated Chinese medical treatment on the survival time of patients with advanced non-small-cell lung cancer: a clinical study

    Institute of Scientific and Technical Information of China (English)



    Objective To observe clinical effect of integrated Chinese medical(CM)treatment(as maintenance therapy)on the progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small-cell lung cancer(NSCLC)after first-line chemotherapy.Methods The study was a prospective,randomized,controlled clinical trial.Totally 69 non-progressive advanced NSCLC patients treated with first-line chemotherapy were

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

    Directory of Open Access Journals (Sweden)

    Bart eEverts


    Full Text Available 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.

  14. The Ease of Language Understanding (ELU model: theoretical, empirical, and clinical advances

    Directory of Open Access Journals (Sweden)

    Jerker eRönnberg


    Full Text Available 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. A revised ELU model is proposed 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.

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

    Directory of Open Access Journals (Sweden)

    Sweet K


    Full Text Available Kendra Sweet,1 Javier Pinilla-Ibarz,1 Ling Zhang21Malignant Hematology, 2Hematopathology, H Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: 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.Keywords: chronic myeloid leukemia, bosutinib, treatment options

  16. Predicting Performance in Technical Preclinical Dental Courses Using Advanced Simulation. (United States)

    Gottlieb, Riki; Baechle, Mary A; Janus, Charles; Lanning, Sharon K


    The aim of this study was to investigate whether advanced simulation parameters, such as simulation exam scores, number of student self-evaluations, time to complete the simulation, and time to complete self-evaluations, served as predictors of dental students' preclinical performance. Students from three consecutive classes (n=282) at one U.S. dental school completed advanced simulation training and exams within the first four months of their dental curriculum. The students then completed conventional preclinical instruction and exams in operative dentistry (OD) and fixed prosthodontics (FP) courses, taken during the first and second years of dental school, respectively. Two advanced simulation exam scores (ASES1 and ASES2) were tested as predictors of performance in the two preclinical courses based on final course grades. ASES1 and ASES2 were found to be predictors of OD and FP preclinical course grades. Other advanced simulation parameters were not significantly related to grades in the preclinical courses. These results highlight the value of an early psychomotor skills assessment in dentistry. Advanced simulation scores may allow early intervention in students' learning process and assist in efficient allocation of resources such as faculty coverage and tutor assignment.

  17. Using business intelligence to monitor clinical quality metrics. (United States)

    Resetar, Ervina; Noirot, Laura A; Reichley, Richard M; Storey, Patricia; Skiles, Ann M; Traynor, Patrick; Dunagan, W Claiborne; Bailey, Thomas C


    BJC HealthCare (BJC) uses a number of industry standard indicators to monitor the quality of services provided by each of its hospitals. By establishing an enterprise data warehouse as a central repository of clinical quality information, BJC is able to monitor clinical quality performance in a timely manner and improve clinical outcomes.

  18. Using advanced electron microscopy for the characterization of catalytic materials (United States)

    Pyrz, William D.

    Catalysis will continue to be vitally important to the advancement and sustainability of industrialized societies. Unfortunately, the petroleum-based resources that currently fuel the energy and consumer product needs of an advancing society are becoming increasingly difficult and expensive to extract as supplies diminish and the quality of sources degrade. Therefore, the development of sustainable energy sources and the improvement of the carbon efficiency of existing chemical processes are critical. Further challenges require that these initiatives are accomplished in an environmentally friendly fashion since the effects of carbon-based emissions are proving to be a serious threat to global climate stability. In this dissertation, materials being developed for sustainable energy and process improvement initiatives are studied. Our approach is to use materials characterization, namely advanced electron microscopy, to analyze the targeted systems at the nano- or Angstrom-scale with the goal of developing useful relationships between structure, composition, crystalline order, morphology, and catalytic performance. One area of interest is the complex Mo-V-M-O (M=Te, Sb, Ta, Nb) oxide system currently being developed for the selective oxidation/ammoxidation of propane to acrylic acid or acrylonitrile, respectively. Currently, the production of acrylic acid and acrylonitrile rely on propylene-based processes, yet significant cost savings could be realized if the olefin-based feeds could be replaced by paraffin-based ones. The major challenge preventing this feedstock replacement is the development of a suitable paraffin-activating catalyst. Currently, the best candidate is the Mo-V-Nb-Te-O complex oxide catalyst that is composed of two majority phases that are commonly referred to as M1 and M2. However, there is a limited understanding of the roles of each component with respect to how they contribute to catalyst stability and the reaction mechanism. Aberration

  19. Clinical Impact of Education Provision on Determining Advance Care Planning Decisions among End Stage Renal Disease Patients Receiving Regular Hemodialysis in University Malaya Medical Centre (United States)

    Hing (Wong), Albert; Chin, Loh Ee; Ping, Tan Li; Peng, Ng Kok; Kun, Lim Soo


    Introduction: Advance care planning (ACP) is a process of shared decision-making about future health-care plans between patients, health care providers, and family members, should patients becomes incapable of participating in medical treatment decisions. ACP discussions enhance patient's autonomy, focus on patient's values and treatment preferences, and promote patient-centered care. ACP is integrated as part of clinical practice in Singapore and the United States. Aim: To assess the clinical impact of education provision on determining ACP decisions among end-stage renal disease patients on regular hemodialysis at University Malaya Medical Centre (UMMC). To study the knowledge and attitude of patients toward ACP and end-of-life issues. Materials and Methods: Fifty-six patients were recruited from UMMC. About 43 questions pretest survey adapted from Lyon's ACP survey and Moss's cardiopulmonary resuscitation (CPR) attitude survey was given to patients to answer. An educational brochure is then introduced to these patients, and a posttest survey carried out after that. The results were analyzed using SPSS version 22.0. Results: Opinion on ACP, including CPR decisions, showed an upward trend on the importance percentage after the educational brochure exposure, but this was statistically not significant. Seventy-five percent of participants had never heard of ACP before, and only 3.6% had actually prepared a written advanced directive. Conclusion: The ACP educational brochure clinically impacts patients’ preferences and decisions toward end-of-life care; however, this is statistically not significant. Majority of patients have poor knowledge on ACP. This study lays the foundation for execution of future larger scale clinical trials, and ultimately, the incorporation of ACP into clinical practice in Malaysia.

  20. Identifying clinical course patterns in SMS data using cluster analysis

    DEFF Research Database (Denmark)

    Kent, Peter; Kongsted, Alice


    ABSTRACT: BACKGROUND: Recently, there has been interest in using the short message service (SMS or text messaging), to gather frequent information on the clinical course of individual patients. One possible role for identifying clinical course patterns is to assist in exploring clinically importa...... of cluster analysis. More research is needed, especially head-to-head studies, to identify which technique is best to use under what circumstances.......ABSTRACT: BACKGROUND: Recently, there has been interest in using the short message service (SMS or text messaging), to gather frequent information on the clinical course of individual patients. One possible role for identifying clinical course patterns is to assist in exploring clinically important...... by spline analysis. However, cluster analysis of SMS data in its original untransformed form may be simpler and offer other advantages. Therefore, the aim of this study was to determine whether cluster analysis could be used for identifying clinical course patterns distinct from the pattern of the whole...

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

    Directory of Open Access Journals (Sweden)

    Nikam N


    Full Text Available Navin Nikam, Toby B Steinberg, Daniel H SteinbergDivision of Cardiology, Medical University of South Carolina, Charleston, SC, USAAbstract: The introduction of intracoronary stents represented a major advance in interventional cardiology. While bare metal stents set the benchmark for improved safety over angioplasty, intimal hyperplasia and subsequent restenosis were important limitations. First-generation drug-eluting stents demonstrated significant improvements in efficacy, but not necessarily safety, and further technologic developments have focused on optimizing both. Current advances and understanding in stent design continue to improve on these concepts. This review summarizes past and present technology with particular emphasis on the principles underlying the efficacy and safety of drug-eluting stents, and offers a glimpse into the next generations of stents aimed at treating symptomatic coronary artery disease.Keywords: drug-eluting stents percutaneous coronary intervention, coronary artery disease, bioabsorbable polymers, bioabsorbable struts, polymer free

  2. Clinical evaluation of radiotherapy for advanced esophageal cancer after metallic stent placement

    Institute of Scientific and Technical Information of China (English)

    You-Tao Yu; Guang Yang; Yan Liu; Bao-Zhong Shen


    AIM: To evaluate the therapeutic effect of radiotherapy for esophageal cancer after expandable metallic stent placement.METHODS: Ten cases of advanced esophageal cancer were evaluated, 7 having complete obstruction and 3 with digestive-respiratory fistula. Ten nitinol stents were placed at the site of stenosis. Patients were treated with a total dose of 1 200 cGy divided into 3 fractions of 400 cGy 4-7 d after stents placement.RESULTS: All the 10 stents were placed successfully at one time. After radiotherapy for advanced esophageal cancer, the survival period of the cases ranged from 14 to 22 mo, with a mean survival of 17 mo. No re-stenosis occurred among all the 10 cases.CONCLUSION: Stent placement combined with radiotherapy for esophageal cancer is helpful to prolong patients' survival and reduce occurrence of re-stenosis.

  3. Regeneration of tissues of the oral complex: current clinical trends and research advances. (United States)

    Nguyen, Thomas T; Mui, Brennan; Mehrabzadeh, Mahsa; Chea, Yannie; Chaudhry, Zoya; Chaudhry, Kamran; Tran, Simon D


    Regenerative therapy in oral health care is limited by both the body's natural capacity for regeneration and the materials and methods currently available. Research on various aspects of regenerative therapy, such as tissue engineering and stem cell and gene therapy, has produced promising results. Compelling advances, ranging from the discovery and characterization of stem cell populations in oral tissue to the engineering and transplantation of whole tooth structures, could result in exciting new treatment methods for clinicians in the near future. In this review, we discuss the limitations of natural healing and regeneration of various tissues of the oral complex, including teeth, periodontium and salivary glands, and summarize current treatment methods for tissue damage as well as research advances in oral tissue regeneration.

  4. [A device for mandibular advancement in respiratory disorders of sleep. Clinical study]. (United States)

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


    This study describes the technical steps for the making of a mandibular advancement device for sleep disordered patients (apnea index mandibule forward (SNB angle increases by 1.7 degrees) and downward (mandibular plane angle increases by 3 degrees, which can be related to the 7.4 mm anterior vertical height increase). The hyoid bone adopted a more distant position from the cervical vertebrae. Important individual variations were seen among the patients for the optimal repositioning of the mandible.

  5. Tibial crest fracture correction after tibial tuberosity advancement (TTA using a modified TTA technique

    Directory of Open Access Journals (Sweden)

    Tiago Carmagnani Prada


    Full Text Available Corrective osteotomies are challenging techniques that require specialized training and acquisition of specific materials. Nevertheless, they have been increasingly studied and used in clinical routine in the world. Several variations on the model and the application technique have been developed and refined in search of the improvement of surgical techniques and development of implants more affordable to purchase. The tibial tuberosity advancement (TTA consists on stabilization of tibial plateau perpendicular to the patellar tendon through the tibial tuberosity advancement. Our goal is to report a surgical complication of fracture of the tibial crest after TTA procedure. A dog with a confirmed diagnosis of rupture of the cranial cruciate ligament (CCLR was operated using conventional technique of TTA. After 3 days of surgery, the same animal had a fracture of the proximal tibial crest. The animal was sent back to surgery and was used a variation of TTA technique, with autologous iliac wing and three cortical screws. This variation of the technique was able to replace the original technique successfully.

  6. Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer.

    Directory of Open Access Journals (Sweden)

    Takeshi Ishikawa

    Full Text Available BACKGROUND: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT and that fibronectin CH296 (FN-CH296 together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer. METHODS: Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up. RESULTS: Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%. CONCLUSIONS: The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies. TRIAL REGISTRATION: UMIN UMIN000001835.

  7. Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years

    Directory of Open Access Journals (Sweden)

    Talita Stessuk


    Full Text Available BACKGROUND Chronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. OBJECTIVE This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. METHODS Four patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. RESULTS The results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. CONCLUSIONS Despite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells.

  8. Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years (United States)

    Stessuk, Talita; Ruiz, Milton Artur; Greco, Oswaldo Tadeu; Bilaqui, Aldemir; Ribeiro-Paes, Maria José de Oliveira; Ribeiro-Paes, João Tadeu


    Background Chronic obstructive pulmonary disease is a major inflammatory disease of the airways and an enormous therapeutic challenge. Within the spectrum of chronic obstructive pulmonary disease, pulmonary emphysema is characterized by the destruction of the alveolar walls with an increase in the air spaces distal to the terminal bronchioles but without significant pulmonary fibrosis. Therapeutic options are limited and palliative since they are unable to promote morphological and functional regeneration of the alveolar tissue. In this context, new therapeutic approaches, such as cell therapy with adult stem cells, are being evaluated. Objective This article aims to describe the follow-up of up to 3 years after the beginning of a phase I clinical trial and discuss the spirometry parameters achieved by patients with advanced pulmonary emphysema treated with bone marrow mononuclear cells. Methods Four patients with advanced pulmonary emphysema were submitted to autologous infusion of bone marrow mononuclear cells. Follow-ups were performed by spirometry up to 3 years after the procedure. Results The results showed that autologous cell therapy in patients having chronic obstructive pulmonary disease is a safe procedure and free of adverse effects. There was an improvement in laboratory parameters (spirometry) and a slowing down in the process of pathological degeneration. Also, patients reported improvements in the clinical condition and quality of life. Conclusions Despite being in the initial stage and in spite of the small sample, the results of the clinical protocol of cell therapy in advanced pulmonary emphysema as proposed in this study, open new therapeutic perspectives in chronic obstructive pulmonary disease. It is worth emphasizing that this study corresponds to the first study in the literature that reports a change in the natural history of pulmonary emphysema after the use of cell therapy with a pool of bone marrow mononuclear cells. PMID:24255620

  9. Evaluation of Resin Dissolution Using an Advanced Oxidation Process - 13241

    Energy Technology Data Exchange (ETDEWEB)

    Goulart de Araujo, Leandro; Vicente de Padua Ferreira, Rafael; Takehiro Marumo, Julio [Nuclear and Energy Research Institute, Av. Lineu Prestes, 2242., Sao Paulo, SP. (Brazil); Passos Piveli, Roque; Campos, Fabio [The Polytechnic School of the University of Sao Paulo, Av. Prof. Almeida Prado, 83, trav.2. Sao Paulo, SP (Brazil)


    The ion-exchange resin is widely used in nuclear reactors, in cooling water purification and removing radioactive elements. Because of the long periods of time inside the reactor system, the resin becomes radioactive. When the useful life of them is over, its re-utilization becomes inappropriate, and for this reason, the resin is considered radioactive waste. The most common method of treatment is the immobilization of spent ion exchange resin in cement in order to form a solid monolithic matrix, which reduces the radionuclides release into the environment. However, the characteristic of contraction and expansion of the resin limits its incorporation in 10%, resulting in high cost in its direct immobilization. Therefore, it is recommended the utilization of a pre-treatment, capable of reducing the volume and degrading the resin, which would increase the load capacity in the immobilization. This work aims to develop a method of degradation of ion spent resins from the nuclear research reactor of Nuclear and Energy Research Institute (IPEN/CNEN-SP), Brazil, using the Advanced Oxidative Process (AOP) with Fenton's reagent (hydrogen peroxide and ferrous sulphate as catalyst). The resin evaluated was a mixture of cationic (IR 120P) and anionic (IRA 410) resins. The reactions were conducted by varying the concentration of the catalyst (25, 50, 100 e 150 mM) and the volume of the hydrogen peroxide, at three different temperatures, 50, 60 and 70 deg. C. The time of reaction was three hours. Total organic carbon content was determined periodically in order to evaluate the degradation as a function of time. The concentration of 50 mM of catalyst was the most effective in degrading approximately 99%, using up to 330 mL of hydrogen peroxide. The most effective temperature was about 60 deg. C, because of the decomposition of hydrogen peroxide in higher temperatures. TOC content was influenced by the concentration of the catalyst, interfering in the beginning of the

  10. Using Machine Learning for Advanced Anomaly Detection and Classification (United States)

    Lane, B.; Poole, M.; Camp, M.; Murray-Krezan, J.


    Machine Learning (ML) techniques have successfully been used in a wide variety of applications to automatically detect and potentially classify changes in activity, or a series of activities by utilizing large amounts data, sometimes even seemingly-unrelated data. The amount of data being collected, processed, and stored in the Space Situational Awareness (SSA) domain has grown at an exponential rate and is now better suited for ML. This paper describes development of advanced algorithms to deliver significant improvements in characterization of deep space objects and indication and warning (I&W) using a global network of telescopes that are collecting photometric data on a multitude of space-based objects. The Phase II Air Force Research Laboratory (AFRL) Small Business Innovative Research (SBIR) project Autonomous Characterization Algorithms for Change Detection and Characterization (ACDC), contracted to ExoAnalytic Solutions Inc. is providing the ability to detect and identify photometric signature changes due to potential space object changes (e.g. stability, tumble rate, aspect ratio), and correlate observed changes to potential behavioral changes using a variety of techniques, including supervised learning. Furthermore, these algorithms run in real-time on data being collected and processed by the ExoAnalytic Space Operations Center (EspOC), providing timely alerts and warnings while dynamically creating collection requirements to the EspOC for the algorithms that generate higher fidelity I&W. This paper will discuss the recently implemented ACDC algorithms, including the general design approach and results to date. The usage of supervised algorithms, such as Support Vector Machines, Neural Networks, k-Nearest Neighbors, etc., and unsupervised algorithms, for example k-means, Principle Component Analysis, Hierarchical Clustering, etc., and the implementations of these algorithms is explored. Results of applying these algorithms to EspOC data both in an off

  11. The committee for advanced therapies' of the European Medicines Agency reflection paper on management of clinical risks deriving from insertional mutagenesis. (United States)

    Aiuti, Alessandro; Cossu, Giulio; de Felipe, Pablo; Galli, Maria Cristina; Narayanan, Gopalan; Renner, Matthias; Stahlbom, Axel; Schneider, Christian K; Voltz-Girolt, Caroline


    In the European Union, the Committee for Advanced Therapies of the European Medicines Agency takes the lead in the scientific assessment for marketing authorization applications for advanced therapy medicinal products, which include gene therapy medicinal products, somatic cell therapy medicinal products, and tissue-engineered products. The Committee for Advanced Therapies also takes the lead in defining the scientific framework for the quality, nonclinical and clinical development of such products. This reflection paper represents the Committee's current thinking on management of clinical risks deriving from insertional mutagenesis. A multidisciplinary approach to insertional mutagenesis is provided. This reflection paper has been adopted by the committee in its April 2013 meeting.

  12. Assessment of enthesitis in patients with psoriatic arthritis using clinical examination and ultrasound (United States)

    Kristensen, Salome; Christensen, Jeppe Hagstrup; Schmidt, Erik Berg; Olesen, Jens Lykkegaard; Johansen, Martin Berg; Arvesen, Kristian Bakke; Schlemmer, Annette


    Summary Background Enthesitis is a major feature of psoriatic arthritis. However, clinical assessment of enthesitis is known to lack accuracy and have poor interobserver reliability. Objective To determine effect of training on clinical assessment of enthesitis and to compare ultrasonography with clinical examination for the detection of entheseal abnormalities. Methods 20 rheumatologists performed repeated assessment of enthesitis in patients with established psoriatic arthritis before and after a 2-hour training session in standardised enthesitis count according to Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). Moreover, 20 patients underwent clinical and ultrasonographic examination of entheses to evaluate consensus-based elementary lesions of enthesitis. Results Training significantly increased Intra-class Correlation Coefficient for LEI from 0.18 to 0.82 and for SPARCC from 0.38 to 0.67. Ultrasound examination showed high associations between hypoechogenicity and increased thickness of the entheses and clinical examination. There was no correlation between erosions and enthesophytes found by ultrasound and clinical assessments. Conclusion Training in standardised enthesitis scoring systems significantly improved clinical assessments of enthesitis and should be performed before use in daily clinical practice. Ultrasound revealed more advanced stages of enthesitis, such as enthesophytes and erosions, which were not detected with clinical examination. PMID:27900299


    Directory of Open Access Journals (Sweden)

    V. N. Grygorenko


    Full Text Available The purpose of the work was to improve the treatment results among patients with clinically local and locally advanced prostate cancer while using neo-and/or adjuvant hormone- and radiotherapy.Materials and methods. Radical prostatectomy results estimation was conducted among 170 patients. An average survey period continued 35,99 ± 1,88 (1–102 months. An average age was 61,66 ± 0,45 (40–75 years. Moreover, after operation 125 (73,5 % patients proved to have clinically local forms of prostate cancer (рТ1а,b,c,2aN0М0 – 99, рТ2b,cN0М0 – 26, 25 (14,7 % patients – locally advanced forms (рТ3a,bN0М0 and 19 (11,2 % – generalized forms of prostate cancer (рТ4N0М0, рТ2а,bN1М0,. Metastases in pelvic lymph nodes developed among 10 (5,9 % patients. 43 (25,3 % patients with ІІ–III stages received neoadjuvant hormone therapy treatment due to maximum androgen blockade scheme. An average neoadjuvant hormone therapy duration: 10,14 ± 1,98 (1–60 months. The typical characteristic of modified radical prostatectomy is accurate ejection of urinary bladder neck and proximal area of prostatic urethra part from prostate gland. Already formed urethra-urethral anastomosis is additionally fixed to lateral part of endopelvic fascia.Results. An average 3-year survival made up 95,5 ± 3,5 %, 5-year – 84,1 ± 4,7 %, 7-year – 71,7 ± 6,8 % respectively. 3- and 5-year relapse-free survival comprised 87,05 ± 3,20 %, 79.64 ± 3,03 % 67,11 ± 3,93 % respectively. 5-year survival among patients with localized prostate cancer made up 97,18 ± 3,27 %. 48 (28,2 % patients proved to have biochemical relapse so that they were prescribed adjuvant hormone- and/or radiotherapy treatment. Gleason index ≥ and initial PSA level ≥ 20 ng/ml, and their combination are considered as significant factors that foresee Т > Т2 category and biochemical relapse. For рN+ category initial PSA ≥ 20 ng/ml level is principle. Frequency of disease relapse


    Directory of Open Access Journals (Sweden)

    V. N. Grygorenko


    Full Text Available The purpose of the work was to improve the treatment results among patients with clinically local and locally advanced prostate cancer while using neo-and/or adjuvant hormone- and radiotherapy.Materials and methods. Radical prostatectomy results estimation was conducted among 170 patients. An average survey period continued 35,99 ± 1,88 (1–102 months. An average age was 61,66 ± 0,45 (40–75 years. Moreover, after operation 125 (73,5 % patients proved to have clinically local forms of prostate cancer (рТ1а,b,c,2aN0М0 – 99, рТ2b,cN0М0 – 26, 25 (14,7 % patients – locally advanced forms (рТ3a,bN0М0 and 19 (11,2 % – generalized forms of prostate cancer (рТ4N0М0, рТ2а,bN1М0,. Metastases in pelvic lymph nodes developed among 10 (5,9 % patients. 43 (25,3 % patients with ІІ–III stages received neoadjuvant hormone therapy treatment due to maximum androgen blockade scheme. An average neoadjuvant hormone therapy duration: 10,14 ± 1,98 (1–60 months. The typical characteristic of modified radical prostatectomy is accurate ejection of urinary bladder neck and proximal area of prostatic urethra part from prostate gland. Already formed urethra-urethral anastomosis is additionally fixed to lateral part of endopelvic fascia.Results. An average 3-year survival made up 95,5 ± 3,5 %, 5-year – 84,1 ± 4,7 %, 7-year – 71,7 ± 6,8 % respectively. 3- and 5-year relapse-free survival comprised 87,05 ± 3,20 %, 79.64 ± 3,03 % 67,11 ± 3,93 % respectively. 5-year survival among patients with localized prostate cancer made up 97,18 ± 3,27 %. 48 (28,2 % patients proved to have biochemical relapse so that they were prescribed adjuvant hormone- and/or radiotherapy treatment. Gleason index ≥ and initial PSA level ≥ 20 ng/ml, and their combination are considered as significant factors that foresee Т > Т2 category and biochemical relapse. For рN+ category initial PSA ≥ 20 ng/ml level is principle. Frequency of disease relapse

  15. The Effect of“Metacognitive Strategy”on the Use of“Advance Organizer”

    Institute of Scientific and Technical Information of China (English)



    Advance organizer”is a practical teaching strategy proposed by American modern educational psychologist Ausubel in 1960. This research considers learners’use of metacognitive strategy in the teaching activities of“advance organizer”, trying to explore the effects of metacognitive strategy in the“advance organizer”teaching practices and testing whether“advance organiz⁃er”can effectively help students understand and retain reading materials. Further researches should be focused on how to conduct learners’“metacognitive strategy”training and employ learners’metacognitive strategies into“advance organizer”teaching activ⁃ities.

  16. Low dose dynamic myocardial CT perfusion using advanced iterative reconstruction (United States)

    Eck, Brendan L.; Fahmi, Rachid; Fuqua, Christopher; Vembar, Mani; Dhanantwari, Amar; Bezerra, Hiram G.; Wilson, David L.


    Dynamic myocardial CT perfusion (CTP) can provide quantitative functional information for the assessment of coronary artery disease. However, x-ray dose in dynamic CTP is high, typically from 10mSv to >20mSv. We compared the dose reduction potential of advanced iterative reconstruction, Iterative Model Reconstruction (IMR, Philips Healthcare, Cleveland, Ohio) to hybrid iterative reconstruction (iDose4) and filtered back projection (FBP). Dynamic CTP scans were obtained using a porcine model with balloon-induced ischemia in the left anterior descending coronary artery to prescribed fractional flow reserve values. High dose dynamic CTP scans were acquired at 100kVp/100mAs with effective dose of 23mSv. Low dose scans at 75mAs, 50mAs, and 25mAs were simulated by adding x-ray quantum noise and detector electronic noise to the projection space data. Images were reconstructed with FBP, iDose4, and IMR at each dose level. Image quality in static CTP images was assessed by SNR and CNR. Blood flow was obtained using a dynamic CTP analysis pipeline and blood flow image quality was assessed using flow-SNR and flow-CNR. IMR showed highest static image quality according to SNR and CNR. Blood flow in FBP was increasingly over-estimated at reduced dose. Flow was more consistent for iDose4 from 100mAs to 50mAs, but was over-estimated at 25mAs. IMR was most consistent from 100mAs to 25mAs. Static images and flow maps for 100mAs FBP, 50mAs iDose4, and 25mAs IMR showed comparable, clear ischemia, CNR, and flow-CNR values. These results suggest that IMR can enable dynamic CTP at significantly reduced dose, at 5.8mSv or 25% of the comparable 23mSv FBP protocol.

  17. Clinical and prognostic significance of pathological and inflammatory markers in the surgical treatment of locally advanced colorectal cancer (United States)

    Sokolov, M; Angelov, K; Vasileva, M; Atanasova, MP; Vlahova, A; Todorov, G


    Background Locally advanced colorectal cancer (CRC) may vary in its clinical and pathological appearance. It is now accepted that progression of disease in patients with locally advanced CRC is determined not only by local tumor characteristics but also by the immune system and inflammatory response in the body. Methods We investigated patients with confirmed CRC who were treated in the surgical clinic at the University Hospital Alexandrovska over a 10-year period and retrospectively evaluated the histological features of the preoperative biopsies and operative specimens removed during radical multivisceral resections. We also collected prospective data for serum C-reactive protein levels and Jass-Klintrup score, Petersen Index score, and Glasgow Prognostic Score in patients with locally advanced CRC. Results Of 1,105 patients with CRC, 327 (29.6%) were diagnosed with locally advanced disease. In total, 108 combined multivisceral resections (79 for primary tumors and 29 for recurrent tumors) were performed. Overall survival was 34 months for pR0 cases and 12 months for pR1 cases (P<0.05). Our data confirmed that C-reactive protein is a prognostic marker of overall survival. Data for 48 patients with histologically confirmed locally advanced tumors showed significantly increased survival with a higher Jass-Klintrup score (P=0.037). In patients with node-negative disease, 5-year survival was 49%. However, where there were high-risk pathological characteristics according to the Petersen Index, survival was similar to that for node-positive disease (P=0.702). Our data also showed a significant difference in survival between groups divided according to whether they had a modified Glasgow Prognostic Score of 1 or 2 (P=0.031). Conclusion In order to maintain a reasonable balance between an aggressive approach and so-called meaningless “surgical exorbitance”, we should focus on certain histopathological and inflammatory markers that can be identified as additional

  18. A Clinical Study on Global TCM Therapy in Treating Senile Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)


    Objective:To assess the clinical efficacy of global traditional Chinese medicine(TCM)therapy in treating senile advanced non-small cell lung cancer(NSCLC),with the aim of seeking a standardized,rational and economical way to treat advanced NSCLC in old patients.Methods:A retrospective analysis and comparison was carried out in 86 patients with senile advanced NSCLC,44 treated by global TCM(TCM group)and 42 by chemotherapy(control group)through dynamical observation on related indexes including tumor size,quality of life and the survival time,as well as on the fee for medical service at various time points in the course of the treatment.Results:The changes of tumor size,score of clinical main symptoms and behavior condition(by ZPS scoring),as well as survival rates in the two groups at corresponding time points,were not different significantly(P>0.05).The mean survival time in the TCM group was 13.20±1.52 months and that in the chemotherapy group was 13.45±1.94 months,showing insignificant difference between them.However,the median survival time in the TCM group(12 months)was actually longer than that in the chemotherapy group (9 months,P<0.05).The mean daily expense and the mean expense(RMB yuan)for each patient in the TCM group were significantly lower than that in the control group,which was 180.73±93.21 vs 825.84±329.63 for the mean daily expense and 34 077.21±14 638.04 vs 58 516.59±45 429.76 for the mean expense for each patient(both P<0.01).Conclusion:Treatment of senile advanced NSCLC with TCM alone has its apparent superiority in stabilizing tumor focus,improving clinical symptoms,elevating quality of life and prolonging the survival time.TCM is also less expensive,making it a good alternative therapeutic approach for this specific group of people.

  19. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances. (United States)

    Vrooman, Lynda M; Silverman, Lewis B


    While the majority of children and adolescents with newly diagnosed childhood acute lymphoblastic leukemia (ALL) will be cured, as many as 20 % of patients will experience relapse. On current treatment regimens, the intensity of upfront treatment is stratified based upon prognostic factors with the aim of improving cure rates (for those at the highest risk of relapse) and minimizing treatment-related morbidity (for lower-risk patients). Here we review advances in the understanding of prognostic factors and their application. We also highlight novel treatment approaches aimed at improving outcomes in childhood ALL.

  20. EDITORIAL: Advanced fractions? or use it or lose it (United States)

    Dobson, Ken


    kind of mixture of skill, knowledge and understanding required for successful mathematical operations is use it or lose it. We went `decimal' a long time ago, and the ideas of pence as 12ths of a shilling and shillings as 20ths of a pound are positively mediaeval for everyone under 40 or so. Remember farthings? In those days fractions were everywhere. Nowadays they are somewhat esoteric for the average citizen - and physicist. Yet fractions are vital in advanced mathematics, e.g. involving the differentiation and integration of polynomial fractions, as Peter Gill pointed out. This is why he was teaching simple fractions to his students, and possibly why their competence at these was such a good indicator of success in their end-of-year mathematics exam. What can we conclude from all this? I suggest two things. First, that fractions as illustrated above might well be considered as advanced mathematics, a fit and intriguing topic for an A-level course. Ordinary citizens should be taught - very thoroughly - to understand and use that useful kind of fraction based on dividing things into 100 parts, called percentages. Secondly, and more fundamentally, we should learn from this example to take a hard look at what we teach and what we need to teach, removing or adapting those things that exist in syllabuses and the National Curriculum for reasons of purely historical inertia. I hope that the IoP Working Party on Mathematics and Physics, due to report in the autumn, has looked hard at issues like this. And, of course, anyone interested in this topic is cordially invited to the Education Group's 16 - 19 Day Conference, which this year is about this vexed question of what mathematics physics learners need - and how they get it. At IoP Headquarters on Saturday, 15 November 1997. Details from Catherine Wilson.

  1. Quantitative (177)Lu SPECT imaging using advanced correction algorithms in non-reference geometry. (United States)

    D'Arienzo, M; Cozzella, M L; Fazio, A; De Felice, P; Iaccarino, G; D'Andrea, M; Ungania, S; Cazzato, M; Schmidt, K; Kimiaei, S; Strigari, L


    Peptide receptor therapy with (177)Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of (177)Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher (177)Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using μ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of (177)Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators.

  2. Using a clinical collaborative model for nursing education: application for clinical teaching. (United States)

    Maguire, Denise J; Zambroski, Cheryl H; Cadena, Sandra V


    The promise of a clinical collaborative model (CCM) is that it engages hospital partners in a mutually beneficial partnership by providing the entire student clinical experience in one institution. The CCM prepares students for the day-to-day reality of patient care through the use of individual staff nurse preceptors, enhancing the relationship between the student and hospital upon graduation. The authors describe a successful paradigm for student nurse clinical education across the baccalaureate program.

  3. Clinical and neurobiological advances in promoting regeneration of the ventral root avulsion lesion

    NARCIS (Netherlands)

    Eggers, R.; Tannemaat, Martijn R; De Winter, F.; Malessy, Martijn J A; Verhaagen, J.


    Root avulsions due to traction to the brachial plexus causes complete and permanent loss of function. Until fairly recent, such lesions were considered impossible to repair. Here we review clinical repair strategies and current progress in experimental ventral root avulsion lesions. The current gold

  4. Advanced echocardiography and clinical surrogates to risk stratify and manage patients with structural heart disease

    NARCIS (Netherlands)

    Debonnaire, Philippe Jean Marc Rita


    Part I focuses on the potential role of 3-dimensional echocardiography. At first a clinical risk score model for prediction of outcome in patients undergoing TAVI is presented (Chapter 2). Second the role of 3D-echocardiography is explored in depth in patients with mitral valve disease. Different no

  5. Clinical application of brain MRI in parkinsonism. From basic to advanced imaging

    NARCIS (Netherlands)

    Meijer, F.J.A.


    Parkinson’s disease is a neurodegenerative disorder with increased prevalence at raising age, and the most frequent cause of parkinsonism. In clinical practice, differentiating Parkinson’s disease from the various forms of neurodegenerative atypical parkinsonism can be difficult, especially in the e

  6. Clinical use of an enterprise data warehouse. (United States)

    Evans, R Scott; Lloyd, James F; Pierce, Lee A


    The enormous amount of data being collected by electronic medical records (EMR) has found additional value when integrated and stored in data warehouses. The enterprise data warehouse (EDW) allows all data from an organization with numerous inpatient and outpatient facilities to be integrated and analyzed. We have found the EDW at Intermountain Healthcare to not only be an essential tool for management and strategic decision making, but also for patient specific clinical decision support. This paper presents the structure and two case studies of a framework that has provided us the ability to create a number of decision support applications that are dependent on the integration of previous enterprise-wide data in addition to a patient's current information in the EMR.

  7. Use of the human patient simulator to teach clinical judgment skills in a baccalaureate nursing program. (United States)

    Rhodes, Mattie L; Curran, Cynthia


    Nurse educators are finding it increasingly more challenging to prepare undergraduate students for the ever-changing and more acute clinical environment. As an answer to this dilemma, the human patient simulator can provide students with the opportunity to enhance knowledge, to facilitate skill acquisition, to decrease anxiety, and to promote clinical judgment in a safe environment. These experiences assist the novice nursing student to progress to the advanced beginner stage of practice. This article describes how faculty used the human patient simulator in creating a case scenario that enhanced critical thinking in senior nursing students.

  8. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

    Directory of Open Access Journals (Sweden)

    LM Benneker


    Full Text Available Intervertebral disc (IVD degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

  9. The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Masanobu Takahashi

    Full Text Available 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.

  10. Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

    Directory of Open Access Journals (Sweden)

    Asanuma Hiroko


    Full Text Available Abstract Background We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. Methods We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. Results In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1, and another had general malaise (grade 1 and fever (grade 1. Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD. Immunologically, in 3 of the 10 patients (30%, an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%, although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. Conclusion This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more

  11. Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying


    Objective: To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods: Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores(NRS), Corrected serum calcium(CSC) and CSC effective rate. The vital signs, biochemical and hematological parameters were determined. Results: Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion(5.92 vs 3.25,P<0.01;6.13 vs 4.38, P<0.01, respectively). The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion: Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

  12. Comparison of prone versus supine 18F-FDG-PET of locally advanced breast cancer: Phantom and preliminary clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Jason M.; Rani, Sudheer D.; Li, Xia; Whisenant, Jennifer G.; Abramson, Richard G. [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 and Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232 (United States); Arlinghaus, Lori R. [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 (United States); Lee, Tzu-Cheng [Department of Bioengineering, University of Washington, Seattle, Washington 98195 (United States); MacDonald, Lawrence R.; Partridge, Savannah C. [Department of Radiology, University of Washington, Seattle, Washington 98195 (United States); Kang, Hakmook [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 and Department of Biostatistics, Vanderbilt University, Nashville, Tennessee 37232 (United States); Linden, Hannah M. [Department of Medical Oncology, University of Washington, Seattle, Washington 98195 (United States); Kinahan, Paul E. [Department of Radiology, University of Washington, Seattle, Washington 98195 (United States); Department of Bioengineering, University of Washington, Seattle, Washington 98195 (United States); Department of Physics, University of Washington, Seattle, Washington 98195 (United States); Department of Electrical Engineering, University of Washington, Seattle, Washington 98195 (United States); Yankeelov, Thomas E., E-mail: [Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Physics, Vanderbilt University, Nashville, Tennessee 37232 (United States); Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232 (United States)


    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

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

    NARCIS (Netherlands)

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


    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

  14. Bridging the gap between education and appropriate use of benzodiazepines in psychiatric clinical practice (United States)

    Dell’Osso, Bernardo; Albert, Umberto; Atti, Anna Rita; Carmassi, Claudia; Carrà, Giuseppe; Cosci, Fiammetta; Del Vecchio, Valeria; Di Nicola, Marco; Ferrari, Silvia; Goracci, Arianna; Iasevoli, Felice; Luciano, Mario; Martinotti, Giovanni; Nanni, Maria Giulia; Nivoli, Alessandra; Pinna, Federica; Poloni, Nicola; Pompili, Maurizio; Sampogna, Gaia; Tarricone, Ilaria; Tosato, Sarah; Volpe, Umberto; Fiorillo, Andrea


    More than half a century after their discovery, benzodiazepines (BDZs) still represent one of the largest and most widely prescribed groups of psychotropic compounds, not only in clinical psychiatry but also in the entire medical field. Over the last two decades, however, there has been an increased focus on the development of antidepressants and antipsychotics on the part of the pharmaceutical industry, clinicians, and researchers, with a reduced interest in BDZs, in spite of their widespread clinical use. As a consequence, many psychiatric residents, medical students, nurses, and other mental health professionals might receive poor academic teaching and training regarding these agents, and have the false impression that BDZs represent an outdated chapter in clinical psychopharmacology. However, recent advances in the field, including findings concerning epidemiology, addiction risk, and drug interactions, as well as the introduction of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition with related diagnostic changes, strongly encourage an updated appraisal of the use of BDZs in clinical practice. During a recent thematic event convened with the aim of approaching this topic in a critical manner, a group of young Italian psychiatrists attempted to highlight possible flaws in current teaching pathways, identify the main clinical pros and cons regarding current use of BDZs in clinical practice, and provide an updated overview of their use across specific clinical areas and patient populations. The main results are presented and discussed in this review. PMID:26257524

  15. Use of the experience sampling method in the context of clinical trials (United States)

    Verhagen, Simone J W; Hasmi, Laila; Drukker, Marjan; van Os, J; Delespaul, Philippe A E G


    Objective The experience sampling method (ESM) is a structured diary technique to appraise subjective experiences in daily life. It is applied in psychiatric patients, as well as in patients with somatic illness. Despite the potential of ESM assessment, the improved logistics and its increased administration in research, its use in clinical trials remains limited. This paper introduces ESM for clinical trials in psychiatry and beyond. Methods ESM is an ecologically valid method that yields a comprehensive view of an individual's daily life. It allows the assessment of various constructs (eg, quality of life, psychopathology) and psychological mechanisms (eg, stress-sensitivity, coping). These constructs are difficult to assess using cross-sectional questionnaires. ESM can be applied in treatment monitoring, as an ecological momentary intervention, in clinical trials, or in single case clinical trials. Technological advances (eg, smartphone applications) make its implementation easier. Results Advantages of ESM are highlighted and disadvantages are discussed. Furthermore, the ecological nature of ESM data and its consequences are explored, including the potential pitfalls of ambiguously formulated research questions and the specificities of ESM in statistical analyses. The last section focuses on ESM in relation to clinical trials and discusses its future use in optimising clinical decision-making. Conclusions ESM can be a valuable asset in clinical trial research and should be used more often to study the benefits of treatment in psychiatry and somatic health. PMID:27443678

  16. Stealing the Sword: Limiting Terrorist Use of Advanced Conventional Weapons (United States)


    sniper rifles and their accessories and advanced ammunition. For those weapons, only awareness and the precautions taken by security forces can...Qa’idat AI-Jihad fi Bilad al-Rafidayn Revolutionary Armed Forces of Colombia (FARC) al-Fatah Moro Islamic Liberation Front (MILF) Liberation Tigers of...a small terrorist cell that had to raise operational funds on its own. 14 For additional discussion of counterstrategies, see Jackson, Chalk, et al

  17. Elements Explaining Learning Clinical Reasoning Using Simulation Games

    Directory of Open Access Journals (Sweden)

    Jaana-Maija Koivisto


    Full Text Available This article presents the findings on which elements in a game-based simulation affect learning clinical reasoning in nursing education. By using engaging gaming elements in virtual simulations and integrating the clinical reasoning process into game mechanics, games can enhance learning clinical reasoning and offer meaningful learning experiences. The study was designed to explore how nursing students experience gaming and learning when playing a simulation game, as well as which gaming elements explain learning clinical reasoning. The data was collected by questionnaire from nursing students (N = 166 in autumn 2014 over thirteen gaming sessions. The findings showed that usability, application of nursing knowledge, and exploration have the most impact on learning clinical reasoning when playing simulation games. Findings also revealed that authentic patient-related experiences, feedback, and reflection have an indirect effect on learning clinical reasoning. Based on these results, more efficient simulation games to improve clinical reasoning may be developed.   

  18. Clinical experience with temsirolimus in the treatment of advanced renal cell carcinoma. (United States)

    Zanardi, Elisa; Verzoni, Elena; Grassi, Paolo; Necchi, Andrea; Giannatempo, Patrizia; Raggi, Daniele; De Braud, Filippo; Procopio, Giuseppe


    Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR) kinase, a protein that has been shown to be particularly active in metastatic renal cell carcinoma (mRCC) with poor prognosis. Therefore, temsirolimus should be considered as the first-line treatment indicated in mRCC patients classified as poor risk. The benefits of temsirolimus are not limited to an increased survival but are also related to a better quality of life, which is certainly one of the most important aspects in the clinical management of these frail patients. Temsirolimus is a well-tolerated treatment, and the most frequent adverse events are manageable with supportive care. To this end, the identification of predictive factors of response to temsirolimus could help us to better select patients and obtain a more tailored clinical management of mRCC.


    Benneker, L.M.; Andersson, G.; Iatridis, J.C.; Sakai, D.; Härtl, R.; Ito, K.; Grad, S.


    Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encourageing results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium “Where Science meets Clinics”, sponsored by the AO Foundation and held in Davos, Switzerland, from September 5–7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imageing methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neurogenesis. Discogenic pain, originating from “black discs” or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in outline order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects. PMID:24802611

  20. Advancing our thinking in presence-only and used-available analysis

    NARCIS (Netherlands)

    Warton, D.; Aarts, G.M.


    1. The problems of analysing used-available data and presence-only data are equivalent, and this paper uses this equivalence as a platform for exploring opportunities for advancing analysis methodology. 2. We suggest some potential methodological advances in used-available analysis, made possible vi

  1. A multidisciplinary clinical treatment of locally advanced rectal cancer complicated with rectovesical fistula: a case report

    Directory of Open Access Journals (Sweden)

    Zhan Tiancheng


    Full Text Available Abstract Introduction Rectal cancer with rectovesical fistula is a rare and difficult to treat entity. Here, we describe a case of rectal cancer with rectovesical fistula successfully managed by multimodality treatment. To the best of our knowledge, this is the first such case report in the literature. Case presentation A 51-year-old Chinese man was diagnosed as having rectal cancer accompanied by rectovesical fistula. He underwent treatment with neoadjuvant radiochemotherapy combined with total pelvic excision and adjuvant chemotherapy, as recommended by a multimodality treatment team. Post-operative pathology confirmed the achievement of pathological complete response. Conclusions This case suggests that a proactive multidisciplinary treatment is needed to achieve complete cure of locally advanced rectal cancer even in the presence of rectovesical fistula.

  2. Clinical evaluation of intra-arterial infusion chemoradiotherapy for advanced or recurrent cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kaneyasu, Yuko; Fukuhara, Noboru; Karasawa, Kumiko; Isobe, Madoka; Himei, Kengo; Kojima, Nahoko; Toda, Jo; Okawa, Tomohiko [Tokyo Women`s Medical Coll. (Japan); Kita, Midori


    Fifty two patients with advanced or recurrent cervical cancer were treated by intraarterial infusion chemotherapy (IAIC) with or without radiotherapy. IAIC regimen was separated into two groups: group I consisted of 5-FU+MMC{+-}ADR (30 patients) and group II consisted of CDDP+MMC{+-}5-FU (22 patients). The tip of the catheter was placed in the bifurcation of abdominal aorta or the bilateral internal iliac arteries (7 patients). Overall response rate (CR+PR) was 71% for all patients, 87% in patients who received radiotherapy, 50% in those not receiving radiotherapy, and 100% in primary patients. Five-year survival rate was 20% in primary patients, 14% in recurrent patients, 3% in group I and 38% in group II (p=0.00182) by chemotherapy regimen, 30% in CR patients, and 13% in non-CR patients (p=0.00436), respectively. Acute hematological side effects of grade III-IV was 48% for all patients, but recovered from by interruption of drugs. Among the 7 patients which the tip of the catheter was placed in internal iliac arteries, there were severe skin ulcers in 2 cases, and severe leg or gluteal region pain, for which narcotics were needed in 2 patients. These data suggest that IAIC mainly with cisplatin with or without radiotherapy was not particularly effective treatment for advanced cervical cancer, but it might be one of the effective treatment for residual cervical cancer after surgery and recurrent cervical cancer once the patient has obtained CR. One should check the blood flow distribution periodically, and control the concentration of drugs. In order to improve prognosis of these patients, one should furthermore consider a combination of IAIC and systemic chemotherapy. (author)

  3. 21 CFR 862.2485 - Electrophoresis apparatus for clinical use. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrophoresis apparatus for clinical use. 862.2485 Section 862.2485 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Instruments § 862.2485 Electrophoresis apparatus for clinical use. (a) Identification. An...

  4. Characteristics of student preparedness for clinical learning: clinical educator perspectives using the Delphi approach

    Directory of Open Access Journals (Sweden)

    Chipchase Lucinda S


    Full Text Available Abstract Background During clinical placements, clinical educators facilitate student learning. Previous research has defined the skills, attitudes and practices that pertain to an ideal clinical educator. However, less attention has been paid to the role of student readiness in terms of foundational knowledge and attitudes at the commencement of practice education. Therefore, the aim of this study was to ascertain clinical educators’ views on the characteristics that they perceive demonstrate that a student is well prepared for clinical learning. Methods A two round on-line Delphi study was conducted. The first questionnaire was emailed to a total of 636 expert clinical educators from the disciplines of occupational therapy, physiotherapy and speech pathology. Expert clinical educators were asked to describe the key characteristics that indicate a student is prepared for a clinical placement and ready to learn. Open-ended responses received from the first round were subject to a thematic analysis and resulted in six themes with 62 characteristics. In the second round, participants were asked to rate each characteristic on a 7 point Likert Scale. Results A total of 258 (40.56% responded to the first round of the Delphi survey while 161 clinical educators completed the second (62.40% retention rate. Consensus was reached on 57 characteristics (six themes using a cut off of greater than 70% positive respondents and an interquartile deviation IQD of equal or less than 1. Conclusions This study identified 57 characteristics (six themes perceived by clinical educators as indicators of a student who is prepared and ready for clinical learning. A list of characteristics relating to behaviours has been compiled and could be provided to students to aid their preparation for clinical learning and to universities to incorporate within curricula. In addition, the list provides a platform for discussions by professional bodies about the role of placement

  5. Advance in clinical research of Exendin-4%Exendin-4临床研究进展

    Institute of Scientific and Technical Information of China (English)

    全会标; 高勇义


    Exendin-4是胰高血糖素样肽-1(GLP-1)受体激动剂,Exendin-4与GLP-1具有53%的同源性.GLP-1是主要的肠促胰素(进餐后肠道分泌的激素),它通过葡萄糖依赖的方式促进胰岛素分泌、抑制胰高糖素分泌、延缓胃排空、增加饱腹感等作用维持血糖的稳定.在2型糖尿病(T2DM)患者中,它可以改善B细胞功能.天然的GLP-1半衰期很短,仅约2min,无法应用于临床;Exendin-4是从巨蜥唾液中分离得到的一种多肽,可与GLP-1受体结合,产生与GLP-1相似的生理效应,半衰期长达9.6h,用于治疗T2DM每天皮下注射两次可得到满意的疗效.临床研究显示Exendin-4可显著降低T2DM患者空腹及餐后血糖、HbAIc,显著降低体重和改善脂代谢.动物研究表明Exendin-4增加B细胞数量.由于Exendin-4的独特疗效,新近的糖尿病治疗指南已将其列入2型糖尿病的治疗药物.%Exendin-4 is a agonist of mammalian glucagon-like peptide-1 ( GLP-1 ) receptor,which has a 53% amino acid sequence overlap with GLP-1. Incretins are gut hormones,which stimulate insulin secretion after meal. One of the incretin hormones,GLP-1,contributes to glucose homeostasis by stimulation of insulin secretion in a glucose dependent manner,suppression of glucagon secretion, slowing of gastric emptying, and induction of satiety. It can also improve beta cell function in type 2 diabetes. However,due to its short biological half-life (less than 2 minutes), GLP-1 itself is not practical for type 2 diabetes therapy. Exendin-4 is a peptide found in the lizard's saliva and has a high similarity to GLP-1. It has a much longer biological half-life (about 9.6 hours) than GLP-1 and is a GLP-1 receptor agonist that can be used for therapeutic purpose by twice daily injection. Clinical studies with exendin-4 have shown a significant reduction in fasting and postprandial glucose,HbA1c and body weight in type 2 diabetic patients,it also ameliorated the patient's lipid metabolism. Animal

  6. Reexamination of the ethics of placebo use in clinical practice. (United States)

    Asai, Atsushi; Kadooka, Yasuhiro


    A placebo is a substance or intervention believed to be inactive, but is administered by the healthcare professional as if it was an active medication. Unlike standard treatments, clinical use of placebo usually involves deception and is therefore ethically problematic. Our attitudes toward the clinical use of placebo, which inevitably includes deception or withholding information, have a tremendous effect on our practice regarding truth-telling and informed consent. A casual attitude towards it weakens the current practice based on shared decision-making and mutual trust between patients and healthcare professionals. Issues concerning the clinical use of placebo are thus intimately related to patient-provider relationships, the public's trust in medicine, and medical education. A review of recent survey studies suggests that the clinical use of placebo appears to be fairly well accepted among healthcare professionals and is common in clinical settings in various countries. However, we think that an ethical discussion is urgently needed because of its controversial nature. If judged to be ethically wrong, the practice should end. In the present paper, we discuss the ethicality of the clinical use of placebo with deception and argue against it, concluding that it is unethical and should be banned. We will show that most arguments in favor of the clinical use of placebo can be refuted and are therefore incorrect or weak. These arguments will be presented and examined individually. Finally, we will briefly consider issues relevant to the clinical use of placebo without deception.

  7. Advances in functional and structural imaging of the human lung using proton MRI. (United States)

    Miller, G Wilson; Mugler, John P; Sá, Rui C; Altes, Talissa A; Prisk, G Kim; Hopkins, Susan R


    The field of proton lung MRI is advancing on a variety of fronts. In the realm of functional imaging, it is now possible to use arterial spin labeling (ASL) and oxygen-enhanced imaging techniques to quantify regional perfusion and ventilation, respectively, in standard units of measurement. By combining these techniques into a single scan, it is also possible to quantify the local ventilation-perfusion ratio, which is the most important determinant of gas-exchange efficiency in the lung. To demonstrate potential for accurate and meaningful measurements of lung function, this technique was used to study gravitational gradients of ventilation, perfusion, and ventilation-perfusion ratio in healthy subjects, yielding quantitative results consistent with expected regional variations. Such techniques can also be applied in the time domain, providing new tools for studying temporal dynamics of lung function. Temporal ASL measurements showed increased spatial-temporal heterogeneity of pulmonary blood flow in healthy subjects exposed to hypoxia, suggesting sensitivity to active control mechanisms such as hypoxic pulmonary vasoconstriction, and illustrating that to fully examine the factors that govern lung function it is necessary to consider temporal as well as spatial variability. Further development to increase spatial coverage and improve robustness would enhance the clinical applicability of these new functional imaging tools. In the realm of structural imaging, pulse sequence techniques such as ultrashort echo-time radial k-space acquisition, ultrafast steady-state free precession, and imaging-based diaphragm triggering can be combined to overcome the significant challenges associated with proton MRI in the lung, enabling high-quality three-dimensional imaging of the whole lung in a clinically reasonable scan time. Images of healthy and cystic fibrosis subjects using these techniques demonstrate substantial promise for non-contrast pulmonary angiography and detailed

  8. Comparison of desired radiographic advancement distance and true advancement distance required for patellar tendon-tibial plateau angle reduction to the ideal 90° in dogs by use of the modified Maquet technique. (United States)

    Pillard, Paul; Livet, Veronique; Cabon, Quentin; Bismuth, Camille; Sonet, Juliette; Remy, Denise; Fau, Didier; Carozzo, Claude; Viguier, Eric; Cachon, Thibaut


    OBJECTIVE To evaluate the validity of 2 radiographic methods for measurement of the tibial tuberosity advancement distance required to achieve a reduction in patellar tendon-tibial plateau angle (PTA) to the ideal 90° in dogs by use of the modified Maquet technique (MMT). SAMPLE 24 stifle joints harvested from 12 canine cadavers. PROCEDURES Radiographs of stifle joints placed at 135° in the true lateral position were used to measure the required tibial tuberosity advancement distance with the conventional (A(M)) and correction (A(E)) methods. The MMT was used to successively advance the tibial crest to A(M) and A(E). Postoperative PTA was measured on a mediolateral radiograph for each advancement measurement method. If none of the measurements were close to 90°, the advancement distance was modified until the PTA was equal to 90° within 0.1°, and the true advancement distance (TA) was measured. Results were used to determine the optimal commercially available size of cage implant that would be used in a clinical situation. RESULTS Median A(M) and A(E) were 10.6 mm and 11.5 mm, respectively. Mean PTAs for the conventional and correction methods were 93.4° and 92.3°, respectively, and differed significantly from 90°. Median TA was 13.5 mm. The A(M) and A(E) led to the same cage size recommendations as for TA for only 1 and 4 stifle joints, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Both radiographic methods of measuring the distance required to advance the tibial tuberosity in dogs led to an under-reduction in postoperative PTA when the MMT was used. A new, more accurate radiographic method needs to be developed.

  9. Using cost accounting data to improve clinical value. (United States)

    Andrianos, J; Dykan, M


    Value in health care can be defined as the provision of appropriate care at appropriate cost. While appropriate care is the province of clinical providers, cost data usually is maintained by financial managers. Collaboration between clinical providers and financial managers therefore is essential if optimum value is to be created. To this end, cost data are frequently given to providers for use in clinical care improvement projects. One such project has been implemented successfully at Virginia Mason Medical Center, Seattle, Washington.

  10. Use of "big data" in drug discovery and clinical trials. (United States)

    Taglang, Guillaume; Jackson, David B


    Oncology is undergoing a data-driven metamorphosis. Armed with new and ever more efficient molecular and information technologies, we have entered an era where data is helping us spearhead the fight against cancer. This technology driven data explosion, often referred to as "big data", is not only expediting biomedical discovery, but it is also rapidly transforming the practice of oncology into an information science. This evolution is critical, as results to-date have revealed the immense complexity and genetic heterogeneity of patients and their tumors, a sobering reminder of the challenge facing every patient and their oncologist. This can only be addressed through development of clinico-molecular data analytics that provide a deeper understanding of the mechanisms controlling the biological and clinical response to available therapeutic options. Beyond the exciting implications for improved patient care, such advancements in predictive and evidence-based analytics stand to profoundly affect the processes of cancer drug discovery and associated clinical trials.

  11. Positive Porn: Educational, Medical, and Clinical Uses (United States)

    Watson, Mary Ann; Smith, Randyl D.


    Despite its widespread use, pornography has been vilified as a symptom of personal and cultural depravity and as a cause of rape, aggression, devaluation of women, and marital dissolution. Yet in some cases there may be personal, relational, and social value to the use of sexually explicit material. In this paper, we briefly review the literature,…

  12. The Use of Bibliotherapy in Clinical Practice. (United States)

    Smith, Darrell; Burkhalter, Johnny K.


    Surveyed 158 members of American Academy of Psychotherapists in attempt to identify primary users of bibliotherapy, problems for which bibliotherapy seems most applicable, and reading resources that are being used effectively. Found that bibliotherapy was used often, particularly with childrearing skills and sexual dysfunctions. Years of…

  13. Attitudes and Beliefs towards Disease and Treatment in Patients with Advanced Cancer Using Anthroposophical Medicine. (United States)

    von Rohr, E.; Pampallona, S.; van Wegberg, B.; Cerny, T.; Hürny, C.; Bernhard, J.; Helwig, S.; Heusser, P.


    BACKGROUND: In Switzerland, anthroposophical medicine has a long tradition, offers a special tumor treatment, is frequently used by cancer patients, and has been approved in 1998 by the Swiss government to be reimbursed by health insurances. This popularity contrasts with the fact that to date no sound evidence of the effectiveness of anthroposophical cancer treatments exists. In this study we draw a profile on a population of patients with advanced disease attending treatment at the anthroposophical Lukas Clinic (LC) regarding patients' attitudes, experiences and expectations. PATIENTS AND METHODS: All newly admitted patients with a diagnosis of locally advanced or metastasized breast, gastrointestinal, lung or gynecological cancer were recruited into a registration study. In parallel, a population of patients with the same inclusion criteria attending a conventional institution (Institute of Medical Oncology, University of Bern, IMO) was taken as a reference sample. Data were collected by means of a fully structured interview, and simple descriptive statistics was used for evaluation. RESULTS: 221 and 280 patients accrued at LC and at IMO, respectively. LC patients were mainly women (87%), had a good education (36% with completed college or university education), and were admitted on average 3.5 months after the diagnosis of advanced disease. With respect to their advanced cancer, they put very little hope in the effectiveness of conventional medicine, but expected great help from anthroposophical treatment. Compared with the reference population they cared more for psychological well-being and quality of life, but an important factor for choosing treatment at the LC was clearly the patients' strong belief in the effectiveness of anthroposophical treatment. CONCLUSIONS: With its holistic approach, anthroposophical medicine intends to provide tumor treatment together with supportive care throughout the course of the illness. To some patients this is an attractive

  14. The use of PRA in the development of ALWR (advanced light water reactor) design requirements. [Advanced Light Water Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Summitt, R.L. (Safety and Reliability Optimization Services, Inc., Knoxville, TN (USA)); Additon, S.L. (TENERA, L.P., Bethesda, MD (USA)); Pasedag, W.F. (USDOE, Washington, DC (USA))


    The current hiatus in nuclear power plant orders provides an opportunity for the development of advanced light water reactor (ALWR) design concepts and regulatory requirements which incorporate the insights gained from the application of the probabilistic risk assessment. The US Department of Energy is assisting the Electric Power Research Institute (EPRI) in the incorporation of PRA insights into the specification of the utility requirements, and reactor vendors in support of the conceptual design of safety systems, for such advanced plants. This paper reviews the applications of PRA methods in this development of specifications for, and the design of simplified, rugged ALWRs with a significantly improved risk profile. Specific examples of the impact of utilizing published PRA insights, construction and use of functional PRA models, and feedback of PRA experience into the specification of the key assumptions and groundrules for ALWR PRAs are presented. 13 refs., 3 tabs.

  15. Defending Against Advanced Persistent Threats Using Game-Theory. (United States)

    Rass, Stefan; König, Sandra; Schauer, Stefan


    Advanced persistent threats (APT) combine a variety of different attack forms ranging from social engineering to technical exploits. The diversity and usual stealthiness of APT turns them into a central problem of contemporary practical system security, since information on attacks, the current system status or the attacker's incentives is often vague, uncertain and in many cases even unavailable. Game theory is a natural approach to model the conflict between the attacker and the defender, and this work investigates a generalized class of matrix games as a risk mitigation tool for an advanced persistent threat (APT) defense. Unlike standard game and decision theory, our model is tailored to capture and handle the full uncertainty that is immanent to APTs, such as disagreement among qualitative expert risk assessments, unknown adversarial incentives and uncertainty about the current system state (in terms of how deeply the attacker may have penetrated into the system's protective shells already). Practically, game-theoretic APT models can be derived straightforwardly from topological vulnerability analysis, together with risk assessments as they are done in common risk management standards like the ISO 31000 family. Theoretically, these models come with different properties than classical game theoretic models, whose technical solution presented in this work may be of independent interest.

  16. Defending Against Advanced Persistent Threats Using Game-Theory (United States)

    König, Sandra; Schauer, Stefan


    Advanced persistent threats (APT) combine a variety of different attack forms ranging from social engineering to technical exploits. The diversity and usual stealthiness of APT turns them into a central problem of contemporary practical system security, since information on attacks, the current system status or the attacker’s incentives is often vague, uncertain and in many cases even unavailable. Game theory is a natural approach to model the conflict between the attacker and the defender, and this work investigates a generalized class of matrix games as a risk mitigation tool for an advanced persistent threat (APT) defense. Unlike standard game and decision theory, our model is tailored to capture and handle the full uncertainty that is immanent to APTs, such as disagreement among qualitative expert risk assessments, unknown adversarial incentives and uncertainty about the current system state (in terms of how deeply the attacker may have penetrated into the system’s protective shells already). Practically, game-theoretic APT models can be derived straightforwardly from topological vulnerability analysis, together with risk assessments as they are done in common risk management standards like the ISO 31000 family. Theoretically, these models come with different properties than classical game theoretic models, whose technical solution presented in this work may be of independent interest. PMID:28045922

  17. Advanced clinical interpretation of the WAIS-IV and WMS-IV: prevalence of low scores varies by level of intelligence and years of education. (United States)

    Brooks, Brian L; Holdnack, James A; Iverson, Grant L


    Clinicians can use the base rates of low scores in healthy people to reduce the likelihood of misdiagnosing cognitive impairment. In the present study, base rates were developed for the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and Wechsler Memory Scale-Fourth Edition (WMS-IV) using 900 healthy adults and validated on 28 patients with moderate or severe traumatic brain injuries (TBIs). Results indicated that healthy people obtain some low scores on the WAIS-IV/WMS-IV, with prevalence rates increasing with fewer years of education and lower predicted intelligence. When applying the base rates information to the clinical sample, the TBI patients were 13 times more likely to be identified as having a low cognitive profile compared with the controls. Using the base rates information is a psychometrically advanced method for establishing criteria to determine low cognitive abilities on the WAIS-IV/WMS-IV.

  18. Chemotherapies and targeted therapies in advanced hepatocellular carcinoma: from laboratory to clinic. (United States)

    Voiculescu, Mihai; Winkler, Robert E; Moscovici, Marius; Neuman, Manuela G


    Chronic liver diseases alone or in conjunction with other risk factors result in increased liver damage leading to inflammation and fibrosis of the liver and rising rates of liver cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). This review will address the determinants of liver injury at the initiation of the tumor and the risk factors for rapid disease progression. Regardless of the etiology, the unifying feature of these tumors are their propensity to arise upon a background of inflammation and fibrosis. Liver disease is often associated with enhanced hepatocyte apoptosis, which is the case in viral and autoimmune hepatitis, cholestatic diseases, and metabolic disorders. Disruption of apoptosis is responsible for HCC. The mechanisms by which apoptosis occurs in the liver might provide insights into HCC and suggest possible treatments. We aim to better understand the factors that distinguish a relatively long course of HCC from one with rapid progression. We will accomplish this task with three integrated ideas: 1 - the role of epidemiology in establishing the risk factors of co-morbidity with alcohol and hepatitis viruses; 2 - the role of apoptosis and anti-apoptotic signals in the progression of HCC; and 3 - the role of new advancements that have emerged in the field of molecular-directed chemotherapeutics in HCC in recent years. This review will also aim to describe the molecular targeted therapies of non-resectable HCC and the ways of effective combination in this otherwise chemo-resistant tumor.

  19. Clinical utility of vandetanib in the treatment of patients with advanced medullary thyroid cancer

    Directory of Open Access Journals (Sweden)

    Deshpande H


    Full Text Available Hari Deshpande1,3, Vicky Marler3, Julie Ann Sosa2,31Department of Medicine, 2Department of Surgery, Yale University School of Medicine, 3Yale Cancer Center, New Haven, CT, USAAbstract: Vandetanib (ZD6474 became the first systemic agent to be approved for the treatment of metastatic or locally advanced medullary thyroid cancer. It was a proof of principle, because it is an orally bioavailable medication that targets the growth factors felt to be important in the pathogenesis of this disease, ie, the rearranged during transfection proto-oncogene and vascular endothelial growth factor receptor. It was tested initially in two Phase II studies at doses of 100 mg and 300 mg daily. Although activity was seen at both doses, the higher dose was chosen for a randomized, placebo-controlled Phase II study. This trial, which accrued more than 300 patients, showed a statistically significant benefit for the group taking vandetanib compared with those taking placebo medication. Progression-free survival for the vandetanib arm has not been reached, compared with 19 months for the placebo arm. The main toxicity appears to be diarrhea, although some patients experienced significant side effects, including torsades de pointes and sudden cardiac death. Therefore, it is now necessary for practitioners to enroll in a Risk Evaluation Mitigation Strategy before being allowed to prescribe this medication, to reduce the risk of serious side effects occurring.Keywords: ZD6474, medullary thyroid cancer, vandetanib

  20. Efficacy and clinical/molecular predictors of erlotinib monotherapy for Chinese advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHU Yu-jia; XIA Ying; REN Guan-jun; WANG Meng-zhao; ZENG Xuan; ZHANG Li


    Background A retrospective analysis of clinical data were conducted reviewing patients who were given erlotinib at Peking Union Medical College (PUMC) Hospital from May 2005 to December 2009. Relationships between clinical factors, epidermal growth factor receptor (EGFR) mRNA expression, EGFR gene mutations, KRAS gene mutations and clinical outcomes were investigated in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods Patients with stage ⅢB/Ⅳ NSCLC who had not previously participated in erlotinib related clinical trials were enrolled into this study. All patients were given oral erlotinib 150 mg per day. Tumor samples of some patients were accessed with mutant-enriched polymerase chain reaction assay (EGFR, KRAS gene mutations) and multiplex branched DNA assay (EGFR mRNA expression).Results Seventy-nine patients were enrolled in this study, 23 patients had a partial response (PR), 36 patients had a stable disease (SD), 20 patients had a PD, with an objective response rate of 29.1%, and a disease control rate of 74.7%.Females (P=0.023), non-smokers (P=0.013), patients with a skin rash (P=0.047), and with highly differentiated tumors (P=0.037) were significantly correlated with the objective response rate. Patients with a lower ECOG PS (P=0.002),highly differentiated tumors (P=0.014), non-smokers (P=0.002), and patients with a skin rash (P <0.001) were significantly correlated with the disease control rate. The median progression-free survival was 35 weeks (95% CI: 13-57 weeks) and 1-year survival was 72.3%. Highly-differentiated tumors (P=0.027) and patients with a skin rash (P <0.001)were significantly correlated with PFS. Seventeen patients were tested for EGFR/KRAS gene mutations and EGFR mRNA expression. Progression-free survival (PFS) of patients with EGFR exon 19/21 mutations was 66 weeks, longer than patients with wild type EGFR exon 19/21 (P=0.018). No significant relationships were found between EGFR mRNA expression, EGFR

  1. Almanac 2011: acute coronary syndromes. The national society journals present selected research that has driven recent advances in clinical cardiology. (United States)

    Knight, Charles J; Timmis, Adam D


    This overview highlights some recent advances in the epidemiology, diagnosis, risk stratification and treatment of acute coronary syndromes. The sheer volume of new studies reflects the robust state of global cardiovascular research but the focus here is on findings that are of most interest to the practising cardiologist. Incidence and mortality rates for myocardial infarction are in decline, probably owing to a combination of lifestyle changes, particularly smoking cessation, and improved pharmacological and interventional treatment. Troponins remain central for diagnosis and new high-sensitivity assays are further lowering detection thresholds and improving outcomes. The incremental diagnostic value of other circulating biomarkers remains unclear and for risk stratification simple clinical algorithms such as the GRACE score have proved more useful. Primary PCI with minimal treatment delay is the most effective reperfusion strategy in ST elevation myocardial infarction (STEMI). Radial access is associated with less bleeding than with the femoral approach, but outcomes appear similar. Manual thrombectomy limits distal embolisation and infarct size while drug-eluting stents reduce the need for further revascularisation procedures. Non-culprit disease is best dealt with electively as a staged procedure after primary PCI has been completed. The development of antithrombotic and antiplatelet regimens for primary PCI continues to evolve, with new indications for fondaparinux and bivalirudin as well as small-molecule glycoprotein (GP)IIb/IIIa inhibitors. If timely primary PCI is unavailable, fibrinolytic treatment remains an option but a strategy of early angiographic assessment is recommended for all patients. Non-ST segment elevation myocardial infarction(NSTEMI) is now the dominant phenotype and out-comes after the acute phase are significantly worse than for STEMI. Many patients with NSTEMI remain undertreated and there is a large body of recent work seeking to

  2. Mapping clinically useful terminology to a controlled medical vocabulary. (United States)

    Barrows, R. C.; Cimino, J. J.; Clayton, P. D.


    We have mapped clinically used diagnostic terms from a legacy ambulatory care system to the separate controlled vocabulary of our central clinical information system. The methodology combines elements of lexical and morphologic text matching techniques, followed by manual physician review. Results of the automated matching algorithm before and after partial manual review are presented. The results of this effort will permit the migration of coded clinical data from one system to another. Output from the system after the term review process will be fed back to the target vocabulary via automated and semi-automated means to improve its clinical utility. PMID:7949922

  3. Clinical efficacy evaluation of Liujunzi decoction combined with EP chemotherapy regiment for advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xin-Jun Xiong; Long-Jun Xiong


    Objective:To analyze the clinical efficacy of Liujunzi decoction combined with EP chemotherapy regiment for advanced non-small cell lung cancer.Methods:A total of 72 cases of patients with non-small cell lung cancer were included in the study, the range of patients’ treatment was from August 2012 to October 2014, and according to different treatment, they were divided into observation group 36 cases and control group 36 cases. Control group received EP chemotherapy, observation group received Liujunzi decoction combined with EP chemotherapy regiment, and then differences in serum tumor marker levels, tumor tissue-related protein levels, PDCD5, Nrf2, HIF-1α and GLUT1 levels, and levels of VEGF, GSTs, TSGF and so on were compared between two groups.Results:Serum CY211, SCC, NSE, CEA and CA199 levels of observation group after treatment were lower than those of control group; TUBB3, ERCC-1, MT and P53 expression levels of observation group after treatment were lower while Mcll and Fbw7 expression levels were higher; PDCD5 level of observation group after treatment was higher than that of control group while Nrf2, HIF-1α and GLUT1 levels were lower than those of control group; CD4+CD25+Foxp3+ Treg/CD4+ T, VEGF, GSTs and TSGF values of observation group after treatment were lower than those of control group. Conclusion:Liujunzi decoction combined with EP chemotherapy regiment for patients with advanced non-small cell lung cancer can effectively inhibit tumor cell proliferation as well as invasion and metastasis, is helpful for disease control and prognosis improvement, and has positive clinical significance.

  4. Enhancing endothelial progenitor cell for clinical use

    Institute of Scientific and Technical Information of China (English)


    Circulating endothelial progenitor cells (EPCs) havebeen demonstrated to correlate negatively with vascularendothelial dysfunction and cardiovascular risk factors.However, translation of basic research into the clinicalpractice has been limited by the lack of unambiguousand consistent definitions of EPCs and reduced EPCcell number and function in subjects requiring them forclinical use. This article critically reviews the definitionof EPCs based on commonly used protocols, their valueas a biomarker of cardiovascular risk factor in subjectswith cardiovascular disease, and strategies to enhanceEPCs for treatment of ischemic diseases.

  5. Recent advances in Gilles de la Tourette syndrome: implications for clinical practice and future research. (United States)

    Leckman, J F; Cohen, D J


    The clinical presentation and natural history of Gilles de la Tourette syndrome (TS) are reviewed. The waxing and waning of symptoms, the rostrocaudal progression of areas of motor involvement, complex stereotypies, and the familial aggregation of TS and chronic multiple tics are suggestions of underlying neurochemical disturbance; whereas attentional problems, impulsivity and obsessive-compulsive behaviors create interesting links with other disorders. The most robust metabolic findings are the lowered CSF HVA in many TS patients, and the positive response of symptoms to dopamine blockers and clonidine particularly, which would be consistent with dopamine receptor hypersensitivity and possible noradrenergic-dopaminergic interactions in TS. However, no definitive account of patho-physiology or genetic contributions to the disorder is yet available.

  6. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. (United States)

    Sechi, Gianpietro; Serra, Alessandro


    Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from thiamine deficiency, which is associated with significant morbidity and mortality. According to autopsy-based studies, the disorder is still greatly underdiagnosed in both adults and children. In this review, we provide an update on the factors and clinical settings that predispose to Wernicke's encephalopathy, and discuss the most recent insights into epidemiology, pathophysiology, genetics, diagnosis, and treatment. To facilitate the diagnosis, we classify the common and rare symptoms at presentation and the late-stage symptoms. We emphasise the optimum dose of parenteral thiamine required for prophylaxis and treatment of Wernicke's encephalopathy and prevention of Korsakoff's syndrome associated with alcohol misuse. A systematic approach helps to ensure that patients receive a prompt diagnosis and adequate treatment.

  7. Stress and coping research. Methodological challenges, theoretical advances, and clinical applications. (United States)

    Somerfield, M R; McCrae, R R


    Coping is among the most widely studied topics in contemporary psychology. However, the explosion of interest in coping has yielded little and the field is in crisis. This section offers a survey of the state of the art in theory and research on stress and adaptational processes. The four core articles in the section take up, respectively, problems in research design, the neglect of unconscious reactions to stress, the selection of adaptational outcomes, and the link between research on adaptational processes and clinical practice. The final article by Richard S. Lazarus offers a commentary. The present introduction provides the historical backdrop for the section. Then, after a brief overview of research on adaptational processes, the authors summarize the scope and yield of coping research and preview the four core articles in the section. The strengths and limits of individual coping efforts and the need for realistic expectations and redoubled efforts are discussed.

  8. It's Elementary: Expanding the Use of School-Based Clinics (United States)

    Lear, Julia Graham


    Governor Arnold Schwarzenegger has declared his intention to open health centers in 500 elementary schools across the state, which would bring the total number of such school-based clinics to 646. This initiative builds on California's 30-year history of using the school setting to increase access to care for children, improve clinical outcomes,…

  9. Reasoning Processes Used by Paramedics to Solve Clinical Problems (United States)

    Alexander, Melissa


    The purpose of this exploratory qualitative study was to determine the reasoning processes used by paramedics to solve clinical problems. Existing research documents concern over the accuracy of paramedics' clinical decision-making, but no research was found that examines the cognitive processes by which paramedics make either faulty or accurate…

  10. Preclinical evaluation of intraoperative low-energy photon radiotherapy using sphericalapplicators in locally advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    François eBuge


    Full Text Available Background: Surgery plus adjuvant radiotherapy is standard care for locally advanced prostatecancer (stage pT3R1. Intraoperative low-energy photon radiotherapy offers several advantages overexternal beam radiotherapy, and several systems are now available for its delivery, using sphericalapplicators which require only limited shielding. The aim of this study was to evaluate the feasibilityof this technique for the prostate bed.Materials & Methods: Applicators were assessed using MRI image data and cadavericdissection. In cadavers, targeted tissues, defined as a urethral section, both neurovascular bundlesections, the bladder neck and the beds of the seminal vesicles, were marked with metallic surgicalclips. Distances between clips and applicator were measured using CT. A dosimetric study of theapplication of 12 Gy at 5mm depth was performed using CT images of prostatectomized cadavers.Results: Using MRI images from 34 prostate cancer patients, we showed that the ideal applicatordiameter ranges from 45 to 70 mm. Using applicators of different sizes to encompass the prostate bedin nine cadavers, we showed that the distance between target tissues and applicator was less than 2mm for all target tissues except the upper extremity of the seminal vesicles (19 mm. Dosimetric studyshowed a good dose distribution in all target tissues in contact with the applicator, with a lowprobability of rectum and bladder complication.Conclusions: Intraoperative radiotherapy of the prostate bed is feasible, with good coverage oftargeted tissues. Clinical study of safety and efficacy is now required.

  11. Clinical consequences of nonnarcotic analgesic use. (United States)

    Matzke, G R


    The accuracy of the economic analysis of the selected adverse events evaluated by McGoldrick and Bailie is questionable. The quantitative perspective on the economics of the adverse events associated with nonnarcotic analgesic use proposed by these authors is limited by the fact that they have combined data on over 30 different NSAIDs into a single value for comparison with two single-entity agents: acetaminophen and aspirin. The relative prevalence of major organ system toxicities varies markedly among the NSAIDs, and this variance invalidates the use of a class conclusion approach. Their conservative incidence estimates, the lack of data in some areas (i.e., hepatic injury), and the exclusion of combination analgesics further limit the utility of their conclusions. However, it is difficult to argue authoritatively that the relative costs of toxicities associated with the three analgesic classes they reviewed are not representative. The ultimate question is, "What is the optimal analgesic for a given patient?" This question can be addressed only if one considers the underlying cause of pain, its chronicity/acuity, the patient's concurrent disease states, if any, and the potential for drug interactions with the patient's concomitant medications. McGoldrick and Bailie concluded on an economic basis that acetaminophen is the analgesic of choice for most patients, including those with impaired renal function. This recommendation is in agreement with those of the Analgesics and the Kidney Ad Hoc Committee of the National Kidney Foundation. It also would seem prudent to use acetaminophen as the first-line agent for those patients in whom aspirin and NSAID use should be avoided or used only with caution along with frequent monitoring of renal function, blood pressure, electrolytes, and/or coagulation status. Thus, there is little to no controversy in their recommendation to initiate treatment with acetaminophen. The authors, however, also suggested that switching

  12. Clinical study on the D4 lymph nodes excision in advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Bo Jian Jiang; Hong Qiang Wang; Rong Xun Sun; You Fu Gao; Hao Shen


    AIM To study the safety and the traumatic degree of D4 approach by retrospective analysis of the para-operative data from the para-aortic lymph nodes excision in comparison with those from standard radicalresection in advanced gastric cancer (AGC).METHODS Several para-operative data including the resectability, the mortality, the complicatedmorbidity, the amount of transfused blood, and the hospitalized days relating to the operation were analyzedstatistically between D4(n = 30) and D2 lymph nodes excision (n = 34) groups. The data expressed as means±SD was analyzed statistically by Student t test. Percentage of the data was analyzed by x2 test statistically.It was taken as significant difference if P value was less than 0.05.RESULTS The percentage of palliated resection in D4 group was significantly lower than that in D2 group(16.67% vs 47.06%, P<0.05). This D4 radical resection would indeed prolong the drainage time (7.35±0.98 days vs 14.78±2.16 days, P < 0.01). The amount of transfused blood during operation (774.32±112.09mL) and the operative consuming time in D4 group (7.14±0.39h) increased significantly toocompared with those in D2 group (538.67±59.87mL, P < 0.05; 4.12±0.18h, P < 0.05), suggesting that thedraumatic degree of D4 operation was severer than that of D2 operation. But the mortality, the morbidity ofcomplication and the hospitalized time after D4 operation did not increase significantly, indicating that D4lymph nodes excision as a choice of the surgical treatment of AGC was safe and feasible.CONCLUSION D4 lymph nodes excision for AGC is safe, reasonable and feasible.

  13. Recent advances in bariatric/metabolic surgery: appraisal of clinical evidence. (United States)

    Lee, Wei-Jei; Almulaifi, Abdullah


    Obesity and associated type 2 diabetes mellitus (T2DM) are becoming a serious medical issue worldwide. Bariatric surgery has been shown to be the most effective and durable therapy for the treatment of morbid obese patients. Increasing data indicates bariatric surgery as metabolic surgery is an effective and novel therapy for not well controlled obese T2DM patients. The review of recent developments in bariatric/metabolic surgery covers 4 major fields. 1) Improvement of safety: recent advances in laparoscopic/metabolic surgery has made this minimal invasive surgery more than ten times safer than a decade ago. The safety profile of laparoscopic/metabolic surgery is compatible with that of laparoscopic cholecystectomy now. 2) New bariatric/metabolic surgery: laparoscopic sleeve gastrectomy (LSG) is becoming the leading bariatric surgery because of its simplicity and efficacy. Other new procedures, such as gastric plication, banded plication, single anastomosis (mini) gastric bypass and Duodeno-jejunal bypass with sleeve gastrectomy have all been accepted as treatment modalities for bariatric/metabolic surgery. 3) Mechanism of bariatric/metabolic surgery: Restriction is the most important mechanism for bariatric surgery. Weight regain after bariatric surgery is usually associated with loss of restriction. Recent studies demonstrated that gut hormone, microbiota and bile acid changes after bariatric surgery may play an important role in durable weight loss as well as in T2DM remission. However, weight loss is still the cornerstone of T2DM remission after metabolic surgery. 4) PATIENT SELECTION: patients who may benefit most from bariatric surgery was found to be patients with insulin resistance. For Asian T2DM patients, the indication of metabolic surgery has been set to those with not well controlled (HbA1c > 7.5%) disease and with their BMI > 27.5 Kg/m(2). A novel diabetes surgical score, ABCD score, is a simple system for predicting the success of surgical therapy

  14. Plan of advanced satellite communications experiment using ETS-VI (United States)

    Shiomi, Tadashi


    Communications Research Laboratory (CRL, Ministry of Posts and Telecommunications, Japan) has been engaged in development of three advanced satellite communication payloads aiming at experiments by Japan's 2-ton class Engineering Test Satellite VI (ETS-VI) which is to be launched in H-II rocket by NASDA in August 1992. CRL's three experimental systems are: (1) S-band inter-satellite communications; (2) millimeter-wave inter-satellite and personal-satellite communications; and (3) optical inter-satellite communications. CRL develops experimental optical communication system with telescope of 75 mm diameter which has gimbal mirror beam pointing/tracking mechanism. The onboard system has fundamental optical communication functions with laser diode transmitter of wavelength 0.83 micron, laser beam point-ahead mechanism, receiver of wavelength 0.51 micron, modulation/demodulation subsystem, and so on.

  15. Clinical efficacy of Colgate Total Advanced Fresh and a commercially available breath-freshening dentifrice in reducing mouth-odor-causing bacteria. (United States)

    Vazquez, Joe; Pilch, Shira; Williams, Malcolm I; Cummins, Diane


    The objective of this double-blind clinical study was to compare the long-lasting overnight (10- to 12-hour) and 4-hour effects of Colgate Total Advanced Fresh toothpaste to a commercial fluoridated breath-freshening dentifrice in controlling the level of mouth-odor-causing bacteria. Thirty-two adult men and women from New Jersey participated in the randomized, crossover design clinical study. After a 1-week "washout" period of brushing with a regular fluoride dentifrice, subjects refrained from dental hygiene, eating, and drinking in preparation for the morning visit. After providing a baseline salivary sample, subjects were issued a soft-bristled toothbrush and instructed to brush their teeth twice a day (once in the morning and once before bed) for 1 minute with the assigned test dentifrice. After a 7-day product use cycle, the subjects returned to the test site, having refrained from dental hygiene, eating, and drinking. Subjects provided an overnight salivary sample (10 to 12 hours postbrushing). Subjects then ate, brushed for 1 minute with the assigned dentifrice, and returned for 2- and 4-hour postbrushing evaluations. Subjects refrained from dental hygiene, eating, or drinking during the 4-hour evaluation period. To collect the oral microflora samples, subjects rinsed with 10 mL of sterile water for 10 seconds and deposited their samples into sterile tubes. Each collected sample was serially diluted in sterile phosphate-buffered saline and duplicate-plated onto lead acetate agar. When plated onto this medium, mouth-odor-causing bacteria that produce hydrogen sulfide appear as dark pigmented colonies. After 96 hours of incubation, hydrogen-sulfide-producing bacteria were counted, expressed as log colony-forming units per milliliter, and reduction from baseline was calculated. The results of this clinical study support the conclusion that Colgate Total Advanced Fresh provides a significantly greater reduction in mouth-odor-causing bacteria than a commercial

  16. Using advanced mobile devices in nursing practice--the views of nurses and nursing students. (United States)

    Johansson, Pauline; Petersson, Göran; Saveman, Britt-Inger; Nilsson, Gunilla


    Advanced mobile devices allow registered nurses and nursing students to keep up-to-date with expanding health-related knowledge but are rarely used in nursing in Sweden. This study aims at describing registered nurses' and nursing students' views regarding the use of advanced mobile devices in nursing practice. A cross-sectional study was completed in 2012; a total of 398 participants replied to a questionnaire, and descriptive statistics were applied. Results showed that the majority of the participants regarded an advanced mobile device to be useful, giving access to necessary information and also being useful in making notes, planning their work and saving time. Furthermore, the advanced mobile device was regarded to improve patient safety and the quality of care and to increase confidence. In order to continuously improve the safety and quality of health care, advanced mobile devices adjusted for nursing practice should be further developed, implemented and evaluated in research.

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

    Directory of Open Access Journals (Sweden)

    Vázquez S


    Full Text Available Sergio Vázquez,1 Joaquín Casal,2 Francisco Javier Afonso Afonso,3 José Luis Fírvida,4 Lucía Santomé,5 Francisco Barón,6 Martín Lázaro,7 Carolina Pena,7 Margarita Amenedo,8 Ihab Abdulkader,9 Carmen González-Arenas,10 Laura Fachal,11 Ana Vega11 On behalf of the Galician Lung Cancer Group (GGCP1Medical Oncology Department, Lucus Augusti University Hospital, Lugo, 2Medical Oncology Department, University Hospital Complex of Vigo, Pontevedra, 3Medical Oncology Department, University Hospital Complex of Ferrol, Ferrol, 4Medical Oncology Department, University Hospital Complex of Ourense, Ourense, 5Medical Oncology Department Povisa Hospital, Vigo, 6Medical Oncology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 7Medical Oncology Department, Hospital Complex of Pontevedra, Pontevedra, 8Medical Oncology Department, Oncology Center of Galicia, A Coruña, 9Anatomical Pathology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 10AstraZeneca, Madrid, 11Galician Public Foundation of Genomic Medicine-SERGAS, Santiago de Compostela Clinic Hospital, Santiago de Compostela, Spain 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

  18. Policy Implications of the Use of Retail Clinics. (United States)

    Weinick, Robin M; Pollack, Craig Evan; Fisher, Michael P; Gillen, Emily M; Mehrotra, Ateev


    Retail clinics, located within larger retail stores, treat a limited number of acute conditions and offer a small set of preventive services. Although there are nearly 1,200 such clinics in the United States, a great deal about their utilization, relationships with other parts of the health care system, and quality of care remains unknown. The federal government has taken only limited action regarding retail clinics, and little evidence exists about the potential costs and benefits of integrating retail clinics into federal programs and initiatives. Through a literature review, semistructured interviews, and a panel of experts, the authors show that retail clinics have established a niche in the health care system based on their convenience and customer service. Levels of patient satisfaction and of the quality and appropriateness of care appear comparable to those of other provider types. However, we know little about the effects of retail clinic use on preventive services, care coordination, and care continuity. As clinics begin to expand into other areas of care, including chronic disease management, and as the number of patients with insurance increases and the shortage of primary care physicians continues, answering outstanding questions about retail clinics' role in the health care system will become even more important. These changes will create new opportunities for health policy to influence both how retail clinics function and the ways in which their care is integrated with that of other providers.

  19. Recent advances in bariatric/metabolic surgery: appraisal of clinical evidence

    Institute of Scientific and Technical Information of China (English)

    Wei-Jei Lee; Abdullah Almulaifi


    Obesity and associated type 2 diabetes mellitus (T2DM) are becoming a serious medical issue worldwide.Bariatric surgery has been shown to be the most effective and durable therapy for the treatment of morbid obese patients.Increasing data indicates bariatric surgery as metabolic surgery is an effective and novel therapy for not well controlled obese T2DM patients.The review of recent developments in bariatric/metabolic surgery covers 4 major fields.1) Improvement of safety:recent advances in laparoscopic/metabolic surgery has made this minimal invasive surgery more than ten times safer than a decade ago.The safety profile of laparoscopic/metabolic surgery is compatible with that of laparoscopic cholecystectomy now.2) New bariatric/metabolic surgery:laparoscopic sleeve gastrectomy (LSG) is becoming the leading bariatric surgery because of its simplicity and efficacy.Other new procedures,such as gastric plication,banded plication,single anastomosis (mini) gastric bypass and Duodeno-jejunal bypass with sleeve gastrectomy have all been accepted as treatment modalities for bariatric/metabolic surgery.3)Mechanism of bariatric/metabolic surgery:Restriction is the most important mechanism for bariatric surgery.Weight regain after bariatric surgery is usually associated with loss of restriction.Recent studies demonstrated that gut hormone,microbiota and bile acid changes after bariatric surgery may play an important role in durable weight loss as well as in T2DM remission.However,weight loss is still the cornerstone of T2DM remission after metabolic surgery.4) Patient selection:patients who may benefit most from bariatric surgery was found to be patients with insulin resistance.For Asian T2DM patients,the indication of metabolic surgery has been set to those with not well controlled (HbA1c > 7.5%) disease and with their BMI > 27.5 Kg/m2.A novel diabetes surgical score,ABCD score,is a simple system for predicting the success of surgical therapy for T2DM.

  20. Advanced oxidation protein products in plasma: stability during storage and correlation with other clinical characteristics. (United States)

    Matteucci, E; Biasci, E; Giampietro, O


    Proteins are susceptible to free radical damage. We measured advanced oxidation protein products (AOPP) in the plasma of 56 hospitalised patients. Concentrations of AOPP were expressed as chloramine-T equivalents by measuring absorbance in acidic conditions at 340 nm in the presence of potassium iodide. We also determined erythrocyte sedimentation rate (ESR), circulating urea, creatinine, glucose, uric acid, electrolytes, lipids, total proteins and fractions and fibrinogen. Twenty-four samples were processed both immediately and after 7, 15, 30, 90, 180 and 438 days of storage at both at -20 degrees C and -80 degrees C (aliquots were frozen and thawed only once) to evaluate AOPP stability. The remaining 32 samples were also processed for thiobarbituric-acid-reactive substances (TBARS). Mean AOPP concentration in all 56 patients was 48.3+/-37.2 microM. Mean basal concentration of AOPP in the 24 plasma samples (55.0+/-47.1 microM) showed no significant change at each intermediate determination, yet significantly increased after 438 days of storage both at -80 degrees C (96.6+/-83.2, p<0.01) and, markedly, at -20 degrees C (171.3+/-94.6, p<0.001). TBARS concentration was 1.59+/-0.65 micromol/l. Multiple regression analysis evidenced that AOPP concentration was positively correlated (multiple r=0.62, p<0.001) with serum urea and triglycerides, but negatively correlated with patient age (indeed, serum albumin and total proteins decreased with increasing age, r=0.3, p<0.05). TBARS concentration was associated with ESR and serum glucose (multiple r=0.73, p<0.001), yet positively with AOPP (r=0.39, simple p<0.05). We conclude that AOPP remain stable during sample storage both at -20 degrees C and -80 degrees C for 6 months. Renal failure and hypertriglyceridemia probably enhance the in vivo process of AOPP formation. Oxidative damage as measured by TBARS may be increased because of exposure to hyperglycemia causing nonenzymatic glycation of plasma proteins.

  1. Clinical and neurobiological advances in promoting regeneration of the ventral root avulsion lesion. (United States)

    Eggers, Ruben; Tannemaat, Martijn R; De Winter, Fred; Malessy, Martijn J A; Verhaagen, Joost


    Root avulsions due to traction to the brachial plexus causes complete and permanent loss of function. Until fairly recent, such lesions were considered impossible to repair. Here we review clinical repair strategies and current progress in experimental ventral root avulsion lesions. The current gold standard in patients with a root avulsion is nerve transfer, whereas reimplantation of the avulsed root into the spinal cord has been performed in a limited number of cases. These neurosurgical repair strategies have significant benefit for the patient but functional recovery remains incomplete. Developing new ways to improve the functional outcome of neurosurgical repair is therefore essential. In the laboratory, the molecular and cellular changes following ventral root avulsion and the efficacy of intervention strategies have been studied at the level of spinal motoneurons, the ventral spinal root and peripheral nerve, and the skeletal muscle. We present an overview of cell-based pharmacological and neurotrophic factor treatment approaches that have been applied in combination with surgical reimplantation. These interventions all demonstrate neuroprotective effects on avulsed motoneurons, often accompanied with various degrees of axonal regeneration. However, effects on survival are usually transient and robust axon regeneration over long distances has as yet not been achieved. Key future areas of research include finding ways to further extend the post-lesion survival period of motoneurons, the identification of neuron-intrinsic factors which can promote persistent and long-distance axon regeneration, and finally prolonging the pro-regenerative state of Schwann cells in the distal nerve.

  2. Recent advances in the pathogenesis and clinical evaluation of pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    G.A. Margaritopoulos


    Full Text Available Interstitial lung diseases (ILDs are a group of heterogeneous disorders, either idiopathic or associated with injurious or inflammatory causes, in which the major site of damage is the lung interstitium. For a long time, knowledge regarding pathogenesis was trivial and there were difficulties in diagnosing and subsequently treating these diseases. During the past decade, however, there has been an impressive development in the field of ILDs. Idiopathic pulmonary fibrosis, the most common and fatal form of ILD, was initially believed to be due to an inflammatory response to unknown lung injury, whereas nowadays it is believed to be the result of multiple injuries at different sites of the lung followed by aberrant repair. The integration of clinical, radiological and histological data, namely a multidisciplinary team (MDT approach, has provided grounds for a more accurate diagnosis of ILDs, and helped the identification of different entities and development of different therapeutic approaches. However, because of the complexity of ILDs, even this approach may fail to establish a confident diagnosis. How should the clinician behave in this case and what are the pitfalls of the MDT approach? In addition, since diagnosis is the major predictor of prognosis, are there any other tools available to predict prognosis?

  3. Posaconazole: An Update of Its Clinical Use

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    Simon Leung


    Full Text Available Posaconazole (PCZ is a relatively new addition to the azole antifungals. It has fungicidal activities against Aspergillus fumigatus, Blastomyces dermatitidis, selected Candida species, Crytopcoccus neoformans, and Trichosporon. PCZ also has fungistatic activities against Candida, Coccidioides, selected Fusarium spp., Histoplasma, Scedosporium and Zygomycetes. In addition, combining the drug with caspofungin or amphotericin B results in a synergistic interaction against A. fumigatus, C. glabrata and C. neoformans. The absorption of PCZ suspension is enhanced when given with food, nutritional supplements, and carbonated beverages. Oral administration of PCZ in divided doses also increases its bioavailability. PCZ has a large volume of distribution and is highly protein bound (>95%. The main elimination route of PCZ is fecal. PCZ is an inhibitor of the CYP3A4 enzyme; therefore, monitoring for drug-drug interactions is warranted with other CYP3A4 substrates/inhibitors/inducers. The most common adverse effects include headache, fatigue, nausea, vomiting and elevated hepatic enzymes. PCZ, with its unique antifungal activities, expands the azole class of antifungal agents. Because of its limit in formulation, PCZ oral suspension is recommended in immunocompromised patients with functional gastrointestinaltracts who fail conventional antifungal therapies or who are suspected to have a breakthrough fungal infection. However, a delayed-release tablet formulation and intravenous (IV injection became available in 2014, expanding the use of PCZ in other patient populations, including individuals who are unable to take oral formulations.

  4. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. (United States)

    Yuan, Jianda; Adamow, Matthew; Ginsberg, Brian A; Rasalan, Teresa S; Ritter, Erika; Gallardo, Humilidad F; Xu, Yinyan; Pogoriler, Evelina; Terzulli, Stephanie L; Kuk, Deborah; Panageas, Katherine S; Ritter, Gerd; Sznol, Mario; Halaban, Ruth; Jungbluth, Achim A; Allison, James P; Old, Lloyd J; Wolchok, Jedd D; Gnjatic, Sacha


    Ipilimumab, a monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4), has been shown to improve survival in patients with advanced metastatic melanoma. It also enhances immunity to NY-ESO-1, a cancer/testis antigen expressed in a subset of patients with melanoma. To characterize the association between immune response and clinical outcome, we first analyzed NY-ESO-1 serum antibody by ELISA in 144 ipilimumab-treated patients with melanoma and found 22 of 140 (16%) seropositive at baseline and 31 of 144 (22%) seropositive following treatment. These NY-ESO-1-seropositive patients had a greater likelihood of experiencing clinical benefit 24 wk after ipilimumab treatment than NY-ESO-1-seronegative patients (P = 0.02, relative risk = 1.8, two-tailed Fisher test). To understand why some patients with NY-ESO-1 antibody failed to experience clinical benefit, we analyzed NY-ESO-1-specific CD4(+) and CD8(+) T-cell responses by intracellular multicytokine staining in 20 NY-ESO-1-seropositive patients and found a surprising dissociation between NY-ESO-1 antibody and CD8 responses in some patients. NY-ESO-1-seropositive patients with associated CD8(+) T cells experienced more frequent clinical benefit (10 of 13; 77%) than those with undetectable CD8(+) T-cell response (one of seven; 14%; P = 0.02; relative risk = 5.4, two-tailed Fisher test), as well as a significant survival advantage (P = 0.01; hazard ratio = 0.2, time-dependent Cox model). Together, our data suggest that integrated NY-ESO-1 immune responses may have predictive value for ipilimumab treatment and argue for prospective studies in patients with established NY-ESO-1 immunity. The current findings provide a strong rationale for the clinical use of modulators of immunosuppression with concurrent approaches to favor tumor antigen-specific immune responses, such as vaccines or adoptive transfer, in patients with cancer.

  5. Effects of Narrative Script Advance Organizer Strategies Used to Introduce Video in the Foreign Language Classroom (United States)

    Ambard, Philip D.; Ambard, Linda K.


    The study compared participant comprehension of foreign language video content using two advance organizer (AO) strategies while exploring the benefits of AOs as proficiency increases. Participants were 50 advanced-beginner Spanish college students in three sections. Collaborative reading condition participants read a target language narrative…

  6. Clinical outcomes and immune reconstitution in 103 advanced AIDS patients undergoing 12-month highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    DAI Yi; QIU Zhi-feng; LI Tai-sheng; HAN Yang; ZUO Ling-yan; XIE Jing; MA Xiao-jun; LIU Zheng-yin; WANG Ai-xia


    Background Highly active antiretroviral therapy (HAART) roduces profound suppression of HIV replication, substantial increase in CD4+ T cells, and partial reconstitution of the immune system. However, the numbers of subjects were small in previous Chinese studies. This study evaluated the efficacy and side effects of HAART in Chinese advanced AIDS patients.Methods One hundred and three antiretroviral drug naive AIDS patients were enrolled in this study and were divided into two groups by their baseline CD4+ count: <100 cells/ μl or ≥ 100 cells/μl. Clinical, virological and immunological outcomes were monitored at baseline and at 1, 3, 6, 9 and 12 months during the course of treatment with HAART.Results One patient died and another was lost from the follow-up. For the remaining 101 HIV/AIDS patients at the 12th month during the HAART, the plasma viral load (VL) was reduced to (3.2±0.7) lg copies/ml, the CD4+ count increased to (168±51) cells/μl [among which the naive phenotype (CD45RA+CD62L+) increased to (49±27) cells/μl and the memory phenotype (CD45RA ̄) increased to (119±55) cells/μl], and the percentage of CD4+CD28+ cells increased. At the same time, there was a significant reduction of CD8+ T cell activation. In the 69 patients with the baseline CD4+ count <100 cells/μl, 37 had a VL <50 copies/ml; while in the 34 patients with the baseline CD4+ count ≥ 100 cells/μl, 25 had a VL <50 copies/ml, the difference between the two groups was statistically significant. The CD4+ T cell count showed a two-phase increase during HAART and a significant positive correlation was shown between the change of CD4+ count and plasma VL. Over 12 months of HAART,10 patients had gastrointestinal side effects, 13 peripheral neuritis, 7 hepatic lesions, 8 hematological side effects,8 skin rashes, 10 lipodystrophy and 1 renal calculus.Conclusions Immune reconstitution as well as the significantly improved clinical outcomes is observed in Chinese advanced AIDS

  7. Modified coronally advanced flap with and without orthodontic button application in management of multiple proximate gingival recession defects: A randomized clinical trial (United States)

    Khobragade, Sumedh; Kolte, Abhay; Kolte, Rajashri; Shrirao, Tushar; Potey, Anushree


    Background: Gingival recession indicates oral display of the root surface due to apical movement of gingival margin. Coronally advanced flap (CAF) is often used periodontal plastic surgical technique to accomplish root coverage. The purpose of this clinical trial is to assess and compare the effectiveness of modified CAF with orthodontic button application (CAF+B) and without orthodontic button application (CAF) for the correction of multiple recession defects. Materials and Methods: Twenty patients exhibiting bilateral multiple proximate Millers Class I and/or Class II gingival recession defects were included in the study. Each set of proximate recession defects was designated randomly to test or control group. Control group was treated by CAF alone and test group by CAF+B. Baseline and postoperative clinical parameters at 2, 4, and 6 months time interval were recorded. Results: Mean root coverage percentage from baseline to 6 months in control group was 78.30% ± 20.75% and in test group was 92.23% ± 15.6%. Complete root coverage was 43.8% in control group and 77.47% in test group. Visual analog scale pain measurements did not reveal any difference among both the groups. Patient satisfaction with esthetics was very high in CAF+B group when compared with CAF group. Conclusion: Both treatment modalities, i.e., CAF and CAF+B are effectual in the treatment of proximate Miller's Class I and Class II gingival recession defects, but CAF+B showed significantly superior clinical results. PMID:27994426

  8. Using systematically observed clinical encounters (SOCEs to assess medical students’ skills in clinical settings

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    George R Bergus


    Full Text Available George R Bergus1–3, Jerold C Woodhead4, Clarence D Kreiter2,51Performance Based Assessment Program, Office of Student Affairs and Curriculum, 2Department of Family Medicine, 3Department of Psychiatry, 4Department of Pediatrics, 5Office of Consultation and Research in Medical Education, Roy J and Lucille A Carver College of Medicine, The University of Iowa, Iowa City, IA, USAIntroduction: The Objective Structured Clinical Examination (OSCE is widely used to assess the clinical performance of medical students. However, concerns related to cost, availability, and validity, have led educators to investigate alternatives to the OSCE. Some alternatives involve assessing students while they provide care to patients – the mini-CEX (mini-Clinical Evaluation Exercise and the Long Case are examples. We investigated the psychometrics of systematically observed clinical encounters (SOCEs, in which physicians are supplemented by lay trained observers, as a means of assessing the clinical performances of medical students.Methods: During the pediatrics clerkship at the University of Iowa, trained lay observers assessed the communication skills of third-year medical students using a communication checklist while the students interviewed and examined pediatric patients. Students then verbally presented their findings to faculty, who assessed students’ clinical skills using a standardized form. The reliability of the combined communication and clinical skills scores was calculated using generalizability theory.Results: Fifty-one medical students completed 199 observed patient encounters. The mean combined clinical and communication skills score (out of a maximum 45 points was 40.8 (standard deviation 3.3. The calculated reliability of the SOCE scores, using generalizability theory, from 10 observed patient encounters was 0.81. Students reported receiving helpful feedback from faculty after 97% of their observed clinical encounters.Conclusion: The SOCE can

  9. Classification and Regression Tree Analysis of Clinical Patterns to Predict the Survival of Patients with Advanced Non-small Cell Lung Cancer Treated with Erlotinib

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    Yutao LIU


    Full Text Available Background and objective Erlotinib is a targeted therapy drug for non-small cell lung cancer (NSCLC. It has been proven that, there was evidence of various survival benefits derived from erlotinib in patients with different clinical features, but the results are conflicting. The aim of this study is to identify novel predictive factors and explore the interactions between clinical variables as well as their impact on the survival of Chinese patients with advanced NSCLC heavily treated with erlotinib. Methods The clinical and follow-up data of 105 Chinese NSCLC patients referred to the Cancer Hospital and Institute, Chinese Academy of Medical Sciences from September 2006 to September 2009 were analyzed. Multivariate analysis of progressive-free survival (PFS was performed using recursive partitioning referred to as the classification and regression tree (CART analysis. Results The median PFS of 105 eligible consecutive Chinese NSCLC patients was 5.0 months (95%CI: 2.9-7.1. CART analysis was performed for the initial, second, and third split in the lymph node involvement, the time of erlotinib administration, and smoking history. Four terminal subgroups were formed. The longer values for the median PFS were 11.0 months (95%CI: 8.9-13.1 for the subgroup with no lymph node metastasis and 10.0 months (95%CI: 7.9-12.1 for the subgroup with lymph node involvement, but not over the second-line erlotinib treatment with a smoking history ≤35 packs per year. The shorter values for the median PFS were 2.3 months (95%CI: 1.6-3.0 for the subgroup with lymph node metastasis and over the second-line erlotinib treatment, and 1.3 months (95%CI: 0.5-2.1 for the subgroup with lymph node metastasis, but not over the second-line erlotinib treatment with a smoking history >35 packs per year. Conclusion Lymph node metastasis, the time of erlotinib administration, and smoking history are closely correlated with the survival of advanced NSCLC patients with first- to

  10. Review: Advances in delta-subsidence research using satellite methods (United States)

    Higgins, Stephanie A.


    Most of the world's major river deltas are sinking relative to local sea level. The effects of subsidence can include aquifer salinization, infrastructure damage, increased vulnerability to flooding and storm surges, and permanent inundation of low-lying land. Consequently, determining the relative importance of natural vs. anthropogenic pressures in driving delta subsidence is a topic of ongoing research. This article presents a review of knowledge with respect to delta surface-elevation loss. The field is rapidly advancing due to applications of space-based techniques: InSAR (interferometric synthetic aperture radar), GPS (global positioning system), and satellite ocean altimetry. These techniques have shed new light on a variety of subsidence processes, including tectonics, isostatic adjustment, and the spatial and temporal variability of sediment compaction. They also confirm that subsidence associated with fluid extraction can outpace sea-level rise by up to two orders of magnitude, resulting in effective sea-level rise that is one-hundred times faster than the global average rate. In coming years, space-based and airborne instruments will be critical in providing near-real-time monitoring to facilitate management decisions in sinking deltas. However, ground-based observations continue to be necessary for generating complete measurements of surface-elevation change. Numerical modeling should seek to simulate couplings between subsidence processes for greater predictive power.

  11. Fluvial Morphodynamics: advancing understanding using Multibeam Echo Sounders (MBES) (United States)

    Parsons, D. R.; Best, J. L.


    Accurately and reliably determining riverbed morphology is key to understanding linkages between flow fields, sediment transport and bed roughness in a range of aquatic environments, including large fluvial channels. Modern shallow-water multibeam echo sounder (MBES) systems are now allowing us to acquire bathymetric data at unprecedented resolutions that are millimetric in precision and centimetric in accuracy. Such systems, and the morphological resolution they can supply, are capable of revealing the complex three-dimensional patterns in riverbed morphology that are facilitating a holistic examination of system morphodynamics, at the field scale, that was unimaginable just a few years ago. This paper presents a range of MBES acquired examples to demonstrate how the methodological developments in this technology are leading to advances in our substantive understanding of large river systems. This includes examples that show linkages across scales, and in particular the morphodynamics of superimposed bedforms and bars revealed by such high-resolution data, which have broad implications for a range of applications, including flood prediction, engineering design and reconstructing ancient sedimentary environments.

  12. Fine coal circuitry using advanced physical cleaning processes

    Energy Technology Data Exchange (ETDEWEB)

    Honaker, R.Q.; Mohanty, M.K.; Wang, D. [Southern Illinois Univ., Carbondale, IL (United States). Dept. of Mining Engineering; Ho, K. [Illinois Clean Coal Inst., Carterville, IL (United States)


    Recent investigations have found that enhanced gravity separators (EGS) and flotation columns are highly efficient for cleaning fine coal. The test results presented in this publication show that a circuit comprised of two advanced gravity separators, i.e., a hindered-bed classifier and an EGS, and a flotation column provides an enhanced cleaning efficiency for the treatment of {minus}16 mesh coal. From in-plant experiments, the hindered-bed classifier was found to be a more efficient separation device (E{sub p} = 0.12) than coal spirals (E{sub p} = 0.18) for the treatment of a nominally 16 x 100 mesh coal. Since its efficiency declines for particle sizes less than 48 mesh, the hindered-bed classifier overflow was screened to produce a final +48 mesh concentrate and a {minus}48 mesh fraction that was subsequently treated by circuits incorporating the EGS and flotation column in combination and separately. The best overall circuits in terms of both ash and total sulfur reductions for treating the -16 mesh coal was found to be the Hindered Bed-EGS-EGS and Hindered Bed-EGS-Column circuits. Both circuits rejected over 70% of the ash and over 60% of the pyritic sulfur while recovering over 85% of the combustible material.

  13. 21 CFR 862.2860 - Mass spectrometer for clinical use. (United States)


    ... clinical use is a device intended to identify inorganic or organic compounds (e.g., lead, mercury, and drugs) in human specimens by ionizing the compound under investigation and separating the resulting...

  14. Use of crowdsourcing for cancer clinical trial development. (United States)

    Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D


    Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct.

  15. Advanced Clinical Decision Support for Transport of the Critically Ill Patient (United States)


    muscle use • Inspiratory /expiratory wheezes Children I Adolescents: • Prefer sitting upright • Short phrases, one word answers • Inspiratory other scenarios and arenas. Another potential area of use would be in training army and navy flight medics, such as at Fort Rucker training ...with beta agonist use compared to adults d)AIIow patient to assume position of comfort (usually tripod NOT supine) to allow for accessory muscle

  16. Clinical usefulness of the Vaughan Williams classification system. (United States)

    Cobbe, S M


    The clinical usefulness of the Vaughan Williams classification scheme is limited by the complexity of the mechanisms of arrhythmia formation in man, which offer multiple potential sites for intervention. The properties of antiarrhythmic drugs may be considerably altered in abnormal myocardium. Despite these limitations, however, the classification provides a valuable conceptual framework for the understanding of the clinical electrophysiological properties of antiarrhythmic drugs and for their use.

  17. Surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft (United States)

    Bellver-Fernández, Ricardo; Martínez-Rodriguez, Ana-María; Gioia-Palavecino, Claudio; Caffesse, Raul-Guillermo


    Background A coronally advanced flap with subepithelial connective tissue graft is the gold standard surgical treatment of gingival recessions, since it offers a higher probability of achieving complete root coverage compared with other techniques. However, optimum short- and middle-term clinical results have also been obtained with coronally advanced flaps alone. The aim of the present study was to evaluate the results obtained by the surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft. Material and Methods The reduction of recession height was assessed, together with the gain in gingival attachment apical to the recession, and total reduction of recession, in a comparative study of two techniques. Twenty-two gingival recessions were operated upon: 13 in the control group (coronally advanced flap) and 9 in the test group (coronally advanced flap associated to subepithelial connective tissue graft). Results After 18 months, the mean reduction of recession height was 2.2 ± 0.8 mm in the control group and 2.3 ± 0.7 mm in the test group, with a mean gain in gingival attachment of 1.3 ± 0.9 mm and 2.3 ± 1.3 mm, respectively. In percentage terms, the mean reduction of recession height was 84.6 ± 19.6% in the control group and 81.7 ± 17.8% in the test group, with a mean gain in gingival attachment of 20.5 ± 37.4% and 184.4 ± 135.5%, respectively. Conclusions Significant reduction of gingival recession was achieved with both techniques, though the mean gain in gingival attachment (in mm and as a %) was greater in test group. Key words:Gingival recession, coronally advanced flap, subepthelial connective tissue graft. PMID:26595836

  18. Assessment of advanced glycated end product accumulation in skin using auto fluorescence multispectral imaging. (United States)

    Larsson, Marcus; Favilla, Riccardo; Strömberg, Tomas


    Several studies have shown that advanced glycation end products (AGE) play a role in both the microvascular and macrovascular complications of diabetes and are closely linked to inflammation and atherosclerosis. AGEs accumulate in skin and can be detected using their auto fluorescence (AF). A significant correlation exists between AGE AF and the levels of AGEs as obtained from skin biopsies. A commercial device, the AGE Reader, has become available to assess skin AF for clinical purposes but, while displaying promising results, it is limited to single-point measurements performed in contact to skin tissue. Furthermore, in vivo imaging of AGE accumulation is virtually unexplored. We proposed a non-invasive, contact-less novel technique for quantifying fluorescent AGE deposits in skin tissue using a multispectral imaging camera setup (MSI) during ultraviolet (UV) exposure. Imaging involved applying a region-of-interest mask, avoiding specular reflections and a simple calibration. Results of a study conducted on 16 subjects with skin types ranging from fair to deeply pigmented skin, showed that AGE measured with MSI in forearm skin was significantly correlated with the AGE reference method (AGE Reader on forearm skin, R=0.68, p=0.005). AGE measured in facial skin was borderline significantly related to AGE Reader on forearm skin (R=0.47, p=0.078). These results support the use of the technique in devices for non-touch measurement of AGE content in either facial or forearm skin tissue over time.

  19. Clinical usefulness of calcaneal measurements using dual energy x-ray absorptiometry

    Energy Technology Data Exchange (ETDEWEB)

    Kohno, Jun [Nagasaki Saiseikai Hospital (Japan); Nakata, Tomoko; Ito, Masako


    To investigate the clinical usefulness of calcaneal measurement using dual-energy x-ray absorptiometry (DXA), the ability to detect bone loss and fracture risk were evaluated in comparison with spinal bone mineral density (BMD) measured using DXA and quantitative CT (QCT) and with calcaneal quantitative ultrasound (QUS). Furthermore, to investigate the region in calcaneus in which to detect bone change sensitively, the ability to detect bone loss and fracture risk were also evaluated using new regions of interest (ROIs) that were manually defined. The subjects were 165 healthy women, and 188 female patients with fracture, estrogen deficiency, and steroid-induced osteoporosis. Calcaneal BMD with some manually defined ROIs showed lower precision and less sensitivity in detecting bone loss than BMD measured with automatically defined ROIs. Calcaneal DXA, spinal DXA, and QCT demonstrated significant age-related bone loss, and all measurements could discriminate fracture cases from non-fracture cases. Calcaneal DXA could discriminate the bone loss associated with estrogen deficiency as well as spinal DXA. Furthermore, calcaneal measurements showed a greater ability to detect steroid-induced bone loss than spinal DXA, probably because this group included subjects of advanced age with spondylosis. In conclusion, calcaneal DXA is useful to assess BMD in subjects who are not suitable for spinal measurement, although the ability to detect age-related bone loss in calcaneal DXA is less than in spinal measurements. (author)

  20. Data management by using R: big data clinical research series. (United States)

    Zhang, Zhongheng


    Electronic medical record (EMR) system has been widely used in clinical practice. Instead of traditional record system by hand writing and recording, the EMR makes big data clinical research feasible. The most important feature of big data research is its real-world setting. Furthermore, big data research can provide all aspects of information related to healthcare. However, big data research requires some skills on data management, which however, is always lacking in the curriculum of medical education. This greatly hinders doctors from testing their clinical hypothesis by using EMR. To make ends meet, a series of articles introducing data management techniques are put forward to guide clinicians to big data clinical research. The present educational article firstly introduces some basic knowledge on R language, followed by some data management skills on creating new variables, recoding variables and renaming variables. These are very basic skills and may be used in every project of big data research.

  1. Enhancing Patient Safety Using Clinical Nursing Data: A Pilot Study. (United States)

    Choi, Jeeyae; Choi, Jeungok E


    To enhance patient safety from falls, many hospital information systems have been implemented to collect clinical data from the bedside and have used the information to improve fall prevention care. However, most of them use administrative data not clinical nursing data. This necessitated the development of a web-based Nursing Practice and Research Information Management System (NPRIMS) that processes clinical nursing data to measure nurses' delivery of fall prevention care and its impact on patient outcomes. This pilot study developed computer algorithms based on a falls prevention protocol and programmed the prototype NPRIMS. It successfully measured the performance of nursing care delivered and its impact on patient outcomes using clinical nursing data from the study site. Results of the study revealed that NPRIMS has the potential to pinpoint components of nursing processes that are in need of improvement for preventing patient from falls.

  2. The art of effectively teaching clinical interviewing skills using role-playing: a primer. (United States)

    Barney, Christine; Shea, Shawn Christopher


    Time pressure on trainees and supervisors alike places a premium on efficiency in training students to master clinical skills. Through role-playing, a supervisor can create multiple iterations of the desired skill until competence is obtained. The skill training can be advanced in intensity and complexity until the trainer and trainee are confident that the interviewing skill is accessible on demand and that the trainee is comfortable with its use. This article focuses on practical methods of creating believable roles for role-playing and how to use them to teach specific interviewing skills strategically.

  3. Quantitative Clinical Chemistry Proteomics (qCCP) using mass spectrometry: general characteristics and application. (United States)

    Lehmann, Sylvain; Hoofnagle, Andrew; Hochstrasser, Denis; Brede, Cato; Glueckmann, Matthias; Cocho, José A; Ceglarek, Uta; Lenz, Christof; Vialaret, Jérôme; Scherl, Alexander; Hirtz, Christophe


    Proteomics studies typically aim to exhaustively detect peptides/proteins in a given biological sample. Over the past decade, the number of publications using proteomics methodologies has exploded. This was made possible due to the availability of high-quality genomic data and many technological advances in the fields of microfluidics and mass spectrometry. Proteomics in biomedical research was initially used in 'functional' studies for the identification of proteins involved in pathophysiological processes, complexes and networks. Improved sensitivity of instrumentation facilitated the analysis of even more complex sample types, including human biological fluids. It is at that point the field of clinical proteomics was born, and its fundamental aim was the discovery and (ideally) validation of biomarkers for the diagnosis, prognosis, or therapeutic monitoring of disease. Eventually, it was recognized that the technologies used in clinical proteomics studies [particularly liquid chromatography-tandem mass spectrometry (LC-MS/MS)] could represent an alternative to classical immunochemical assays. Prior to deploying MS in the measurement of peptides/proteins in the clinical laboratory, it seems likely that traditional proteomics workflows and data management systems will need to adapt to the clinical environment and meet in vitro diagnostic (IVD) regulatory constraints. This defines a new field, as reviewed in this article, that we have termed quantitative Clinical Chemistry Proteomics (qCCP).

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

    Directory of Open Access Journals (Sweden)

    Holly Keyt


    Full Text Available 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.

  5. [Clinical and economic evaluation of the introduction of the combinazion trametinib + dabrafenib in the management of advanced melanoma in the Italian market

    Directory of Open Access Journals (Sweden)

    Lorenzo Pradelli


    Full Text Available Melanoma is the most aggressive type of all skin cancers. In Italy the incidence is increasing both in men and in women with 13,800 new cases expected in 2016. The advanced melanoma therapy has changed in recent years with the use of immunotherapy and targeted therapies. In particular, treatment with BRAF inhibitors in patients with advanced BRAF V600 mutated melanoma has shown high rates of rapid response and survival. Due to development of acquired resistance with disease progression the rapid response observed with BRAF inhibitor therapy is not long lasting. Combining a BRAF inhibitor with a MEK inhibitor may help to delay the development of resistance and to enhance the antitumor activities with a further increase in the response and survival rate. Trametinib, an inhibitor of MEK kinases, and dabrafenib, an inhibitor of BRAF kinase, have authorizations as monotherapies and in combination with each other for treating adults with unresectable or metastatic melanoma with BRAF V600 mutation. Purpose of this report is to describe the combination in terms of clinical efficacy, safety, and economic impact. In particular, a cost-effectiveness analysis and a budget impact analysis were performed in order to evaluate the combination versus monotherapy and the financial sustainability of trametinib + dabrafenib on the Italian market. [In Italian

  6. Clinical experience and critical evaluation of the role of everolimus in advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sun M


    Full Text Available Maxine Sun1, Firas Abdollah2, Jan Schmitges1, Claudio Jeldres1, Shahrokh F Shariat3, Paul Perrotte4, Pierre I Karakiewicz1,4 1Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada; 2Department of Urology, Vita Salute San Raffaele University, Milan, Italy; 3Department of Urology, Weill Medical College of Cornell University, New York, NY, USA; 4Department of Urology, University of Montreal Health Center, Montreal, CanadaAbstract: The efficacy of sequential everolimus, an orally administered inhibitor of mammalian target of rapamycin (mTOR, was proven in a placebo-controlled phase III study, where median progression-free survival was 4.9 vs 1.9 months for placebo (hazard ratio: 0.33, P < 0.001. Placebo crossovers (80% contaminated overall survival data. Adverse event discontinuation rate was of only 10% and health-adjusted quality-of-life was sustained. These data represent the first placebo-controlled evidence of efficacy for a seque ntially used targeted agent. Everolimus resulted in the strongest hazard ratio ever recorded for progression-free survival, despite it being tested in a population with the most aggressive natural history ever recorded in all available phase III metastatic renal cell carcinoma trials. Everolimus use after exclusively one prior antivascular endothelial growth factor f ailure resulted in an even longer progression-free survival time (5.4 months than in the entire population (4.9 months. These benefits should also be considered in the light of sustained and unimpaired health-related quality of life. Use in first line other than second or subsequent lines remains to be validated.Keywords: everolimus, metastatic renal cell carcinoma, targeted therapy, sequential therapy, mTOR

  7. Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived advanced glycation endproducts : An overview of current clinical studies, evidence, and limitations

    NARCIS (Netherlands)

    Mulder, Douwe J.; Van de Water, Tara; Lutgers, Helen L.; Graaff, Reindert; Gans, Rijk O.; Zijlstra, Felix; Smit, Andries J.


    Background: Advanced glycation endproducts (AGES) predict long-term complications in age-related diseases. However, there are no clinically applicable markers for measuring AGES in vivo. Methods: We have recently introduced the AGE-Reader (DiagnOptics B.V., Groningen, The Netherlands) to noninvasive

  8. The frequencies and clinical implications of mutations in 33 kinase-related genes in locally advanced rectal cancer: a pilot study.

    LENUS (Irish Health Repository)

    Abdul-Jalil, Khairun I


    Locally advanced rectal cancer (LARC: T3\\/4 and\\/or node-positive) is treated with preoperative\\/neoadjuvant chemoradiotherapy (CRT), but responses are not uniform. The phosphatidylinositol 3-kinase (PI3K), MAP kinase (MAPK), and related pathways are implicated in rectal cancer tumorigenesis. Here, we investigated the association between genetic mutations in these pathways and LARC clinical outcomes.

  9. 75 FR 7990 - Use of Community Development Loans by Community Financial Institutions To Secure Advances... (United States)


    ...'s separate rulemaking addressing Bank membership for community development financial institutions... Use of Community Development Loans by Community Financial Institutions To Secure Advances; Secured... eligible collateral that community financial institution (CFI) members may pledge to secure Federal...

  10. Simulation of advanced ultrasound systems using Field II

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt


    The background and basic features of the Field II simulation program are described. It can simulate any linear ultrasound system, which can use single or multi-element transducers. Any kind of apodization, focusing, and excitation can be used. The basic theory behind the program's use of spatial...

  11. Advances in the clinical management of inhibitors in hemophilia A and B. (United States)

    Leissinger, Cindy A


    Inhibitors to factor (F)VIII or FIX are the most serious and challenging complication of hemophilia treatment, increasing morbidity and mortality because bleeds no longer respond to standard clotting factor replacement therapy. For patients with high-titer inhibitors, immune tolerance induction achieved through regular factor exposure is the only proven therapy capable of Inhibitor eradication and is almost always indicated for inhibitors of recent onset. Bypassing therapy is used to treat and prevent bleeding, but neither of the two currently available bypassing agents has the predictable hemostatic efficacy of factor replacement in hemophilia patients without inhibitors. Major research efforts are focused on the development of new, more potent therapies for the management of patients with inhibitors.

  12. The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy. (United States)

    Faloppi, Luca; Del Prete, Michela; Casadei Gardini, Andrea; Santini, Daniele; Silvestris, Nicola; Bianconi, Maristella; Giampieri, Riccardo; Valgiusti, Martina; Brunetti, Oronzo; Bittoni, Alessandro; Andrikou, Kalliopi; Lai, Eleonora; Dessì, Alessandra; Cascinu, Stefano; Scartozzi, Mario


    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.

  13. The effectiveness of enamel matrix protein (Emdogain® in combination with coronally advanced flap in the treatment of multiple marginal tissue recession: A clinical study

    Directory of Open Access Journals (Sweden)

    Gagan R Jaiswal


    Full Text Available Background: Gingival recession resulting in root exposure is a common problem faced by clinicians. This clinical study compared the results obtained by treating gingival recession using enamel matrix derivative (Emdogain gel® along with coronally positioned flap and coronally positioned flap alone. Materials and Methods: Twenty patients with a total of 46 gingival recession defects, each patient with a minimum of two recession defects, were included in the study. The test group, which consisted of 10 patients with 22 recession defects, was treated by enamel matrix derivatives (Emdogain gel in combination with a coronally positioned flap, while the control group, which consisted of 10 patients with 24 gingival recession defects, was treated with 24% ethylenediaminetetraacetic acid (EDTA; Prefgel® in combination with coronally positioned flap. Results: Student′s paired and unpaired t-test was used for statistical analysis. If the probability value (P was less than 0.05, it was considered significant. Data from this study demonstrated that application of (EMD Emdogain gel resulted in a statistically significant increase in root coverage, gain in the clinical attachment level (CAL, and probing pocket depth (PPD reduction when compared with coronally advanced flap (CAF alone, but there was no statistically significant difference in the width of keratinized gingiva (WKG between the two groups.

  14. Advances in the meta-analysis of heterogeneous clinical trials I: The inverse variance heterogeneity model. (United States)

    Doi, Suhail A R; Barendregt, Jan J; Khan, Shahjahan; Thalib, Lukman; Williams, Gail M


    This article examines an improved alternative to the random effects (RE) model for meta-analysis of heterogeneous studies. It is shown that the known issues of underestimation of the statistical error and spuriously overconfident estimates with the RE model can be resolved by the use of an estimator under the fixed effect model assumption with a quasi-likelihood based variance structure - the IVhet model. Extensive simulations confirm that this estimator retains a correct coverage probability and a lower observed variance than the RE model estimator, regardless of heterogeneity. When the proposed IVhet method is applied to the controversial meta-analysis of intravenous magnesium for the prevention of mortality after myocardial infarction, the pooled OR is 1.01 (95% CI 0.71-1.46) which not only favors the larger studies but also indicates more uncertainty around the point estimate. In comparison, under the RE model the pooled OR is 0.71 (95% CI 0.57-0.89) which, given the simulation results, reflects underestimation of the statistical error. Given the compelling evidence generated, we recommend that the IVhet model replace both the FE and RE models. To facilitate this, it has been implemented into free meta-analysis software called MetaXL which can be downloaded from

  15. Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells. (United States)

    Li, Jun; Song, Wei; Pan, Guangjin; Zhou, Jun


    Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.

  16. Evaluation of Pediatric Manual Wheelchair Mobility Using Advanced Biomechanical Methods



    There is minimal research of upper extremity joint dynamics during pediatric wheelchair mobility despite the large number of children using manual wheelchairs. Special concern arises with the pediatric population, particularly in regard to the longer duration of wheelchair use, joint integrity, participation and community integration, and transitional care into adulthood. This study seeks to provide evaluation methods for characterizing the biomechanics of wheelchair use by children with sp...

  17. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

    Directory of Open Access Journals (Sweden)

    Fine Howard A


    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  18. Using multimodal mining to drive clinical guidelines development. (United States)

    Pasche, Emilie; Gobeill, Julien; Teodoro, Douglas; Vishnyakova, Dina; Gaudinat, Arnaud; Ruch, Patrick; Lovis, Christian


    We present exploratory investigations of multimodal mining to help designing clinical guidelines for antibiotherapy. Our approach is based on the assumption that combining various sources of data, such as the literature, a clinical datawarehouse, as well as information regarding costs will result in better recommendations. Compared to our baseline recommendation system based on a question-answering engine built on top of PubMed, an improvement of +16% is observed when clinical data (i.e. resistance profiles) are injected into the model. In complement to PubMed, an alternative search strategy is reported, which is significantly improved by the use of the combined multimodal approach. These results suggest that combining literature-based discovery with structured data mining can significantly improve effectiveness of decision-support systems for authors of clinical practice guidelines.

  19. Clinical outcome of advanced and metastatic renal cell carcinoma treated with targeted therapy: is there a difference between young and old patients?

    Directory of Open Access Journals (Sweden)

    Zhang G


    Full Text Available Guiming Zhang,1,2,* Yao Zhu,1,2,* Dahai Dong,3 Weijie Gu,1,2 Hailiang Zhang,1,2 Lijiang Sun,3 Dingwei Ye1,2 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; 3Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China *These authors contributed equally to this work Background: To assess whether the clinical outcome of advanced and metastatic renal cell carcinoma (mRCC treated with targeted therapy differs between young and old patients. Patients and methods: A total of 327 patients with advanced renal cell carcinoma and mRCC who received targeted therapy in two Chinese clinical centers were analyzed retrospectively. The patients were stratified into three groups: young (aged <45 years, middle-aged (aged 45–64 years, and old (aged ≥65 years. Overall survival (OS and progression-free survival (PFS curves were drawn using the Kaplan–Meier method, and Cox's proportional hazard regression model was used to compare OS and PFS within age groups. Results: There were no significant differences among young, middle-aged, and old groups in terms of OS (P=0.087, whereas PFS in the old group was significantly better than in the young and middle-aged groups (P=0.043. Both OS and PFS in the younger groups (aged <65 years were significantly worse than in the old group (age ≥65 years; median OS, 28.1 vs 28.7 months [P=0.029]; median PFS, 11.4 vs 14 months [P=0.015]. No difference in OS or PFS was found between the young and middle-aged groups. After adjusting for sex, body mass index, smoking status, hypertension, diabetes mellitus, Eastern Cooperative Oncology Group score, history of cytokines, and Fuhrman grade, old age was an independent favorable prognostic factor for OS and PFS compared with younger age (<65 years (OS, hazard ratio, 0.552 [95

  20. Conocimientos de los alumnos de últimos años de Medicina y residentes sobre indicadores de riesgo epidemiológico utilizados en ensayos clínicos Knowledge of epidemiological risk indicators used in clinical trials among medical students in advanced years and medical residents

    Directory of Open Access Journals (Sweden)

    Alonso Zea-Vera


    Full Text Available Estudio que evaluó el conocimiento de 182 estudiantes de los dos últimos años de medicina y 70 residentes de un hospital nacional de Perú, sobre los indicadores de riesgo utilizados en la presentación de resultados en ensayos clínicos. Se realizó un estudio transversal en el que se aplicó un cuestionario que evaluó la capacidad de reconocer y calcular los indicadores de riesgo epidemiológico más utilizados en la literatura médica. El 19,4% no reconoció ninguno de los indicadores y el 81,4% no logró calcularlos. La reducción de riesgo relativo fue el indicador más reconocido (55,2%, seguida del número necesario a tratar (51,6%; reducción de riesgo absoluto (26,6%, y hazard ratio (9,5%. En conclusión, los alumnos de los dos últimos años de medicina y los residentes, no reconocen ni calculan adecuadamente los indicadores de riesgo utilizados en ensayos clínicos.A cross-sectional study evaluated 182 students in the last two years of medical school and 70 residents of a national hospital in Peru on the risk indicators used for reporting results in clinical trials. A questionnaire was used to assess the ability to recognize and calculate risk indicators most widely used in the epidemiological literature. From the participants, 19.4% did not recognize any of the indicators and 81.4% was not able to calculate them. The relative risk reduction was the most recognized indicator (55.2%, followed by the number needed to treat (51.6%, the absolute risk reduction (26.6%, and the hazard ratio (9.5%. In conclusion, medical students in the last two years of school and medical residents do not recognize or are able to calculate properly the risk indicators used in clinical trials.

  1. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Rothschild SI


    Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

  2. Advances in levodopa therapy for Parkinson disease: Review of RYTARY (carbidopa and levodopa) clinical efficacy and safety. (United States)

    Dhall, Rohit; Kreitzman, David L


    Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative disorder with progressive motor symptoms that can be managed with treatments. Levodopa is generally recognized as the most effective and widely used treatment for PD. It improves function and quality of life, morbidity, and mortality, and therefore reduces individual and societal costs. Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease. Immediate-release and controlled-release formulations have been used with success, but motor fluctuations remain a problem. RYTARY (levodopa and carbidopa, IPX066) is an oral extended-release therapy composed of carbidopa-levodopa microbeads designed to dissolve at various rates that allows for quick absorption and sustained levodopa release over an extended period. In development studies, RYTARY improved symptoms in patients with both early and advanced PD and offered significantly improved Unified Parkinson Disease Rating Scale scores and "on" times, without worsening troublesome dyskinesias when compared to other levodopa formulations. Tolerability and safety were comparable to other formulations. This section reviews the data that support the use of RYTARY in the treatment of PD.

  3. Plan of advanced satellite communication experiments using ETS-6 (United States)

    Ikegami, Tetsushi


    In 1992, an Engineering Test Satellite 6 is scheduled to be launched by an H-2 rocket. The missions of ETS-6 are to establish basic technologies of inter-satellite communications using S-band, millimeter waves and optical beams and of fixed and mobile satellite communications using multibeam antenna on board the satellite. A plan of the experiments is introduced.

  4. Using systems thinking to support clinical system transformation. (United States)

    Best, Allan; Berland, Alex; Herbert, Carol; Bitz, Jennifer; van Dijk, Marlies W; Krause, Christina; Cochrane, Douglas; Noel, Kevin; Marsden, Julian; McKeown, Shari; Millar, John


    Purpose - The British Columbia Ministry of Health's Clinical Care Management initiative was used as a case study to better understand large-scale change (LSC) within BC's health system. Using a complex system framework, the purpose of this paper is to examine mechanisms that enable and constrain the implementation of clinical guidelines across various clinical settings. Design/methodology/approach - Researchers applied a general model of complex adaptive systems plus two specific conceptual frameworks (realist evaluation and system dynamics mapping) to define and study enablers and constraints. Focus group sessions and interviews with clinicians, executives, managers and board members were validated through an online survey. Findings - The functional themes for managing large-scale clinical change included: creating a context to prepare clinicians for health system transformation initiatives; promoting shared clinical leadership; strengthening knowledge management, strategic communications and opportunities for networking; and clearing pathways through the complexity of a multilevel, dynamic system. Research limitations/implications - The action research methodology was designed to guide continuing improvement of implementation. A sample of initiatives was selected; it was not intended to compare and contrast facilitators and barriers across all initiatives and regions. Similarly, evaluating the results or process of guideline implementation was outside the scope; the methods were designed to enable conversations at multiple levels - policy, management and practice - about how to improve implementation. The study is best seen as a case study of LSC, offering a possible model for replication by others and a tool to shape further dialogue. Practical implications - Recommended action-oriented strategies included engaging local champions; supporting local adaptation for implementation of clinical guidelines; strengthening local teams to guide implementation; reducing

  5. Appreciative inquiry enhances cardiology nurses’ clinical decision making when using a clinical guideline on delirium

    DEFF Research Database (Denmark)

    Vedsegaard, Helle; Schrader, Anne-Marie; Rom, Gitte


    and axial coding drawing on the principles of grounded theory. The study shows that appreciative inquiry was meaningful to cardiology nurses in providing them with knowledge of using a guideline on delirium in clinical decision making, the main reasons being a) data on a current patient were included, b...

  6. Performance-Based Assessment of Clinical Ethics Using an Objective Structured Clinical Examination. (United States)

    Singer, Peter A.; And Others


    Final-year Ontario medical students (n=88) took a 4-station objective structured clinical examination (OSCE) using standardized patients and involving decisions to forgo life-sustaining treatment. Performance was scored on a checklist of behaviors unique to each case. Results indicated that because of low reliability, the OSCE is not a feasible…

  7. Experimental verification of Advanced Collapsed-cone Engine for use with a multichannel vaginal cylinder applicator. (United States)

    Cawston-Grant, Brie; Morrison, Hali; Menon, Geetha; Sloboda, Ron S


    Model-based dose calculation algorithms have recently been incorporated into brachytherapy treatment planning systems, and their introduction requires critical evaluation before clinical implementation. Here, we present an experimental evaluation of Oncentra(®) Brachy Advanced Collapsed-cone Engine (ACE) for a multichannel vaginal cylinder (MCVC) applicator using radiochromic film. A uniform dose of 500 cGy was specified to the surface of the MCVC using the TG-43 dose formalism under two conditions: (a) with only the central channel loaded or (b) only the peripheral channels loaded. Film measurements were made at the applicator surface and compared to the doses calculated using TG-43, standard accuracy ACE (sACE), and high accuracy ACE (hACE). When the central channel of the applicator was used, the film measurements showed a dose increase of (11 ± 8)% (k = 2) above the two outer grooves on the applicator surface. This increase in dose was confirmed with the hACE calculations, but was not confirmed with the sACE calculations at the applicator surface. When the peripheral channels were used, a periodic azimuthal variation in measured dose was observed around the applicator. The sACE and hACE calculations confirmed this variation and agreed within 1% of each other at the applicator surface. Additionally for the film measurements with the central channel used, a baseline dose variation of (10 ± 4)% (k = 2) of the mean dose was observed azimuthally around the applicator surface, which can be explained by offset source positioning in the central channel.


    Directory of Open Access Journals (Sweden)

    D. A. Sychev


    Full Text Available Apixaban is a "new" oral anticoagulant, direct Xa factor inhibitor with a good evidence base of the efficacy in the prevention of ischemic stroke in patients with atrial fibrillation. The article is devoted to apixaban use in clinical practice: examination before apixaban administration, clinical situation when laboratory control and monitoring are needed, drugs interactions (at the level of CYP3A4, P-gp, management of patients with bleeding because of apixaban therapy (including antidotes application, perioperative management of patients receiving apixaban.


    Directory of Open Access Journals (Sweden)

    D. A. Sychev


    Full Text Available Apixaban is a "new" oral anticoagulant, direct Xa factor inhibitor with a good evidence base of the efficacy in the prevention of ischemic stroke in patients with atrial fibrillation. The article is devoted to apixaban use in clinical practice: examination before apixaban administration, clinical situation when laboratory control and monitoring are needed, drugs interactions (at the level of CYP3A4, P-gp, management of patients with bleeding because of apixaban therapy (including antidotes application, perioperative management of patients receiving apixaban.

  10. Characterization of PTFE Using Advanced Thermal Analysis Techniques (United States)

    Blumm, J.; Lindemann, A.; Meyer, M.; Strasser, C.


    Polytetrafluoroethylene (PTFE) is a synthetic fluoropolymer used in numerous industrial applications. It is often referred to by its trademark name, Teflon. Thermal characterization of a PTFE material was carried out using various thermal analysis and thermophysical properties test techniques. The transformation energetics and specific heat were measured employing differential scanning calorimetry. The thermal expansion and the density changes were determined employing pushrod dilatometry. The vi